Aminopyrimidines as syk inhibitors.

(54) Title: AMINOPYRIMIDINES AS SYK INHIBITORS. (54) Title: AMINOPYRIMIDINES AS SYK INHIBITORS.

(57) Summary

The present invention provides new pyrimidine amines of formula (I) that are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, and rheumatoid arthritis.

(57) Abstract

The present invention provides novel pyrimidine amines of formula (I) which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis.

AMINOPYRIMIDINES AS SYK INHIBITORS

BACKGROUND OF THE INVENTION

Spleen Tyrosine Kinase (Syk) is a protein tyrosine kinase that has been described as a key mediator of immunoreceptor signaling, in a host, by inflammatory cells including mast cells, B cells, macrophages, and neutrophils. These immuno receptors, including Fe receptors and B cell receptor, are important for both allergic and autoimmune diseases mediated by antibodies and therefore pharmacologically interfering with Syk could possibly treat these disorders.

Allergic rhinitis and asthma are diseases associated with hypersensitivity reactions and inflammatory events involving a multitude of cell types including mast cells, eosinophils, T cells, and dendritic cells. After allergen exposure, high affinity immunoglobulin receptors for IgE and IgG cross-link and activate downstream processes in mast cells and other cell types leading to the release of pro-inflammatory mediators and spasmogens from the airways. In mast cells, for example, allergen IgE receptor crosslinking leads to the release of mediators including histamine from pre-formed granules, as well as synthesis and release of newly synthesized lipid mediators including prostaglandins and leukotrienes.

Syk kinase is a non-receptor-linked tyrosine kinase that is important in the transduction of cellular signals in the 3 'direction associated with Fc.épsilon.RI and / or Fc.épsilon.RI receptor crosslinking and is located at the beginning of the cascade. Signaling. In mast cells, for example, the early signaling sequence of Fc.épsilon.RI after allergen crosslinking of the receptor-IgE complexes involves first Lyn (a family of Src tyrosine kinases) and then Syk. Inhibitors of Syk activity would therefore be expected to inhibit all signaling cascades in the 3 'direction thus alleviating the immediate allergic response and adverse events initiated by the release of pro-inflammatory mediators and spasmogens (Wong et al 2004, Expert Opin Investig. Drugs (2004) 13 (7) 743-762).

Recently, it has been shown that the kinase inhibitor of

Syk R112 (Rigel), dosed intranasally in a phase l / ll study for the treatment of allergic rhinitis, gave a statistically significant decrease in PGD2, a key immune mediator that is highly correlated with improvements in allergic rhinorrhea, as well as being safe across a range of indicators, thus providing the first evidence for the clinical safety and efficacy of a topical Syk kinase inhibitor. (Meltzer, Eli O .; Berkowitz, Robert B .; Grossbard, Elliott B, Journal of Allergy and Clinical Immunology (2005), 115 (4), 791-796). In a more recent phase II clinical trial for allergic rhinitis (Clinical Trials.gov identifier

NCT0015089), R112 showed no efficacy against placebo.

Rheumatoid Arthritis (RA) is an autoimmune disease that affects approximately 1% of the population. It is characterized by joint inflammation that leads to weakening of bone and cartilage destruction. Recent clinical studies with Rituximab, which causes reversible B-cell depletion, ((JCW Edwards et al 2004, New Eng. J. Med. 350: 2572-2581) have shown that targeting B cell function is an appropriate therapeutic strategy in autoimmune diseases such as RA. The clinical benefit correlates with a reduction in auto-reactive antibodies (or Rheumatoid Factor) and these studies suggest that the function of B cells and indeed the production of autoantibodies is essential for the ongoing pathology in the disease. Studies using cells from mice lacking Spleen Tyrosine Kinase (Syk) have shown a non-redundant role for this kinase in B cell function. Syk deficiency is characterized by a block in B cell development. (M. Turner et al 1995 Nature 379: 298302 and Cheng et al 1995, Nature 378: 303-306). These studies, together with studies on Syk deficient mature B cells (Kurasaki et al 2000, Immunol. Rev. 176: 19-29), demonstrate that Syk is required for differentiation and activation of B cells. Therefore, inhibition of Syk in RA patients is likely to block B cell function and therefore reduce the rheumatoid factor production. In addition to the role of Syk in the function of B cells and of greater importance for the treatment of

AR, is the need for Syk activity in Fe receptor signaling (FcR). Activation of FcR by immune complexes in RA has been suggested to contribute to the release of multiple pro-inflammatory mediators.

The present invention relates to novel compounds, which are inhibitors of Syk kinase activity. These compounds therefore have potential therapeutic benefit in the treatment of disorders associated with inadequate Syk activity, in particular in the treatment and prevention of Syk-mediated pathologies. These pathologies can include inflammatory, allergic and autoimmune diseases, for example, asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), ulcerative colitis, Crohn's disease, bronchitis, dermatitis, allergic rhinitis, psoriasis, scleroderma, urticaria, rheumatoid arthritis, idiopathic thrombocytopenic purpura (ITP), multiple sclerosis, cancer, HIV, and lupus.

BRIEF DESCRIPTION OF THE INVENTION

The present invention provides novel compounds that are potent SYK inhibitors as well as pharmaceutical compositions containing them. As the SYK inhibitor compounds of the present invention they are useful in the treatment and prevention of diseases and disorders mediated by the SYK protein; such diseases and disorders include, but are not limited to, asthma, COPD, rheumatoid arthritis, cancer, and idiopathic thrombocytopenic purpura.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides compounds of formula (I) or a pharmaceutically acceptable salt thereof:

<img file="MX2012007154A_D0001.tif" />

where:

R¹ is selected from the group consisting of (a) hydrogen, (b) halogen, (c) CN, (d) Ci alkyl.₆ optionally substituted with one or more groups selected independently from the group consisting of OR^to, cycloalkyl of C₃-6, and halogen, (e) C2.6 alkenyl optionally substituted with C- | O-alkyl.₆, (f) C-alkynyl₂-6, (g) C cycloalkyl₃.₆, (h) OH, (i) O-Ci alkyl.₆ optionally substituted with one or more groups independently selected from (i) aryl, (ii) 5- or 6-membered heteroaryl optionally substituted with one or more groups independently selected from Ci_6-alkyl, (ii) 4-8 membered heterocyclyl optionally substituted with one or more groups independently selected from oxo, halogen, Cv-alkyl₆, (iv) -CO₂R^to, (v) -CONR^bR^c, (vi) -NR^b R^c, and (vii) -OR^to, (j) -AX, wherein A is a bond or O, X is selected from the group consisting of (i) 4- to 8-membered heterocyclyl optionally substituted with one or more groups independently selected from halogen, C ^ alkyl , haloalkyl of Ci-₆, hydroxyalkyl from Cv₆, COR³ , CO2R^to, (ii) C3 cycloalkyl.₆optionally substituted with one or more groups independently selected from 0_Ί_₆ alkyl, -OR^to, -CO2R^to, -NR ^bR^c, and (iii) heteroaryl optionally substituted with a benzyl that is optionally substituted with OR^to, (k) O-CH 2 (l) -S (O) N-alkyl of C ^, (m) -COR³, (n) -CO2R^to, (or) 10 CONR^bR_c, and (p) -NR^bR^c;

R² is selected from the group consisting of (a) H, (b) halogen, (c) Ci alkyl.₆, (d) C-i_alkyl_₆, (e) C ^ haloalkyl and (f) O- Ci-6i haloalkyl, or

R1 and R2 on adjacent carbon atoms together represent (CH ^;

R3 is H, halogen, OR^to, or C1-4alkyl,

R⁴ is selected from the group consisting of (a) H, (b) halogen, (c) C- | alkyl.₆ optionally substituted with one or more independently selected groups (i) halogen, (ii) OR^to, (iii) OC (O) R^to, (iv)

NR^bR^c, (v) NHC (O) R^to, and (vi) NHC (O) NHR^b; (d) C2.6 alkenyl, (e) C2.6 alkynyl, (f) C3.6 cycloalkyl, (g) OR^to, (h) NO2, (i) NR^bR^c, ü) NHC (O) R^to, (k) NHC (O) NHR^b and (I) NHC (O) NHC (O) NR^bR^c;

R⁵ is selected from the group consisting of (a) H, (b) halogen, (c) C ^ g alkyl, C2-6 alkenyl, C2-6 alkynyl, each of which is optionally substituted with one or more groups independently selected from Ry, (d) C carbocycle₃.₁₂, or a carbon-linked 3 to 12-membered heterocyclyl each optionally substituted with one or more independently selected groups of RZ, (e) heteroaryl optionally substituted with C1-3 alkyl (optionally substituted with one or more OH or CN or heterocycle ), (f) -C (O) R^to, (g) -C (O) 2R^to, and (h) -C (O) NR^bR^c,

R5 (i) is selected from the group consisting of H and alkyl of

-3’

R^to is selected from the group consisting of (a) H, (b) 0 ^ 6 alkyl optionally substituted with one or more groups independently selected from (i) halogen, (ii) CN, (iii) OH, (iv) O- C1-4alkyl, (V) heterocyclyl optionally substituted with oxo, (vi) C (O) C1-6alkyl optionally substituted with OH, (vii) CO₂H, (viii) CO₂C alkyl₁₆, (¡X)

CONR^b(go^c(¡), (X) SO₂C ^ -alkyl, (xi) -NR^b(go^c(i), (xii)

NR^b(i) C (O) NR^b(go^c(i), (xiii) phenyl, and (xiv) heteroaryl optionally substituted with OH, (c) alkenyl of C₂.₆, (d) C3.6 cycloalkyl optionally substituted with one or more groups independently selected from (i) OH, (ii) CO2H, (iii) CO₂Ci_6alkyl, (iv) CONR^b(go^c(i), (e) phenyl optionally substituted with one or more groups independently selected from (i) C-alkynyl₂-6, (ii) CN, (iii) halogen, (iv) OH, (V) OC (O) -C1.6 alkyl, (vi) CO₂H, (vii) CO₂C1.6-alkyl, (f) heteroaryl optionally substituted with one or more groups independently selected from Ci-alkyl.₆, haloalkyl of Ci._6l (CH2)₀-2CO₂H, OH, halogen, phenyl optionally substituted with CO₂H, and (g) heterocyclyl optionally substituted with oxo,

R^b and R^c is independently selected from the group consisting of (i) H, (b) Ci_alkyl₆ optionally substituted with one or more groups selected independently of (i) OR^to, (ii) halogen, (ii) heterocyclyl optionally substituted with oxo, OH, C1-6 alkyl (optionally substituted with OH), (iv) C3.6 cycloalkyl optionally substituted with one or two groups selected from alkyl of Cm, CH2OH, CONR^b(go^c(i), and CO2R^to, (V) heteroaryl optionally substituted with C1.6 alkyl optionally substituted with OH, CO₂H or heteroaryl optionally substituted with a heteroaryl, (vi) SO₂NR^b(go^c(i), (vii) SO2 C1-4alkyl, (viii) CONR^b(go^c(i), (ix) NR^b(go^c(¡), (X) CO2R^to, (xi) aryl optionally substituted with one or more selected halogen groups, OR^to, Ci-6 alkyl (optionally substituted with halogen, heterocycle (optionally substituted with oxo), or OR), SO₂NH₂, and heteroaryl optionally substituted with CH₂OH, (xii) SO₃H, (xiii) R^b(i) CONR^b(go^c(i), (xiv) CN, and (xv) NHC (O) R^to, (c) C alkenyl₃.₆optionally substituted with F; (d) C3.6 cycloalkyl (optionally fused to a benzene ring) optionally substituted with one or more groups independently selected from (i) C1-4alkyl, (ii) OR^to, (iii) CH₂OH, (iv) CO₂R^to, and (v) CONR^b(go^c(i), (e) aryl optionally substituted with one or two groups independently selected from (i) Ci.6 alkyl (optionally substituted with OR^to), (ii) CN, (iii) OR^to, (iv) halogen, and (V) OCOalkyl of Cm! (f) heteroaryl optionally substituted with one or more groups selected independently of (i) OR^to, (ii) CO₂R^to and (iii) Ci-6 alkyl optionally substituted with OH, (g) heterocyclyl optionally substituted with one or more groups independently selected from (i) oxo, (ii) OH and (iii) Ci-6 alkyl, or

R^b, R^c and the nitrogen atom to which they are attached together form a 5-, 6- or 7-membered heterocycle having O or 1 additional heteroatom selected from O, P (0) (C-, _alkyl₆), S (O) N and NR^x, and optionally substituted with one or more groups independently selected from (a) oxo, (b) thioxo, (c) Ci-6 alkyl optionally substituted with one or more groups selected independently from (i) 0R^to, (I) CO2Ra, (iii) OP (O) (Ci 6 alkyl) 2, (iv) aryl, and (v) halogen, (d) OR^to, (e) C (O) R^to, (f) C (0) 2R^to, (g) CONR^b(go^c(i), (h) P (O) (OH)₂, (i) SO₂R^to, and (j) CN, or

R^b, R^c and the nitrogen atom to which they are attached form together

<img file="MX2012007154A_D0002.tif" />

R^b(i) and R^c(i) are independently selected from the group consisting of (a) H and (B) Ci_alkyl₆ optionally substituted with OH, CO₂H or CO₂Ci__alkyl₆; or

R^b(go^c(i) and the nitrogen atom to which they are attached together form a 5- or 6-membered heterocycle having O or 1 additional heteroatom selected from O, S, and N-RX, and optionally substituted by one or more groups independently selected from oxo,

R^or is selected from the group consisting of (a) Ci_6 alkyl optionally substituted with one to three groups selected from halogen, OH, SO2R^to, CONR^bR^c, NR^bR^c, phenyl, heterocyclyl and heteroaryl, (b) C3.8 cycloalkyl optionally substituted with OH, CO2R^to , -CONH2, (c) heterocycle optionally substituted with oxo, (d) aryl optionally substituted with C-alkynyl₂-6, CN, halogen, OR^to, and (e) heteroaryl optionally substituted with OH;

R^x is selected from the group consisting of (a) H, (b) Ci-6 alkyl optionally substituted with heterocycle, (c) phenyl optionally substituted with OH or C-alkyl, (d) -C (O) -C1-alkyl .6, (e) -C (O)₂10 C- | alkyl.₆, (f) -C (O) NH₂ , -C (O) NH-C1-6alkyl, -C (O) N (C1alkyl₆) 2, (g) -C (O)₂NHC (O) NH₂, -C (O)₂NHC (O) NH C ^, -C (O) alkyl₂NHC (O) N (alkyl of (h) -SO2-alkyl of C-i_₆ (optionally substituted with halogen), -S02-heteroaryl (optionally substituted with alkyl), (i) S (O)₂NH₂, -S (O)₂NH-C1.6-alkyl, -S (O)₂N (Ci_alkyl₆ )₂, and Ü) -SO₂NHC (O)₂-alkyl from Ονε!

Ry is selected from the group consisting of (a) aryl optionally substituted with one or more groups independently selected from (i) halogen, (ii) C1.6 alkyl optionally substituted with OH or CO₂R^to, (iii) C alkenyl₂-6 optionally substituted with CO₂R^to, (iv) phenyl optionally substituted with CO₂R^to, (v) COR³, (vi) CO2R^to, (vii) CONR^bR^c, (viii) OR^to, (ix) S (O) nR^to, (X) SO2NR^bR^c, (xi) SO2NHC (O) R^to, (xii) NO₂, and (xiii) NHC (O) R^to, (b) heteroaryl optionally substituted with one or more groups selected independently from (i) halogen, (ii) C1.6 alkyl optionally substituted with CO2R^to, (iii) C3.6 cycloalkyl, (iv) aryl optionally substituted with CO2R^to, (v) CONR^bR^c, (vi) OR^to, (vii) SC&gt; 2R^to, and (viii) CC&gt; 2R^to, (c) C3.8 cycloalkyl optionally substituted with one or more groups independently selected from (i) Cv6 alkyl, (ii) CO2R^to, and (iii)

NR^bR^c, (d) C6.8 cycloalkenyl (optionally substituted with CO2R^to), (e) halogen, (f) CN, (G) -C (O) R^to, (H) -C (O) 2R^to, (i) C (O) CO2R^to, (j) -C (O) NR^bR^c, (k) -C (O) NHC (O) NR^bR^c, (I) -OR^to, (m) OC (O) R^to, (n) -NR^bR^c, (o) -NHC (O) R^OR, (p) -NHC (O) NR^bR^c, (q) -NHC (O) NHC (O) NH2, (r) -NHSO_mR^to, (s) -NHSO2NR^bR^c, (t) SOnR^to, (u) SO2NR^bR^c, (v) -SO2NHC (O) R^to, (w) SO2NHC (O) 2R^to, (x) SO3H, (y) -P (O) (OR^to) 2, (z) CONHOH, and (aa) heterocyclyl optionally substituted with one or more groups selected independently from oxo, thioxo, Ci alkyl.₆, and CO₂R^to;

R^z is selected from the group consisting of (a) a group selected from Ry, (b) Ci-6 alkyl optionally substituted with one or more groups selected independently of the halogen, NR^bR^c, OR^to, CN, phenyl (optionally substituted with C1-6 alkanoic acid), CONRbRc, and -CO₂R^to, (c) oxo, and (d) = NOR^to;

m is 1 or 2, n is 0, 1 or 2.

In a group of formula (I) are compounds where R2 and r5 (¡) are each hydrogen. In a second group of formula (I) are compounds where R2, r3 and r5 (¡)_SWn each hydrogen.

In another group of formula (I) [Group R5-I] are compounds wherein R5 is selected from (a) C1-8alkyl, optionally substituted with one or more groups selected independently from Ry, and (b) carbocycle of C₃.₁₂ or 3-12 membered heterocyclyl each optionally substituted with one or more groups selected independently of

R².

In another group of formula (I) the [Group R5-II] are compounds where R⁵ is selected from:

[I] C-alkyl_V8;

[II] haloalkyl of 0_ν8;

wherein said alkyl and haloalkyl are each optionally substituted with one to four groups independently selected from (A) cycloalkyl from C₃.₄ optionally substituted with one or two groups independently selected from OH, benzyloxy and C1.3 alkyl; (B) phenyl optionally substituted with one or two independently selected groups of (i) O-C1.3 alkyl optionally substituted with one or two independently selected groups of CO2R alkyl^{a (a)}, (¡I) (CH₂) o-iC0₂H, (iii) SO₂CH₃, and (¡v) C (O) C1.3 alkyl; (C) heteroaryl optionally substituted one or two groups independently selected from C ^ s alkyl, halogen, C ^ O-alkyl, (CH₂)₀.

₂CO₂H, SO₂CH₃ And so₂Ph (D) heterocycle optionally substituted with one or two groups independently selected from oxo and CO₂R^{a (a)}, C- | _3 alkyl, and halogen, (E) CN, (F) OR^{a (a)}, (G) OC (O) C1.4alkyl (H) CO-C1.4alkyl, (I) CO₂R^{a (a)}, (J) CONR^{a (a)}R^{a (a)}, (K) CO-4-morpholinyl, (L) NR^{b (a)}R^AC), (M) NHC (O) NH₂, (N) NHSO₂C alkyl_M, (O) NHSO₂haloalkyl of C_M, (P) NHSO₂NH2, (Q) SO₂NH_2i (R) SO₂C 1-4 alkyl;

[III] carbocycle of C₃_₁₀, and [IV] 4-10 membered heterocyclyl;

wherein said carbocycle and heterocyclyl are each optionally substituted with one to six groups independently selected from (A1) C- | alkyl.₆, (A2) Ci_6 haloalkyl wherein each (A1) and (A2) is optionally substituted with one or two groups independently selected from OH, CN, NH₂, CONH₂ and CO₂ R^{a (a&gt;}, (B) aminocyclopropyl, (C1) C3.6 cycloalkyl, (C2) cyclohexenyl of Οβ-β, each of (C1) and (C2) is optionally substituted with CO2R^{a (a)}; (D) phenyl optionally substituted with one or two groups selected independently from fluoro, methyl and CO2R^{a (a)}, (E) benzyl, (E) heteroaryl selected from pyridyl optionally substituted with CO₂R^{a (a)} and 1,3,4-oxadiazolyl optionally substituted with methyl, (G) halogen, (H) CN, (I) OH, (J) O-C alkyl_M optionally substituted with OH, (K) oxo, (L1) CO C1-4alkyl, (L2) COhaloalkyl of Ci ^, each (L1) and (L2) is optionally substituted with one to three groups independently selected from

OR^{a (a)}, CN, NR^{a (a)}R^{a (a)}, NHCONH2, CO2R^{a &lt;a)}, CONR^{a (a)}R^{a (a)}SO2CH₃, heteroaryl optionally substituted with OH, and heterocyclyl optionally substituted with oxo, (M) COPh optionally substituted with one or two groups selected from ethynyl, CN, F, OH, CO₂R^{a (a)} and OC (O) CH₃, (N) C (O) 14 heteroaryl optionally substituted with one or two groups independently selected from halogen, OH, CF₃ and Cm alkyl, (O) C (O) heterocycle optionally substituted with oxo, (P) CO-cycloalkyl of C₃.₆optionally substituted with a selected group of OH and CO2R^{a (a)}, (Q)

CO₂R^{a (a)}, (R) COCO2R^{a (a)}, (S) C (O) NR^{b (a)}R^AC), (T1) NR^{a (a)}R^{a (a)}, (T2) 1pyrrolidinyl optionally substituted with oxo, (U) NHC (O) alkyl of Ον3 optionally substituted with one or two OH, SO groups₂CH₃, CONR^{a (a)}R^{a (a)}, imidazolyl, pyridyl, pyrazolyl, triazolyl, tetrazolyl, pyrimidinyl, 2oxotetrahydrofuranyl, tetrahydrofuranyl, tetrahydropyranyl, and phenyl, (V) NHC (O) 10 Y, (W) NHC (O) NH2, (X) NHC (O) NHC (O ) NH₂, (Y) NHSO2NH2, (Z1) NHSO2 C- | -3-alkyl, (Z2) NHSO2-C1-3alkyl, (AA1) SO2-alkyl

C1-4, (AA2) SO2 C1.4alkyl, (BB) SO2Ph, (CC) SO2-heteroaryl optionally substituted with C1-4alkyl, (DD) SO2NH2, (EE)

SO2NHCOci_4alkyl, (FF) SO2NHCO2C1-4alkyl, (GG) SO3H, (HH) hydroxyimino; (II) 1,3,4-oxadiazol-2 (3H) -one and 1,2,4-oxadiazol-5 (4H) -one, (JJ) P (O) (OEt)₂;

R^to(^to) is H or C1-4alkyl,

R^{b (a)} and R^AC) are independently selected from (A) Η, (B) optionally C-cycloalkyl₃_6 benzofused optionally substituted with OH, (C) heteroaryl selected from imidazolyl, pyridyl and indolyl, (D) tetrahydrofuranyl, (E) benzyl, (F) phenyl optionally substituted with one or two groups selected from (CH₂)₀-₂OH and F, (G1) Ci alkyl.₄and (G2) halo alkyl of Cu wherein (G1) and (G2) are each optionally substituted with one to three groups independently selected from (i) OH, (ii) C3.6 cycloalkyl optionally substituted with one or two groups independently selected from C1-4alkyl, CONH₂, CO₂H and

CH₂OH, (iii) C3-6 1-carboxy-cycloalkyl, (¡v) CONH_2l (V) SO₂NH₂, (vi) SO₂Cm alkyl, (vii) optionally 4-7 membered benzofused fused heterocyclyl optionally substituted with one or two groups independently selected from oxo, (CH₂)₀.2OH, and alkyl of Cm, (viii) monocyclic or bicyclic 5-10 membered heteroaryl optionally substituted with one or two groups independently selected from carboxy, (CH₂)₀.₂OH, and C-i_ alkyl₄, (ix) CN, (X) C1.4alkyl, (xi) CO₂H, (xii) NR^{a (a)}C (O) C ^, (xiii) phenyl alkyl optionally substituted with one or two groups selected from (CH₂)or-₂OH SO₂NH₂, CF3, F and Cl, (xiv) OPh, (xv) 1 -pyrrolidinyl optionally substituted with oxo, (xvi) 1 -imidazolidinyl optionally substituted with oxo, (xvii) 1- piperidinyl optionally substituted with oxo, and (xviii) 4morpholinyl ; or

R^{b (a)} and R^AC) together with the nitrogen atom to which they are attached they form a 6 to 7 membered heterocycle having 0 to 1 additional heteroatom selected from N, O and S, wherein said heterocycle is optionally substituted with one or two groups independently selected from oxo, CN, (CH₂)₀-₂OH, acetyl, benzyl, SO₂Cm alkyl, CONH_2imethoxymethyl, carboxymethyl, CO₂R^{a (a)} and C ^ alkyl;

Y is selected from CH (OH) CF₃, CH2CH (NH₂) CF₃, cycloalkyl of C₄_₆ (optionally substituted with OH or CO2R^to(^to)), imidazolyl, pyridyl (optionally substituted with OH), pyrazolyl, triazolyl, tetrazolyl, pyrimidinyl, phenyl (optionally substituted with one or two groups selected from OH, F, CN and ethinyl), heterocycle selected from imidazolidinyl, tetra h id break nor lo, tetrahydropyranyl, piperidinyl, each is optionally substituted with oxo.

In a subset of [Group R5-II] R5 is C310 carbocycle selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, decalinyl bicyclo [3.3.0] octyl, bicyclo [4.1. Ojheptyl, indanyl , octahydroindenyl, tetrahydronaphthyl bicyclo [2.2.1 jheptyl, bicyclo [2.2.2] octyl, bicyclo [3.3.1] nonyl, bicyclo [3.2.1 joctyl, espio [3.3] heptyl, esp¡ro [2.5] octílo, diespiro [2.1.2.3] declo, Adamantilo, and tr¡c¡clo [2.2.1.0^{2 6}] heptyl. In one aspect within this subset, the carbocycle is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl; and in one embodiment thereof, the carbocycle is cyclohexyl. In another aspect within this subset, the carbocycle is substituted with one to three groups independently selected from hydroxymethyl, aminomethyl, OH, OCH₃, OCH2CH2OH, oxo, F, CN, 1,3,4-oxadiazolyl, 1,3,4 oxadiazol-2 (3H) -one, 1,2,4-oxadiazol-5 (4H) -one, CO2R^to(^to), CONR^b(a) R^AC), NRa (a) Ra (a)_i NHC (O) C1-3alkyl (optionally substituted with OH),

NHC (O) NH₂, NHC (O) NHC (O) NH₂, NHC (O) (1-C (O) NH₂-cPr), NHSO2NH₂, NHSO2 C1-3alkyl and NHSO2haloC1-3alkyl, and optionally further substituted with one to four methyl groups. In one embodiment thereof, the substituted carbocycle is cyclohexyl substituted with one to three groups selected from F, OH, CO2H, CONH₂₎ CONHFWa), NH₂, NHC (O) C1-3alkyl optionally substituted with OH, and optionally substituted with one or two methyl groups.

In another subset of [Group R5-II] R5 is 4-10 membered heterocyclyl selected from oxethanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, tetrahydropyridyl, tetrahydroazepinyl, 8-azabyl. 7azabicyclo [2.2.1] heptyl, 1,3-dioxanyl, 3-azabicyclo [3.2.0] heptyl, 1,410 dioxospiro [4.5] decyl, 1-azaspiro [4.5] decyl and 3-oxa-9-azabicyclo [3.3.1 ] non¡lo. In one aspect within this subset, heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, and azepanil; and in one embodiment thereof the heterocyclyl is azepanyl. In another aspect within this subset, the heterocycle is substituted with one to three groups selected from hydroxymethyl, aminomethyl, OH, OCH₃, OCH2CH2OH, oxo, F, CN, CO2R^to(^to), CONRB (a) RC (a)_t NRaíajRafa), NHC (O) C1-3 alkyl (optionally substituted with OH), NHC (O) NH₂, NHC (O) NHC (O) NH₂, NHC (O) (1C (O) NH₂-cPr), NHSO2NH₂, NHSO2alkyl of Ο_ν3 and NHSO2halo C1-3alkyl, and optionally further substituted with one to four methyl groups. In one embodiment thereof the substituted heterocycle is hydroxy-substituted azepan-2-one.

In another subset of [Group R5-II] R⁵ is Ci- alkyl₆ optionally substituted with one to three groups selected independently of (A) cycloalkyl from C₃_₄; (B) phenyl optionally substituted with one or two groups selected independently of (i) OCH₃ optionally substituted with CO₂H, (ii) (CH2) o-iCC&gt; 2H, (iii) SO2CH3, and (iv) C (O) CH3¡ (C) heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, de thiazolyl, triazolyl, pyridyl 1,2,4-oxadiazolyl, and pyrazinyl, each optionally substituted with one or two groups independently selected from CH₃, halogen, OCH₃, (CH₂)or₂CO₂H, SO₂CH₃ And so₂Ph; (D) OR^{a (a)}, (E) NR^{b (a)}R^AC), (F) NHC (O) NH₂, (G)

NHSO2CH3, (H) CO₂R^{a (a)}, (I) NHSO2NH2, (J) CONR^{a (a)}R^{a (a)}, (K) SO₂NH₂ and (L) SO₂CH3.

In another subset of [Group R5-II] R5 is C 16 fluoroalkyl optionally substituted with one or two hydroxy groups.

In another group of formula (I) the [Group R5-III] are compounds having the formula (la) or a pharmaceutically acceptable salt thereof:

<img file="MX2012007154A_D0003.tif" />

(la) where R1 and R⁴ they are as defined under formula (I);

R⁵ (^to) and R⁵ (^b) are each independently selected from the group consisting of: (a) H, (b) C- | -8 alkyl optionally substituted with one or more independently selected groups of Ry¡ and (c) a group selected from Ry¡ or

R5 (a), _R5 (b) and the carbon to which the two are attached together form a C3-12 carbocyl or 3-12 member heterocyclyl each optionally substituted with one or more groups independently selected from R^z;

RY (a) is selected from the group consisting of hydroxymethyl, aminomethyl, ORa, CC&gt; 2R^to, CONRbRC SO2NRbRC SC&gt; 2R^to, SC&gt; 2NHC (O) Ra, NHC (O) RU, NHC (O) NH2, NHC (O) NHC (O) NH2, NHSO_mR^to, NHSO2NRbRC

NRbRc, 1,3,4-oxadiazolyl, CN and halogen.

In a subset of formula (la) they are compounds where

Ry (a) is aminomethyl, OH, OCH3, OCH2CH2OH, F, CN, CO2R^to(^to),

CONRb (a) Rc (a)_i NRa (a) Ra (^to), NHC (O) C1-3alkyl (optionally substituted with OH), NHC (O) NH2, NHC (O) NHC (O) NH2, NHC (O) (1-C (O) NH2cPr), SO2NH2, SO2CH3, SO2NHC (O) CH3, NHSO2NH2, NHSO2 C1-3alkyl, or NHSO2halo C1-3alkyl, and at least one of R5 (a) and R5 (b) is different from H.

In another subset of formula (la) are compounds where

R5 (a)_t R5 (b) and the carbon to which the two are attached together form a C3-10 carbocycle. In one aspect within this subset they are compounds where Ry (^to) is OH. In another aspect they are compounds where R5 (a), R5 (b) and_andThe carbon to which the two are attached together form a carbocycle selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, indane, bicyclo [3.3.0] octane, decalin, bicyclo [3.3.1] nonane, tetrahydronaphthalene, adamantane, spiro [3.3] heptane, bicyclo [3.1.0] hexane, tricycle [2.2.1.02-6] heptane, and diespiro [2.1.2.3] decane.

In another subset of formula (la) are compounds where Ry (a) is aminomethyl, OH, OCH3, OCH2CH2OH, F, CN, 1,3,4-oxadiazolyl,

CO2R^to(^to), CONRbCajRcía), NRa (a) Ra (a), NHC (O) C1-3 alkyl (optionally substituted with OH), NHC (O) NH2, NHC (O) NHC (O) NH2,

NHC (O) (1-C (O) NH2-cPr), SO2NH2, SO2CH3, SO2NHC (O) CH3, NHSO2NH2, NHSO2-C1-3alkyl, or R5 (a) _R5 NHSO2-haloalkyl (b) and the carbon to which they are attached together form a monocyclic C3-8cycloalkyl optionally substituted with a group selected from the group consisting of (a) C1.4alkyl optionally substituted with one or more groups independently selected from OH, NH2, CN, CO2R^to(^to) and CONH2, (b) halogen, (c) CN, (d) -C (O) R^to(^to), (e) -C (O) 2R^to(^to), (f) -C (O) NRb (a) Rc (a), (g). ORa (a), (h) -OC (O) Ra (a), (¡) -NRb (a) Rc (a), (j) -NHC (O) C1-3 alkyl (optionally substituted with OH) , (k) -NHSO2 C1-3alkyl, (I)

-NHSO2NH2, (m) oxo, (n) phenyl, (o) hydroxyimino, (p) 1-aminocyclopropyl, (q)

1,3,4-oxadiazole-2 (3H) -one, and (r) 1,2,4-oxadiazol-5 (4H) -one, and optionally further substituted with one to four methyl groups. In one aspect they are compounds where RY (a) is OH, F, OCH3, CONH2 and CN. In another aspect they are compounds where R5 (a \ R5 (b) and the carbon to which the two are attached together form a cyclohexyl ring optionally substituted with a group selected from -CO2H, -CO2 C1-4alkyl, C (O ) NH₂, CON C1-3alkyl optionally substituted with NRb (a) Rc (a)_i and -NHC (O) C1-3alkyl (optionally substituted with OH), and optionally further substituted with one or two methyl groups.

In another subset of formula (la) are compounds where

Ry (a) is aminomethyl, OH, OCH₃, OCH₂CH₂OH, F, CN, 1,3,4-oxadiazolyl, CO₂R^{a (a)}, CONR^{b (a)}R^AC), NR^{a (a)}R^{a (a)}, NHC (O) C-alkyl_v3 (optionally substituted with OH), NHC (O) NH₂, NHC (O) NHC (O) NH₂, NHC (O) (1C (O) NH₂-cRp), SO₂NH₂, SO₂CH₃, SO₂NHC (O) CH_3i NHSO₂NH₂, NHSO₂Ci__alkyl₃, or NHSO₂halo C- | alkyl.₃, and R^{5 (a)}, R^{5 (b)} and the carbon to which the two are attached together form (a) a 4-6 membered monocyclic heterocyclyl having an O or S ring, and optionally substituted with one or two groups selected from the group consisting of oxo and methyl, or ( b) a 4-7 membered monocyclic heterocyclic having an NH ring or N-Ry group (b), and optionally substituted with one or two groups selected from oxo, methyl, trifluoromethyl, and CO₂R^{a (a)}, where R^{and (b)} is selected from (ia) Ci alkyl.₃ optionally substituted with one or more independently selected groups of OH, NH2, CN, CO2R^{a (a)} and CONH2, (ib) C1.3 haloalkyl (optionally substituted with NH2 or OH), (iia) CO C1.4 alkyl or C (O) C1.4 haloalkyl (where alkyl and haloalkyl are each optionally substituted with OR^{a (a)}, CN, CO2R^{a (a)}, CONR^toR^{a (a)}, NR^{a (a)}R^{a (a)}, SO₂CH₃, heterocyclyl optionally substituted with oxo, heteroaryl optionally substituted with OH), (ib) CO-phenyl (optionally substituted with one or two selected groups of ethynyl, CO₂R^to(a), CN, F and OH), (iic) COheteroaryl (optionally substituted with methyl, Cl, CF₃), (Id) CO-heterocyclyl (optionally substituted with oxo), (iie) CO-cycloalkyl of C₃.₆ (optionally substituted with OH or CO2R^to(a)), (iii) C0.3-CO2R alkyl^to(a), (iva) CONR^to(a) R^to(a), (ivb) CONH-phenyl (optionally substituted with one or two selected groups of C1.4alkyl, OC (O) Ci_3alkyl, CN, and Cl), (ivc) CONH-C3-6cycloalkyl , (V) SO2NH2, (vi) SO2NHCO2R^{a (a)}, (viia) SO₂Ci__alkyl₃, (viib) SO2haloalkyl of C ^, (viic) SO₂PhH, (viid) SO₂fifteen heteroaryl (optionally substituted with methyl), (viii) SO₃H. In one aspect within this subset they are compounds where R5 (a), R5 (b) and θ | Carbon to which the two are attached together forms pyrrolidinyl, oxetanyl, piperidinyl, and azepanil. Within said aspect it is a modality in which Ry (a) is OH.

R^to(^to), Rb (^to), R^c(^to) in the aforementioned subsets are as defined in [Group R5-II].

In another group of formula (I) the [Group R5-IV] are compounds of formula I (B) or a pharmaceutically acceptable salt thereof:

<img file="MX2012007154A_D0004.tif" />

where R1 and R4 are as defined under formula (I);

Cy is a monocyclic C3-7 carbocycle or 4-7 membered heterocycle having a heteroatom selected from N, S, or O;

RY (a) is defined under the formula la;

R^z(a) is selected from (A) Cm alkyl optionally substituted with one to three groups selected independently of

OH NH₂, CN, CO₂R^{a (a)} and CONH2, (B) C -, - 3 fluoroalkyl, (C) halogen, (D) CN, (E) CO, C1.4alkyl (optionally substituted with one or two groups selected independently from OR^{a (a)}, CN, CO2R^{a (a)}, CONR^{a (a)}R^to(a), and NR^{a (a)}R^{a (a)}), (F) CO-phenyl (optionally substituted with one or two groups selected independently from ethynyl, CO2R^{a (a)}, CN, F and OH), (G) CO20 C3-6 cycloalkyl (optionally substituted with OH or CO2R^to(a)), (H) C0-3-CO2R alkyl^{a (a)}, (I) -C (O) NR^{b (a)}R^AC), (J) -OR^{a (a)}, (K) -OC (O) R^{a (a)}, (L) -NR^{B (a)}R^AC), (M) -NHC (O) C 1-4 alkyl (optionally substituted with one to three OH or a CONR^{a (a)}R^{a (a)}), (N) -NHSO2 C ^ -alkyl, (O) -NHSO₂NH₂, (P) oxo, (Q) 1,3,4-oxadiazol-2 (3H) -one, (R) 1,2,4-oxadiazol-5 (4H) -one, SO2NH2, (T) SC&gt; 2alqu That of C1.3, (U) SC&gt; 2haloalkyl of C1.3, and (V) SC ^ Ph;

Ra (a), Rb (a) and RC (a) are as defined in Group [R5-II]; p is O to 4; and q is O, 1 or 2.

In a subset of formula (Ib) they are compounds where p is O to 4; q is O, 1 or 2;

cy is selected from C4-7 cycloalkyl, oxetanyl, pyrrolidinyl, piperidinyl, and azepanil;

R1 is selected from H, C1-4alkyl, haloalkyl of

C1-4, C3-6 cycloalkyl, and C1-4 Oalkyl;

R4 are selected from H, C1-4 alkyl, and C3-4 cycloalkyl;

Ry (a) is aminomethyl, OH, OCH3, OCH2CH2OH, F, CN,

C02R^to(^to), CONRb (a) Rc (a), NRa (a) Ra (a), NHC (O) C1-3alkyl (optionally substituted with OH), NHC (0) NH2, NHSO2NH2, NHSO2C1-3alkyl , or Ci-3 NHSO2haloalkyl;

Rz (a) is selected from (A) C1-4 alkyl optionally substituted with one to three groups independently selected from OH,

NH2, CN, C02R^to(^to) and CONH2, (B) Cfluoroalkyl of 1-3. (C) halogen, (D)

CN, (E) COC- | -4alkyl (optionally substituted with one or two selected groups of ORa (a), CN, CO2R^to(^to), CONRa (a) Ra (a), _and NRa (a) Ra (a)), (F) CO-phenyl (optionally substituted with one or two independently selected groups of ethynyl, CO2R^to(^to), CN, F and OH), (G)

CO-C_c3-6 chloalkyl (optionally substituted with OH or CO2R^to(^to)), (H) Co-3-C02R alkyl^to(^to), (I) -C (O) NRb (a) RC (a), (j) -OR^to(^to), (K)

-OC (O) Ra (a), (L) -NRb (a) Rc (a), (M) -NHC (O) C1-4alkyl (optionally substituted with one to three OH or CONRaíajRaía)), ( N) -NHSO2 C1-3alkyl, (O) -NHSO2NH2, (P) oxo, (Q) 1,3,4-oxadiazol-2 (3H) -one, (R) 1,2,4-oxadiazol10 5 ( 4H) -one, (S) SO2NH2, (T) SO2 C1-3alkyl, (U) SO2haloC1-3alkyl, and (V) SO2Ph;

Ra (a) is H or C1-4 alkyl;

R^{b (a)} and R^AC) are independently selected from (A) Η, (B) cycloalkyl from C₃.₆ optionally substituted with OH, (C) heteroaryl selected from imidazolyl, pyridyl and indolyl, (D) tetra h id cleavage or lo, (E) benzyl, (F) phenyl optionally substituted with one or two groups independently selected from (CH₂)₀.₂OH and F. (θ1) Ci_4-alkyl and (G2) halo-alkyl-Cm, where (G1) and (G2) are each optionally substituted with one to three groups independently selected from (i) OH, (ii) cycloalkyl of C3.6 optionally substituted with one or two independently selected groups of alkyl from Cm, CONH₂, CO₂H and

CH2OH, (iii) CONH₂, (iv) SO₂NH2, (V) SO2 alkyl deCi.₄, (vi) 4-7 membered monocyclic heterocyclyl optionally substituted with one or two groups independently selected from oxo, (CH₂)₀.₂OH, Y alkyl of Cm, (v¡¡) 5-6 membered heteroaryl optionally substituted with one or two groups independently selected from carboxy, (CH₂) o-20H, and C1.4alkyl, (viii) CN, (X) Oalkyl of Cm, (ix) CO₂H, (xíi) NR^{a &lt;a)}C (O) alkyl of Cm, (X) phenyl optionally substituted with one or two groups independently selected from (CH₂)₀.₂OH SO₂NH₂, CF₃, F and Cl, (xi) 1-pyrrolidinyl optionally substituted with oxo, (xi!) 1 -imidazolidinyl optionally substituted with oxo, (xiii) 1 -piperidinyl optionally substituted with oxo, and (xiv) 4-morpholinyl; o pb (a) and pc (a) j_{unt0 CQn} θ | ¿|_how Nitrogen to which they are attached form a 6- or 7-membered heterocycle having 0 to 1 additional heteroatoms selected from N, O and S, wherein said heterocycle is optionally substituted with one or two groups independently selected from oxo, CN, (CH₂)₀.₂OH, acetyl, benzyl, SO₂Cm alkyl, CONH_2i methoxymethyl, carboxymethyl, CO₂R^to(a) and CmΕπ alkyl another subset of formula (Ib) are compounds where Cy is cyclohexyl. In one aspect cyclohexyl is substituted with a selected group of CO2Ra (a), CONRb (a) R^c(a) γ NHC (O) C1-4alkyl optionally substituted with OH, and said cyclohexyl optionally is further substituted with one or two methyl groups.

In another subset of formula (Ib) are compounds in which

Cy is piperidinyl. In one aspect the piperidinyl nitrogen atom is substituted with a group selected from (i) CO-alkyl of Cm (optionally substituted with OR^to(a), CN, CO 2R^{a (a)}, CONR^{a (a)}R^{a (a)}, and NR^{a (a)}R^{a (a)}), (ii) CO-phenyl (optionally substituted with one or two independently selected groups of ethynyl, CO₂R^{a (a)}, CN, F and OH), (iii) C3-6 CO-cycloalkyl (optionally substituted with OH or CO2R^{a (a)}), (iv) C0-3-CO 2R alkyl^{a (a)}, (v) CONR^{a (a)}R^{a (a)}, (vi) CONH-phenyl (optionally substituted with one or two groups independently selected from Cu, CN, and Cl alkyl), (vii) CONH-C3 cycloalkyl.₆, (viii) SO₂NH₂, (ix) SO2 C1.3 alkyl, (x)

SO2halo C1-3alkyl, and (xi) SO2Ph.

In another subset of formula (Ib) they are compounds where

Cy is azepanil. In one aspect, azepanil is substituted with an oxo group at position 2 of the ring.

In another subset of formula (Ib) are compounds where (3)

Ry is OH. In one aspect, Cy is cyclohexyl. In one embodiment thereof, cyclohexyl is substituted with a selected group from selected CO2R^to(^to), CONHRb (a) and NHC (O) C1-4alkyl optionally substituted with OH, and said cylochloxyl optionally is further substituted with one or two methyl groups. In another aspect, Cy is 2-oxoazepanyl.

In another subset of formula (Ib) they are compounds where

Ry (θ) is CONH₂. In one aspect, Cy is cyclohexyl. In one embodiment thereof the cyclohexyl is substituted with a group selected from selected from C02R^to(^to), CONHRb (a) and NHC (O) C1-4alkyl optionally substituted with OH, and said cylochloxyl optionally is further substituted with one or two methyl groups.

In another group of formula (I) the [Group R5-V] are compounds of formula l (c) or a pharmaceutically acceptable salt thereof:

<img file="MX2012007154A_D0005.tif" />

where

Z is -CRz (b) Rz (c)._i _N (Rz (d)) _, -CH2-N (Rz (d)) -, or -NHC (O) -;

p 'is 0 to 3, provided that p is 0 when Z is -NHC (O) -;

Rz (b) _{it is} selected from (A) Η, (B) alkyl of 0_ν4 optionally substituted with one to three groups selected independently of

OH NH₂, CN, CO2R^to(^to) and CONH₂, (C) halogen, (D) CN, (E) -C (O) Ra (a), (F) -C (O) 2Ra (a), (G) -C (O) NRB (a) RC (a), (H) -ORa (a), (|) -OC (O) Ra (a), (J)

-NRB (a) RC (a)_i (K) -NHC (O) C- | -4-alkyl (optionally substituted with OH), (L) -NHSO2-Cl-3-alkyl. (M) -NHSO2NH2, (N) 1,3,4-oxadiazol-2 (3H) one, and (O) 1,2,4-oxadiazol-5 (4H) -one;

Rz (c) is H or methyl;

R^z(d) is selected from (A) Η, (B) C1.3 alkyl optionally substituted with a selected group of CO2R^{a (a)} and CONH2, (C) fluoroalkyl of C1.3, (D) COalkyl of C-i_₄ (optionally substituted with one or two groups selected independently of OR^{a (a)} , CN, CO2R^{a (a)}, CONR^{a (a)}R^{a (a)}, and NR^{a (a)}R^{a (a)}), (E) CO-phenyl (optionally substituted with one or two independently selected groups of ethynyl, CO2R^{a (a)}, CN, F and AH), (F) CO-cycloalkyl of C3_6 (optionally substituted with OH or CO2R^{a (a)}), (G) C0 alkyl.₃-CO₂R^{a (a)}, (H) CONR^{a (a)}R^{a (a)}, (I) CONH-phenyl (optionally substituted with one or two groups independently selected from C ^, CN, and Cl alkyl), (J) CONH-C3.6 cycloalkyl, (K) SO₂NH₂, (L) SO₂C1.3 alkyl, (M) SO₂C1.3 haloalkyl, and (N) SO₂Ph; and

R1 is selected from H, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, and C1-4alkyl;

R4 is selected from H, C1.4 alkyl, and C3-4 cycloalkyl;

Ry (a) is aminomethyl, OH, OCH3, OCH2CH2OH, F, CN, CO2R^to(^to), CONRb (a) Rc (a), NRa (a) Ra (a), NHC (O) C1-3alkyl (optionally substituted with OH), NHC (O) NH2, NHSO2NH2, NHSO2C1-3alkyl, or NHS02-haloalkyl of C- | -3;

Ra (a) is H or C1-4 alkyl;

R^{b, a)} and R^AC)are independently selected from (A) Η, (B) C3.6 cycloalkyl optionally substituted with OH, (C) heteroaryl selected from imidazolyl, pyridyl and indolyl, (D) tetrahydrofuranyl, (E) benzyl, (F) phenyl optionally substituted with one or two independently selected groups of (CH2) or -20H and F, (G1) alkyl of and (G2) haloalkyl of C1.4, where (G1) and (G2) are each optionally substituted with one to three groups independently selected from (i) OH, (ii) C 3-6 cycloalkyl optionally substituted with one or two groups independently selected from C1.4 alkyl, CONH₂, CO2H and CH₂OH, (iii) CONH₂, (iv) SO₂NH₂, (v) SO₂ C1_4alkyl, (vi) heterocyclyl of

4-7 monocyclic members optionally substituted with one or two groups independently selected from oxo, (CH₂) o-20H, and C1.4 alkyl, (vii) 5-6 membered heteroaryl optionally substituted with one or two groups independently selected from carboxy, (CH₂)₀.2OH, and C1.4 alkyl, (viii) CN, (X) or C alkyl₁₄, (ix) CO₂H, (xii) NR^{a (a)}C (O) C alkyl₁₄, (X) phenyl optionally substituted with one or two groups selected independently from (CH₂) o-20H, SO₂NH2, CF₃, F and Cl, (xi) 1-pyrrolidinyl optionally substituted with oxo, (xii) 1-imidazolidinyl optionally substituted with oxo, (xiii) 1-piperidinyl optionally substituted with oxo, and (xiv) 4-morpholinyl; or

R^{b (a)} and R^AC) together with the nitrogen atom to which they are attached they form a 6- or 7-membered heterocycle having 0 to 1 additional heteroatoms selected from N, O and S, wherein said heterocycle is optionally substituted with one or two groups independently selected from oxo , CN, (CH₂)or-₂OH, acetyl, benzyl, SO₂C1-4alkyl, CONH₂, methoxymethyl, carboxymethyl, CO₂R^{a (a)} and C1.4 alkyl.

In a subset of formula (le) are compounds where Ry (a) is aminomethyl, OH, OCH₃, OCH₂CH₂OH, F, CN, CO2^{a (a)}, CONR^{b (a)}R^AC),

NR^{a (a)}R^{a (a)}, NHC (O) Cv alkyl₃ (optionally substituted with OH), NHC (O) NH₂, SO₂NH₂, SO₂CH_3i NHSO₂NH_2i NHSO₂Ci__alkyl₃, or NHS0₂haloalkyl of C₁₃.

In another subset of formula (le) are compounds where Z is -N (Rz (d)) -_t and p 'is 0. In a modality of the same Ry (^to) is OH.

In another subset of formula (le) are compounds where Z is -NHC (O) -. In an embodiment thereof Ry (a) is OH.

In another subset of formula (le) are compounds where Z is -CHRz (b) -_ and p 'is 0, 1 or 2. In one embodiment Ry (a) is OH. In another modality of the same R^{and &lt;a)} is CONH₂.

In another subset of formula (le) are compounds where Z is -CHRzfb)., _p· Is 0, 1 or 2, and Ry (a) is OH or CONH₂. In an embodiment of the same Rz (b) is- C (O) 2Ra (a); preferably Rz (b) is- C (O)₂H. In another embodiment Rz (b) is -C (O) NHRb (a), preferably Rz (b) is -C (O) NH2 or C (O) NH (CH₂)₃- (2-oxo-1-pyrrolidinyl). In another embodiment of the same Rz (b) is

-NHC (O) C1-4alkyl (optionally substituted with OH).

In another group of formula (I) the [Group R5-VI] R5 is CONRbRc or

C (O) R^to.

In another group of formula (I) [Group R5-VII] R5 is a different group from H.

In another group of formula (I) the [Group R5-VIII] R5 is a group other than H or halogen.

For the compounds of formulas (I), (la), and (Ib) as well as various applicable groups, subsets, aspects and modalities mentioned above, there is a group the [Group R1] in which R¹ is (a) Cve alkyl optionally substituted with one or more groups selected independently from the group consisting of OR, C3-6 cycloalkyl, and halogen, (b) C cycloalkyl₃_₆, (c) OH, (d) -O-C1.6-alkyl optionally substituted with one or more independently selected groups of (i) aryl, (ii) 5-6-membered heteroaryl optionally substituted with one or more independently selected groups alkyl Ci_₆ , (iii) 4-8 membered heterocyclyl optionally substituted with one or more groups independently selected from oxo, halogen, C- | alkyl.₆ , (¡V) CO₂R^to'(v) -CONRbRc, (vi) -NR^bR^c, (vii) -NH-heterocycle (piperidine) optionally substituted with alkyl, and (viii) -OR^to, and (e) -OX, wherein X is selected from the group consisting of (i) 4-8 membered heterocyclyl optionally substituted with one or more groups independently selected from halogen, C- | alkyl.₆, C1-6 haloalkyl, COR³, CO2R^to, and (ii) C3-6 cycloalkyl optionally substituted with one or more groups independently selected from Cm alkyl, OR^to, benzyl, CO2R^to, NR^bR^c.

In a subset of the [Group R1] are compounds wherein R1 is C -, alkyl. Θ optionally substituted with one or more groups selected independently from the group consisting of OR^to, cycloalkyl of C₃.₆, and halogen. In one aspect thereof R1 is Ci5 alkyl 4; Examples thereof are methyl, ethyl, isopropyl, and t-butyl. In another aspect of the same R1 is C1-4alkyl substituted with one or two hydroxy groups; examples of it are CH (OH) CH₃, CH (OH) CH2OH, C (CH₃)₂Oh

CH2C (CH3)₂Oh In another aspect of the same R1 is C1-4 haloalkyl, especially C1-3 fluoroalkyl; Examples thereof are difluoromethyl, trifluoromethyl, 2-fluoroethyl and 1-fluoroethyl. In another aspect of the same R1 is C1-4alkyl substituted with C3-6cycloalkyl and optionally with a second group selected from OH and halogen; examples thereof are CH (OH) -cPr, -CH (F) -cPr, -C (OH) (CH3) -cPr.

In another subset of the [Group R1] are compounds where R1 is C3.6 cycloalkyl. In one aspect thereof R1 is cyclopropyl.

In another subset of [Group R1] are compounds where R¹ is —OX where X is selected from (a) C4.6 cycloalkyl optionally substituted with one to two groups independently selected from Ci alkyl._3t OH, Oalqullo de Ο_Ί.₃, benzyl, CO₂H, CO₂C alkyl_or NH₂,

NHalkyl of Ci_₃, and N (C-alkyl₁.₃)₂; and (B) a heterocycle selected from azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, tetra h id rofuranyl, tetrahydropyranyl, wherein said heterocycle is optionally substituted with one to two groups independently selected from C1.3 alkyl, halogen, C1 haloalkyl. 3, CO2H, CO₂C1-4alkyl.

In another subset of [Group R1] are compounds where R¹ is -O-alkyl of Ci.₆ optionally substituted with one to two groups independently selected from (i) phenyl, (ii) 5-6-membered heteroaryl selected from pyridyl, imidazolyl, pyrimidinyl, pyrazolopyridine, pyrazolyl, isoxazolyl, triazolyl, tetrazolyl, each of which is optionally substituted with one or two methyl groups, (iii) 4-8 membered heterocyclyl selected from tetrahydropyranyl, 1,4-dioxanyl, tetrahydrofuranyl, pyrrolidinyl, azetidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl, 2,3-dihydroindolyl, 1,4-diazepanyl, oxazolidinyl, optionally substituted with one or more groups independently selected from oxo, fluoro and methyl, (iv) -CO₂H or CO₂C1-alkyl.₄, (v) -CONH₂ (vi) -NH₂, C ^ -NHalkyl, 4-morpholinyl, 1-pyrrolidinyl, 1,4-diazepan-1-yl, oxazolidin-3-yl, each ring to be optionally substituted with one or two groups selected from oxo, methyl and fluoro; (vii) -NH-piperidine optionally substituted with methyl, (viii) OH or Oalkyl of

C1-4.

In another subset of [Group R1] are compounds where R¹ it is -O-C1-alkyl.₄; Examples thereof are methoxy, ethoxy, and isopropoxy.

In another subset of [Group R1] are compounds where

R1 is selected from -O- (CH2) 1-2-ring and ring is selected from phenyl, 2-, 3-, and 4- pyridyl, 1,4-dioxan-2-yl, 4- tetrahydropyranyl, 3-tetrahydrofuranyl, 4- piperidinyl, 3-azetidinyl, 3-oxo-4-morpholinyl, 3,4-difluoro35

1-pyrrolidinyl, 1-methyl-2-imidazolyl, 4-imidazolyl, 3- tetrahydropyranyl, 4pyrimidinyl, pyrazolo [1,5-a] pyrimidin-7-yl, 1-methyl-4-pyrazolyl, 3-isoxazolyl , 4azepanil, 1,2,3-triazol-1-yl, 2,3-dihydro-2-indolyl, 1-methyl-5-pyrazolyl, 1-methyl-2-pyrrolidinyl, 1,4-diazepan-1-yl, 1 , 4-dimethyl-2-piperazinyl, tetrazolyl, 1-methyl-2-oxo-4-pyrrolidinyl, 3-methyl-3-piperidinyl, 4-methyl-2morpholinyl, 5-methyl-2-oxo-3-oxazolidinyl, 2-oxo-1 -pyrrolidin i lo.

In another subset of [Group R1] are compounds where R¹ is selected from -O- (CH₂)₂-3-OH, O- (CH₂)₂.₃-OCH₃, O- (CH₂)₂.₃ OCH₂Ph, O- (CH₂)₂-₃-NHCH₃, O-alkyl substituted with CO₂H

CO₂Ci alkyl.₃or CONH group₂.

In another subset of [Group R1] are compounds where R1 is selected from H, C- | _4 alkyl, C- | -4 haloalkyl, θ3-6 cycloalkyl. And C1-4alkyl. Examples of R1 include H, methyl, isopropyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, cyclopropyl, and isopropyloxy.

For the compounds of formulas (I), (la), and (Ib) as well as various applicable groups, subsets, aspects and modalities mentioned above, there is a group [Group R4] of compounds wherein R4 is selected from H, halogen, C1-3alkyl (optionally substituted with OH, OCH₃, OCOCH₃, NH_2i NHCONH2 or NHCOCH₃), C1-3 haloalkyl, C3-4 cycloalkyl, NRbíajRcía), NHCO C1-3alkyl, NHCOC3-6cycloalkyl, NHCONHRb^(to). In one embodiment, R4 is H. In another embodiment, R4 is C1-4alkyl, preferably methyl. In another embodiment R4 is C3-4 cycloalkyl, preferably cyclopropyl.

In another group of formula (I) are compounds having formula I (d) or a pharmaceutically acceptable salt thereof:

RZ (b)

<img file="MX2012007154A_D0006.tif" />

(Id) where p 'is 0, 1 or 2;

Ry (a) is selected from OH, OCH₃, F, CN and CONH₂;

Rz (b) is selected from (a) C1.4 alkyl optionally substituted with one or more groups independently selected from OH, NH2, CN, CO2Ra (a) and CONH₂, (b) CN, (c) -C (O) 2Ra (a), (d) -C (O) NHRB (a), (e) -NHC (0) C1-4alkyl (optionally substituted with OH ), (f) 1,3,4-oxadiazol-2 (3H) -one, and (g) 1,2,4-oxadiazol-5 (4H) -one;

R1 is selected from H, methyl, isopropyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, cyclopropyl, and isopropyloxy;

R4 is selected from H, methyl and cyclopropyl;

Ra (a) is H or C- | -4 alkyl;

Rb (a) is H, optionally substituted C1.4alkyl 2-oxo-1pyrrolidinyl.

In a subset of formula (Id) they are compounds where

Ry (a) is OH.

In another subset of formula (Id) are compounds where Rz (b) is CO2H, CONH2, CONH (CH2) 3- (2-oxo-1-pyrrolidinyl), or NHC (O)

CH2OH.

In another group of formula (I) are compounds having formula I (e) or a pharmaceutically acceptable salt thereof:

<img file="MX2012007154A_D0007.tif" />

(him) where

Ry (a) is selected from OH, NH₂, OCH₂CH₂OH, and aminomethyl,

R¹ is selected from H, methyl, isopropyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, cyclopropyl, and isopropyloxy; and

R⁴ it is selected from H, methyl and cyclopropyl.

In a subset of the formula (le) Ry (a) is OH.

Representative compounds of the present invention are as follows (each compound is intended to include pharmaceutically acceptable salts thereof):

1- [5- (2-fluoro-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yljcyclobutanol;

1- [5- (2-methoxy-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclobutanol;

1- [5- (2-chloro-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclobutanol;

1- {5- [2- (trifluoromethoxy!) -5 - {[4- (trifluoromethyl) pyrimidin-2!] Amino} phenyl] -1,3-t¡azol-2-l} cyclobutanol!

1- {5- [2- (benzyloxy) -5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] 15 1,3-thiazol-2-yl} cyclobutanol!

2- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -4 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenol;

1- [5- (2-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclobutanol;

1- {5- [3- (trifluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} cyclobutanol!

1- [5- (3-chloro-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-yl] cyclobutanol;

2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] propan-2-ol¡

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,3thiazol-2-yl ] cyclobutanol;

1,1,1 -trifluoro-2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] propan-2-ol ;

1,1,1,3,3,3-hexafluoro-2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propan- 2-ol;

2- [5- (3-bromo-5 - {[4- (trfluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,310 thiazol-2-yl] propan-2- ol;

cyclopropyl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] methanol;

1- [5- (3 - {[4- (trfluoromethyl) pinm-din-2-yl] amino} phenyl) -1,3-thiazol-2l] cycloheptanol;

3,3-dimethyl-2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-l] amino} phenyl) -1,3 thiazol-2-yl] butan-2-ol;

2- methyl-1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopentanol;

1-acetyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] piperidin-4-ol;

2,2-Difluoro-1-phenyl-1 - [5- (3 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2-yl] ethanol¡

3- (dimethylamino) -2,2-dimethyl-1 - [5- (3 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] propan-1 -ol;

1,1,1-trif luoro-2- [5- (3 - {[4- (trif luorometi I) p ¡rim id in-2-il] am inojfe n ¡I)

1,3-thiazol-2-yl] butan-2-ol;

1,1 -difluoro-2- [5- (3 - {[4- (trifluoromethyl) p¡r¡midin-2-l] amino} phenyl) 1.3-thiazol-2-yl] propan-2- ol;

1-cyclohexyl-2,2,2-trifluoro-1 - [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

1- [1- (phenylsulfonyl) -1H-pyrrol-3-yl] -1- [5- (3 - {[410 (trifluoromethyl) pyrimid in-2-yl] amino} phenyl) -1,3-thiazole- 2-yl] ethanol;

1- (5-bromopyridin-2-yl) -2,2-difluoro-1- [5- (3 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-yl] ethanol;

- (4-fluorophenyl) -3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolid ¡N-3-ol;

1- (dimethylamino) -2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol;

cyclopentyl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methanol;

(1R, 5S) -3-hydroxy-3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] -8- ethyl azabicyclo [3.2.1] octane-8-carboxylate

1- (1-methyl-1H-pyrrol-3-yl) -1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

furan-3-yl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] methanol;

furan-3-yl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-yl] methanone;

pyridin-3-yl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] methanol;

(1-methyl-1H-pyrazol-5-yl) [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methanol;

Soxazol-3-yl [5- (3 - {[4- (trifluoromethyl) pyrimide-2-yl] amino} phenyl) -1,310 thiazol-2-yl] methanone;

[1 - (1 -methylethyl) -1 H-pyrazol-4-yl] [5- (3 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-t¡ azole-2-yl] methanol;

-p¡r¡d¡n-3-¡l-1- [5- (3 - {[4- (tr¡fluoromet¡l) p¡r¡míd¡n-2-¡l] am¡no} phenyl) 1,3-thiazol-2-yl] ethanol;

1-pyrazin-2-yl-1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl ]ethanol;

1-cyclobutyl-1- [5- (3 - {[4- (trifluoromethyl) pyrmididin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] ethanol;

2₎4-dimethyl-3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 20 thiazol-2-yl] pentan-3-ol;

3-hydroxy-3- [5- (3 - {[4- (trifluoromethyl) pyrimydin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] butyl acetate;

1-cyclopropyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] piperid in-4-ol;

3- {2-hydroxy-2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] cyclohexyl} propaneitrile;

Ethyl 1- {1 -hydroxy-1 - [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] ethyl} cyclopropanecarboxylate;

1,3,4-Oxadiazol-2-yl (pyridin-3-yl) [5- (3 - {[4- (trifluoromethyl) pyridin-2 yl] amino} phenyl) -1.3 -thiazol-2-yl] methanol;

Ethyl 4- hydroxy-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] piperidine-1-carboxylate;

1- (1-methylethyl) -4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] piperid in-4-ol;

4-hydroxy-4- [5- (3 - {[4- (tr¡fluoromethyl) pyr¡m¡din-2-l] amino} phenyl) -1,3-thiazol-2- yl] hexan-3-one;

(3aR, 5s, 6aS) -5-hydroxy-5- [5- (3 - {[4- (trifluoromethyl) pyridine-2yl] amino} phenyl) -1,3-thiazole- 2-yl] hexahydropentalen-2 (1H) -one;

- [5- (meth Is ulfon i I) th ioph en-2-yl] -1 - [5- (3 - {[4 (tnfluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] ethanol;

2,2,6_I6-tetramethyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] tetrahydro-2H-thiopyran-4-ol;

pyridin-2-yl (1,3-thiazol-2-yl) [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methanol ;

9-benzyl-7- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -3-oxa-9-azabicyclo [3.3.1] nonan-7-ol;

1- (phenylcarbonyl) -4- [5- (3 - {[4- (tr¡fluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2-yl] piperidin-4- ol;

3,3,4,4,5,5,5-heptafluoro-2- [5- (3 - {[4- (tr¡fluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2- L] pentan-2-ol;

2- [5- (3 - {[4- (tr¡fluoromethyl) p¡r¡m¡din-2-yl] amino} phenyl) -1,3-t¡azol-2-yl] 7-azabicyclo [ 2.2.1] heptan-2-ol;

3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-210 yl] oxetane-3-ol;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2-yl] amino} phenyl) -1,3thiazol-2-yl] oxetane-3-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2-yl] amino} phenyl) -1,3thiazol-2-yl] tetrahydro-2H-pyran-4-ol;

1-methoxy-2- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol ;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol;

1-fluoro-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol;

1,3-Difluoro-2- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propan- 2-ol;

1- (1-methyl-1H-1,2,4-triazol-5-yl) -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrim¡din-2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol!

1- (5-methyl-1,2,4-oxadiazol-3-yl) -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

dicyclopropyl [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methanol;

2,2-dimethyl-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} fen yl) -1,3-thiazol-2-yl] -1,3- dioxan-5-ol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] propan- 1,2,3-triol;

8- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -1,4-dioxaspiro [4.5] decan-8 -ol;

3- (1H-ym¡dazol-4-yl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] am harmless I) -1, 3-thiazol-2-yl] propa n-1 -ol;

8- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-i I)

1,4-dioxaspiro [4.5] decan-8-ol;

2- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2yl) propan-1,2,3-triol;

3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-220 yl] pentan-1,3,5-triol;

2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] propan-1,2-diol;

2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] propan-1,2-diol;

2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] propan-1,2-diol;

2-methyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] butan-2,3-diol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] propan-1,2-diol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] propa n-1, 2-diol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-II] propan-1,2-diol;

2.2.2- trifluoro-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡mid¡n-2¡l] amino} phenyl) -1,3- thiazol-2-yl] ethanol;

2,2,2-trif luoro-1 - [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] ethanone;

2.2.2- trifluoro-1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] ethanol;

2.2.2- trifluoro-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

2,2,2-trifluoro-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

2.2.2- trifluoro-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] ethanone;

3.3.3- trifluoro-2-hydroxy-2- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin 2-yl] amino} phenyl) -1,3-t Ethyl azole-2-yl] propanoate;

3,3,3-tr¡fluoro-2- [5- (3-metíl-5 - {[4- (tr¡fluoromet¡l) p¡r¡m¡din-2¡l] amino} fen L) -1,3-thiazol-2-yl] propan-1,2-diol;

3.3.3- trifluoro-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2¡l] amino} feníl) -1,3-thiazol-2-¡l ] propan-1,2-diol;

3.3.3- trifluoro-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-210 yl] am inojfen il) -1,3-thiazol-2-yl] propa n- 1,2-diol;

2,2,4,4-Tetramethyl-1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-l ] cyclobutan-1,3-diol;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanone ;

c¡s-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] cyclohexan-1,4 -diol;

trans-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] cyclohexan-1, 4-diol;

trans-1-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] am inojphenyl) -1,3-thiazol-2-yl] cyclohexan-1,4- diol;

cis-1-methyl-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2¡l] amino} phenil) -1,3-thiazole- 2-yl] cyclohexan-1,4-diol;

5-hydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan -2-one

5-hydroxy-5- (5- {3 - [(4-methoxypyrim¡d-2-yl) amino] -5-methylphenyl} -1,3 t¡azol-2-yl) azepan- 2-one;

cyclopropyl [5- (3 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3thiazol-2-yl] methanone;

1-cyclopropyl-2,2,2-tr-fluoro-1- [5- (3 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

N- {3-metíl-5- [2- (1-metíletíl) -1,3-t¡azol-5-¡l] fen¡l} -410 (trifluorometíl) p¡ rim¡d¡n-2-amína;

N- [3- (2-cyclobutyl-1,3-thiazol-5-yl) -5-methylphenyl] -4 (trifluoromethyl) pyridine-2-amine;

4- {1-h¡droxi-1- [5- (3 - {[4- (tr¡fluoromethyl) p¡r¡m¡d¡n-2-¡] amino} phenyl) 1.3- thiazol-2 -yl] ethyl} piperidine-t-butyl 1-carboxylate

1- (p¡per¡d¡n-4-yl) -1- [5- (3 - {[4- (trifluoromethyl) p¡r¡midin-2il] amíno} feníl) -1, 3-thiazol-2-yl] ethanol;

dicyclopropyl [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 t¡azol-2-yl] methanol!

1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-t¡azol-220 ¡Ijciclopentanol;

1-cyclopropyl-1- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] ethanol;

1,1,1-trifI-uoro-2- [5- (3-met¡l-5 - {[4- (trifl uorometi l) pi rim id i n-2yl] amino} phenyl) -1,3-thiazole -2-yl] propan-2-ol;

- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yljetanol;

N- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) acetamide;

- [5- (3-amino-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] cyclobutanol;

N- (3- [2- (1 -h id roxycyclobuti I) -1,3-thiazol-5-yl] -5 - {[410 (trifluoromethyl) pyrim¡din-2-yl] amino} phenyl) butanam¡ gives;

N- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) cyclopropancarboxamide;

- [5- (3-nitro-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

1-cyclopentyl-3- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) urea;

1-ethyl-3- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) urea;

- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) urea;

1- (3- (2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) p¡r¡midin-2-yl] amino} phenyl) - 3-methylurea;

1- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -3- (1-methylethyl ) N- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) dicarbonimidic urea diamide;

4- [5- (3 - [(ethylcarbamoyl) amino] -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

2- methyl-2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] propan-1-ol;

N- {3- [2- (tetrahydrofuran-2-yl) -1,3-thiazol-5-yl] phenyl} -410 (trifluoromethyl) pyrimidin-2-amine!

N- {3- [2- (4-methylmorpholin-2-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- (3- {2 - [(methylsulfonyl) methyl] -1,3-thiazol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidin-2-amine!

N- {3- [2- (1-methyl-1 H-pyrazol-4-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- {3- [2- (tetrahydrofuran-3-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- {3- [2- (morpholin-4-ylmethyl) -1,3-thiazol-5-yl] phenyl} -420 (tnfluoromethyl) pyrimidin-2-amine!

N- {3- [2- (2,3-dihydro-1 H-inden-1-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

4- (diethylamino) -2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) ·

1,3-thiazol-2-yl] butan-2-ol;

N- {3- [2- (3,3-difluorocyclobutyl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

3 - {[5- (3 - {[4- (trifluoromethyl) pyrimydin-2-yl] amino} phenyl) -1,3-thiazol-2yl] methyl} -1,3-oxazolidin-2- ona;

methyl trans-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] cyclohexancarboxylate;

trans-N- (2-hydroxyethyl) -4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxam! gives;

trans-N-cyclopropyl-4- [5- (3 - {[4- (trifluoromethyl) pyridine-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] pyrrolidin-2-one;

N- {3- [2- (1,4-dioxan-2-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

1- {2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] ethyl} pyrrolidin-2-thione;

1-methyl-5- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] piperidin-2-one;

N- {3- [2- (1-methylazepan-2-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

trans-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] cyclohexanecarboxylic;

trans-N-cyclopropyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

trans-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

dicyclopropyl {5- [3- (morpholin-4-yl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} methanol;

1- [5- (3-morpholin-4-yl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 10 1,3-thiazol-2-yl] ethanol;

N- {3- [2- (2-methyl-1,3-dioxolan-2-yl) -1,3-thiazol-5-yl] -5-morpholin-4ylphenyl} -4- (trifluoromethyl) pyrimidine -2-amine;

1- [5- (3-morpholin-4-yl-5 - {[4- (tr¡fluoromethyl) p¡rim¡d¡n-2-yl] amino} phenil) 1.3- thiazol-2-yl ] ethanone;

one - [5- (3- [4- (methylsulfonyl) piperazin-1-yl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclobutanol;

- [5- (3-morpholin-4-yl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] cyclobutanol;

-cyclopropyl-1 - [5- (3-morpholin-4-yl-5 - {[4- (trifluoromethyl) pyrimidine-220 yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

1,1,1 -trif I uoro-2- [5- (3-morfol in-4-yl-5 - {[4- (trif luorometi l) pi ri m id i n-2yl] amino} phenyl) - 1,3-thiazol-2-yl] propan-2-ol;

(cis) 4-fluoro-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate of t -butyl;

(trans) 4-fluoro-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2 yl] amino} phenyl) -1,3-thiazol-2-yl] c¡ t-butyl chlohexancarboxylate;

4-fluoro-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

trans-4-fluoro-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyr¡m¡d¡n-2 yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexancarboxylic;

N- {3- [2- (1-fluorocyclobutyl) -1,3-thiazol-5-yl] -5-morpholin-4-ylphenyl} -410 (trifluoromethyl) pyrimidin-2-amine;

N- {3- [2- (1-fluorocyclobutyl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

cis -4-fluoro-4- [5- (3 - {[4- (trifluoromethyl) p¡rim¡d¡n-2-¡l] amino} phenyl)

Ethyl 1,3-thiazol-2-yl] cyclohexancarboxylate;

ethyl trans -4-fluoro-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate;

trans-4-fluoro-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

1- [5- (3 - [(2,2,2-trifluoroethyl) amino] -5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

2,2-dfluoro-1- [5- (3 - [(2,2,2-trifluoroethyl) amino] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] ethanol;

1,1,1-trif luoro-2- [5- (3 - [(2,2,2-trif I uoroethyl) am i ηο] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino } phenyl) -1,3-thiazol-2-yl] propan-2-ol;

1- {5- [3- (difluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} cyclobutanol;

2- {5- [3- (difluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl] -1,3-thiazol-2-yl} propan-2-ol;

2- [5- (3-ethynyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol;

2- [5- (3-ethyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] propan-2-ol;

2- [5- (3-cyclopropyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-iI] propan-2-ol;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-¡ l] ethyl cyclohexancarboxylate trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3- thiazol-2-yl] cyclohexancarboxylic;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

trans-4-hydroxy-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

cis-4-hydroxy-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

Ethyl cis-4-hydroxy-4- [5- (3 - {[4- (trIforomethyl) pyrimyl-2-yl] amino} phenyl) 1.3-thiazol-2-yl] cyclohexanecarboxylate;

trans-4-hydroxy-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

Ethyl 1,3-thiazol-2-yl] cyclohexancarboxylate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyr¡m¡d¡n-2yl] amino} phenil) -1,3-thiazol- 2-yl] cyclohexancarboxylate; ethyl cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

ethyl trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylate;

trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 [l] amino} phenyl) -1,3-thiazol-2- acid L] cyclohexancarboxylic;

cis-4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

trans-4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

trans-4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 meth Ifen i I} -1,3-thiazol-2-yl) -1-methylcyclohexancarboxylic acid;

cis-4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -1-methylcyclohexanecarboxylic acid;

cis-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxylic acid;

trans-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxylic acid;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -1-phenylcyclohexanecarboxylic acid;

trans-4-hydroxy-1-methyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

cis-4-hydroxy-1-methyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

c¡s-4-h¡droxi-1-methyl-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-210 yl] amino} phenyl) -1.3 -thiazol-2-yl] ethyl cyclohexancarboxylate;

trans-4-hydroxy-1-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate ethyl;

trans-4-hydroxy-1-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid ] cyclohexancarboxylic;

Cis-4-hydroxy-1-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] acid cyclohexancarboxylic;

1- (acetylamino) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylate methyl;

1- (acetylamino) -4-hydroxy-4- [[(3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] cyclohexancarboxylic;

9-hydroxy-9- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] bicyclo [3.3.1] nonane -3-carboxylic;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanecarboxylic acid, 3-hydroxy acid -3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopentancarboxylic acid;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmididin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohex-3-ene-1 -ethyl carboxylate;

Ethyl ethyl 4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmididin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate;

4- [5- (3-Methyl-5 - {[4- (trifluoromethyl) pyridin-2-yl] amino} phenyl) 10 1,3-thiazole acid -2-yl] cyclohexancarboxylic;

4- [5- (3 - {[4- (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,3-thiazol-2l] cyclohex-3-ene-1- ethyl carboxylate;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohex-3- ethyl ene-1-carboxylate;

Ethyl ethyl 4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] cyclohex-3-ene-1-carboxylic;

trans-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 20 1,3-thiazol-2-yl] cyclohexancarboxylic acid;

methyl trans-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] cyclohexancarboxylate;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarbonitrile;

trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarbonitrile;

trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexancarboxamide;

4- [5- (3 - {(t-butoxycarbonyl) [4- (trifluoromethyl) pyrimidin-2-yl] aiTiino} -510 methylphenyl) -1,3-thiazol-2-yl] -4-hydroxy! ethyl cyclohexancarboxylate;

2 - ({3- [2- (cis-4-Carboxy-1-methoxycyclohexyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) -4- (trifluorometyl ) pyrimidin-1-io trifluoroacetate;

cis-4-methoxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

2 - ({3- [2- (trans-4-Carboxy-1 -methoxycyclohexyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) -4- (trifluoromethyl) pyrimidin-1-io trifluoroacetate ;

trans-4-methoxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

4-methoxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 20 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

1-amino-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole acid -2-yl] cyclohexancarboxylic;

(1 S.4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 acid , 3-thiazol-2-yl] cyclohexanecarboxylic;

(1S.4R) -4-hydroxy-2,2-dimethyl-4- {5- [3- (2H3) methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid] -1,3-thiazol-2-yl} cyclohexanecarboxylic;

(1R.4s) -4-hydroxy-2,2-dimethyl-4- {5- [3- (2H3 de) methyl-5 - {[4 (tr-fluoro-methyl) pyrmidine- 2-yl] amino} phenyl] -1,3-thiazol-2-yl} cyclohexanecarboxylic;

(1S.4R) -4-hydroxy-2,2-dimethyl-4- {5- [3- (2H2 de) methyl-5 - {[4 (trifluoromethyl) pyrimidine-2-yl] acid - amino} phenyl] -1,3-thiazol-2-yl} -cyclohexan-carboxylic;

(1R.4s) -4-hydroxy-2,2-dimethyl-4- {5- [3- (2H2 de) methyl-5 - {[4 (trifluoromethyl) pyrim id in-2-yl] am inojfen acid! I] -1,3-thiazol-2-yl} cyclohexane-carboxylic;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine-1-carboxylate t-butyl;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡m¡din-2-¡l] amino} phenyl) -1,3thiazol-2-yl ] piperidin-4-ol;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimide-2i l] to minojfen I) -1,3-thiazol-2- il] pi perid ¡na-1 -carboxamide;

({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-1-yl} t-butyl sulfonyl) carbamate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-220 yl] am harmless yl) -1,3-thiazol-2-yl] p iperid Na-1-sulfonamlda;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -1 - (phenylsulfonyl) p¡per¡ d-n-4-ol;

- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-1 -yljetanone;

hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] am inojfen i I) -1,3-thiazol-2-i IJpiperid i na-1 -carboxamide;

2- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] azetidin-1 acid -yl} -2-methylpropanoic;

2 - [(2- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimide-2-yl] amino} phenyl acid) -1,3-thiazol-2-yl] azetidin-1-yl} -2-methylpropanoyl) oxy] -2methylpropanoic;

{[4-hydroxy-4- (5- {3 - [(4-methoxypyrim¡din-2-yl) amino] -5-methylphenyl} -1.3 thiazol-2-yl) piperidin-1-yl ] methyl sulfonyl} carbamate;

4-chloro-4- (5- {3 - [(4-methoxyprimidin-2-yl) amino] -5-methiphenyl} -1,3-thiazol-2-yl) piperidine-1-sulfonam! gives;

1 - [(1-methylethyl) sulfonyl] -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin15 2-yl] amino} phenyl) -1,3-thiazol-2-yl ] piperidin-4-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -1 - [(trifluoromethyl) sulfonyl ] piperidin-4-ol;

- [(1-methyl-1 H-imidazol-4-yl) sulfonyl] -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] piperidin-4-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -1-propanoylpiperidin-4-ol;

1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin- 4-ol;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-1-yl } -3-oxopropanonitrile;

1- (N, N-dimethylglycyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] p¡ peridin-4-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -1- (pyridin-3-ylcarbonyl) piperidin- 4-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -1- (pyridin-2-ylcarbonyl) piperidin-4-ol;

1- (2- {4-h¡droxi-4- [5- (3-metíl-5 - {[4- (trifluoromet¡l) p¡r¡midin-210 il] am nojfen ¡I) -1,3-thiazol-2-l] piperid-n-1-yl} -2-oxoeti l) p-rrolid i n-2-one;

1- (cyclopropylcarbonyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-4-ol;

N-cyclohexyl-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) p¡rimidin-2 yl] ami nojfe n ¡I) -1,3- thiazol-2-yl] piperidin-1-carboxamide;

4-hydroxy-N- (1-met¡let¡l) -4- [5- (3-met¡l-5 - {[4- (trifluoromet¡l) p¡r¡m¡d¡n

2-yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine-1-carboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N-propylpiperidine-1-carboxamide ;

4-hydroxy-N, N-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 · 20 yl] amino} phenyl) -1,3-thiazol-2-yl ] piperidine-1-carboxamide;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidine-1 -carboxamide;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidine-1-carboxamide;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am inojfen i I) -1,3-thiazol-2-yl] azetid i na-1 -carboxamide ;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidine-1 - t-butyl carboxylate;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] pyrrolidin-3-ol;

4- hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine-210 yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine -1-sulfonamide;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] p¡rrolid¡na-1- sulfonamide;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2¡l] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidine- 1 -carboxamide;

({3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-1 - ilJsulfoniIJ t-butylcarbamate;

N- (dimethylcarbamoyl) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) piperidine-1-carboxamide;

{[4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3 20 thiazol-2-yl) piperidin-1-yl] sulfonyl} methyl carbamate;

3-hydroxy-3- (5- {3 - [(4-methoxy-pyr-m-din-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) pyrrolidine- 1-carboxamide;

4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) piperidine-1-carboxamide;

3- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) pyrrolidin-3-ol;

4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2¡l) piperidin-4-ol;

1- [5- (3-methyl-5 - {[4- (propan-2-yl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-210 yl) cyclobutanol;

1- (5- {3 - [(4-ethylpyrididin-2-yl) amino] -5-methylenyl} -1,3-thiazol-2yl) cyclobutanol;

1- (5- {3 - [(4-cyclopropylpyr¡m¡d¡n-2-yl) amino] -5-methylphenyl} -1,3-thiazole 2-yl) cyclobutanol;

1- [5- (3-methyl-5 - {[4- (methylsulfanyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

2- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5-fluorophenyl} 1,3-thiazol-2-yl) propan-1,2-diol ;

2- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} 20 1,3-thiazol-2-yl) -3,3,3-trifluoropropan -1,2-diol;

N- {3- [2- (3-Aminooxetan-3-yl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- {3- [5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-yl] oxetane-3- yl} methanesulfonamide;

2- methyl-N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] oxetane-3- yl} propan-2-sulfonamide;

N- {3- [2- (1-aminocyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

1.1.1 -trifluoro-N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2-yl] oxetane -3-yl} methanesulfonamide;

2.2.2- trifluoro-N- {1- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡d¡n-210 yl] amino} phenyl) -1,3-thiazol- 2-yl] cyclobutyl} ethanesulfonamide;

1-fluoro-N- {1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutyl} methanesulfonamide ;

2.2.2- trifluoro-N- {3- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pinmidin-2¡l] amino} phenyl) -1,3-thiazole -2-yl] oxetane-3-yl} ethanesulfonamide;

N- {d-cyclopropyl [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} methanesulfonamide;

1.1 -d if I uoro-N- {3- [5- (3-methyl-5 - {[4- (trif I uoromethyl) pyrim id i n-2yl] amino} phenyl) -1,3-thiazole -2-yl] oxetane-3-yl} methanesulfinamide;

N- {3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 20 yl] oxetane-3-yl} methanesulfonamide;

N- {dicyclopropyl [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} -2- Methylpropan-2-sulfinamide!

N- {1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutyl} methanesulfonamide;

N- {3- [2- (1-amino-1 -methylethyl) -1,3-thiazol-5-yl] -5-methylenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- {1-methyl-1- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} methanesulfonamide ;

1,1,1 -trifluoro-N- {1 - [5- (3-methyl-5 - {[4- (trif I uoromethyl) pyrim id i n-2yl] amino} phenyl) -1,3-thiazole -2-yl] cyclobutyl} methanesulfonamide;

N- {3- [2- (1-Aminocyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} -410 cyclopropylpyrimidin-2-amine;

N- {3- [2- (1-aminocyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} -4cyclopropylpyrimidin-2-amine;

N- {3- [2- (1-aminocyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} pyrimidin-2amine;

N- {3- [2- (1-aminocyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} -4methoxypyrimidin-2-amine;

N- [3-methyl-5- (1,3-thiazol-5-yl) phenyl] -4- (piperidin-4-yloxy) pyrimidin-2amine;

N- {3- [5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 20 yl] amino} phenyl) -1,3-thiazol-2-yl] oxetane-3-yl diamide }sulfuric;

N- {1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutyl} sulfamide;

N- {d-cyclopropyl [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol- 2-yl] methyl} sulfamide;

- {1 - [5- (3-methyl-5 - {[4- (trif luorometi l) pi rim id i η-2-yl] am ino} fen i I) -1,3 thiazol-2-yl] cyclobutyl }urea;

1- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] oxetane-3-yl} urea;

1- {dicyclopropyl [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} urea;

- [1 - (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,310 thiazol-2-yl) cyclobutyl] urea;

- (1 - {5- [3-methyl-5- (pyrimidin-2-ylamino) phenyl] -1,3-thiazol-2l} cyclobutyl) urea;

- [1 - (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylfenyl} -1,3-thiazol-2 · yl) cyclobutyl] urea;

1- {1- [5- (3-methyl-5 - {[4- (p¡per¡d¡n-4-Iloxy) pyrim¡din-2-yl] amino} fenyl) 1,3-thiazol-2-yl] cyclobutyl} urea;

N- [1 - (5- {3 - [(4-cyclopropyl-5-f luoropi ri mid i n-2 yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) cyclobutyl trifluoroacetate ]urea;

N- [1- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -520 fluorophenyl} -1,3-thiazol-2-yl) cyclobutyl] urea;

Diamide N- {dicyclopropyl [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} dicarbonimidic;

diamide N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] oxetane-3-yl} dicarbonimidic ;

diamide N- [1- (5- {3 - [(4-methoxyprimidin-2-yl) amino] -5-methylphenyl}

1,3-thiazol-2-yl) cyclobutyl] dicarbonimidic;

N- (1- {5- [3-methyl-5- (pyrimidin-2-ylamino) phenyl] -1,3-thiazol-2 yl} cyclobutyl) dicarbonimidic diamide;

diamide N- [1- (5- {3 - [(4-cyclopropylpyrididine-2-yl) amino] -5 methylphenyl} -1 .S-thiazole ^ -iQcyclocyclobutylJdicarbonimidic;

Diamide N - {1- [5- (3-methyl-5 - {[4- (piperidin-4-yloxy) pyrimidin-2 10 yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclobutyl} dicarbonim id ica;

N- {1- [5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutyl} acetamide;

N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] oxetane-3-yl} acetamida;

N- {D-cyclopropyl [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am inojfen i I) -1,3-thiazol-2-yl] methyl} cyclopropa n-1,1 -dicarboxamide;

N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] oxetan-3-yl} cyclopropan-1 , 1-dicarboxamide;

2 - ({3-Methyl-5- [2- (1,1,1-trifluoro-2-hydroxypropan-2-yl) -1,3 20 thiazol-5-yl] phenyl} amino) pyrimidin-4- acid carboxylic;

2 - ({3- [2- (1-Hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 methylphenyl} amino) pyrimidin-5-carboxylic acid;

1- [5- (3 - {[4- (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] cyclobutanol;

[2 - ({3-methyl-5- [2- (1,1,1 -trifluoro-2-hydroxypropan-2-yl) -1,3-thiazol-5yl] phenyl} amino) pyrimidin-4-yl] (piperazin-1-yl) methanone;

1,1,1-trifluoro-2- [5- (3-methyl-5 - {[4- (morpholin-4-ylcarbonyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-yl] propan-2-ol;

2- [5- (3-nitro-5 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3tiazol-2-yl] propan-2-sulfonamide;

2- [5- (3-amino-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] propan-2-sulfonamide;

N- (3- [2- (2-Sulfamoylpropan-2-yl) -1,3-thiazol-5-¡l] -5 - {[4 (tr¡fluoromet¡l) p¡rim¡d¡n- 2-yl] amino} phenyl) acetamide;

N- (3-Methyl-5- {2- [2- (methylsulfonyl) propan-2-yl] -1,3-t¡azol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidin-2-amine;

N - ({1- [5- (3-Methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2-yl] amino} phenyl) -1.3 thiazol-2-yl] cyclobutyl} sulfonyl) acetamide;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] propan-2-sulfonamide;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] cyclobutansulfonamide;

N- (3-Methyl-5- {2- [1- (methylsulfonyl) cyclobutyl] -1,3-thiazol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidin-2-amine;

N- (3- {2- [1 - (Methylsulfonyl) cyclobutyl] -1,3-thiazol-5-yl} -5-nitrophenyl) -4 (trifluoromethyl) pyrimidin-2-amine!

5- {2- [1 - (meth Isu Ifon il) cyclobuty I] -1,3-thiazol-5-yl} -N- [4 (trifluoromethyl) pyrimidin-2-yl] benzene-1,3-diamine ;

N- (3- {2- [1- (Methylsulfonyl) cyclobutyl] -1,3-thiazol-5-yl} -5 - {[4 (trifluoromethyl) pyrimydin-2-yl] amino} phenyl) acetamide;

N- (3- {2- [2- (Methylsulfonyl) propan-2-yl] -1,3-thiazol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidin-2-amine;

2- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-210 yl] propan-2-sulfonamide;

2- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2 yl) propan-2-sulfonamide¡

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methanesulfonamide;

1- [5- (3 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3-thiazol-2¡IJmethanesulfonamide;

1- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2 yl) methanesulfonamide;

(2R) -2-methyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pinmidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] methyl propanoate ;

Methyl 2,2-dimethyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propanoate;

2,2-Dimethyl-3- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] propanoic acid ;

N- (3-Methyl-5- {2- [2-methyl-2- (1,3,4-oxadiazol-2-yl) propyl] -1,3-thiazol-5 · yl} phenyl) -4- (trifluoromethyl) pyrimidin-2-amine;

Ethyl 3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propanoate;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] propanamide;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 10 1,3-thiazol-2-yl] propanoic acid;

N, N-dimethyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2l] amino} phenyl) -1,3-thiazol-2- il] propanamide;

N- {3-Methyl-5- [2- (3-morpholin-4-yl-3-oxopropyl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N- (2-hydroxyethyl) -3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] propanamide;

N- (3-Methyl-5- {2- [2- (1,3,4-oxadiazol-2-yl) ethyl] -1,3-thiazol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidine- 2-amine;

N- (3-Methyl-5- {2- [2- (5-methyl-1,3,4-oxadiazol-2-yl) ethyl] -1,3-thiazol-520 yl} phenyl) -4 - (trifluoromethyl) pyrimidin-2-amine;

N- (3- {2- [2- (5-cyclopropyl-1,3,4-oxadiazol-2-yl) ethyl] -1,3-thiazol-5-yl} -5methylphenyl) -4- (trifluoromethyl) pyrimidin-2-amine;

2,2-dimethyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} pheníl) -1,3-thiazol-2-yl] propaganda

N, N, 2,2-tetramethyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propanamide;

2-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) ·

1,3-thiazol-2-yl] butan-2-ol;

2-methyl-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) ·

T-Butyl 1,3-thiazol-2-yl] propanoate;

N- (3-Methyl-5- {2- [2- (1,3,4-oxadiazol-2-yl) propan-2-yl] -1,3-thiazol-510 yl} phenyl) -4- (trifluoromethyl) pyrimid in-2-amine;

- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopropancarboxylate t- butyl;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] cyclopropancarboxylic;

N- (3-Methyl-5- {2- [1 - (1,3,4-oxadiazol-2-yl) cyclopropyl] -1,3-thiazol-5yl} phenyl) -4- (trifluoromethyl) pyrimidin-2 -amine;

2-methyl-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) ·

1,3-thiazol-2-yl] propanamide;

N, N, 2-trimethyl-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-220 yl] am ino} phenyl) -1,3-thiazol-2- il] propanamide;

N- {3- [2- (1,1-Dimethyl-2-morpholin-4-yl-2-oxoethyl) -1,3-thiazol-5-yl] -5methylphenyl} -4- (trifluoromethyl) p¡rimid ¡N-2-am¡na;

N- (3-Methyl-5- {2- [1-methyl-1- (5-methyl-1,3,4-oxadiazol-2-yl) ethyl] -1,3-thiazol-5-yl } phenyl) -4- (trifluoromethyl) pyrimidin-2-amine;

N, N-dimethyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2l] amino} phenyl) -1,3-thiazole- 2-l] cyclopropancarboxamida;

N-Methyl-1 - [5- (3-methyl-5 - {[4- (trif luoromethyl) pyrimid in-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopropancarboxamide;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopropancarboxamide;

N- (3-Methyl-5- {2- [1 - (5-methyl-1,3,4-oxadiazol-2-yl) cyclopropyl] -1,310 thiazol-5-yl} phenyl ) -4- (trifluoromethyl) pyrimidin-2-amine;

5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid)

1,3-thiazol-2-carboxylic;

N - [(2R) -2,3-dihydroxypropyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole- 2-carboxamide;

N- (1-methylethyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- {3-methyl-5- [2- (pyrrolidin-1-ylcarbonyl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol20 2-carboxamide;

N- (2,3-dihydroxypropyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N - [(2R) -2,3-dihydroxypropyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- [2- (methylsulfonyl) etl] -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- (2-hydroxyethyl) -N-methyl-5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2 · l] amino} phenyl) -1, 3-thiazol-2-carboxamide;

N- (2-hydroxypropyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- (2-hydroxy-1 -methylethyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimide-210 yl] amino} phenyl) -1 , 3-thiazol-2-carboxamide;

N- [1- (hydroxymethyl) cyclopropyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2- carboxamide;

N- [1- (hydroxymethyl) propyl] -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2- carboxamide;

N- (2-hydroxy-2-methylpropyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din

2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] carbonyl} piperazin-2-one;

N- (3-methyl-5- {2 - [(4-methylpiperazin-1-yl) carbonyl] -1,3-thiazol-520 yl} phenyl) -4- (trifluoromethyl) pyrimidin-2-amine ;

N- [2-h id roxy-1 - (h id roxymethyl) -1 -methylethi l] -5- (3-meth l-5 - {[4 (trifluoromethyl) pyrimyd-2-yl] amino } phenyl) -1,3-thiazol-2-carboxamide;

N - [(1-methyl-1 H-pyrazol-4-yl) methyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- thiazol-2-carboxamide;

N - [(1-methyl-1 H-imidazol-5-yl) methyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-carboxamide;

N- [2- (1 H-imidazol-4-yl) ethyl] -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine

2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

1-methyl-4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine-2yl] amino} phenyl) -1,3-thiazol-2-yl ] carbonyl} piperazin-2-one;

N- [1- (hydroxymethyl) cyclopentyl] -5- (3-methyl-5 - {[410 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- {3- [2- (3,4-dihydropyrrolo [1,2-a] pyrazin-2 (1 H) -ylcarbonyl) -1,3t¡azol-5-yl] -5-methylphenyl} - 4- (trifluoromethyl) pyrimidin-2-amine;

1,3-dimethyl-4 - {[5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimide-2yl] amino} phenyl) -1 , 3-thiazol-2-yl] carbonyl} piperazin-2-one;

N- (3- {2¿ (4-acetylpraze-1-yl) ca rbon i I] -1,3-thiazol-5-yl} -5methylphenyl) -4- (trifluoromethyl) pyrimidine- 2-amine;

N- [2- (1,3-dioxolan-2-yl) ethyl] -N-methyl-5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-carboxamide;

N - [(1-methyl-1 H-1,2,4-triazol-5-yl) methyl] -5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl ) -1,3-thiazol-2-carboxamide;

N- (2-fluoroprop-2-en-1-yl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-carboxam gives;

3-methyl-4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] carbon L} morpholin-2-ol;

N- (1,4-dioxan-2-ylmethyl) -5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-carboxamide ;

N- {3- [2- (5,6-dihydroimidazo [1,2-a] pyrazin-7 (8H) -ylcarbonyl) -1,3t¡azol-5-¡l] -5-methylfenil} - 4- (trifluoromethyl) pyrimidin-2-amine;

N-methyl-N - [(1-methyl-1H-imidazol-2-yl) methyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-carboxamide;

N- (dicyclopropylmethyl) -N-methyl-5- (3-methyl-5 - {[410 (trif luoromethyl) pyrimidine-2-yl] am inojphenyl) -1,3-thiazol-2-carboxamide;

2- (4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] carbonyl } morpholin-2-yl) ethanol;

N- (1,4-dioxan-2-ylmethyl) -N-methyl-5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phen! l) -1,3-thiazole-2-carboxamide;

[(3R) -1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] carbonyl} pyrrolidir »-3-yl] methanol;

3- methyl-1 - {[5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] carbonyl} pyrrolidin-3 -ol;

N- (2-hydroxy-3-methoxypropyl) -5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- carboxamida;

N- (3-methyl-5- {2 - [(1-oxide-1,4-thiazepan-4-yl) carbonyl] -1,3-thiazol-5yl} phenyl) -4- (trifluoromethyl) pyrimidine -2-amine;

N- (1 H-imidazol-2-ylmethyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine

2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N- (3- {2 - [(1,1-dioxidothiomorpholin-4-yl) carbonyl] -1,3-thiazol-5-yl} -5methylphenyl) -4- (trifluoromethyl) pyrimidin-2-amine;

N- (2,3-dihydroxypropyl) -N-methyl-5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- thiazol-2-carboxamide;

N-methyl-N- [2- (methylsulfonyl) ethyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-carboxamide;

N-ethyl-N-methyl-5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N, Nb¡s (2-hydroxyethyl) -5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2- carboxamida;

N-methylN- [2- (methylamino) -2-oxoethyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-carboxamide;

N- [3-methyl-5- (2 - {[4- (2,2,2-tnfluoroethyl) p! Peraz-1-l] carbonyl} -1,3thiazol-5 -il) phenyl] -4- (trfluoromethyl) p¡r¡m¡din-2-amína;

[(3S) -1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] carbonyl} pyrrolidin-3-yl] methanol;

N - [(2S) -2,3-dihydroxypropyl] -5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2carboxamide:

5 - [({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) methyl ] pyrrolidin-2-one;

N- (3-methyl-5- {2 - [(pyrimidin-5-ylamino) methyl] -1,3-thiazol-5-yl} phenyl) -4 (trifluoromethyl) pyrimidin-2- amine;

1,1-dfluoro-3 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) propan-2-ol;

5 - [({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) methyl] -2, 4-dihydro-3H-1,2,4-triazol-3-one;

5 - [(methyl {[5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimid-2-l] amino} phenyl) 10 1,3-thiazol-2 -yl] methyl} amino) methyl] -2,4-d ihyd ro-3H-1,2,4-triazol-3-one;

N- [3- (2 - {[(1,1-dioxidotetrahydroth¡ophen-3-yl) amino] methyl} -1,3-thiazol-5-yl) -5-methylphenyl] -4- (tr¡fluoromethyl) pyrimin-2-amine;

N- {3-methyl-5- [2 - ({[(3-methyloxetan-3-yl) methyl] amino} methyl) -1,3-thiazole ·

5-yl] phenyl} -4- (trifluoromethyl) pyrimidin-2-amine;

N- [3- (2 - {[(d-cyclopropylmethyl) (methyl) amino] methyl} -1,3-thiazol-5-yl) -5methylphenyl] -4- (tr¡ fluoromethyl) pyridin-2-amine;

N- [3- (2 - {[(2-fluoroprop-2-en-1-yl) amino] methyl} -1,3-thiazol-5-yl) -5methylphenyl] -4- (trifluoromethyl) pyrmidine -2-amine;

N- [3-methyl-5- (2 - {[(1-pyridin-2-ylethyl) amino] methyl} -1,3-t¡azol-5-l) phenyl] 20 4- (trifluoromethyl ) pyrimidin-2-amine!

N- {3-methyl-5- [2 - ({[1- (1 -methylethyl) -1 H-1,2,3-triazol-4-yl] amino} methyl) 1,3-thiazol-5- il] phenyl} -4- (trifluoromethyl) p¡rim¡din-2-amina¡ η

2- ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) ethanesulfonamide;

3- methyl-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} piperidin -3-ol;

3-methyl-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} pyrrolidin-3-ol ;

N- (3-methyl-5- {2 - [(1-oxidothiomorpholin-4-yl) methyl] -1,3-thiazol-5-yl} phenyl) 4- (trifluoromethyl) pyrimidin-2-amine;

N- (3-methyl-5- {2 - [(1-oxido-1,4-t-acezepan-4-l) methyl] -1,3-thiazol-510 yl} phenyl) - 4- (trif I uoromethyl) pyrimid i η-2-ami na;

4- methyl-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡m¡d¡n-2yl] amino} phenyl) -1,3-thiazol-2-yl ] methyl} piperidin-4-ol;

2- (methyl {[5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2-l] amino} phenyl) 1,3-thiazol-2-l]] methyl} amino) ethanol;

2,2 '- ({[5- (3-methyl-5 - {[4- (t rif I uorometi I) pi rim id i η-2-yl] ami nojfen ¡I) -1.3 thiazol-2 -yl] methyl} amino) diethanol;

2-methyl-2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) propane- 1,3-diol;

2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] methyl} amino) propan-1-ol;

2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) butan-1-ol;

1- ({[5- (3-methyl-5 - {[4- (tr¡fluoromet¡l) pyrim¡d¡n-2-¡l] amíno} feníl) -1,3thiazol-2 -yl] methyl} amino) propan-2-ol;

2- ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) ethanol;

3 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3tzolol-2- L] methyl} amine) propan-1-ol;

4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) butan -1-ol;

1 - ({[5- (3-methyl-5 - {[4- (trif luorometi I) pi ri m id i n-2 yl] ami nojfen i I) -1,3-thiazol-2-yl] acid methyl} amino) cyclopropancarboxylic;

N ~ 2 ~ - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] methyl} gl¡c¡nam gives;

N ~ 3 ~ - {[5- (3-metíl-5 - {[4- (tr¡fluoromet¡l) pyr¡m¡d¡n-2-¡l] amino} fen¡l) 1,3-thiazol-2-yl] methyl} -beta-alaninamide;

N- (3- {2 - [(4-acetylpiperazin-1-yl) methyl!] -1,3-thiazol-5-yl} -5-met ylphenyl) -4 (trifluoromethyl) pyrimidin-2-amine ;

1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} -1,4-diazepane-5- ona;

4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] methyl} piperazin-2-one;

N- {3-methyl-5- [2 - ({[2- (methylsulfonyl) ethyl] amino} methyl) -1,3-thiazol-5yl] phenyl} -4- (trifluoromethyl) pyrimidin-2-amine;

N- {3-methyl-5- [2 - ({methyl [2- (methylsulfonyl) ethyl] amino} methyl) -1,3-thiazol5-yl] phenyl} -4- (trfluoromethyl) pyrimid-2-amine;

4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-il] metíl} -1,4-diazepane-2-one;

N- [3- (2 - {[(1 -ethyl-1 H-1,2,3-triazol-4-yl) amino] methyl} -1,3-thiazol-5-yl) -5methylphenyl] -4- (trifluoromethyl) pyrimid-2-amine;

1 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amine} phenyl acid)

1,3-thiazol-2-yl] methyl} amino) cyclobutanecarboxylic;

3- (Methyl {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimide-2-l] amino} phenyl) 10 1, 3-thiazol-2- yl] methyl} amino) propan-1,2-diol;

3- ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) azepan-2- ona;

4- [2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] methyl} amino) ethyl] piperazin- 2-one;

N-methyl-2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) ethanesulfonamide;

5 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) -1 H- acid pyrazole-3-carboxylic;

2-methyl-1 - ({[5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl ] methyl} amino) propan-2-ol,

N- [3-methyl-5- (2 - {[4- (methylsulfonyl) piperazin-1-yl] methyl} -1,3-thiazol-5yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine;

2- [3-methyl-5 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am inojfen ¡I) -1,3-thiazol-2-yl] methylJamino) -1 H-pyrazol-1-yl] ethanol;

3- ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] methylJamino) pyrrolidin-2-one;

4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methylJamino) pyrrolidin-2-one;

3- ({1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] ethyl} amino) pyrrolidin-2- ona;

N- (3- {2- [1 - (dimethylamino) etII-1,3-thiazol-5-yl} -5-methylphenyl) -410 (trifluoromethyl) pyrimidin-2-amine;

4- ({1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} amino) pyrrolidin-2-one;

[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methanol;

N- {3- [2- (Bromomethyl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

Ethyl ethyl 3-{[5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methylJ-2-oxopyrrolidin-3-carboxylate ;

3 - {[5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 20 1,3-thiazol-2-yl] methyl} -2-oxopyrrolid acid 3-carboxylic acid;

3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1,3thiazol-2-yl] methyl} -1,3-oxazolidin-2-one;

1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} pyrrolidin-2-one;

3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidid-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} -2-oxopyrrolidin- Ethyl 3-carboxylate;

1-methyl-3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} imidazolidin-2-one ;

3 - {[5- (3-Methyl-5 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] methyl} -2-oxopyrrolidin-3-carboxylic;

1- [5- (3 - {[4- (azet¡din-3-yloxy) pyr¡m¡din-2-¡l] amino} -5-methylphenyl) -1,310 thiazol-2-yl ] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (oxetane-3-yloxy) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (p¡r¡din-4-ylmethoxy)) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (pyridin-3-ylmethoxy) pyrimin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (pyridin-2-ylmethoxy) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (1,4-dioxan-2-ylmethoxy) pyrimidin-2-yl] amino} -520 methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- {5- [3-methyl-5 - ({4- [2- (tetrahydro-2H-pyran-4-yl) ethoxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2-yl } cyclobutanol;

- [5- (3 - {[5-fluoro-4- (tetrahydrofuran-3-yloxy) pyrimidin-2-yl] amino} -5methyllfenyl) -1,3-thiazole -2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (tetrahydro-2H-pyran-4-ylmethoxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol ;

one - {5- [3-methyl-5 - ({4 - [(3R) -tetrahydrofuran-3-yloxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4- [2- (benzyloxy) ethoxy] pyrimidin-2-yl} amino) -5-methylphenyl] 1.3-thiazol-2-yl} cyclobutanol!

1- {5- [3-Methyl-5 - ({4 - [(3S) -tetrahydrofuran-3-yloxy] pyrimidin-210 yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol ;

1- {5- [3 - ({4- [4- (benzyloxy) butoxy] pyrimidin-2-yl} amino) -5-methylphenyl] 1.3-thiazol-2-yl} cyclobutanol;

1- [5- (3 - {[4- (3-methoxypropoxy) pyrimin-2-yl] amino} -5-methylphenyl) -1,3 thiazol-2-yl] cyclobutanol;

one - {5- [3 - ({4- [3- (benzyloxy) propoxy] pyrimydin-2-yl} amino) -5-methylphenyl] 1,3-thiazol-2-yl} cyclobutanol ;

1- [5- (3 - {[4- (2-methoxyethoxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3thiazol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (tetrahydrofuran-3-ylmethoxy) pyrimidin-220 yl] amino} phenyl) -i, 3-thiazol-2-yl] cyclobutanol;

4 - {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5met¡lfen¡l} amino) pyrim¡din-4-¡l] oxy } ethyl cyclohexancarboxylate;

1- [5- (3-methyl-5 - {[4- (tetrahydro-2H-pyran-4-yloxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol,

1- {5- [3 - ({4 - [(4-aminocyclohexyl) oxy] pyrimidin-2-yl} amino) -5methylphenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4 - [(3-amino-8-oxabicyclo [3.2.1] oct-6-yl) oxy] pyrimidin-2yl} amino) -5-methylphenyl] -1,3- thiazol-2-yl} cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(7-methylazepan-4-yl) oxy] p¡r¡m¡din-2il} amino) phenyl] -1,3-thiazol-2 -yl} cyclobutanol;

1- [5- (3 - {[4- (azepan-4-yloxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,310 thiazol-2-yl] cyclobutanol;

(2R) -2 - {[2 - ({3- [2- (1-Hydroxycyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} amino) pyrimidin-4-yl] oxy} propanoic;

1- {5- [3-methyl-5 - ({4- [2- (methylamino) ethoxy] pyrimidin-2-yl} amino) phenyl] 1.3-thiazol-2-yl} cyclobutanol;

one - [5- (3-methyl-5 - {[4- (p¡per¡din-4-ylmethoxy) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] cyclobutanol;

T-Butyl 2- {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5-methylphenyl} amino) pyrimidin-4-yl] oxy} -2-methylpropanoate ;

2- [5- (3 - {[4- (benzyloxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol20 2-yl] -1,1,1 -trifluoropropan-2 -ol;

- [5- (3-methyl-5 - {[4- (piperidin-3-yloxy) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (azetidin-3-ylmethoxy) pinmidin-2-yl] amino} -5-methylphenyl)

1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (azetidin-3-yloxy) p¡rim¡d¡n-2-yl] amino} -5-methylphenyl) -1,3 thiazol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (tetrahydrofuran-3-yloxy) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

- [5- (3 - {[4- (cyclobutyloxy) pyrimidin-2-yl] amine} -5-methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (cyclopentyloxy) pyrimidin-2-yl] amino} -5-methylenyl) -1,310 thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (cyclohexyloxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

1-methyl-4 - {[2 - ({3-methyl-5- [2- (2,2,2-trifluoro-1-hydroxy-1-methylethyl) 1.3-thiazol-5-yl ] phenyl} amino) pinm¡din-4-l] ox¡} cyclohexanol;

2- (5- {3 - [(4 - {[4- (benzyloxy) cyclohexyl] ox¡} p¡rimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2- yl) -1,1,1 -trifluoropropan-2-ol;

1,1,1 -t rif I uoro-2- (5- {3 - [(4 - {[3-f luoropiperid i n-4-yl] oxy} p iri m id in-2yl) amino] -5 -methylphenyl} -1,3-thiazol-2-yl) propan-2-ol;

3-fluoro-4 - {[2 - ({3-methyl-5- [2- (2,2,2-trifluoro-1-hydroxy-1-methylethyl) 20 1,3-thiazol-5-yl] phenyl } amino) pyrimidin-4-yl] oxy} piperidine-1-carboxylate t-butyl;

1,1,1 -trifluoro-2- [5- (3-methyl-5 - {[4- (piperidin-4-yloxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propan-2-ol;

1.1.1- trifluoro-2- (5- {3 - [(4 - {[3-fluoropiperidin-4-yl] oxy} pyrimidin-2yl) amino] -5-methylphenyl} -1,3-thiazol-2- il) propan-2-ol;

1.1.1- trifluoro-2- {5- [3-methyl-5 - ({4 - [(3R) -pyrrolidin-3-yloxy] pyrimidin-2 yl} amino) phenyl] -1,3-thiazol-2 -il} propan-2-ol;

1,1,1-trifluoro-2- {5- [3-methyl-5 - ({4 - [(3S) -pyrrolidin-3-ylox¡] p¡rimid¡n-2¡l} amino) phenyl] -1,3-thiazol-2-yl} propan-2-ol;

- [5- (3-methyl-5 - {[4- (piperidin-4-yloxy) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (piperidin-4-yloxy) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-210 yljetanol;

2 - {[2 - ({3- [2- (1 -h id roxycyclobuti I) -1,3-thiazo l-5-yl] -5 methylphenyl} amino) pyrimidin-4-l acid ] oxy} -2-methylpropanoic;

4 - {[2 - ({3-methyl-5- [2- (1,1,1-trifluoro-2-hydroxypropan-2-yl) -1,3-thiazol5-yl] phenyl} amino) pyrimidin-4 -L] oxy} cyclohexanol;

4 - {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 methylphenyl} amino) pyrimidin-4-yl] oxy} cyclohexanecarboxylic acid;

2- (5- {3 - [(4-chloropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) 1,1,1 -trifluoropropan-2-ol;

2 - {[2 - ({3-methyl-5- [2- (1,1,1-trifluoro-2-hydroxypropan-2-yl) -1,3-thiazol20 5-yl] phenyl} amino) pyrimidin- 4-yl] oxy} acetamide;

1.1.1- trifluoro-2- (5- {3-methyl-5 - [(5-methylpyrimidin-2-yl) amino] phenyl} 1,3-thiazol-2-yl) propan-2-ol;

1- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

1,1,1-Trifluoro-2- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5-methylphenyl}

1,3-thiazol-2-yl) propan-2-ol;

1- (5- {3-methyl-5 - [(4-methylpyrimin-2-yl) amino] phenyl} -1,3-thiazol-2yl) cyclobutanol;

1- {5- [3-methyl-5- (pyrimide-2-ylamino) phenyl] -1,3-t-acezol-2-yl-cyclobutanol;

1,1,1-tnfluoro-2- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} 10 1,3-thiazol-2-yl) propan-2-ol;

1,1,1-Trifluoro-2- (5- {3 - [(5-methoxy-rim¡d-n-2-yl) amino] -5-methylphenyl}

1,3-thiazol-2-yl) propan-2-ol;

1- (5- {3 - [(5-fluoropyrimid-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

1- (5- {3 - [(5-chloropyrimid-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

1- (5- {3 - [(5-ethylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

2- (5- {3 - [(5-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol20 2-i I) -1,1,1 -trifluoropropan-2-ol;

2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrimidine-4-carbonitrile;

1,1,1 -trifluoro-2- {5- [3-methyl-5- (pirim id in-2-i la m ¡no) fen ¡I] -1, 3-thiazol2-il} propan-2 -ol;

1- [5- (3-methyl-5 - {[4- (methylsulfanyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclobutanol;

1- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) cyclobutanol;

1- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) cyclobutanol;

1- (5- {3 - [(4-ethenylpyrim¡d¡n-2-yl) amino] -5-methylphenyl} -1,3-thiazol-210 yl) cyclobutanol;

1- [2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrimidin-4-yl] ethan-1,2-diol;

1- [2 - ({3-methyl-5- [2- (1,1,1-trifluoro-2-hrodroxypropan-2-yl) -1,3-t¡azol5-yl] phenyl} amino) pyrimidin-4-yl] ethanone;

1- (5- {3 - [(4-cyclobutylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

1- (5- {3 - [(4-cyclopentylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) cyclobutanol;

1- (5- {3 - [(4-cyclohexylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2 20 yl) cyclobutanol;

1- (5- {3 - [(4-ethoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(1-methyl-1 H-imidazol-2-yl) methoxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2- il} cyclobutanol;

1- [5- (3 - {[4- (1H-imidazol-4-ylmethoxy!) Pyrimidin-2-yl] amino} -5methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

4- (2 - {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrinnidin-4-yl] oxy} ethyl) morpholin-3 -ona;

1- [5- (3-methyl-5 - {[4- (tetrahydro-2H-pran-3-ylmethoxy) pyridin-2yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclobutanol;

1- (5- {3 - [(4- {2 - [(3S, 4S) -3,4-difluoropyrrol¡din-1-yl] ethoxy} p¡rimid¡n-2 10 ¡l) amino ] -5-methylphenyl} -1,3-thiazol-2-yl) cyclobutanol;

1- [5- (3 - {[4- (2-amino-1-pyrimidin-4-yeloxy) pyrimidin-2-yl] amino} -5methylphenyl) -1,3-thiazole- 2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (pyrazolo [1,5-a] pyridin-7-ylmethoxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2- L] cyclobutanol;

1- {5- [3-met¡l-5 - ({4- [2- (1-met¡l-1H-p¡razol-4-¡l) etox¡] p¡r¡m¡d¡ n-2yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- [5- (3 - {[4- (isoxazol-3-ylmethoxy) pyrimidin-2-yl] amino} -5-methylphenyl)

1,3-thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (azepan-4-yloxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,320 thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (azepan-4-yloxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- {5- [3-methyl-5 - ({4- [2- (2H-1,2,3-triazol-2-yl) ethoxy] pyrimin-2yl} amino) phenyl] -1,3 -thiazol-2-yl} cyclobutanol;

- {5- [3-methyl-5 - ({4- [2- (1 H-1,2,3-tr-acezol-1-yl) ethoxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- (5- {3-methyl-5 - [(4- {2 - [(1-methylpiperidin-4-yl) amino] ethoxy} pyrim¡d¡n2-yl) amino] phenyl} -1,3 -thiazol-2-yl) cyclobutanol;

1- [5- (3 - {[4- (2,3-dihydro-1H-indole-2-ylmethoxy) pyrimidin-2-yl] amino} -5 methylphenyl) -1,3-thiazol-2-yl] cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(1-methyl-1H-pyrazol-5-yl) methoxy] pyrimidin-210 yl} amino) phenyl] -1,3-thiazole- 2-yl} cyclobutanol;

1- {5- [3-methyl-5 - ({4- [2- (1-methylp¡rrolidin-2-yl) ethoxy] pyrimidine-2¡l} amino) phenyl] -1,3-thiazole -2-yl} cyclobutanol;

1- {5- [3 - ({4- [2- (1,4-diazepan-1-yl) ethoxy] pyrimidin-2-yl} amino) -5methylphenyl] -1,3-thiazole- 2-yl} cyclobutanol;

one - {5- [3 - ({4 - [(1,4-dimethylpyraz-2-yl) methoxy] pyrimidine-2-yl} amino) 5-methylphenyl] -1,3 -thiazol-2-yl} cyclobutanol;

1- {5- [3-methyl-5 - ({4- [2- (1 H-tetrazol-5-yl) ethoxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(3-pyrimidin-5-ylprop-2-in-1-yl) oxy] pyrimidin-220 yl} amino) phenyl] -1,3 -thiazol-2-l} cyclobutanol;

4 - ({[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrimidin-4-yl] oxy} methyl) -1 - methylpyrrolidin-2-one;

- {5- [3-methyl-5 - ({4 - [(3-methylpiperidin-3-yl) methoxy) pyrmidine-2yl} amino) phenyl] -1,3-thiazol-2-yl} cyclobutanol!

1- {5- [3-methyl-5 - ({4- [2- (4-methylmorpholin-2-yl) ethoxy] pyrimidin-2yl} amino) phenyl] -1,3-thiazol-2-yl } cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(2,2,6,6-tetramethylpiperidin-4-yl) oxy] pyrimidin-2 yl} amino) phenyl] -1 , 3-thiazol-2-yl} cyclobutanol!

3- (2 - {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyryridine-4-yl] oxy } propyl) -5-methyl-1,3-oxazolidin-2-one;

3- (2 - {[2 - ({3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -510 methylphenyl} amino) pyrimidin-4-yl] oxy} ethoxy) phenol;

- [5- (3-methyl-5 - {[4- (3-pyridin-3-ylpropoxy) pyrimidin-2-yl] amino} phenyl) ·

1,3-thiazol-2-yl] cyclobutanol;

- (2 - {[2 - ({3- [2- (1-hydroxy-cyclobutyl) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrimidin-4-yl] oxy} ethyl) pyrrolidin-2-one

one - [5- (3 - {[4- (4-hydroxybutoxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3thiazol-2-yl] cyclobutanol;

- {5- [3 - ({4 - [(1 R, 4R, 5S) -2-azabicyclo [2.2.1] hept-5-yloxy] pyrimidin-2 yl} amino) -5-methylphenyl] -1 , 3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4 - [(1R, 4R, 5R) -2-azabicyclo [2.2.1] hept-5-yloxy] pyrimidin-2 20 yl} amino) -5-methylphenyl] -1 , 3-thiazol-2-yl} cyclobutanol;

- [5- (3 - {[4- (2-hydroxyethoxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (3-hydroxypropoxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1.3 thiazol-2-yl] cyclobutanol;

1- (5- {3 - [(4-ethoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2l) cyclobutanol;

1- [5- (3-methyl-5 - {[4- (1 -methylethoxy¡) p¡r¡midin-2-¡l] amino} phenyl) -1,3t¡azol-2-¡l ] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (methylsulfinyl) pyrmididin-2-yl] amino} phenyl) -1,3t-acezol-2-yl] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (methylsulfonyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] cyclobutanol;

1- [5- (3 - {[4- (ethylsulfanil) p¡rim¡d¡n-2-yl] amino} -5-methylenyl) -1,3-thiazole

2-yl] cyclobutanol;

1- [5- (3 - {[4- (butylsulfanyl) p¡rim¡d¡n-2-¡l] amíno} -5-met¡lfenil) -1,3thiazol-2-¡l ] cyclobutanol;

1- [5- (3-methyl-5 - {[4- (propylsulfanyl) p¡rim¡d¡n-2-yl] amino} phenil) -1,3thiazol-2- yl] cyclobutanol;

1- {5- [3-methyl-5 - ({4 - [(1-methylethyl) sulfanyl] pyrimidin-2-yl} amino) phenyl] 1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4 - [(2-hydroxyethyl) sulfanyl] pyrimidin-2-yl} amino) -5-metitphenyl] 20 1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4 - [(3-hydroxypropyl) sulfanyl] p¡rimidin-2-yl} amino) -5methylfenyl] -1,3-thiazol-2-yl} cyclobutanol;

1- {5- [3 - ({4 - [(4-hydroxybutyl) sulfanyl] pyrimidin-2-yl} amino) -5methylphenyl] -1,3-thiazol-2-yl} cyclobutanol;

4 - {[2 - ({3- (acetylamino) -5- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5yl] phenyl} amino) pyrimidin-4-yl] oxy} piperidin-1-carboxylate t-butyl;

N- (3- [2- (1 -h id roxycyclob uti I) -1,3-thiazol-5-yl] -5 - {[4- (piperid in-4-loxy) pyrimidin-2-yl] amino } phenyl) acetamide;

1-cyclohexyl-3- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (piperidin-4-yloxy) pyrimidin-2-yl] amino} phenyl )urea;

1- (5- {3-amino-5 - [(4 - {[1- (2,2,2-trifluoroethyl) piperidin-410 yl] oxy} pyrim id in-2-yl) amino] phenyl} -1 , 3-thiazol-2-yl) cyclobutanol;

N- {3 - ({4 - [(1 -acetylpiperidin-4-yl) oxy] pyrimidin-2-yl} amino) -5- [2- (1 hydroxycyclobutyl) -1,3-thiazole- 5-yl] phenyl} acetamide;

1- (5- {3-amino-5 - [(4 - {[1- (trifluoroacetyl) piperidin-4-yl] oxy} pyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2- il) cyclobutanol;

1- {5- [3 - ({4 - [(1 -acetylpiperidin-4-yl) oxy] pyrimidin-2-yl} amino) -5aminophenyl] -1,3-thiazol-2-yl} cyclobutanol;

2,2,2-trifluoro-N- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4 (tetrahydro-2H-pyran-4-yloxy) pyrimidine -2-yl] amino} phenyl) acetamide;

N- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4- (tetrahydro-2H20 pyran-4-yloxy) pyrimidin-2-yl] amino} phenyl ) acetamide;

1- [5- (3-amino-5 - {[4- (tetrahydro-2H-pyran-4-yloxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanol ;

3 - {[2 - ({3-amino-5- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5yl] phenyl} amino) pyrimidin-4-yl] oxy} azetidin-1-carboxylate t-butyl;

1- (3- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5-yl] -5 - {[4- (piperidin-4yloxy) pyrimidin-2-yl] amino} phenyl) urea;

1- [5- (3-amino-5 - {[4- (piperidin-4-yloxy) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] cyclobutanol;

3- {[2 - ({3-amino-5- [2- (1-hydroxycyclobutyl) -1,3-thiazol-5yl] phenyl} amino) pyrimidin-4-yl] oxy} azetidin-1-carboxylate ethyl; and

1- [5- (3-amino-5 - {[4- (azetidin-3-yloxy) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] cyclobutanol.

Cis-4- (aminomethyl) -1- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanol;

T rans-4- (aminomethyl) -1 - (5- {3-methyl-5 - [(4-methylpyrimidin-2l) amino] phenyl} -1,3-thiazol-2-l ) cyclohexanol;

4- (aminomethyl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

4- (2-aminoethyl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

trans-4- (hydroxymethyl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 20 yl] amino} phenyl) -1,3-thiazol-2- il] cyclohexanol;

4- (hydroxymethyl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

cis-4- (hydroxymethyl) -1- (5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

4- (hydroxymethyl) -1- (5- {3-methyl-5 - [(4-methylpyridin-2-yl) amino] phenyl} 1,3-thiazol-2-yl) cyclohexa nol ;

1-amino-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

Cis- [3-hydroxy-1-methyl-3- (5- {3-methyl-5-[- 4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2- acid il) cyclohexyl] acetic;

Trans- [3-hydroxy-1-methyl-3- (5- {3-methyl-5 - [(4-methylpyridine-2 10 yl) amino] phenyl} -1,3-thiazol-2- acid il) cyclohexyl] acetic;

Ethyl ethyl 4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) 4-hydroxy-1-methylcyclohexancarboxylate;

{cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl acid }acetic;

{trans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin acid

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acetic;

7- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] spiro [2.5] octane-4,7-diol;

(4-hydroxy-2- (1-methylethyl) -4- (5- {3-methyl-5 - [(4-methylpyrimidin-220 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxylate methyl;

methyl 4- (5- {3 - [(5-chloropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazole

2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylate;

Cis-4- (1-aminocylpropyl) -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexanol;

Trans-4- (1-aminocyclopropyl) -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol ;

Ethyl 3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡IJaminoJphenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate;

(1R) - {(3S) -3-hydroxy-1-methyl-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexyl} acetic;

(1R) - {(3R) -3-hydroxy-1-methyl-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pi rim id i η-2-yl] am i nojfen i I) -1,3-thiazol-2-yl] cyclohex, IJacetic;

Ethyl 4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl) -2-phenylcyclohexancarboxylate;

4-hydroxy-2- (1-methylethyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1,3- methyl thiazol-2-yl] cyclohexancarboxylate;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2 yl] aminojphenyl) -1,3-thiazol-2-yl] cyclohexyl} acid - 2,2-dimethylpropanoic;

Ethyl 4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl) -2- (2-methylphenyl) cyclohexanecarboxylate ;

2- (4-fluorophenyl) -4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-220 yl) amino] phenyIJ-1,3-thiazol-2-yl ) ethyl cyclohexancarboxylate;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2ylja mi nojfen ¡I) -1,3-thiazol-2-yl] cyclohexylJ-2 - (1 H-imidazol-1-yljacetamide;

(2R) -N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexyl} -5-oxotetrahydrofuran-2-carboxyamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl } -5-oxotetrahydrofuran-2-carboxamide¡

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} - 2-pyridin-3-ylacetamide;

4- (dimethylamino) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

5- hydroxy-5- (5- {3-methyl-5 - [(4-methylp¡r¡m¡d¡n-2-yl) amino] phenyl} -1,310 thiazol-2-yl) azepan-2-one;

1-cyclopropyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2yl] amino} phenyl) -1,3-thiazol-2-yl] p¡peridin- 4-ol;

- (2-methylfenyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1.3 -thiazol-2-yl] piperidin-4-ol;

1- (3-fluorophenyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-4- ol;

1- (2-fluorophenyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-4- ol;

1- (4-fluorophenyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-4 -ol;

5- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] p¡perid acid N-1-ylJ-5-oxopentanoic;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piper¡d 1-t-butyl 2-methyl n-1,2-dicarboxylate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -2 - t-butyl (trifluoromethyl) piperidin-1-carboxylate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2yl] amino} phenyl) -1,3-t¡azol-2 -il] butanontrile;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡mid¡n-2-¡l] amino} phenyl) -1,3thiazol-2-¡ l] pent-4-en-1-ol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] hex-5-en-2-ol ;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmmdn-2l] amino} phenyl) -1.3 -t¡azol-2-l] butanamída;

4-amino-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-tlazol- 2-yl] pentan-2-ol;

5-amino-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2-¡l] pentan -2-ol;

5-hydroxy-5- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimydn-2 yl] amino} phenyl) -1,3-thiazole- 2-yl] hexanoic;

3- hydroxy-2,2-dimethyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-220 [l] amino} phenyl) -1,3-thiazole- Methyl 2-yl] butanoate;

2-methyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) ·

1,3-thiazol-2-yl] -1 -p irid ¡η-2-ilp ropan-1 -ol;

1- (3-methoxy-thiophene-2-yl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazole -2-yl] ethanol;

1- (4- (1 -hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2¡l] amino} phenyl) -1,3-thiazol-2- yl] ethyl} phenyl) ethanone;

Methyl 4- {hydroxy [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] methyl} benzoate;

3- {1-Hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} benzoic acid ;

3 - ((1 S) -1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin 10 2-yl] amino} phenyl) -1,3- thiazol-2-yl] ethyl} benzoic;

3 - {(1R) -1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin 2-yl] amino} phenyl) -1,3-thiazol-2-yl acid ] ethyl} benzoic;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -1- (4- nitrophenyl) ethanol;

1- [4- (methylsulfanyl) phenyl] -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2- yl] ethanol;

(4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} acid phenyl) acetic;

(4 - ((1 S) -1-hydroxy-1 - [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 acid -yl] ethyl} phenyl) acetic;

(4 - ((1 R) -1-hydroxy-1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 acid -yl] ethyl} phenyl) acetic;

4- {2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] propyl} benzoic acid ;

2,2-d-methoxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am inojfen il) -1,3-thiazol-2-yl] -1 - pyridin-2-iletanol;

(5- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] etí acid l} thiophene-3-yl) acetic;

4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl acid} -2-methoxybenzoic;

4 - {(1S) -1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin 10 2-yl] amino} phenyl) -1,3-thiazole acid -2-yl] ethyl} -2-methoxybenzoic;

4 - {(1 R) -1-hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin 2-yl] amino} phenyl) -1,3- acid thiazol-2-yl] ethyl} -2-methoxybenzoic;

(3- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl acid} phenoxy) acetic;

(1S) -1- (6-bromopyridin-3-yl) -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yljamino} phenyl) -1,3-thiazol-2 -yl] ethanol;

(1 R) -1 - (6-bromopyridin-3-yl) -1 - [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] ethanol;

1- (6-bromopyridin-3-yl) -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin20 2-yl] amino} fen yl) -1.3 -thiazol-2-yl] ethanol;

1- (5-bromopyridin-2-yl) -1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol;

100 methyl 4- {1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl } -2-methoxybenzoate;

4- {1-hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} -N, N-dimethylbenzenesulfonamide;

5- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2 l] amino} phenyl) -1,3-thiazol-2-yl acid] ethyl} -3-methylthiene [2,3-b] pyridin-2-carboxylic;

3 '- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl acid } biphenyl-3-carboxylic;

4- {2-hydroxy-2- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2 10 yl] amino} phenyl) -1,3-thiazole- 2-yl] -2-phenylethyl} benzoic;

N - [(4- {1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl } phenyl) sulfonyl] acetamide;

1 - (4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrmidine-2 yl] amino} phenyl) -1 acid, 3-thiazol-2-yl] ethyl} phenyl) -5-oxopyrrolidin-3-carboxylic;

4- [1-hydroxy-1- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) ethyl] benzoic acid;

4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl) -1azatric¡clo [3.3.1.1 ~ 3,7 ~ ] decan-4-ol;

2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,320 thiazol-2-yl] bicyclo [4.1.0] heptan-2-ol;

6- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -3-azabicyclo [3.2.0] heptan-6 -ol;

101

5-hydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] hexahydropentalen-2 (1H) -one;

4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} acid

1,3-thiazol-2-yl) decahydronaphthalen-1-carboxylic;

4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl acid}

1,3-thiazol-2-yl) decahydronaphthalen-1-carboxylic;

cis-8-hydroxy-8- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -1-azaspiro [4.5] decan-2-one;

trans-8-hydroxy-8- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] am i nojfen i I) -1,3-thiazol-2-yl] - 1 -azaspiro [4.5] decan-2-one;

3a, 5-dihydroxy-7a-methyl-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyridine-2-i l] am inojfen il) -1.3 -thiazol-2-yl] octa h id ro-1 H-inden-1 -one;

{5-Hydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-t¡azol-2-l] octah! dropentalen-2-IJacetic;

6,6-Dimethyl-7- [5- (3-methyl-5 - {[4- (tr-fluorine-methyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-yl] -1,4-dioxaspiro [4.5] decan-7-ol;

4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2yl) tricycle [3.3.1.1 ~ 3.7 ~] decane-1, 4-diol;

Cis-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) tricycle acid [3.3.1.1 ~ 3 , 7 ~] decan-1-carboxylic;

T rans-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phen¡IJ-1,3-thiazol-2-l) tricyclo acid [ 3.3.1.1-3,7 ~] decan-1-carboxylic;

102 3-hydroxy-4,7,7-trimethyl-3- (5- {3-methyl-5 - [(4-methylpinmidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) bicyclo acid [2.2.1] heptan-1-carboxylic;

5-hydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am ynojfen il) -1,3-thiazol-2-yl] tricyclo [2.2.1.02.6 acid ] heptan-3-carboxylic;

4-methyl-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] bicyclo [2.2.2 ] octan-1,3-diol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] tricyclo [3.3.1.13.7] decane- 1,4-diol;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl] tricycle [3.3.1.13. 7] decan-2-carboxylic acid;

3-hydroxy-4,7,7-tr-methyl-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole- 2-yl] bicyclo [2.2.1] heptan-1 carboxylic;

Cis-N- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 yl] amino} phenyl) -1,3-thiazol-2-yl] tricycle [3.3.1.13.7] dec-1-yl} acetamide;

Trans-N- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] am inojfen i I) -1,3-thiazole- 2-yl] tricycle [3.3.1.13.7] dec-1-yljacetamide;

5-Bromo-2-hydroxy-2- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] bicyclo [ 2.2.1] heptan-720 carboxylic;

1- [5- (3-methyl-5 - {[4- (trifIuoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclohept-2-en-1 -ol;

103

9- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] dispiro [2.1.2.3] decan-4 , 9-diol;

4-hydroxy-2,3-dimethyl-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyridin-2 yl] amino} phenyl) Ethyl 1,3-thiazol-2-yl] cyclohexanecarboxylate;

4,4,5-trimethyl-5- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} 1.3-thiazol-2-yl) dihydrofuran-2 ( 3H) -one;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -4-oxobutanenitrile;

5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] dih id rof u ra n-2 (3 H ) -ona;

4,4,5-trimethyl-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-l ] hydrofuran-2 (3H) -one;

6- hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] hexan-1,4-dione;

2- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) propan-1,2-diol;

(2R) -2- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} 1.3-thiazol-2-yl) propan-1,2-diol;

(2S) -2- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} 20 1,3-thiazol-2-yl) propan-1,2- diol;

2- (5- {3 - [(5-chloropyridin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) propan-1,2-diol;

104 (2R) -2- (5- {3 - [(5-chloropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) propan-1,2-diol;

(2S) -2- (5- {3 - [(5-chloropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) propan-1,2-diol;

2- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) propan-1,2-diol;

2- (5- {3 - [(5-fluoro-4-methoxy_Pirimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) propan-1,2-diol;

2- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} 10 1,3-thiazol-2-yl) propan-1,2-diol;

(2R) -2- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) propane-1,2-diol;

(2S) -2- (5- {3 - [(4-cyclopropyl-5-fluoropyrimin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) propane- 1,2-diol;

2- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) propan-1,2-diol;

2- (5- {3 - [(5-chloropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) propan-1,2,3-triol;

cis-1- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3 20 t¡azol-2-yl) cyclohexan-1,4- diol;

cis-1- (5- {3 - [(5-chloro-4-methylpyrim¡din-2-yl) amino] -5-methylphenyl} -1,3t¡azol-2-yl) cyclohexan-1, 4-diol;

105 cis-1- (5- {3 - [(5-fluoro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 1,3-thiazol-2-yl) cyclohexan-1,4-diol;

cis-1 - (5- {3 - [(4-cyclop ropil-5-f luoropi rim id i n-2-iI) a mi no] -5methylfen ¡I} -1,3-thiazol-2-yl) cyclohexan-1,4-diol;

cis-1- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 1,3-thiazol-2-yl) cyclohexan-1,4-diol ;

(1S, 4R) -3,3-dimethyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3- thiazol-2-yl] cyclohexan-1,4-diol;

(1R, 4S) -3,3-dimethyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexan-1,4-diol;

4- (5- {3 - [(5-fluoro-4-methylpyrimid-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxycyclohexanone;

3-hydroxy-2,2-d-methyl-3- [5- (3-methyl-5 - {[4- (trifluorometyl) pyridin-2yl] amino} phenyl) - 1,3-thiazol-2-yl] cyclohexanone;

cis-2,2-dimethyl-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2!] amino} phenyl) -1,3-thiazol-2- yl] cyclohexa n-1,3-diol;

trans-2,2-dimethyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexan-1, 3-diol;

1- [4- (1-hydroxyethyl) phenyl] -1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine 20 2-yl] amino} fen ¡I) -1,3- thiazol-2-yl] ethanol;

2- (4- {1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] et¡ l} phenyl) propan-2-ol;

106 (5S) -5-hydroxy-5- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan- 2-one;

(5R) -5-hydroxy-5- [5- (3-methyl-5 - {[4- (1 -methylethyl) pyrimydin-2yl] amino} phenyl) -1,3-thiazole- 2-yl] azepan-2-one;

(5S) -5-hydroxy-5- {5- [3- (methoxymethyl) -5 - {[4- (trfluoromethyl) pyrimidn2-yl] amino} phenyl] -1,3- thiazol-2-yl} azepan-2-one;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -5,6-dihydropyrid¡ n-2 (1H) -one;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1_l310 thiazol-2-i I] -1,5,6,7-tetrahydro-2H-azepin-2-one;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) p¡rim¡d¡n-2yl] amino} phenyl) -1,3- t-butyl thiazol-2-yl] cyclohexancarboxylate;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethoxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylate de t-butyl;

[cis-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl) -1,3-thiazol-2-yl) cyclohexyl] acetic acid;

[trans-4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexyl] acetic acid;

{4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acetic acid;

(4- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acid phenyl) acetic;

107 cis-4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-h id roxy-1 - acid methylcyclohexancarboxylic acid;

trans-4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenII} -1.3 thiazol-2-yl) -4-hydroxy-1-methylcyclohexanecarboxylic acid;

trans-4- [5- (3-chloro-5 - {[4- (trifluoromethyl) pyrimin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxycyclohexanecarboxylic acid;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2 [l] amino} phenyl) -1,3-thiazol-2-yl acid ] cyclohexyl} propane;

cis-3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 10 yl] amino} phenyl) -1,3-thiazol-2-yl acid] cyclohexyl} propanic;

trans-3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin 2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] cyclohexyl} propanic;

cis-4- (5- {3 - [(4-cyclopropyl-5-fluoropyridin-2-yl) amino] -5-methylphenyl} -1,3-t-acezol-2- acid yl) -4-hydroxy-cyclohexanecarboxylic;

trans-4- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxycyclohexanecarboxylic acid;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmididin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} propanoate ethyl;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 20-methylphenyl} -1,3-thiazol-2-yl) - acid 2,2-dimethylcyclohexanecarboxylic acid;

(1R, 4S) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -2.2 acid -dimethylcyclohexanecarboxylic;

108 4-hydroxy-2,2-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl cyclohexancarboxylate;

(1R, 2S, 4S) -4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- acid thiazol-2-yl] cyclohexancarboxylic;

(1 S, 2R, 4R) -4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 acid , 3-thiazol-2-yl] cyclohexancarboxylic;

{(1 R, 3R) -3-hydroxy-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclopentyl} acetic;

{(1S, 3R) -3-hydroxy-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimydin-2-yl] amino} phenyl) -1,3-thiazole acid -2-yl] cyclopentyl} acetic;

{(1S, 3S) -3-hydroxy-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid ] cyclopentyl} acetic;

{(1R, 3S) -3-hydroxy-3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid ] cyclopentyl} acetic;

(1 R, 2S, 4S) -4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazole- 2-yl) cyclohexancarboxylic;

(1 S, 2R, 4R) -4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazole- 2-yl) cyclohexancarboxylic;

(1S, 2S, 4R) -4-hydroxy-2- (1-methylethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethiopyrimidin ^ -yljaminoJfeniO-IS-thiazole ^ -illcicIohexancarboxylic acid;

109 (1 S, 2S, 4R) -4-hydroxy-2- (1 -methylethyl) -4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} - acid 1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1S, 2S, 4R) -4-hydroxy-2- (1-methylethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) acid - 1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 2R, 4S) -4-hydroxy-2- (1-methylethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino acid) phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1S, 2S, 4R) -4-hydroxy-2- (1-methylethyl) -4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1.3 acid -thiazol-2-yl) cyclohexancarboxylic;

(1R, 2R, 4S) -4-hydroxy-2- (1-methylethyl) -4- (5- {3-methyl-5 - [(4-methylp irimid in-2-yl) amino] phenyl) -1 acid , 3-thiazol-2-yl) cyclohexanecarboxylic;

(1 R, 2R, 4S) -4-hydroxy-2-methoxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimyrid-2-yl] amino acid)} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylic acid;

(1 R, 2S, 4S) -4-hydroxy-2-methoxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrim¡din-2-l]] amino} fen acid L) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

4- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} benzoic acid ;

3- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} benzoic acid ;

2- [4 - ({2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 20 yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclopentyl} methyl] phenyl] propanic;

4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclopentanecarboxylic;

110 4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] cycloheptanecarboxylic;

4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

4- (5- {3 - [(5-chloropyrimidin-2-yl) amino] -5-methlfenyl} -1,3-thiazole acid

2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 2S) -4-h-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyridine-2 10 yl) am i no] phenyl} -1.3 acid -thiazol-2-yl) -2-phenylcyclohexanecarboxylic acid (1 S, 2S) -4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl } -1,3-thiazol-2-yl) -2- (2-methylphenyl) cyclohexanecarboxylic acid;

(1 S, 2S) -4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) - acid 2-thiophene-3-ylcyclohexanecarboxylic;

(1S, 2S) -2- (4-fluorophenyl) -4-hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1.3 acid -t¡azol-2-yl) cyclohexanecarboxylic acid (1 R, 4S) -4- [5- (3-cyclopropyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1, 3-thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4- [5- (3-cyclopropyl-5 - {[4- (trifluoromethyl) pyrimidin-2 20 yl] amino} phenyl) -1,3-thiazol-2-yl] -4 acid -hydroxy-2,2-dimethylcyclohexanecarboxylic;

4-hydroxy-4- {5- [3- (hydroxymethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} -2,2 -methyl dimethylcyclohexancarboxylate;

111 4-hydroxy-4- {5- [3- (hydroxymethyl) -5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl] -1,3-thiazol-2-yl} -2,2- dimethylcyclohexancarboxylic;

(1 S, 4R) -4-hydroxy-2,2-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2¡l) amino] phenyl} -1,3-thiazole- Methyl 2-yl) cyclohexancarboxylate;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

(1 S, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3 - {[410 (trif I uoromethyl) pyrim id i η-2-yl] ami nojfen ¡I) -1 acid , 3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3 - {[4 (trfluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole acid -2-yl] cyclohexancarboxylic;

4- (5- {3 - [(4-cyclopropyl-5-fluoropyrim¡din-2-yl) amino] -5-methylenyl} 1,3-thiazol-2-yl) -4-h¡ methyl droxy-2,2-d-methylcyclohexancarboxylate;

4- {5- [3- (d¡fluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} -4-hydroxy-2,2 -methyl dimethyl cyclohexancarboxylate;

4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylate methyl;

4- (5- {3 - [(4-cyclopropylpyrimin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

4- {5- [3- (Difluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl] -1,3-thiazol-2-yl} -4-hydroxy-2 acid, 2-dimethylcyclohexanecarboxylic;

112 (1R, 4S) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-h-hydroxy-2 acid , 2-dimethylcyclohexancarboxylic;

(1R, 4S) -4- {5- [3- (Difluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin 2-yl] amino} phenyl] -1,3-thiazol-2-yl} -4 acid -hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4- {5- [3- (difluoromethyl) -5 - {[4- (trifluoromethyl) pyrimidin acid

2-yl] amino} phenyl] -1,3-thiazol-2-yl} -4-hydroxy-2,2-dimethylcyclohexancarboxylic;

(1 R, 4S) -4- [5- (3-fluoro-5 - {[4- (trifluoromethyl) pyrim¡din-2 yl] amino} phenyl) -1,3-thiazol-2-yl] - acid 4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1R, 4R) -4- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] 10 5-methylphen i I} -1,3-thiazol-2-yl) - acid 4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1R, 4S) -4- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino acid]

5-methylphenyl} -1,3-thiazol-2-yl) -4-hroxy-2,2-dimethylcyclohexanecarboxylic;

(1R, 4S) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2 acid -dimethylcyclohexanecarboxylic acid;

(1S, 4R) -4- [5- (3-fluoro-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -4 acid -hydroxy-2,2-d-methylcyclohexancarboxyl;

4- [5- (3-cyclopropyl-5 - {[4- (trifluoromethyl) pyrmididin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] -4-hydroxy-2, Methyl 2-dimethylcyclohexancarboxylate;

4-hydroxy-4- {5- [3- (1-hydroxy-1-methylethyl) -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] -1,3-thiazol-2- yl} -2,2dimethylcyclohexanecarboxylic;

4- [5- (3-cyclopropyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid ;

113 (1 S, 4R) -4-hydroxy-4- {5- [3- (hydroxymethyl) -5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl] Methyl -1,3-thiazol-2-yl} -2,2-dimethylcyclohexancarboxylate;

(1 S, 4R) -4-hydroxy-4- {5- [3- (hydroxymethyl) -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] -1,3-thiazol-2 acid -yl} -2,2dimethylcyclohexanecarboxylic;

(1S, 4R) -4- [5- (3 - [(acetyloxy) methyl] -5 - {[4- (trifluoromethyl) pyrimidin-2yljaminojphenyl) -1,3-thiazol-2-yl] -4-hydroxy- Methyl 2,2-dimethylcyclohexancarboxylate;

4-hydroxy-2,2,3-trimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimid in-2-yl] amino} fen I) -1,3-thiazole -2-yl] cyclohexancarboxylic;

4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxy-2,2,3-trimethylcyclohexanecarboxylic acid;

4-hydroxy-2,2,3-trimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 acid -il] cyclohexancarboxylic;

4-hydroxy-2,3-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] cyclohexancarboxylic;

4-hydroxy-2,3-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] cyclohexancarboxylic;

3-ethyl-4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclohexancarboxylic;

8- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl) 1.4-dioxaspiro [4.5] decan-8-ol;

5-Hydroxy-5- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl}

114

1,3-thiazol-2-yl) bicyclo [2.2.2] octan-2-carboxylic;

4-hydroxy-4- (5- {3-methyl-5 - [(4-methyl-pyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl) tricycle [3.3.1.1^{3 7}acid] decan-1-carboxylic;

6-hydroxy-6- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] sp¡ro [ 3.3] heptan-2-carboxylic;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] bicyclo [3.2. 1] octan-8-carboxylic;

2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2 ¡YJam inojfenil) -1,3-thiazol-2-l] acid b [cyclo [3.1.0] hexan-6-carboxylic acid;

3-h id roxy-3- [5- (3-methyl-5 - {[4- (trif luoromethyl) pi r¡ mid i n-2 yl] am inojfenil) -1,3-t¡azol- 2-yl] bicyclo [3.1.0] hexan-6-carboxylic;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2¡l] aminojphenyl) -1,3-thiazol-2-ll] bicycle [3.1.0 ] hexan-6-carboxylate; ethyl

3- [5- (3-metrl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] aminoJfenyl) -1,315 thiazol-2-yl] azetidin-3-ol;

3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azetidine-1-carboxylate t-butyl;

2- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] aminojphenyl) -1,3-thiazol-2-yl] piperidin-1-yl acid } pyridine-3-carboxylic;

2- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-1-yl } pyridine-3-carboxylate; Ethyl Acid 5-Hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] hexane;

115 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] hexanoic;

(5R) -5-hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - ([4 (5S) -5-hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] hexanoic;

5-hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] hexanoate of methyl;

(3E) -5-hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- acid thiazol-2-yl] hex-3-eneic;

(3E) -5-hydroxy-2,2-dimethyl-5- [5- (3-methyl-5 - {[410 (trif I uoromethyl) pi rim id i n-2-yl] am i nojfen i I) Methyl -1,3-thiazol-2-yl] hex-3-eneate;

2- {2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2 [l] amino} phenyl) -1,3-thiazole- 2-yl] propoxy} -2-methylpropanoic;

2- {2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] propoxyJ-2 -methyl methylpropanoate;

4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl acid] pentanoic;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] pentanoic acid;

(2- {1-hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yljaminojphenyl) -1,3-thiazol-2-yl] ethyl} phenoxy) acetic acid;

(4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trif luoromethyl) pyrim id i n-2 l] amino} phenyl) -1,3-thiazole acid -2-l] etl} phenoxy) acetic;

2- (4- (1-hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 acid

116 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} phenoxy) propanoic;

4 - [(4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trif luoromethyl) pi rim id i n-2 yl] amino} phenyl) -1,3- thiazol-2-yl] ethyl} phenyl) amino] -4-oxobutanoic;

5 - [(4- {1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2 yl] amino} phenyl) -1,3-thiazol-2 acid -yl] ethyl} phenyl) amino] -5-oxopentanoic;

4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trif luoromethyl) pyrimid n-2 yl] amino} phenyl) -1,3-thiazol-2-yl acid] ethyl} benzoic;

4- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (t rif I uorometi l) pyri mid i n-2yl] amino} phenyl) -1,3-thiazol-2- yl] ethyl methyl benzoate;

4- {2-hydroxy-2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] propyl) benzoic acid ;

3- (4- {1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2 yl] amino} phenyl) -1,3-thiazole- 2-yl] ethyl} -3,5-dimethyl-1H-pyrazol-1-yl) propanoic;

5- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 [l] amino} phenyl) -1,3-thiazol-2-yl acid] ethyl} thiophene-2-carboxylic;

5 - {(1R) -1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine acid

2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} thiophene-2-carboxylic;

5 - {(1S) -1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine acid

2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} thiophene-2-carboxylic;

1- {2-hydroxy-1,1-dimethyl-2- [5- (3-methyl-5 - {[4 (tnfluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole acid -2-yl] ethyl} piperidine-4carboxylic;

(2E) -3- (4- {cyclopropyl (hydroxy) [5- (3-methyl-5 - {[4

117 (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} phenyl) prop-2-eneic;

5-hydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -5-pyridin-4 -ilpentanoic;

(2-methyl-3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] am inojfen i I) -1,3-thiazol-2-yl] ca rbon acid i I} -1 H-indole-1-yl) acetic;

3- (3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ca rbon acid I} -1 H-indole-1-yl) propanoic;

4- (2 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] am i nojfen ¡I) -1,3-thiazol-2-l] ca rbon acid! I} -1 H-pyrrole-1-yl) benzoic;

3,3,5-trimethyl-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] d¡h¡ drofuran-2 (3H) -one;

7-hydroxy-7- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-¡ l] spiro [2.5] octan-4-carboxylic;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,315 thiazol-2-yl] cyclopent-2-en-1 -one;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclohex-2-en-1-one;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanone;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cyclohept-2-en-1-one;

3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] cycloheptanone;

118

2,2-Dimethyl-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] aminojfeniI) -1,3-thiazol-2-yl] Methyl cyclohex-3-ene-1-carboxylate;

6,6-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] aminojfeniI) -1,3-thiazol-2-yl] cyclohex-3-ene-1 - methyl carboxylate;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-2-one;

5- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -1,3,4,7 -tetrahydro-2H-azepin-2-one;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 thiazol-2-yl] azepan-2-one;

5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyr¡m¡d¡n-2-yl] amino} phenyl) -1,3thiazol-2-yl] azepan-2- ona;

N- {3- [2- (1,4-dioxaspiro [4.5] dec-8-yl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

(1R, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid) -1 , 3-thiazol-2-yl] cyclohexanecarboxylic;

(1R, 4R) -4-hydroxy-4- {5- [3- (2H3-de) methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] -1,3-thiazol-2 -il} cyclohexancarboxylic;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine-220 [l] amino} phenyl) -1,3-thiazol-2- t-butyl yl] azepan-1-carboxylate;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] t-butyl azepane-1-carboxylate;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3119 thiazol-2-yl] -2- (trifluoromethyl) piper¡din-4 -ol;

Methyl 4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine-2-carboxylate;

({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rmidid-25 yl] aminojphenyl) -1,3-thiazol-2-yl] t-butyl azepan-1-yljsulfonyljcarbamate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am nojfen I) -1,3-thiazol-2-yl] azepan- 1-sulfonamide;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am nojfen i I) -1,3-thiazol-2-yl] azepan- 1-sulfonamide;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] aminojphenyl) -1,3-thiazol-2-yl] azepan-1-sulfonamide;

2- fluoro-5-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1,3-thiazole- 2-yl] cyclohexyl} benzamide;

3- fluoro-4-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[415 (trifluoromethyljpirim id ¡n-2-yljamino} phenyl) -1,3-thiazole -2-yl] cyclohexyl} benzamide;

3- amino-4,4,4-trifluoro-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1, 3-thiazol-2-yl] cyclohexyl} butanamide;

4- ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] methyl cyclohexyl} carbamoyl) cyclohexancarboxylate;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1- carboxamide;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2de

120 il] ami nojfen i 1) -1,3-thiazol-2-yl] azepan-1 -carboxamide;

1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-4- ol;

(4R) -1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) -1,3-thiazol-2-yl ] azepan-4-ol;

(4S) -1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan- 4-ol;

(4R) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] -1 - (4H-1 2,4-triazol-3-ylcarbonyl) azepan-4-ol;

(4S) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2-yl] amino} phenyl) 1.3- thiazol-2-yl] -1- (4H- 1,2,4-triazol-3-ylcarbonyl) azepan-4-ol;

2- fluoro-5-hydroxy-N- {cis-4-hydroxy¡-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡midin-2-l] amino } phenyl) -1,3-thiazol-2-yl] cyclohexyl} benzamide;

3- fluoro-4-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[415 (trifluoromethyl) p¡r¡midin-2-l]] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} benzamide;

3- amino-4,4,4-trifluoro-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) - 1,3-thiazol-2-yl] cyclohexyl} butanamide;

4- ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] c¡ methyl clohexyl} carbamoyl) cyclohexancarboxylate;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am y nojfen ¡I) -1,3-thiazol-2-yl ] azepan-1-carboxamide;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2121 yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1 -carboxamide;

1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan- 4-ol;

(4R) -1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) -1,3-thiazol-2-yl] azepan -4-ol;

(4S) -1 - (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol- 2-l] azepan-4-ol;

(4R) -4¿5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] -1- (4H-1, 2,4-triazol-3-ylcarbonyl) azepan-4-ol;

(4S) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] -1- (4H-1 2,4-triazol-3-ylcarbonyl) azepan-4-ol;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] am inojphenyl) -1,3-thiazol-2-I-Jazepan-1 - sulfonic;

(2R) -2-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[415 (trif I uoromethyl) pi rim id i η-2-yl] am inojfen i I) -1,3-thiazol-2-yl] cyclohexyl} propanamide;

(2S) -2-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- thiazol-2-yl] cyclohexyl} propanamide; N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} propanediamide ;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexyl} -1H-imidazol-2-carboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2¡IJaminoJfeniO-IS-thiazol ^ -ylJcicIohexilJ-IH-imidazole ^ -carboxamide;

122

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl } -1 H-1,2,3-triazol-4-carboxamide;

3-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-25 yl ] cyclohexyl} cyclobutancarboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexyl} butandiamide;

N- {c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2 -il] cyclohexyl} benzamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-t¡azol-2-¡ l] cyclohexyl} -2- (1H-imidazol-4-yl) acetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am nojfen il) -1,3-thiazol-2-l] cyclohex L} -2- (1 H-1,2,4-triazol-1-IJacetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 yl] aminojphenyl) -1,3-thiazol-2-yl] cyclohexyl } -2- (1 H-1,2,3-triazol-1 -¡IJacetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] am ¡nojfen ¡I) -1,3-thiazol-2-il ] cyclohexy l} -2- (1 H-tetrazol-1-IJacetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} cyclohexancarboxamide ;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl } -2-oxoimidazolidin-4-carboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2 -yl] cyclohexyl} tetrahydro-2H-pyran-2-carboxamide;

123

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} - 2- (tetrahydrofuran-3-yl) acetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} tetrah Dro-2H-pyran-3-carboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3- thiazol-2-yl] cyclohexyl} -2- (tetrahydrofuran-2-yl) acetamide;

3-hydroxy-2- (hydroxymethyl) -N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} -2methylpropanamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡d¡n-2yl] amino} pheníl) -1,3-thiazol-2 -il] cyclohexyl} -2-pyridin-2-illacetamide;

N- {c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexyl} -2- (methylsulfonyl) acetamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} -2-pyrimidine-2-ylacetamide;

5- hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- yl] cyclohexyl} pyridine-2carboxamide;

6- hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexyl} pyridine-2carboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} -3- (1 H-pyrazol-4-yl) propanamide;

124

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] am i nojfen ¡I) -1,3-thiazol-2-yl] cyclohex Yl -3- (1H-1,2,4-triazol-1-yl) propanamide;

(2S) -N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexyl} -6-oxopiperidin-2-carboxamide;

N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} -2- (tetrahydro-2H-pyran-4-yl) acetamide;

3,3,3-trifluoro-2-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡m¡din-2-yl ] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} propanamide;

N '- {C¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexyl} -N, N-dimethylbutandiamide;

4-ethynyl-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡d¡n2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexyl} benzamide;

4-cyano-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pinmidin

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexylJbenzamide;

2,2-b¡s (hydroxymethyl) -N- {c¡s-4-hidrox¡-4- [5- (3-metíl-5 - {[4 (tr¡fluorometil) pirímid N-2-yl] amino} phenyl) -1,3-t-acezol-2-yl] cyclohexyl} butanamide;

2- fluoro-5-hydroxy-N- {c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡rimidin-2-yl] amino} phenyl ) -1,3-thiazol-2-yl] cyclohexyl} benzamide;

3- fluoro-4-hydroxy-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexyl} benzamide;

3- amino-4,4,4-trifluoro-N- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrim¡din-2-l]] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} butanamide;

4- ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2125 yl] amino} phenyl) -1,3-thiazol-2- methylcyclohexyl} carbamoyl) methyl cyclohexanecarboxylate;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am inojfeni I) -1,3-thiazol-2-yl] azepan-1-carboxamide;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am inojfeni I) -1,3-thiazol-2-yl] azepan -1 -carboxamide;

- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) p¡r¡midin-2yl] amino} phenyl) -1,3-thiazol-2 -il] azepan-4-ol;

(4R) -1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-210 yl] am inojfeni I) -1,3-thiazol-2-yl ] azepan-4-ol;

(4S) -1- (hydroxyacetyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-4-ol;

(4R) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] -1 - (4H-1 2,4-triazol-3-ylcarbonyl) azepan-4-ol;

(4S) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2-yl] amino} phenyl) 1_I3-thiazol-2-yl] -1- (4H-1,2,4-triazol-3-ylcarbonyl) azepan-4-ol;

N-Butyl-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine-1 - carboxamide;

4-hydroxy-N- (4-methylphenyl) -4- [5- (3-methyl-5 - {[420 (trif I uoromethyl) pi rim id in-2-yl] am i nojfen i I) -1, 3-thiazol-2-yl] p ipe rid i na-1 -carboxamide;

4-hydroxy-N- (3-methylphenyl) -4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] piperidine-1-carboxamide;

N- (4-cyanophenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4126 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl ] piperidine-1-carboxamide; N- (2,5-dimethylphenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -yl] piperidine-1 -carboxamide; N- (2,4-dimethylphenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[45 (trifluoromethyl) pyrmidine-2-yl] amine} phenyl) - 1,3-thiazol-2-yl] piperin-1-carboxamide;

4-hydroxy-N- [4- (1-methylethyl) phenyl] -4- [5- (3-methyl-5 - {[4 (trfluoromethyl) p¡r¡m¡din-2 -yl] amino} phenyl) -1,3-thiazol-2-yl] piperidine-1-carboxamide; N- (5-Chloro-2-methylphenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] piperidine-1-carboxamide; N- (3-chloro-2-methylphenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] piperidine-1-carboxamide; 4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1- carboxamide;

(4R) -4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin15 2-yl] amino} phenyl) 1,3-thiazol-2 -yl] azepan-1-carboxamide;

(4S) -4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) 1,3-thiazol-2-yl] azepan -1-carboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N-prop-2-en -1-ylazepan-1-carboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N-prop¡lazepan- 1-carboxamide;

4-hydroxy-N- (1-methyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin2-l] amino} phenyl) -1.3 -thiazol-2-yl] azepan-1 -carboxamide;

127

N - ({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2!] Amino} phenyl) -1,3-thiazol-2-yl] ethyl azepan-1-yl} carbonyl) glycinate;

4 - [({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1 ethyl -yl} carbonyl) amino] butanoate;

{4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-t¡azol-2-yl] piperidin-1 -methyl iljacetate;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] piperidin-1 -methyl methylpropanoate;

2- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 [l] amino} phenyl) -1,3-thiazole -2-yl] methyl p-peri-1-yljpropanoate;

4- {4-h¡droxi-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2-¡IJp¡ methyl methyl-1-yl-butanoate;

1- (2-fluoroethyl) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-l] azepan-4-ol;

{4-hydroxy-4- [5- (3-methyl-5 - - [[4- (tr¡fluoromethyl) p¡rim¡d¡n-2 yl] am inojphenyl) -1,3- thiazol-2-i IJazepa n-1-iljacetic;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yljam no} phenyl) -1,3-thiazol-2-yl] azepan acid -1 -iljpropanoic;

(4R) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 20 1,3-thiazol-2-yl] -1 - (2, 2,2-trifluoroethyl) azepan-4-ol;

(4S) -4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] -1 - (2 2,2-trifluoroethyl) azepan-4-ol;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3128 thiazol-2-i I] -1 - (2,2,2- trif luoroeti l) azepan-4-ol;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1- methyl} propanoate;

{4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] aminojfeniI) -1,3-thiazol-2-yl] azepan-1-yljacetate t-butyl;

3- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2yl) pyrrolidin-3-ol;

3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] pyrrolidin-3-ol;

3-hydroxy-3- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenylJ-1,3thiazol-2-yl) pyrrolidin-1-carboxamide;

(3S) -3-hydroxy-3- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} ·

1,3-thiazol-2-yl) pyrrolidin-1-carboxamide;

(3R) -3-hydroxy-3- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} 15 1,3-thiazol-2-yl) pyrrolidin-1-carboxamide ;

3- (5- {3 - [(5-fluoro-4-methylpyridine-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -3-hydroxypyrrolidine -1 -carboxamide;

3- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -3-hydroxypyrrolidin-1-carboxamide;

3- (5- {3 - [(5-fluoro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -3-hydroxypyrrolidin-1-carboxamide;

3-hydroxy-3- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] pyrrolidin-1-carboxamide;

129

1- (2-hydroxyethyl) -3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2yl] amino} phenyl) -1,3- thiazol-2-yl] pyrrolidin-3-ol;

2- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am inojfen il) -1,3-thiazol-2-yl] pyrrole id in-1 -i IJacetam ida;

1- (hydroxyacetyl) -3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-3-ol;

{3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-1-yl acid }acetic;

2- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-210 yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-1-yl} -2-oxoacetamide;

{3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-1-yl} acetate methyl;

{3-hydroxy-3- [5- (3-methyI-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] ami nojfen I) -1,3-thiazol-2-yl acid] prolid in-1-yl} (oxo) acetic;

3- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] aminojphenyl) -1,3-thiazol-2-yl] pyrrolidin-1-yl } -3-oxopropanamide;

{3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] pyrrolidin-1-ylJ (oxo ) methyl acetate;

3- {3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] ami nojfen I) -1,3-thiazol-2-yl] pyrrole id i n-1-yl} -3-oxopropa n-1,2-diol;

1- (5- {3 - [(4-tert-butylpyrim¡din-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) cyclobutanol;

N- {3- [2- (3-aminooxetan-3-yl) -1,3-thiazol-5-yl] -5-methylphenyl} -5-chloro-4130 methoxypyrimidin-2-amine;

N- [3- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) oxetane-3-yl] sulfuric diamide ;

diamide N- [3- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) oxetane-3-yl ] sulfuric;

1- [1- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) cyclobutyl] urea;

1- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -7-oxoazepane- 4-yl} urea;

diamide N- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2 yl] amino} phenyl) -1,3-t¡azol-2-l] -7 -oxoazepan-4-yl} dicarbonimidica;

diamide N- {4- [5- (3 - {[5-chloro-4- (trifluoromethyl) pyrimidin-2-yl] amino}

5-methylphenyl) -1,3-thiazol-2-yl] -7-oxoazepan-4-yl} dicarbonimidic;

diamide N- [1- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5 15 methylphenyl} -1,3-thiazol-2-yl) cyclobutyl] dicarbonim;

2- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) propan-2-sulfonamide;

2- [5- (3-methyl-5 - {[4- (1 -methylethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol2-yl] propan-2-sulfonamide;

4- [5- (3-methyl-5¿ [4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -7-oxoazepan-4-carboxamide;

N- [2-hydroxy-1 - (hydroxymethyl) ethyl] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide ;

131

N- [2-h id roxy-1,1-bis (h id roxy met yl) eti l] -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-carboxamide;

N - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] carbonyl} -beta-alanine;

1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] carbonyl} pyrrolidin-3-ol;

N- {3- [bis (2-hydroxyethyl) amino] propyl} -5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-carboxamide;

(3R, 4S) -1 - {[5- (3-methyl-5 - {[4- (tnfluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl] ca rbonyljpirrolid in- 3,4-d iol;

1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] carbonyl} piperidine-4-carboxylic;

4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimydn-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] carbonyl} amino) cyclohexancarboxylic;

(2R, 3R) -2-hydroxy-3 - ({[5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole- 2-yl] carbonyl} amino) -3phenylpropanoic;

4-hydroxy-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] carbonyl} proline;

4-hydroxy-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmididin-2yl] amino} phenyl) -1,3-thiazol-2-yl] carbonyl} prolinate methyl;

4-hydroxy-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] carbon acid L} piperidine-4-carboxylic;

132 (4R) -4-hydroxy-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2-yl ] methyl] carbonyl-D-prolinate;

(4R) -4-hydroxy-1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yljamino} phenyl) -1,3-thiazol-2-yl] carbonyl} -D- proline;

N- {3- [2- (aminomethyl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

3 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) propane- 1,2-diol;

2- [2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] methyl} amino) ethoxy] ethanol;

(2S, 3S) -2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2l] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) butan-1,3-diol;

(2R, 3R) -2 - ({[5- (3-methyl-5 - {[4- (tnfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) butan-1,3-diol;

4-methyl-4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) pentan- 2-ol;

{3 - [({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) methyl] oxetane- 3-yl} methanol;

2- (hydroxymethyl) -2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidid-220 yl] amino} phenyl) -1,3-thiazol-2-yl] methyl } amino) propan-1,3-diol;

N- [3- (2 - {[(1,4-dioxan-2-ylmethyl) (methyl) amino] methyl} -1,3-thiazol-5-yl) -5 methylfenyl] -4- (trifluoromethyl ) pyramid-2-amine;

{4 - [({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3133 thiazol-2-yl] methyl} amino) methyl] tetrahydro -2H-pyran-4-ylJmethanol;

1-methyl-4- [2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] met L} amino) ethyl] piperidin-4-ol;

2,2^,- {[3 - ({[5- (3-methyl-5 - {[4- (trif! Uoromethyl) pyrmidine-2-yl] amino} phenyl) 5 1,3-thiazol-2-yl] methyl} amino) propyl] amino} diethanol;

2 - [(2-hydroxyethyl) {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimydin-2 yl] amino} phenyl) -1,3-thiazol-2 acid -L] methyl] amino] ethanesulfonic;

4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} amino) tetrahydrofuran-3- ol;

4- (methyl {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) 1.3-thiazol-2-yl] methyl} amino) tetrahydrofuran-3-ol;

[2-methyl-2 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] methyl } amino) cyclohexyl] methanol;

[3 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2-yl] amino} phenil) -1,315 t¡azol-2-yl] metyl } amino) -7-oxabicyl [2.2.1] hept-2-yl] methanol;

4 - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1,3-thiazol-2-yl] methyl} amino) tetrahydrothiophene-3-ol 1.1 -dioxide;

4- (ethyl {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] methyl} amino) tetrahydrothiophene-3-ol 1 , 1-dioxide;

2 - [(1,1 -d ioxidotetra h idrothiophene-3-yl) {[5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3- thiazol-2-yl] methyl} amino] ethanol;

4 - [(2-hydroxyethyl) {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] ami nojfen i I) -1,3-thiazol-2-i IJmetiIJam inojtetra h id rotiophene-3-ol 1,1-dioxide;

134

1-methyl-3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} urea;

1-ethyl-3 - {[5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2-l] amino} phenyl) 1.3- thiazol-2 -il] methyl} urea;

1- (1 -methylethyl) -3 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl }urea;

N - ({[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-yl] methyl} carbamoyl) ethyl alaninate;

1- {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,310 t¡azol-2-yl] methyl} piperidine-3-carboxamide;

2- (4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} morpholin-2-yl )ethanol;

(4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} -1,4-oxazepan -2-l) methanol;

N- [3- (2 - {[2- (methoxymethyl) morpholin-4-yl] methyl} -1,3-thiazol-5-yl) -5methylphenyl] -4- (trifluoromethyl) pyrimidin-2-amine;

(4 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid)

1,3-thia zol-2-yl] methyl} morpholin-2-yl) acet ic;

(1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 20 1,3-thiazol-2-yl] methyl} pyrrolidin-2-yl acid ) phosphon;

(1 - {[5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} azetinin-3 -yl) methyl dimethylphosphinate;

N- [3-methyl-5- (2 - {[4- (1-methylethyl) -4-oxide-1,4-azaphosphinan-1-yl] methyl} 135

1,3-thiazol-5-yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine;

[2 - ((3- (2- (1 -h id roxicic lo b uti I) -1,3-thiazol-5-yl] -5methylphenyl} amino) pyrimidin-4-yl] -1,3-diazepane- 4-one;

(1 R, 4S) -4- (5- {3 - [(4,6-dimethylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy! -2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4- (5- {3 - [(4,6-dimethylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-h acid droxy -2,2-dimethylcyclohexanecarboxylic acid;

cis-1- [5- (3 - {[4-methoxy-5 - (trifluoromethyl) pyrimidin-2-yl] amino} -5methylphenyl) -1,3-thiazol-2-yl] cyclohexan-1,4-diol ;

(1 R, 4S) -4- (5- {3 - [(4,6-d imethylpyrimid in-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy- Methyl 2,2-methylcyclohexancarboxylate;

(1 S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxy-5-methylpyrimidin-2-yl) amino] -5-methylfenyl} -1,34iazol-2 acid -L) -2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4-hydroxy-4- {5- [3 - ({4 - [(1 R) -1 -hydroxyethyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3 acid -thiazol-2-yl} -2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 4R) -4-hydroxy-4- {5- [3 - ({4 - [(1 S) -1-hydroxyethyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3 acid -thiazol-2-yl} -2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 4R) -4- [5- (3 - {[4- (dimethylamino) -5-methylpyrimidin-2 yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] - acid 4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid; (1S, 4R) -4-hr-hydroxy-4- [5- (3 - {[4- (1-hydroxy-1-methyl) pyrimidine acid

2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] -2,2-dimethylcyclohexancarboxylic;

(1S, 4R) -4- {5- [3 - ({4 - [(R) -cyclopropyl (hydroxy) methyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3-thiazol-2 acid -yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

136 (1S, 4R) -4- {5- [3 - ({4 - [(S) -cyclopropyl (hydroxy) methyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3-thiazol-2 acid -yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1S, 4R) -4- {5- [3 - ({4- [cyclopropyl (fluoro) methyl] pyrim¡din-2 yl} amino) -5-methylphenyl] -1,3-thiazol-2 acid -yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1S, 4R) -4- {5- [3 - ({4 - [(R) -cyclopropyl (fluoro) methyl] pyrimidin-2-yl} amino) -5-methylphenyl] -1,3-thiazole -2-yl} -4-hydroxy-2,2-dimethyl cyclohexanecarboxylic acid;

acid (1S_I4R) -4- {5- [3 - ({4 - [(S) -cyclopropyl (fluoro) methyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3-thiazol-2-yl} - 4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4-hydroxy-4- {5- [3 - ({4 - [(1 E) -3-hydroxy-3-methylbut-1 en-1-yl] pyrimidin-2- acid yl} amino) -5-methylphenyl] -1,3-thiazol-2-yl} -2,2dimethylcyclohexancarboxylic;

(1 S, 4R) -4- [5- (3 - {[4- (1 -cyclopropyl-1 -hydroxyethyl) pyrimidin-2 yl] amino} -5-methylfenyl) -1.3 acid -thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 4R) -4- {5- [3 - ({4 - [(1 R) -1-cyclopropyl-1 -hydroxyethyljpyrimidin

2-yl} amino) -5-methylfenyl] -1,3-thiazol-2-yl} -4-hid roxy-2,2-dimethylcyclohexanecarboxylic;

(1S, 4R) -4- {5- [3 - ({4 - [(1 S) -1 -cyclopropyl-1 -hydroxyethyl] pyrimidin 2-yl} amino) -5-methylphenyl] -1,3- acid thiazol-2-yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

4-hydroxy-4- [5- (3 - {[4-methoxy-5- (trifluoromethyl) pyrimidin-2-yl] amino} 5-methylphenyl) -1,3-thiazol-2-yl] -2,2 -methyl dimethylcyclohexancarboxylate;

(1S, 4R) -4- {5- [3- (6,7-dihydro-5H-cyclopenta [d] pyrimidin-2-ylamino) -5-methylphenyl] -1,3-thiazol-2-yl} - acid 4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

137 (1 S, 4R) -4- {5- [3- (6,7-dih¡dro-5H-cyclopenta [d] p¡r¡mid¡n-2-¡lam¡no) 5-methylphenyl ] -1,3-thiazol-2-yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylate;

4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-t¡azol-2¡l) -4-h¡ ethyl droxy-2-methyl cyclohexancarboxylate;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1methylethyl) p¡rim¡d¡n-2-yl] am No} phenyl) -1,3-t-acezol-2-l] cyclohexancarbox, methyl tin&gt;

(1 S, 4R) -4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-h¡drox¡ -2,2-methyl dimethylcyclohexancarboxylate;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1-methylethoxy) pyrimidin-2-yl] amino} phenyl) -1.3 -methyl-thiazol-2-yl] cyclohexancarboxylate;

(1S, 4R) -4- (5- {3 - [(4-ethenylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexancarboxylate methyl;

(1 S, 4R) -4- (5- {3 - [(4-c¡clobut¡lp¡r¡m¡din-2-¡l) amino] -5-met¡lfenil} -1,3thiazol- Methyl 2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylate;

(1 S, 4R) -4- (5- {3 - [(4-carbamoylpyrimidin-2-yl) amino] -5-methylphenyl} 1,3-thiazol-2-yl) -4-hydroxy! -2,2-methyl dimethylcyclohexanecarboxylate;

c¡s-4-h¡droxi-4- {5- [3 - ({4- [1- (4-methoxybenzyl) -1H-1,2,3-tr¡azol-420 yl] pyrimidin-2- L-amino) -5-methylphenyl] -1,3-thiazol-2-yl} t-butyl cyclohexancarboxylate;

4-hydroxy-4- [5- (3 - {[4-methoxy-5- (trfluorometll) pyrimidin-2yl] amino} -5-methlfenyl) -1 acid, 3-thiazol-2-yl] -2,2-dimethylcyclohexanecarboxylic;

138 (1S, 4R) -4-hydroxy-4- [5- (3 - {[4-methoxy-5 (trifluoromethyl) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2 acid -yl] -2,2dimethylcyclohexanecarboxylic;

4-hydroxy-4- {5- [3 - ({4 - [(1E) -3-methoxyprop-1-en-1-yl] pyrimidin-25 yl} amino) -5-methylphenyl] -1.3 t-butyl-thiazol-2-yl} cyclohexancarboxylate;

4-hydroxy-4- {5- [3 - ({4 - [(1E) -3-methoxyprop-1-en-1-yl] pyrimidin 2-yl} amino) -5-methylphenyl] -1,3-thiazol-2-l} cyclohexanecarboxylic;

(1 S, 4R) -4- [5- (3 - {[5-bromo-4- (tnfluoromethyl) pyrimidin-2 [l]] amino] -5-methylphenyl) -1,3-thiazole -2-l] -4-hydroxy-2,2-d-methylcyclohexancarboxylic;

(1R, 4S) -4- [5- (3 - {[5-bromo-4- (trifluoromethyl) pyrimidin-2 yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] - acid 4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(5R) -5- [5- (2-bromo-3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol- 2-yl] -5-hydroxyazepan-2-one;

(5S) -5- [5- (2-bromo-3-methyl-5 - {(4- (trifluoromethyl) pyrimidin-215 yl] am inojfeni I) -1,3-thiazol-2-yl] -5- hydroxyzepan-2-one;

acid

2,6-anhydro-3,4-dideoxy-5-C- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -il] hexonic;

cis-4-fluoro-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenylJ-1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

cis-4-hydroxy-4- [5- (3 - {[4- (2-methoxy-ethoxy) pyrimidin-2-yl] amino} acid)

5-methylphenyl) -1,3-thiazol-2-l] cyclohexanecarboxylic acid;

-4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2¡l) amino] phenyl} -1,3-thiazol-2-yl) methyl cyclohexancarboxylate;

139 4-hydroxy-2,5-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-t¡azol-2-yl) cyclohexanecarboxylic acid co;

Ethyl 4-hydroxy-2,5-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxylate;

(1R, 2R, 4S) -4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazole -2-yl) methyl cyclohexancarboxylate;

(1R, 2S, 4R, 5R) -4-hydroxy-2,5-dimethyl-4- (5- {3-methyl-5 - [(4methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazole -2-yl) ethyl cyclohexancarboxylate; (1R, 2S, 4R, 5R) -4-hydroxy-2,5-dimethyl-4- (5- {3-methyl-5 - [(410 methylpyrim idin-2-yl) am ethyl inojfen yl} -1,3-thiazol-2-yl) cyclohexancarboxylate;

(1 R, 2S, 4R, 5S) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino acid) } phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 2S, 4R, 5R) -4-hydroxy-2,5-d-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino acid } phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 2S, 4R, 5S) -4-hydroxy-2,5-d-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl acid ] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R. 2S.4R, 5S) -4-hydroxy-2,5-d-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} acid) phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 2S, 4R, 5R) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1 R, 2S, 4R, 5R) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl acid) -1,3-thiazol-2-yl] cyclohexanecarboxylic;

(1R, 2S, 4R, 5S) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4140 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 Ethyl, 3-thiazol-2-yl] cyclohexancarboxylate;

(1R, 2S, 4R, 5S) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 Ethyl, 3-thiazol-2-yl] cyclohexancarboxylate;

(1R, 2R, 4R) -4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2 -yl) methyl cyclohexancarboxylate;

(1R, 2S, 4R, 5S) -4-hid roxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrim¡din-2-yl] amino} ethyl phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate;

(1R, 2S, 4R, 5R) -4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) - Ethyl 1,3-thiazol-2-yl] cyclohexancarboxylate;

(1s, 2R, 4r, 6S) -4-hydroxyI-2 acid_I6-dimethyl-4- (5- {3-methyl-5 - [(415 methylpyrimidin-2-yl) amino] phen! I} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1 r, 2R, 4s, 6S) -4-hydroxy-2,6-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1 acid , 3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1s, 2R, 4r, 6S) -4-hydroxy-2,6-dimethyl-4- (5- {3-methyl-5 - [(4meti Ip i rim idín-2-il) am inojfen i I} - 1-methylethyl 1,3-thiazol-2-yl) cyclohexancarboxylate;

(1r, 2R, 4s, 6S) -4-hydroxy-2,6-dimethyl-4- (5- {3-methyl-5 - [(4methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazole -2-yl) 1-methylethyl cyclohexancarboxylate;

141 (1 r, 2R, 4r, 6S) -4-hydroxy-2,6-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1,3- 1-methylethyl thiazol-2-yl) cyclohexancarboxylate;

(1s, 2R, 4r, 6S) -4-hydroxy-2,6-dimethyl-4- [5- (3-methyl-5 - {[45 (trifluoromethyl) pyrimidin-2-yl] amino acid) } phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

(1 r, 2R, 4s, 6S) -4-hydroxy-2,6-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrim¡d¡n-2-yl] acid) amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylic;

(1s, 2R, 4r, 6S) -4-hydroxy-2,6-dimethyl-4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) p¡r¡mid¡n-2- yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylate

1-methylethyl;

4-hydroxy-2,6-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] c¡ 1-methylethyl chlohexancarboxylate;

4-hydroxy-3,5-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxyllate ethyl;

4-hydroxy-3,5-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclohexancarboxylic;

4- hydroxy-3,5-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylate de ethyl;

5- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,320 thiazol-2-yl) -5-hydroxyazepan-2-one;

5- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) -5-hydroxyazepane-2-one;

5- [5- (3 - {[4- (1-fluoroethyl) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3142 thiazol-2-yl] -5-hydroxyazepan-2-one;

4- (5- {3 - [(4-ethylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2 (l) -4-hydroxy-2-methylcyclohexanecarboxylic acid;

5- [5- (3 - {[4- (1-fluoroethyl) pyrimidin-2-yl] amino} -5-methylphenyl) -1.35 thiazol-2-yl] -5-hydroxy-acezepan-2-one ;

5- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl) -1,3-thiazol-2-yl) -5-hydroxyazepan-2-one;

5- (5- {3 - [(5-fluoro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -5-hydroxy-acezepan-2-one;

5- [5- (3 - {[4- (d ifluoromethyl) pyrimid in-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] -5-hydroxyazepan-2-one;

5-hydroxy-5- [5- (3 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] azepan-2-one;

5- (5- {3-l (4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-215 µl) -5-hydroxyazepane-2-one;

5-hydroxy-5- [5- (3-methyl-5 - {[4- (1-methylethoxy¡) pyrimidin-2¡l] amino} pheníl) -1,3-thiazol-2-¡l] azepan-2-one;

5- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -5-hydroxyazepan-2-one;

5-hydroxy-5- (5- {3-methyl-5 - [(4-thiophene-2-ylpyrimidin-2-yl) amino] phenyl} 1,3-thiazol-2-yl) azepan-2-one;

4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol2-yl) azepan-4-ol;

143

4- [5- (3-methyl-5 - {[4- (1 -methylethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol2-yl] azepan-4-ol;

(4S) -4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 1,3-thiazol-2-yl) azepan-4-ol;

(4R) -4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 1.3-thiazol-2-yl) azepan-4-ol;

(4R) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxyazepan-1-carboxylate t-butyl ;

(4S) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} -1,310 thiazol-2-yl) -4-hydroxyzepan-1-carboxylate t- butyl;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2-yl] amino} phenyl) 1.3-thiazol-2-yl] t-butyl azepan-1-carboxylate;

(4R) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan- T-butyl 1-carboxylate;

(4S) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] t-butyl azepan-1-carboxylate;

(4S) -4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 1.3-thiazol-2-yl) -4-hydroxyazepane-1-carboxylate t-butyl;

(4R) -4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} 20 1,3-thiazol-2-yl) -4-hydroxyazepane-1 t-butyl carboxylate;

4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -2-methylcyclohexanecarboxylic acid;

acid

4- {1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2

144 L] amino} phenyl) -1,3-thiazol-2-yl] ethenyl} benzoic;

Methyl 4- {1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethenyl} benzoate;

4- {1 - [5- (3-methyl-5 - {[4- (trif luorometi I) pyrimid i n-2 yl] am ino} phenyl) -1,3-thiazol-2-yl] cyclopropyl acid} benzoic;

4 - {(E) -2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] ethenyl} methyl benzoate;

4- {1-Methyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} benzoic acid ;

6- {1 -h id roxy-1 - [5- (3-met¡l-5 - {[4- (trif luoromethyl) pi rim id in-2 ¡l] amino} phenyl) -1,3- thiazol-2-yl] ethyl} pyridine-3-carboxylic;

4- {dfluoro [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} benzoic acid;

Methyl 4- {1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,315 thiazol-2-yl] cyclopropyl} benzoate;

Methyl 4- {1-methyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} benzoate ;

Methyl 4- {difluoro [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] methyl} benzoate;

4-hydroxy-4- (5- {3 - [(4-methoxypropyl-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -2-methylcyclohexanecarboxylic acid ;

(1S, 2R, 4R) -4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl acid) -4-hydroxy-2-methylcyclohexancarboxylic;

145 (1R, 2S, 4S) -4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4 acid -hydroxy-2-methylcyclohexanecarboxylic;

cis-4-hydroxy- 4- [5- (3 - {[4- (3-methoxypropoxy) pyrimidin-2 yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

4- (5- {3 - [(4-cyclopropylpyrimin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-hydroxy-acid 2-methylcyclohexancarboxylic;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] acid cyclohexancarboxylic;

4- (5- {3 - [(5-Chloro-4-methylpyrimid-2-yl) amino] -5-methylphenyl acid}

1,3-thiazol-2-yl) -4-hydroxy-2-methylcyclohexanecarboxylic;

cs-4- [5- (3-chloro-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -4 acid -hydroxycyclohexancarboxylic;

4- (5- {3 - [(5-fluoro-4-methoxypyrimidin-2-yl) amino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxy-2-methylcyclohexanecarboxylic acid;

(1 S, 2 R, 4R) -4- (5- {3 - [(4-ethylpyrim¡din-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy Ethyl -2-methylcyclohexancarboxylate;

(1 R, 2S, 4S) -4- (5- {3 - [(4-ethylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2- ethyl methyl cyclohexancarboxylate;

4- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5 20-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2-methylcyclohexancarboxylic acid;

(1S, 2R, 4R) -4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] 5-methylphenyl} -1,3-thiazol-2-yl) -4 acid -hydroxy-2-methylcyclohexanecarboxylic acid;

(1R, 2S, 4S) -4- (5- {3 - [(5-chloro-4-methoxypmidmidin-2-yl) amino] acid]

146

5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2-methylcyclohexancarboxylic;

4-hydroxy-4- [5- (3 - {[4- (2-methoxyethoxy) pyrimidin-2-yl] amino} -5 methylphenyl) -1,3-thiazol-2-yl] -2-methylcyclohexancarboxylic acid;

acid

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

4-hydroxy-4- [5- (3 - {[4- (3-methoxypropoxy) pyrimidin-2-l] amino acid)}

5-methylphenyl) -1,3-thiazol-2-yl] -2-methylcyclohexanecarboxylic acid;

4-hydroxy-4- {5- [3- (methoxymethyl) -5 - {[4- (tr¡fluoromethyl) pyrimidine acid

2-yl] amino} phenyl] -1,3-thiazol-2-yl} -2-methylcyclohexancarboxylic;

4-hydroxy-4- [5- (3 - {[4- (2-methoxyethoxy) pyrimidin-2-yl] amino} -5methylphenyl) -1,3-thiazol-2-yl] -2-met¡lc Ethyl clohexancarboxylate;

-4-hydroxy-2,5-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2- yl] ethyl cyclohexancarboxylate;

4-hydroxy-4- [5- (3 - {[4- (3-methoxypropoxy) pyrimidin-2-yl] amino} -515 methylphenyl) -1,3-thiazol-2-yl] -2-methylcyclohexancarboxylate ethyl;

acid (1s_I4R) -4- (5- {3 - [(4-ethylpyrimidin-2-yl) amino] -5-methylphenyl}

1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

acid

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1S, 4R) -4- (5- {3 - [(4-cyanop¡rim¡din-2-¡) amino] -5-methylenyl} -1,3thiazol-2-yl) -4- methyl hydroxy-2,2-dimethylcyclohexancarboxylate;

(1 S, 4R) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2 acid, 2-dimethylcyclohexanecarboxylic;

147 (1 S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1 methylethyl) pyrimidin-2-yl] amino} phenyl) -1 acid , 3-thiazol-2-yl] cyclohexanecarboxylic;

(1 S, 4R) -4- (5- {3 - [(4-ethylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2- methyl dimethylcyclohexancarboxylate;

(1 R, 4S) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) -2, Methyl 2-dimethylcyclohexancarboxylate;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxypyridine-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) -2 Methyl 2-dimethylcyclohexancarboxylate;

(1S, 4R) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} 10 1,3-thiazol-2-yl) -4-hydroxy-2,2 -methyl dimethylcyclohexancarboxylate;

4- (5T {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-acid 2,2-methylcyclohexanecarboxylic acid;

(1 S, 4R) -4- (5- {3 - [(4-cyclopropyl-5-fluoropyrimidin-2-yl) amino acid]

5-methylphenyl} -1,3-thiazol-2-yl) -4-h-hydroxy-2,2-dimethylcyclohexanecarboxylic;

4- [5- (3-chloro-5 - {[4- (trifluoromethyl) p¡rimidin-2-yl] amino} phenyl acid)

1,3-thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

(1S, 4 R) -4- [5- (3-chloro-5 - {[4- (trifluoromethyl) pyrim id in-2 yl] amino} phenyl) -1,3-thiazol-2-yl acid] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1 R, 4S) -4- [5- (3-chloro-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] -4- acid hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1 S, 4R) -4-hydroxy-4- {5- [3- (methoxymethyl) -5 - {[4 acid

148 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] -1,3-thiazol-2-yl} -2,2-dimethylcyclohexancarboxylic;

4- [5- (3-chloro-5 - {[4- (trfluoromethyl) pyrmididin-2-yl] amino} phenyl) -1,3thiazol-2-yl] -4-hydroxy-2,2 -methyl dimethylcyclohexancarboxylate;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) (6-²H) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 yljcyclohexanecarboxylic acid;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) (6²H) methyl pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylate;

4-hydroxy-2,3-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazole- 2-l) cyclohexanecarboxylic;

4-hydroxy-2,3-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyridin-2yl) amino] phenyl} -1,3-thiazol-2 -yl) ethyl cyclohexancarboxylate;

4-hydroxy-2,3-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] am inojphenyl) -1,3-thiazol-2 -L] cyclohexancarboxylic;

4-hydroxy-2,3-dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2- yl] ethyl cyclohexancarboxylate;

4-hydroxy-3-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimid-2-yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid ;

4-hydroxy-3-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl}

Ethyl 1,3-thiazol-2-yl) cyclohexancarboxylate;

4-hydroxy-3-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine acid

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

149

4-hydroxy-3-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazole- Ethyl 2-yl] cyclohexancarboxylate;

3,4-dihydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexanecarboxylic acid;

4-hydroxy-3,3-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrim¡din-2 yl) amino] phenyl} -1,3-thiazol-2-yl acid ) cyclohexancarboxylic;

N- {3-methyl-5- [2- (1 H-pyrazol-4-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrmididin-2-amine;

N- {3-methyl-5- [2- (4,5,6,7-tetrahydropyrazolo [1,5-a] pindin-3-yl) -1,310 thiazol-5-yl] fen yl) -4 - (trif luoromethyl) pyrim id in-2-amine;

N- {3-methyl-5- [2- (1 H-pyrazol-5-yl) -1,3-thiazol-5-yl] phenyl} -4 (trifluoromethyl) pyrimin-2-amine;

N- [3-methyl-5- (2-pyr¡din-3-yl-1,3-thiazol-5-yl) phenyl] -4 (trifluoromethyl) p¡r¡m¡din-2-am ¡Na;

N- [3-methyl-5- (2-pyridin-4-I-1,3-thiazol-5-yl) phen yl] -4 (trifluoromethyl) pyrimidin-2-amine;

N- [3-methyl-5- (2-thiophene-2-yl-1,3-thiazol-5-yl) phenyl] -4 (trifluoromethyl) pyrimidin-2-amine;

N- [3-methyl-5- (2-thiophene-3-yl-1,3-thiazol-5-yl) phenyl] -420 (trifluoromethyl) p¡r¡midin-2-amine;

N- [3- (2-furan-2-yl-1,3-thiazol-5-yl) -5-methylphenyl] -4 (trifluoromethyl) pyrimidin-2-amine;

N- {3-methyl-5- [2- (1 H-pyrrol-2-yl) -1,3-thiazol-5-yl] phenyl} -4150 (trifluoromethyl) pyrimidin-2-amine;

N- (3-methyl-5- {2- [1 - (tetra h id ro-2 H-pi ra η-4-yl) -1 H-pyrazol-4-i I] -1,3 thiazole- 5-l} phenyl) -4- (trifluoromethyl) pyrimidin-2-amine;

3- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.35 thiazol-2-yl] -1 H-pyrazole- 1 -iljpropa non itrilo;

2- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-i I] -1 H- pyrazol-1-yljetanol;

3- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-i I] -1 H-pyrazole-1 - i IJpropa n-1 -ol;

(2R) -3- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl)

1,3-thiazol-2-yl] -1 H-pyrazol-1-yl} propan-1,2-diol;

2-methyl-1- {4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2 -il] -1 H-pyrazol-1-yl} propan-2-ol;

4-hydroxy-2- {4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 15 yl] amino} phenyl) -1,3-t-acezol-2-yl] acid -1 H-pyrazol-1-yljbutanoic;

5 - ({4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -1 H-pyrazol-1 - i IJmethyl) -1,3-oxazolidin-2-one;

cis-1 - (5- {3 - [(4,6-dimethylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) cyclohexan-1,4-diol;

t-Butyl cis-4- [5- (3 - {[4- (1 -fluoroethyl) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] -4-hydroxycyclohexancarboxylate;

c¡s-4- (5- {3 - [(5-fluoro-4-methoxyprimidin-2-yl) amino] -5-methylphenyl} 1.3-thiazol-2-yl) -4-hydroxycyclohexancarbox! t-butyl can;

151 cis-4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazole · 2-l) -4-hr-hydroxychlorohexancarboxylate t-butyl;

(1S.4R) 4- {5- [3 - ({4 - [(1R) -1-fluoroethyl] pyrimidin-2 l} amino) -5-methylphenyl] -1,3-thiazole- 2-yl} -4-hydroxy-2₎2-methylcyclohexanecarboxylic acid;

(1S, 4R) 4- {5- [3 - ({4 - [(1 S) -1-fluoroethyl] pyrimidin-2 yl} amino) -5-methylphenyl] -1,3-thiazol-2- acid yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (pentafluoroethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

cis-4- (5- {3 - [(5-chloro-4-methoxy¡p¡r¡midin-2-yl) amino] -5-methylphenyl} 10 1,3-thiazol-2-yl) -4 t-butyl hydroxycyclohexancarboxylate;

cis-4-hydroxy-4- (5- {3-methyl-5 - [(4-thiophene-2-lpyrimid-2-yl) amino] phenyl} -1,3-thiazol-2-yl ) t-butyl cyclohexancarboxylate;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (pentafluoroethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2- yl] t-butyl cyclohexancarboxylate;

cis-4-hydroxy-4- {5- [3 - ({4- [1 - (4-methoxybenzyl) -1 H-1,2,3-triazole acid

4-yl] pyrimidin-2-yl} amino) -5-methylphenyl] -1,3-thiazol-2-yl} cyclohexanecarboxylic;

(1 R, 2S, 4S) acid -4- [5- (3 - {[4- (difluoromethyl) pyrimidin-2-yl] amino} -5 methylphenyl) -1,3-thiazol-2-yl] -4 -hydroxy-2-methylcyclohexanecarboxylic;

(1S, 2R, 4R) -4- [5- (3 - {[4- (Difluoromethyl) pyrmidine-2-yl] amino} -5 methylphenyl) -1,3-thiazol-2-yl] - acid 4-hydroxy-2-methylcyclohexanecarboxylic acid;

cis-4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxycyclohexancarboxylic acid;

4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1.3 acid

152 thiazol-2-yl) -4-hydroxy-2-methylcyclohexanecarboxylic acid;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1-methylethoxy) pyrimin-2 yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclohexancarboxylic;

methyl-4- (5- {3 - [(5-fluoropyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol5 2-yl) -4-hydroxy-2,2-dimethylcyclohexancarboxylate;

4- (5- {3 - [(5-fluoro-4-hydroxypyrimidin-2-yl) amino] -5-methlfenl} acid

1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

2 - [(3- {2 - [(1 S, 4R) -4-carboxy-1-hydroxy-3,3-dimethylcyclohexyl acid]

1,3-thiazol-5-yl} -5-methiphenyl) amino] primidin-4-carboxylic;

Methyl 4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexancarboxylate ;

4- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1 R, 4S) -4- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5 15-methylphenyl} -1,3-thiazol-2-yl ) -4-hydroxy-2,2-d-methylcyclohexanecarboxylic acid;

(1S, 4R) -4- (5- {3 - [(5-fluoro-4-methoxypinmidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4 acid -hydroxy-2,2-dimethylcyclohexanecarboxylic;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

4- (5- {3 - [(5-chloro-4-hydroxypyrimidin-2-yl) amino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1S, 4R) -4- [5- (3 - {[4- (Difluoromethyl) pyrim¡din-2-yl] amino} -5 methylphenyl) -1,3-thiazol-2-yl] -4- acid hydroxy-2,2-dimethylcyclohexancarboxylic;

153 (1 S, 4R) -4- (5- {3 - [(4-cyclobutylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4- acid hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid ;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1 methylethoxy) pyrimidin-2-yl] amino} phenyl) -1 acid, 3-thiazol-2-yl] cyclohexanecarboxylic;

4- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexancarboxylate methyl;

methyl-4- (5- {3 - [(5-fluoro-4-methoxypyrim¡din-2-yl) amino] -5-methylfenl} 10 1,3-thiazol-2-yl) -4 -hydroxy-2,2-dimethylcyclohexancarboxylate;

4- (5- {3 - [(5-chloro-4-methoxypyr¡m¡din-2-yl) amino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (4-methyl-3 - {[4 (trifluoromethyl) pyrimidin-2-yl] amine} phenyl) -1 acid , 3-thiazol-2-yl] cyclohexanecarboxylic;

methyl-4- (5- {3 - [(5-chloro-4-methoxypyridin-2-yl) amino] -5-methylphenyl} 1.3-thiazol-2-yl) -4-hydroxy-2, 2-dimethylcyclohexancarboxylate;

cis-4- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxycyclohexanecarboxylic acid;

1,3-thiazol-2-yl) propan-2-ol;

8- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -1,4-dioxaspiro [4.5] decan-8-ol;

8- (5- {3 - [(5-chloro-4-methylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2-yl) -1,4-dioxaspiro [4.5] decan-8 -ol;

154 cis-4- (5- {3 - [(5-fluoro-4-methoxypyridin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4-hydroxycyclohexanecarboxylic acid ;

cis-4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3 thiazol-2-yl) -4-hydroxycyclohexancarboxylic acid;

c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (1 -methylethexi) pyr¡m¡d¡n-2 ¡l] amino} phenyl) acid - 1,3-thiazol-2-yl] cyclohexanecarboxylic;

cis-4- (5- {3 - [(5-chloro-4-methoxypyrimidin-2-yl) amino] -5-methylenyl-l} -1,3-thiazol-2-yl) -4-hydroxy acid Cyclohexancarboxylic;

cis-4-hydroxy-4- (5- {3-methyl-5 - [(4-thiophene-2-ylpyridin-2 yl) amino] phenyl} -1,3-thiazol-2-yl acid ) cyclohexancarboxylic;

(1S, 3S) -3-hydroxy-3- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole- 2-l] cyclopentancarboxamide;

(1R, 3R) -3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡d¡n-2yl] amino} phenyl) -1 , 3-thiazol-2-yl] cyclopentancarboxamide;

(1 R, 3S) -3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole -2-yl] cyclopentancarboxamide;

(1 S, 3R) -3-hydroxy-3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclopentancarboxamide ;

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} 20 1,3-thiazol-2-yl) cyclohexancarboxamide;

cis-4-hydroxy-2,2-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2yl) amino] phenyl} -1,3-thiazol-2-yl) cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (1 -methylethyl) pyrimidin-2155 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide ;

cis-4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazole

2-l) -4-hydroxyl-cyclohexancarboxamida;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyr¡m¡d¡n-25 ¡l] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

cis-4-h¡droxi-4- [5- (3-metil-5 - {[4- (1-methylethoxy) pyr¡m¡d¡n-2¡l] amino} phenyl) - 1,3-thiazol-2-yl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxypyramidin-2-yl) amino] -5methylphenyl} -1,3-thiazole -2-yl) -2,2-dimethylcyclohexancarboxamide;

4-hydroxy-4- [5- (3 - {[4- (2-hydroxy-ethoxy)) p¡r¡m¡d¡n-2-¡l] amino} -5methylphenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide;

cis-4-h¡droxi-N-metíl-4- [5- (3-methyl-5 - {[4- (tr¡fluoromet¡l) p¡r¡mid¡n-2¡l] am No} phenyl) -1,3-thiazol-2-l] cyclohexancarboxamide;

cis-N, 4-d¡h¡drox¡-4- [5- (3-metíl-5 - {[4- (tr¡fluoromet¡l) p¡r¡m¡din-215 il] amino } phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

cis-4-hydroxy-N, N-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexancarboxamide;

N- (cannomethyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) p¡r¡mid¡n

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

cis-4- (azetid i n-1 -¡ lea rbon ¡I) -1 - [5- (3-met¡l-5 - {[4 (trifluoromethyl) pyrimidin-2-l] amino} phen¡l ) -1,3-thiazol-2-yl] cyclohexanol;

4-h¡drox¡-N- (1 -met¡let¡l) -4- [5- (3-met¡l-5 - {[4- (tr¡fluoromet¡l) p¡r¡mid¡ n2-l] amino} phenyl) -1,3-thiazol-2-l] cyclohexancarboxamide;

156

N-ethyl-4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-N- (2-hydroxyethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexancarboxamide;

N- (cyclopropylmethyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexancarboxamide;

cis-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] -4- (pyrrolidin-1 -ylcarbon L) cyclohexanol;

4-hydroxy-N- (2-methoxy-ethyl) -4- [5- (3-methyl-5 - {[410 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexanecarboxamide;

N - ({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} carbonyl) glycine;

c¡s-4-hydroxy-N-1 H-¡m¡dazol-2-¡l-4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyridine -2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

c¡sN- (2-cyanoethyl) -4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) - 1,3-thiazol-2-yl] cyclohexancarboxamide;

cis-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] -4- (morpholin-4-ylcarbonyl) cyclohexanol ;

cis-N- (3-amino-3-oxopropyl) -4-hydroxy-4- [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-N- (3-methoxypropyl) -4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-l] cyclohexancarboxamida;

N- (2,3-dihydroxypropyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4157 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide;

4-hydroxy-N- [2-hydroxy-1- (hydroxymethyl) ethyl] -4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl ) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) -1,3-thiazol-2-yl] -N-pyridin- 4-ylcyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -Np¡r ¡D-n-2-ilc¡clohexancarboxamida;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidine-2yl] amino} phenyl) -1,3-thiazol-2- L] -N-pyridin-3-ylcyclohexancarboxamida;

one - ({c¡s-4-hydroxy¡-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimide-2¡l] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexyl} carbonyl) prolrolidin-3-carbonitrile;

cis-4-hydroxy-N- (1H-imidazol-2-ylmethyl) -4- [5- (3-methyl-5 - {[4 (trfluoromethyl) p¡rim¡d¡n -2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 [l]] amine} phenyl) -1, 3-thiazol-2-yl] -N- (1H-prazol-5-ylmethyl) cyclohexancarboxamide;

cis-N- (2-cyanoethyl) -N-ethyl-4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexancarboxamide;

cis-4-hydroxy-N- (isoxazol-4-ylmethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- ( 1,3-oxazol-4-ylmethyl) cyclohexancarboxamide;

cis-4-hydroxy-N- (isoxazol-5-ylmethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

158

N-cyclohexyl-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxarnide ;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (1, 2,4-oxadiazol-35 ylmethyljcyclohexanecarboxamide;

4 - [(4-methylpiperazin-1-yl) carbonyl] -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexanol;

1 - ({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-t¡azol-2-yl] cyclohex! l} carbonyl) piperidin-4-ol;

cis-4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] - N- (tetrahydrofuran-3-yl) cyclohexancarboxamide;

cis-N- [2- (acetylamino) ethyl] -4-h¡droxi-4- [5- (3-metil-5 - {[4 (tr¡fluoromethyl) p¡r¡m¡d¡n -2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-N, N-bis (2-hydroxyethyl) -4- [5- (3-methyl-5 - {[415 (tr¡fluoromet¡l) p¡r¡mid¡n-2-¡l] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

N-benzyl-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- ( pyridin-3-ylmethyl) cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (pyridin-4- ylmethyl) cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2¡l] amino} phenyl) -1,3-t¡azol-2-¡l] - N- (pyridin-2-ylmethyl) cyclohexancarboxamide;

159

4-hydroxy-N- (4-hydroxyphenyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide;

cis-4-hydroxy-N- (2-hydroxyphenyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole- 2-yl] cyclohexancarboxamide;

c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimin-2yl] amino} phenyl) -1,3-thiazol-2- yl] -N- (pyrimidin-5-ylmethyl) cyclohexancarboxamide;

c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- ( pyridazin-3-ylmethyl) cyclohexancarboxamide;

1 - ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] am ino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} carbonyl) piperid in-4-carbonitrile;

1 - ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexyl} carbonyl) pperidine-3-carbonitrile;

cis-4-hydroxy-N- (6-hydroxypyridin-3-yl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

c¡sN- (4-fluorophenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (thiophene-2- ylmethyl) cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (2 -pyrrolidin-1-ylethyl) cyclohexanecarboxamide;

cis-4-hydroxy-N - [(3-hydroxyisoxazol-5-yl) methyl] -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrmididin-2-yl] amino } phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

cis-4-hydroxy-N- (isothiazol-5-ylmethyl) -4- [5- (3-methyl-5 - {[4160 (trifluoromethyl) pyrmidid-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexancarboxamide; cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pinmidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- ( 1,3,4-thiadiazol-2ylmethyl) cyclohexancarboxamide;

cis-N- {2- [acetyl (methyl) amino] ethyl} -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimyrid-2 -L] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

N-benzyl-4-hydroxy-N-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrmidine-2-yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (2-phenylethyl ) cyclohexancarboxamide;

c¡s-4-hydroxy-N- (3-hydroxybenzyl) -4- [5- (3-methyl-5 - {[4 (trfluoromethyl) p¡rim¡d¡n-2- yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

c¡s-4-h¡drox¡-N- [4- (hydroxymethyl) phenyl] -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡midin-2- yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide; 15 cis-4-hydroxy-N- [3- (hydroxymethyl) phenyl] -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl ] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide; cis-4-hydroxy-N- (2-hydroxybenzyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide;

4-hydroxy-N- (4-hydroxybenzyl) -4- [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexancarboxamida; cis-N- (2,4-dihydroxyphenyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexancarboxamide;

cis-N- (4-fluorobenzyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4161 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide; cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- [2- (2-oxopyrrolidin-1l) etl] cyclohexancarboxamide;

cs-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyridine-2yl] to minojphenyl) -1,3-thiazol-2- yl] -N- [2- (2-oxoimidazolidin-1 yl) ethyl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2¡l] amino} phenyl) -1,3-thiazole- 2-yl] -N- (2-morpholin-4-yl) cyclohexancarboxamide;

cis-N- [4- (acetylamino) butyl] -4-hydroxy-4- [5- (3-methyl-5 - {[4 (tr¡fluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide;

cis-4-hydroxy-N-1 H-indole-5-yl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 [l]] am ¡nojfen il) -1,3-t¡azol-2-¡l] -N - (3-phenylpropyl) cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) p¡r¡m¡d¡n-2¡l] am¡nojphenyl) -1,3- thiazol-2-yl] -N- (2-phenoxy-etl) cyclohexancarboxamide;

cis-4-hydroxy-N- [4- (hydroxymethyl) benzyl] -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡m¡din-2 -¡L] amino} feníl) -1,3-t¡azol-2-ll] cyclohexancarboxamida;

c¡sN- (3,4-díhidrox¡bencíl) -4-h¡drox¡-4- [5- (3-methyl-5 - {[4 (tr¡fluorometíl) p¡rim D-n-2-yl] amino} phenyl) -1,3-t-acezol-2-yl] cyclohexancarboxamide;

c¡sN- (4-chlorobenzyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡m¡d¡n-2 -L] aminoJphenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

162

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- [3- (2-oxopyrrolidin-1-yl) propyl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) -1,3-thiazol-2-yl] -N- [2 - (2-oxopiperidin-1 yl) etl] cyclohexancarboxamide;

cis-N- (4-carbamoylcyclohexyl) -4-hydroxy-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide;

4 - [({4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-210 yl] am ino} phenyl) -1,3-thiazol-2- acid il] cyclohexyl} carbonyl) amino] cyclohexanecarboxylic

4 - ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2i l] am inojphenyl) -1,3-thiazol-2-yl] cyclohexy l} ca rbon i I) p iperazi n-1 -methyl carboxylate;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-215 yl] am i no} fe ni I) -1,3-thiazol-2-yl] -N- (1,2,3,4-tetrahydronaphthalen-1 yl) cyclohexancarboxamide;

cis-4-hydroxy-N- (imidazo [1,2-a] pyridin-2-ylmethyl) -4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4-hydroxy-N- (2-hydroxy-2,3-dihydro-1H-inden-1-yl) -4- [5- (3-methyl-520 {[4- (trifluoromethyl) pyrimidin-2-yl ] amino} phenyl) -1,3-thiazol-2yl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- [(3-oxo-2,3-dihydro-1H-isoindol-4163 yl) methyl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- [ (3-oxo-2,3-dihydro-1 H-isoindole-5yl) methyl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N - [(1 -oxo-2,3-dihydro-1H-isoindole-4yl) methyl] cyclohexanecarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmididin-2yl] amino} phenyl) -1,3-thiazol-2-yl] - N - [(1 -oxo-2,3-d¡h¡dro-1H-isoindole-510 µl) methyl] cyclohexancarboxamide;

4-hydroxy-4- [5- (3-methyl-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole -2-yl] -N- [4- (trifluoromethyl) benzyl] cyclohexancarboxamide;

c¡s-4-h¡droxi-4- [5- (3-metíl-5¿ [4- (tr¡fluorometíl) p¡rim¡d¡n-2¡l] amino} phenyl) -1,3-thiazol-2-yl] -N - [(3-pyridin-2-yl¡soxazol-515 yl) methyl] cyclohexancarboxamide;

4 - [(4-benzylpiperidin-1-yl) carbonyl] -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexanol;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N - [(2 -oxo-1,2,3,4-tetrahydroquinolin-720 yl) methyl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (4- sulfamoylbenzyl) cyclohexancarboxamide;

cis-4-hydroxy-N- {4- [4- (hydroxymethyl) -1 H-pyrazol-1-yl] benzyl} -4- [5- (3164 methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2yl] cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N- (4- {[(4R) -2-oxo-1,3-oxazolidin-45 yl] methyl} benzyl) cyclohexancarboxamide;

cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] -N - {[6- (2,2,2-trifluoroethoxy) pyridin-3yl] methyl} cyclohexancarboxamide;

N- (cyanomethyl) -4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin10 2-l) am i nojfen ¡I} -1,3-thiazol-2 -il) cyclohexancarboxamide;

4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1,3-thiazol-2yl) -4-hroxy-2-methylcyclohexancarboxamide;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1-methylethoxy) pyrimidin-2yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexancarboxamide;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2 -il] cyclohexancarboxamide;

N- (cyanomethyl) -4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1methylethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] cyclohexancarboxamide;

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} 20 1,3-thiazol-2-yl) -N- ( pyridin-3-ylmethyl) cyclohexancarboxamide;

4-hydroxy-2-methyl-4- [5- (3-methyl-5 - {[4- (1 -methylethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -N - (pyridin-3-ylmethyl) cyclohexancarboxamide;

4-hydroxy-2-methyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl}

165

1,3-thiazol-2-yl) -N- [3- (2-oxopyrrolidin-1-yl) propyl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxyprimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) -2 , 2-dimethylcyclohexancarboxamide;

(1 S, 4R) -4- (5- {3 - [(4-cyclopropylpyrimidin-2-yl) amino] -5-methylphenyl} 5 1,3-thiazol-2-yl) -4-hydroxy-2, 2-dimethylcyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1-methyl-pyrim-din-2-yl) amino} phenyl) - 1,3-thiazol-2-yl] cyclohexanecarboxamide;

(1 S, 4R) -4-hydroxy-4- {5- [3 - ({4 - [(1 S) -1-hydroxyethyl] pyrimidin-2yl} amino) -5-methylphenyl] -1.3 -thiazol-2-yl} -2,2-dimethylcyclohexancarboxamide;

(1S, 4 R) -4-h id rox¡-4- {5- [3 - ({4 - [(1 R) -1 -h id roxieti l] pi rimid i n-2il} amino) -5 -methylphenyl] -1,3-thiazol-2-yl} -2,2-dimethylcyclohexancarboxamide;

(1S, 4R) -4- {5- [3 - ({4 - [(1S) -1-fluoroethyl] p¡rimidin-2-l} amino) -5methylphenyl] -1,3- thiazol-2-yl} -4-hydroxy-2,2-dimethylcyclohexancarboxamide;

(1 S, 4R) -4- {5- [3 - ({4 - [(1 R) -1 -fluoroethyl] pyrim¡din-2-yl} amino) -515 methylphenyl] -1,3-thiazole- 2-yl} -4-hydroxy-2,2-dimethylcyclohexancarboxamide;

N- (cyanomethyl) -4-hydroxy-2,2-dimethyl-4- (5- {3-methyl-5 - [(4methylpyrimidin-2-yl) amino] phenyl} -1,3-thiazol-2-yl ) cyclohexancarboxamide;

(1 S, 4R) -4- (5- {3 - [(4-tert-butylpyrimidin-2-yl) amino] -5-methylphenyl} -1.3 thiazol-2-yl) -4-hydroxy-2 , 2-dimethylcyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (1-methylethoxy) pyrimidin-2-yl] amino} phenyl) -1,3- thiazol-2-yl] cyclohexancarboxamide;

(1 S, 4R) -4-hydroxy-4- [5- (3 - {[4- (1-hydroxy-1 -methylethyl) pyrmidine-2yl] amino} -5-methylphenyl) -1,3- thiazol-2-yl] -2,2-dimethylcyclohexancarboxamide;

166

4-hydroxy-4- [5- (3 - {[4- (2-hydroxy-ethoxy) pyrimidin-2-yl] amino} -5methylphenyl) -1,3-thiazol-2-yl] -2,2- dimethylcyclohexancarboxamide;

(1S_&gt;4R) -4-Hydroxy-4- [5- (3 - {[4- (2-Hydroxyethoxy)) pyrmidine-2-yl] amino} 5-methylphenyl) -1,3-thiazole- 2-yl] -2,2-dimethylcyclohexancarboxamide;

(1R_l4S) -4-hydroxy-4- [5- (3 - {[4- (2-hydroxyethoxy) p¡rimidin-2-yl] amino} 5-methylphenyl) -1,3-t¡azol-2 -yl] -2,2-dimethylcyclohexancarboxamide;

(1R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1 , 3-thiazol-2-yl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[410 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

(1S, 4R) -N- (cyanomethyl) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2yl) amino] -5-methylfenyl} -1,3-thiazole- 2-yl) -2,2-d-methylcyclohexanecarboxamide;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxyprimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) -2, 2-dimethylN- (p¡r¡d¡n-3-ylmethyl) cyclohexancarboxamide;

(1 S, 4R) -4-hydroxy-2,2-dimethyl-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2i l) ami nojfen i I} -1 , 3-thiazol-2-yl) -N- [3- (2-oxoprolol id i n-1 yl) propyl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole -2-yl] -N-pyridin-320 ylcyclohexancarboxamide;

(1S, 4R) -4-hydroxy-4- (5- {3 - [(4-methoxypyrimidin-2-yl) amino] -5methylphenyl} -1,3-thiazol-2-yl) -2,2-dimet LN- [3- (2-oxopyrrolidin-1yl) propyl] cyclohexancarboxamide;

167 (1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) - 1,3-thiazol-2-yl] -N- [3- (2-oxopyrrolidin-1yl) propyl] cyclohexancarboxamide;

(1 S, 4R) -4-hydroxy-4- {5- [3- (hydroxymethyl) -5 - {[45 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl] -1,3-thiazol-2- yl} -2,2dimethylcyclohexancarboxamide;

4-hydroxy-4- {5- [3- (methoxymethyl) -5 - {[4- (trifluoromethyl) pyrimidin-2yl] aminoJphenyl] -1,3-thiazol-2-ylJ-2-methylcyclohexancarboxamide;

(1S, 4R) -4-hydroxy-4- {5- [3- (methoxymethyl) -5 - {[410 (trif I uoromethyl) pi rim id i η-2-yl] am ¡nojfen i I] -1,3-thiazol-2-i IJ-2,2dimethylcyclohexancarboxamide;

(1S, 4R) -4- [5- (3-chloro-5 - {[4- (trfluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -4-h Droxy-2,2-dimethylcyclohexancarboxamide;

cis-4- [4- (3-chloro-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 15 thiazol-2-yl] -4-hydroxycyclohexancarboxamide;

4- [5- (3 - [(acetylamino) methyl] -5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2, 2-methylcyclohexancarboxamide;

2 - ({cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} carbonyl) -1,2,3,4-tetrahydroisoquinolin20 6,7-diol;

4 - {[4- (3-methoxyphenyl) piperazin-1-yl] carbonyl} -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] aminoJphenyl) -1.3 -thiazol-2-yl] cyclohexanol;

cis-4- (1,4-dioxa-8-azaspiro [4.5] dec-8-ylcarbonyl) -1- [5- (3-methyl-5168 {[4- (trifluoromethyl) p¡rimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanol;

3- hydroxy-3- [4- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclobutanecarboxamide;

4- hydroxy-4- (5- {3-methyl-5 - [(4-methylpyrimidin-2-yl) amino] phenyl} -1.35 thiazol-2-yl) decahydronaphthalen-1-carboxamide;

trans-4-hydroxy-1-methyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxamide;

2- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-t¡azol-2-¡ l] piperidin-1-yl} pyridin-3-carboxamide;

4- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rimid¡n-215 ¡l] amino} feníl) -1,3-thiazol-2 -L] piperidin-1-yljbutanamide;

2- {4-hydroxy-4- [4- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acetamide ;

2- {cis-4-hydroxy-4- [4- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acetamide ;

2- {trans-4-hydroxy-4- [4- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} acetamide ;

3- {(4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} propanamide;

169

3 - {(4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} propanamide;

3- {4-hydroxy-4- [5- (3-methyl-5 - {[4- (1-methylethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-1 -il} -3-oxopropanamide;

3- [5- (3 - {[4- (2-hydroxyethoxy) pyrimidin-2-yl] amino} -5-methylenyl) -1,3-thiazol-2-yl] propanamide;

N- [1- (hydroxymethyl) propyl] -3- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propanamide;

N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡rim¡din-2-yl] amino} phenyl) -1,310 thiazoI-2-iI] propanoyl} glycinate of ethyl;

Methyl N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propanoyl} alaninate;

Methyl N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] propanoyl} -beta-alaninate;

Methyl N- {3- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3 thiazol-2-yl] propanoyl} leucinate;

4- {(1S) -1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl }benzamide;

4 - {(1 R) -1-hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl ] ethyl} benzamide;

(1S, 4R) -4- [5- (2-bromo-3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2¡l] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2,2-d-methylcyclohexancarboxamide;

(1R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4170 (trifluoromethyl) p¡rim¡d¡n-2-l] amino} phenyl ) -1,3-thiazol-2-yl] ethyl cyclohexanecarboxylate;

(1R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-t Methyl azole-2-yl] cyclohexancarboxylate;

4- hydroxy-4- [5- (3 - {[4- (3-methoxypropyl) pyrimidin-2-yl] amino} -5-methylphenyl) -1,3-thiazol-2-yl] cyclohexancarboxyllate butyl;

(1S, 4R) -4- {5- [3- (aminomethyl) -5 - {[4- (trifluoromethyl) p¡rim¡din-2yl] amino} phenyl] -1,3-thiazol-2 acid -yl} -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (1S, 4R) -4- [5- (3 - [(carbamoylamino) methyl] -5 - {[4 (trifluoromethyl) p¡rimidin-2 -yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (1 S, 4R) -4- [5- (3 - [(acetylamino) methyl] -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2,215 dimethylcyclohexanecarboxylic

5- (aminomethyl) -5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2l] amino} phenyl) -1,3-thiazol-2-yl] azepan-2- ona;

5- (2-hydroxyethoxy) -5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2- ona;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3t¡azol-2-l] cyclohexancarbonyl;

1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidine-2-yl] amino} phenyl) -1,3t¡azol-2-¡l] cyclohexancarboxamide ;

171

N- [3- (2-cyclohexyl-1,3-thiazol-5-yl) -5-methylfenyl] -4 (trifluoromethyl) pyrimidin-2-amine;

1- [4- (methylsulfonyl) phenyl] -1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin2-yl] amino} phenyl) -1,3-thiazol-2-yl] ethanol ;

N- {3- [2- (4-fluorotetrahydro-2H-thiopiran-4-yl) -1,3-thiazol-5-yl] -5-met ylphenyl} -4- (trifluoromethyl) pyrimidin-2- amine;

N- (3- [2- (3,6-Dihydro-2H-thiopyran-4-yl) -1,3-thiazol-5-yl] -5-methylphenyl} -4 (trifluoromethyl) pyrimidin-2-amine;

N - {3- [2- (4-fluoro-1,1-dioxydotetrahydro-2H-thiopiran-4-yl) -1,310 thiazol- 5-yl] -5-methiphenyl} -4- (trfluoromethyl ) pyrimin-2-amine;

N - (3- (2- (1,1-dioxide-3,6-dihydro-2H-t¡op¡ran-4-¡l) -1,3-t¡azol-5-¡l] -5 -methlfenl} -4- (trfluoromethyl) pyrmdn-2-amine;

A / - (3- [2- (4-fluorotetrah¡dro-2/7-thiopiran-4-yl) -1,3-thiazol-5-yl] -5metiphenyl} -4- (tr¡ fluorometry) p¡r¡m¡d¡n-2-amína;

N - (3- (2- (1,1-dioxidotetrahydro-2H-thiopiran-4-yl) -1,3-thiazol-5-yl] -5methylphenyl} -4- (trifluoromethyl) pyrimidin-2-am ¡Na;

(1 S, 4R) -4-methoxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 acid -thiazol-2-yl] cyclohexanecarboxylic

Cis-5,5-dimethyl-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-220 yl] amino} phenyl) -1,3-thiazol-2-yl] -2- oxabicyclo [2.2.2] octan-3-one;

Trans-1,4-dihydroxy-4- (5- (3-methyI-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid cis-1,4-dihydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin172

2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic

1- {Cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} pyrrolidin -2-one;

4,5-Dihydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2- acid yl] cyclohexancarboxylic 7- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] spiro [2.5] octane-4.7 -diol;

9- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3thiazol-2-yl] dispiro [2.1.2.3] decan-4, 9-diol;

3- [5- (3-methyl-5 - {[4- (trif luoromethyl) pyrimidin-2-yl] am inojphenyl) -1,3thiazol-2-yl] azepan-2-one;

(1 S) -4- {1,2-dihydroxy-1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3- thiazol-2-yl] ethyl} benzoic;

(1 R) -4- {1,2-dihydroxy-1 - [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimin-2-yl] amino} phenyl) acid - 1,3-thiazol-2-yl] ethyl} benzoic;

4 - {(Cis) -1,2-dihyd roxy-2- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazole acid - 2-yl] ethyl} benzoic;

4 - {(E) -2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) 1,3-thiazol-2-yl] ethenyl} benzoate methyl;

4- {2- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} benzoic acid;

5- {1 -hydroxy-1- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrmidine-2 yl] amino} phenyl) -1,3-thiazol-2-yl acid] ethyl} pyridin-2-carboxylic

173 6- {1 -hydroxy-1 - [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] ethyl} pyridine acid -3-carboxylic acid cis-4-fluoro-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl ] cyclohexancarboxylic acid trans-4-fluoro-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid (1S, 4R) -4-hydroxy-2,2-dimethyl-4- {5- [3-methyl-5- (4-methylpyrimidin-2-ylamino) -phenyl] -1,3-thiazol-2- acid il} -c¡clohexancarboxíl¡co

N- (3- {2 - [(E) -2-Methoxyethenyl] -1,3-thiazol-5-yl} -5-methylphenyl) -410 (trifluoromethyl) pyridine-2-amine;

N- (3- {2 - [(Z) -2-Methoxyetenil] -1,3-thiazol-5-yl} -5-methylphenyl) -4 (tr¡fluoromet¡l) p¡rim¡d¡n- 2-amine;

2,2-Dimethyl-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

{cis-1,4-d¡h¡drox¡-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) p¡r¡midin-2íl] amino} phenyl) -1, Diethyl 3-thiazol-2-yl] cyclohexyl} phosphonate;

{trans-1,4-dihydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} phosphonate diethyl;

(3E) -3- (hydroxyimino) -2,2-dimethyl-1 - [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 -thiazol-2-yl] cyclohexanol;

1- {5- [3 - ({4- [1- (2-hydroxy-2-methylpropyl) -1H-pyrazol-4-yl] pyrmidine-2yl} amino) -5-methylphenyl] -1, 3-thiazol-2-yl} cyclobutanol;

2- [5- (3 - {[4- (2-hydroxyethoxy) pyrimidin-2-yl] amino} -5-methylphenyl) -1.3174 thiazol-2-yl] propan-1,2,3- triol;

4-hydroxy-4- [5- (3 - {[4- (2-hydroxyethoxy) pyrimidin-2-yl] amino} -5 methylenyl) -1,3-thiazol-2-yl] -2, 2-dimethylcyclohexancarboxylic

4.5- dihydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2-one;

5.6- dihydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2-one;

4,5-dihydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2-one ;

5,6-dihydroxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2-one ;

5-amino-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan-2- ona;

5- {c¡s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-215 yl] amino} phenyl) -1,3-thiazol-2 -yl] cyclohexyl} -1,3,4-oxadiazol-2 (3H) -one;

3- {cis-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexyl} - 1,2,4-oxadiazol-5 (4H) -one;

(1S.4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4- (propan-2-yloxy) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide c / s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazole -2-yl] -A / - [3- (2-oxopyrrolidin-1 yl) propyl] cyclohexancarboxamide (1 S.4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl- 5 - {[4- (propan-2

175 yloxy) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide acid of (1S, 4R) -4- (5- {3-cyclopropyl-5 - [(4-methylpyrimidin- 2 yl) amino] phenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (1S, 4R) -4- (5- {3-cyclopropyl-5 - [(4 -methylpyrimidin-2 yl) amino] phenyl} -1,3-thiazol-2-yl) -4-hydroxy-2,2-dimethylcyclohexancarboxylic;

(1R, 4S) -4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl) -4 acid -hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1S, 4R) -4- (5- {3 - [(5-fluoro-4-methylpyrimidin-2-yl) amino] -5 methylphenyl} -1,3-thiazol-2-yl acid) -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1S.4R) -4- [5- (2-bromo-3-methyl-5 - {[4 (tr¡fluoromethyl) p¡rimid¡n-2-ll] amino} fen acid L) -1,3-thiazol-2-l] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid trans-4- (5- {3 - [(4-cyclopropylpyrim¡d¡n-2-yl) amino] -5 methylenyl} -1,3-thiazol-2-l) -4-hrodixrochlorohexancarboxylic acid;

cis-4- (5- {3 - [(4-cyclopropylpyrimid in-2-yl) am ino] -5-methylphenyl} acid

1,3-thiazol-2-yl) -4-hydroxycyclohexancarboxylic;

C / s-4 - [(hydroxyacetyl) amino] -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1, 3-thiazol-2-yl] cyclohexancarboxamide.

Preferred compounds include:

(1 R, 4S) -4- [5- (3-cyclopropyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2 yl] amino} phenyl) -1,3-thiazole acid -2-yl] -4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid;

(1 S, 4R) -4- [5- (3-cyclopropyl-5 - {[4- (tr¡fluoromethyl) pyrimidin-2 acid

176 yl] amino} phenyl) -1,3-thiazol-2-yl] -4-hydroxy-2,2-dimethylcyclohexancarboxylic;

(1S.4R) -4-hydroxy-2,2-dimethyl-4- {5- [3-methyl-5- (4-methylpyrimidin-2-ylamino) -phenyl] -1,3-thiazol-2- acid yl} -cyclohexancarboxylic;

(1S, 4R) -4- [5- (3 - {[4- (Difluoromethyl) pyrimidin-2-yl] amino} -55 methylphenyl) -1,3-thiazol-2-yl] -4-hydroxy acid -2,2-dimethylcyclohexanecarboxylic acid;

frans-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrimidin-2yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid;

c / s-4-hydroxy-4- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyrim¡din-2yl] amino} phenyl) -1,3-thiazol-2-yl acid ] cyclohexancarboxylic;

5-hid roxy-5- [5- (3-methyl-5 - {[4- (trifluoromethyl) pyridine in-2yl] amino} phenyl) -1,3-thiazol-2-yl] azepan- 2-one;

c / s-4 - [(hydroxyacetyl) amino] -1- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrmidine-2-l] amine} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide; and (1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[415 (trif I uoromethyl) pi rim id i n-2-yl] am i nojfen i I) -1,3-thiazol-2-yl] -A / - [3- (2-oxopy rrolid i n-1 yl) propyl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 acid -thiazol-2-yl] cyclohexancarboxylic;

(1 R, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[420 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1.3 acid -thiazol-2-yl] cyclohexanecarboxylic acid (1 S, 4S) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) pyrimidin-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexanecarboxylic acid (1 R, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[ 4177 (trifluoromethyl) pyrimidir »-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxylic;

(1R, 4S) -4-hydroxy-2,2-d-methyl-4- [5- (3-methyl-5 - {[4 (trifluoromethyl) p¡r¡m¡din-2-yl]] amine} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

(1S, 4R) -4-hydroxy-2,2-dimethyl-4- [5- (3-methyl-5 - {[45 (trifluoromethyl) pyrimide-2-yl] amino} phenyl) -1,3-thiazol-2-yl] cyclohexancarboxamide;

(1S, 4R) 4- {5- [3 - ({4 - [(1 R) -1-fluoroethyl] pyrimidin-2yl} amino) -5-methylphenyl] -1,3-thiazol-2-yl acid } -4-hydroxy-2,2-dimethylcyclohexanecarboxylic;

(1S, 4R) 4- {5- [3 - ({4 - [(1 S) -1 -fluoroethyljpyrimidin-2yl} amino) -5-methylphenyl] -1,3-thiazol-2-yl} acid -4-hydroxy-2,2-d-methylcyclohexanecarboxylic;

Or a pharmaceutically acceptable salt thereof.

In the application, the various terms are as defined below:

Alkyl refers to a straight or branched chain hydrocarbon radical having the specified number of carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, and the like.

Alkenyl refers to a straight or branched chain hydrocarbon radical having at least one carbon-carbon double bond, and having the specified number of carbon atoms. Examples of alkenyl include, but are not limited to, ethenyl, propenyl, n-butenyl, 3-methylbut-2-enyl, and n-pentenyl.

Alkynyl refers to a straight or branched chain hydrocarbon radical having at least one carbon-carbon triple bond, and having the

178 specified number of carbon atoms. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, 2-butynyl, and 3-methylbutinyl.

Carbocycle refers to a monocyclic ring saturated or partially unsaturated non-aromatic ring in which all of the ring atoms are carbons, and the ring is isolated or fused (including orthofused, spiro-fused, and bridged) to one or two of such rings or to a benzene ring. In the case of a polycyclic carbocycle, the point of attachment can be on any ring. Examples of carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, indane, bicyclo [3.3.0] octane, decalin, bicyclo [3.3.1] nonane, tetrahydronaphthalene, adamantane spiro [ 3.3] heptane, bicycle [3.1.0] hexane, tricycle [2.2.1.02.6] heptane, dispiro [2.1.2.3] decane.

Cycloalkyl refers to a saturated ring that contains the specified number of carbon atoms in the ring, and no heteroatom. In a similar way the term C3-8 cycloalkyl refers to a ring saturated ring having 3 to 8 ring carbon atoms. Exemplary cycloalkyl groups useful in the present invention include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

Halogen or halo refers to fluorine, chlorine, bromine, or iodine.

Haloalkyl refers to an alkyl group as defined above in which one and even all hydrogen atoms are replaced by a halogen; halogen is as defined herein

179 document. Examples of such straight-chain or branched-chain haloalkyl groups useful in the present invention include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, and n-butyl independently substituted by one or more halo, eg, fluorine, chlorine, bromine and iodine. Examples of haloalkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, and perfluoro-n-propyl.

Hydroxyalkyl refers to an alkyl group as defined above in which one hydrogen at each carbon atom can be replaced by a hydroxy group. Examples of hydroxyalkyl include, but are not limited to, hydroxymethyl, hydroxyethyl, propane-1,2-diol.

Heterocyclic or heterocyclyl refers to a saturated or partially unsaturated non-aromatic ring of the monocyclic in which one to three ring atoms are independently selected from N, S, and O, and the ring is isolated or fused (including ortho-fused, spiral- fused and bridged) to one or two other rings, where the latter is selected from heterocycle (as defined above), carbocycle, benzene, and heteroaryl. In the case of a polycyclic heterocycle, the point of attachment can be on any ring. A carbon-linked heterocycle is attached through a ring carbon atom. Examples of heterocycle include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, imidazolidine, oxazolidine, thiazolidine, dihydroazepine, tetrahydroazepine, azepan, diazepan, dihydro-diazepine,

180 Oxetane, Tetrahydrofuran, Dihydropyran, Pyran, Tetrahydroxyran, Tetrahyrothiofn, Tetrahyrothiopiran, Dihirothiopiran, Tetrahyroquinoline Tetrahyroisoquinoline 1,3-Dioxane 1,3-Dioxolane 8-Azabicyclo [3.2.1] Octane 9azabicyclo [3.3.1] [2.2.1] heptane 2-oxabicyclo [2.2.2] octane

1,4-dioxaspiro [4.5] decane 1-azaspiro [5.4] decane 1,4-dioxa-8azaspiro [4.5] decane 1-azatricyclo [3.3.1.13,7] decane tetrahiro-pyrazolo [1,5ajpiridine.

Heteroaryl refers to monocyclic aromatic groups and fused bicyclic aromatic rings containing 1, 2, 3, or 4 heteroatoms selected from N, O, and S. Examples of heteroaryl groups include, but are not limited to, furan, thiophene, pyrrolo, imidazole, pyrazole, triazole, tetrazole, thiazole, isothiazole, oxazole, isoxazole, oxadiazole, thiadiazole, pyridine, pyridazine, pyrazine, pyrimidine, quinoline, isokolinoline , benzofuran, benzoxazole, benzothiazole, naphthyridine, benzothiophene, benzimidazole, indole, thieno [2,3-b] pyridine, pyrazolo [1,515 ajpiridine, imidazo [1,2-ajpiridine, and ndazol.

The term composition, as in the pharmaceutical composition, is intended to encompass a product that comprises the active ingredients, and the inert ingredients (pharmaceutically acceptable excipients) that form the carrier, as well as any product that results, directly or indirectly, from the combination, complexation or the addition of any two or more of the ingredients, or the dissociation of one or more of the ingredients, or other types of reactions or interactions of one or more of the ingredients. Accordingly, the pharmaceutical compositions of the

181 The present invention includes any composition made from the mixture of a compound of formula I and pharmaceutically acceptable excipients.

As used herein, the term optionally means that the event or events described below may or may not occur, and includes both events that occur and events that do not occur.

As used herein, the term "substituted by one or more groups" refers to substitution by the named substituent or substituents, multiple degrees of substitution, until all hydrogen atoms are replaced with the same or different substituents, allowing at least the number of substituents that is explicitly indicated. When the number of substituents is not explicitly indicated, one or more is included.

Each variable is defined independently whenever it is present within the definitions of the generic structural formula. For example, when there is more than one R substituent on the Cy ring, each substituent is independently selected at each occurrence, and each substituent may be the same or different from the other. As another example, for the NR group^{a (a)}R^{a (a)}, each occurrence of the two groups R^{a (a)} it can be the same or different.

As used herein, where the annotation C_or or ”(CH₂) or modifies a substituent, indicates a link between the substituent and the rest of the molecule. Thus, the term alkyl of C₀-3-CO₂H means that the

182 carboxy group is either directly attached to the rest of the molecule, or there is an alkyl group of Cisque interfering between them.

The term Syk inhibitor is used to refer to a compound that inhibits the Syk enzyme.

The term Syk-mediated disease or a disorder, disease or condition mediated by inappropriate Syk activity is used to refer to any pathology mediated or modulated by Syk kinase mechanisms. Such pathologies can include inflammatory, allergic and autoimmune diseases, for example, asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARD), ulcerative colitis, Crohn's disease, bronchitis, dermatitis, allergic rhinitis, psorasis, scleroderma, urticaria, rheumatoid arthritis, multiple sclerosis, cancer, HIV and lupus, in particular asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARD), allergic rhinitis, and rheumatoid arthritis.

As used herein, a compound of the invention means a compound of formula (I) or a physiologically functional salt, solvate or derivative thereof.

As used herein, the term solvate refers to a variable stoichiometry complex consisting of a solute (in this invention, a compound of formula (I), or a salt thereof) and a solvent. Such solvents for the purpose of the invention may not interfere with the biological activity of the solute. Examples of suitable solvents

183 include, but are not limited to, water, acetone, methanol, ethanol, and acetic acid.

Preferably the solvent used is a pharmaceutically acceptable solvent. Examples of suitable pharmaceutically acceptable solvents include water, ethanol, and acetic acid. More preferably the solvent is water.

As used herein, the term "physiologically functional derivative" refers to a compound (eg, a drug precursor) that is transformed in vivo to produce a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate or solvate. of the compound. Transformation can occur by various mechanisms (for example, by metabolic or chemical processes), such as by hydrolysis in the blood. Prodrugs are such derivatives, and a discussion of the use of prodrugs is provided by T. Higuchi and W.

Stella, "Pro-drugs as Novel Delivery Systems," Vol. 14 of the ACS 15 Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward

B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.

Compounds of formula (I) may have the ability to crystallize in more than one way, a characteristic known as polymorphism, and such polymorphic forms (polymorphs) are understood to be within the scope of formula (I). In general, polymorphism can occur as a response to changes in temperature or pressure, or both, and can also be derived from variations in the crystallization process. Polymorphs can be distinguished by various characteristics

184 known in the art, such as x-ray diffraction patterns, solubility, and melting point.

The compounds of Formula (I) can contain chiral or asymmetric centers, and therefore exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of

Formula (I) as well as mixtures thereof, including racemic mixtures, form part of the present invention. Diastereomeric mixtures can be separated into their individual diastereomers by their physicochemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and / or fractional crystallization. The enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (eg, chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (eg, hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Also, some of the compounds of Formula (I) may be atropisomers (eg, substituted biaryls) and are considered as part of this invention.

It should also be appreciated that the compounds of Formula (I) can form tautomers. All tautomers and tautomer mixtures of the compounds of the present invention are understood to be included within the scope of the compounds of the present invention. Some of the compounds described in this document contain olefinic double bonds,

185 and unless otherwise specified, they refer to including both E and Z geometric isomers.

Although the modalities for each variable, in general, have been listed separately for each variable above, this invention also includes compounds in which several or each modality in formula (I) is selected from each of the modalities that have been listed above. Therefore, this invention aims to include all combinations of modalities for each variable.

The compounds of the present invention can be in the form of and / or can be administered as a pharmaceutically acceptable salt. For a review on convenient salts see Berge et al, J. Pharm. Sci. 1977, 66, 119. Typically, the salts of the present invention are pharmaceutically acceptable salts. Salts encompassed by the term "pharmaceutically acceptable salts" refer to non-toxic salts of the compounds of this invention. Suitable pharmaceutically acceptable salts can include acid or base addition salts.

A pharmaceutically acceptable acid addition salt can be formed by reaction of a compound of formula (I) with a suitable, inorganic or organic acid (such as hydrobromic, hydrochloric, sulfuric, nitric, phosphoric, succinic, maleic, formic, acetic, propionic , fumaric, citric, tartaric, lactic, benzoic, salicylic, glutamic, aspartic, Ptoluenesulfonic, benzenesulfonic, methanesulfonic, ethanesulfonic, naphthalenesulfonic as 2-naphthalenesulfonic, or hexanoic acid), optionally

186 in a suitable solvent such as an organic solvent, to give the salt which is generally isolated, for example, by crystallization and filtration. A pharmaceutically acceptable acid addition salt of a compound of formula (I) may comprise or be, for example, a hydrobromide, hydrochloride, sulfate, nitrate, phosphate, succinate, maleate, formate, acetate, propionate, fumarate, citrate, tartrate, lactate, benzoate, salicylate, glutamate, aspartate, ptoluenesulfonate, benzenesulfonate, methanesulfonate, ethanesulfonate, naphthalenesulfonate (eg 2-naphthalenesulfonate) or hexanoate.

A pharmaceutically acceptable base salt can be formed by reacting a compound of formula (I) with a suitable inorganic or organic base. Salts obtained from inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, zinc and the like salts. Particularly preferred are ammonium, calcium, magnesium, potassium and sodium salts. Salts obtained from pharmaceutically acceptable non-toxic organic bases include salts of primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as arginine, betaine, caffeine, choline, Ν, Ν'-dibenzylethylenediamine, diethylamine,

2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, Usin, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, triethylamine, trimethylamine,

187 tripropylamine, tromethamine and the like.

Other salts, which are not pharmaceutically acceptable, for example oxalates or trifluoroacetates, for example, can also be used in the isolation of compounds of the invention, and are included within the scope of this invention.

The invention includes within its scope all possible stoichiometric and non-stoichiometric forms of the compounds of formula (I).

In compounds of formula (I), the atoms may display their natural isotopic abundances, or one or more of the atoms may be artificially enriched for a particular isotope that has the same atomic number, but a different atomic mass or mass number of the atomic mass or mass number predominantly found in nature. The present invention is intended to include all convenient isotopic variations of the compounds of Generic Formula I. For example, the different isotopic forms of hydrogen (H) include protium (1H) and deuterium (¿H). Protium is the predominant naturally occurring hydrogen isotope. Enriching for deuterium can provide certain therapeutic advantages, such as increasing the half-life in vivo or reducing dose requirements, or it can provide a compound useful as a standard for characterizing biological samples. The isotopically enriched compounds within the generic Formula I can be prepared without undue experimentation by conventional techniques well known to

188 Those skilled in the art or by procedures analogous to those described in the Schemes and Examples herein using appropriate isotopically enriched reagents and / or intermediates.

The compounds of formula (I) and the physiologically functional salts, solvates and derivatives thereof are considered inhibitors of Syk activity, and thus are potentially useful in the treatment of diseases and conditions associated with inappropriate Syk activity.

The compound of formula (I) or its pharmaceutically acceptable salts and pharmaceutical compositions can be used to treat or prevent a variety of spleen tyrosine kinase (SYK) mediated conditions or diseases. Such conditions and diseases include, but are not limited to: (1) arthritis, including rheumatoid arthritis, juvenile arthritis, soriatic arthritis, and osteoarthritis; (2) asthma and other obstructive airway diseases, including chronic asthma, late asthma, hyperresponsiveness of the airways, bronchitis, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, dust asthma, adult respiratory distress syndrome , recurrent airway obstruction, and chronic lung obstruction disease including emphysema; (3) autoimmune diseases or disorders, including those designated as single-organ or single-cell type autoimmune disorders, for example Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis,

189 good shepherd's disease, autoimmune thrombocytopenia including thrombopenic ipathic purpura, sympathetic ophthalmia, myasthenia gravis, Graves' disease, primary liver cirrhosis, aggressive chronic hepatitis, ulcerative colitis, and timembrane glomerulopathy, those designated as involving systemic autoimmune disorder, eg systemic lupus erythematosus , immune thrombocytopenic purpura, rheumatoid arteritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis and bullous pemphigoid, and additional autoimmune diseases, which may be based on B (humoral) cells or T cells, including Cogan syndrome, ankylosing spondylitis, Wegener's granulomatosis, autoimmune alopecia, diabetes type activation I or juvenile, and thyroiditis; (4) cancers or tumors, including food / gastrointestinal cancer, colon cancer, liver cancer, skin cancer including mast cell tumor and squamous cell carcinoma, breast and breast cancer, ovarian cancer, prostate cancer, lymphoma and leukemia (including but not limited to acute myelogenous leukemia, chronic myelogenous leukemia, mantle cell lymphoma, B-cell NHL lymphomas (for example B-ALL precursor, marginal zone B-cell lymphoma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt lymphoma, mediastinal large B cell lymphoma), Hodgkin lymphoma, NK and T cell lymphomas; fusion drivers of TELSyk and ITK-Syk) myelomas including multiple myeloma, myeloproliferative disorders, kidney cancer, lung cancer, muscle cancer,

190 bone cancer, bladder cancer, brain cancer, melanoma including oral and metastatic melanoma, Kaposi's sarcoma, proliferative diabetic retinopathy, and associated angiogenic disorders including solid tumors, and pancreatic cancer; (5) diabetes, including Type I diabetes and complications of diabetes; (6) diseases, disorders or conditions of the eye including autoimmune diseases of the eye, keratoconjunctivitis, vernal conjunctivitis, uveitis including uveitis associated with Behcet's disease and lene-induced uveitis, keratitis, herpetic keratitis, cone keratitis, epithelial corneal dystrophy, keratoleucoma, pemphigus eye, Mooren's ulcer, scleritis, Grave's ophthalmopathy, VogtKoyanagi-Harada syndrome, keratoconjunctivitis sicca (dry eye), filceenulo, iridocyclitis, sarcoidosis, endocrine ophthalmopathy, sympathetic ophthalmitis, allergic conjunctivitis, and ocular neovascularization; (7) intestinal inflammations, allergies, or conditions including Crohn's disease and / or ulcerative colitis, inflamed bowel disease, cholelic diseases, proctitis, eosinophilic gastroenteritis, and mastocytosis; (8) neurodegenerative diseases including motor neuron disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, or neurodegenerative disease caused by traumatic injury, cerebrovascular accident, neurotoxicity, or hypoxia of glutamate; ischemic injury / reperfusion in cerebrovascular accident, myocardial ischemia, ischemic ischemia, heart attack, cardiac hypertrophy, atherosclerosis and arteriosclerosis, hypoxia of

191 organ; (9) platelet aggregation and diseases associated with or caused by platelet activation, such as arteriosclerosis, thrombosis, intimal hyperplasia, and restenosis that follows vascular damage; (10) conditions associated with cardiovascular disease, including restenosis, acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, coronary occlusive thrombus that occurs after thrombolytic therapy or after coronary angioplasty, a thrombotic-mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attack, venous thrombosis, deep vein thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombocytopenic thrombotic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation such as cardiac catheterization or other intravascular, coronary or aortic balloon pump heart valve, conditions that require adjustment of prosthetic devices, and the like; (11) skin diseases, conditions, and disorders including atopic dermatitis, eczema, psoriasis, scleroderma, pruritus, and other pruritic conditions; (12) allergic reactions including anaphylaxis, allergic rhinitis, allergic dermatitis, allergic urticaria, angioedema, allergic asthma, or allergic reaction to insect bites, food, drugs, or pollen; (13) transplant rejection, including pancreas islet transplant rejection, marrow transplant rejection

192 bone, graft-versus-host disease, organ transplant rejection, and cells such as bone marrow, cartilage, cornea, heart, intervertebral disc, islet, kidney, limb, liver, lung, muscle, myoblast, nerve, pancreas, skin, small intestine , or trachea and xenotransplantation; (14) low-grade scarring including scleroderma, increased fibrosis, keloids, post-surgical scars, pulmonary fibrosis, vascular spasms, migraine, reperfusion injury, and post-myocardial infarction.

Therefore, the invention provides compounds of formula (I) and physiologically functional salts, solvates, and derivatives thereof for use in therapy, and particularly in the treatment of diseases and conditions mediated by inappropriate Syk activity. The inappropriate Syk activity mentioned herein is any Syk activity that deviates from the normal Syk activity that is expected in a particular mammalian subject. Inappropriate Syk activity can take the form of, for example, an abnormal increase in activity or an aberration in timing and / or control of Syk activity. This inadequate activity may then be the result, for example, of the over-expression or mutation of the protein kinase leading to inadequate or uncontrolled activation.

In another embodiment, the present invention is directed to methods for regulation, modulation, or inhibition of Syk for the prevention and / or treatment of disorders related to unregulated Syk activity.

In another embodiment, the present invention provides a method

193 for treating a mammal suffering from a Syk activity mediated disorder, comprising administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof.

In another embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof or a physiologically functional derivative thereof, in the preparation of a medicament for the treatment of a disorder mediated by the Syk activity.

In a further embodiment, said Syk activity mediated disorder is asthma. In a further embodiment, said disorder is rheumatoid arthritis. In yet another embodiment, said disorder is cancer. In a further embodiment, said disorder is ocular conjunctivitis.

Yet another aspect of the present invention provides a method of treating diseases caused by or associated with Fe receptor signaling cascades, including FceRI and / or FcgRI mediated degranulation as a therapeutic approach towards the treatment or prevention of characterized diseases. by, caused by and / or associated with the release or synthesis of chemical mediators of such Fe receptor receptor signaling or degranulation cascades. Furthermore, it is known that Syk plays a critical role in immunotyrosine-based activation motif (ITAM) signaling, B cell receptor signaling, T cell receptor signaling, and is an essential component of cell signaling.

194 beta (1), beta (2), and beta (3) integrin in neutrophils. Thus, the compounds of the present invention can be used to regulate the signaling cascades of the Fe receptor, ITAM, B-cell receptor, and integrin, as well as the cellular responses produced by these signaling cascades. Examples of non-limiting or cellular responses that can be regulated or can be inhibited include respiratory arrest, cell adhesion, cell degranulation, cell spread, cell migration, phagocytosis, calcium ion flux, platelet aggregation, and cell maturation. .

While it is possible that, for use in therapy, a compound of formula (I), as well as salts, solvates, and functional physiological derivatives thereof, may be administered as the crude chemical, it is possible to present the active ingredient as a composition. pharmaceutical. Accordingly, the invention further provides a pharmaceutical composition, comprising a compound of formula (I) and salts, solvates and functional physiological derivatives thereof and one or more pharmaceutically acceptable carriers, diluents or excipients. The compounds of formula (I) and salts, solvates and functional physiological derivatives thereof, are as described above. The carrier or carriers, diluent or diluents or excipient or excipients must be acceptable in the sense that it is compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. In accordance with another aspect of the invention a

195 process for the preparation of a pharmaceutical composition, including the mixture of a compound of formula (I) or salts, solvates and functional physiological derivatives thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients.

The pharmaceutical compositions of the present invention can be presented in unit dosage forms containing a predetermined amount of an active ingredient per unit dose. Such a unit may contain, for example, 5pg to 1 g, preferably 1 mg to 700 mg, more preferably 5 mg to 100 mg of a compound of formula (I), depending on the condition to be treated, the route of administration and the age, weight, and condition of the patient. These unit doses can therefore be administered more than once a day. Preferred unit dosage compositions are those containing a daily dose or sub-dose (for administration more than once a day), as indicated herein above, or a suitable fraction thereof, of an active ingredient. . Furthermore, these pharmaceutical compositions can be prepared by any of the methods that are well known in the pharmaceutical art.

Pharmaceutical compositions of the present invention can be adapted for administration by any suitable route, for example by oral (including buccal or sublingual), by inhalation, or by nasal, ocular or parenteral route (including intravenous and intramuscular). These compositions can be prepared by any method known in the

196 pharmaceutical technique, for example by associating the active substance with the carrier (s) or excipient (s). Dosage forms include tablets, lozenges, dispersions, suspensions, solutions, capsules, creams, ointments, 5 sprays, and the like.

In another embodiment, the present invention provides a pharmaceutical composition adapted for oral administration, for the treatment, for example, of rheumatoid arthritis.

In another embodiment, the present invention provides a pharmaceutical composition adapted for administration via the nasal route, for the treatment, for example, of allergic rhinitis.

In another embodiment, the present invention provides a pharmaceutical composition adapted for administration by the inhalation route, for the treatment, for example, of asthma, COPD or ARDS.

In a further embodiment, the present invention provides a pharmaceutical composition adapted for administration by the ocular route, for treating eye diseases, for example conjunctivitis.

In a further embodiment, the present invention provides a pharmaceutical composition adapted for administration by the parenteral (including intravenous) route, for treating, for example, cancer.

The pharmaceutical compositions of the present invention that are adapted for oral administration can be presented as individual units such as capsules or tablets; powders or granules;

197 solutions or suspensions in aqueous or non-aqueous liquids; whipped creams or edible foams; or oil-in-water liquid emulsions or water-in-oil liquid emulsions.

For example for oral administration in the form of a tablet or capsule, the active component of the drug can be combined with an inert, pharmaceutically acceptable, non-toxic and oral carrier such as ethanol, glycerol, water and the like. Powders are prepared by grinding the compound to a suitable fine size and mixing it with a similarly ground pharmaceutical carrier, such as an edible carbohydrate, such as, for example, starch or mannitol. Flavoring, preservative, dispersing and coloring agents may also be present.

Capsules are produced by preparing a powder mix, as described above, and filling the formed gelatin shells. Emollients and lubricants such as colloidal silica, talc, magnesium stearate, calcium stearate, or solid polyethylene glycol can be added to the powder mixture prior to the filling operation. A disintegrating or solubilizing agent such as agar-agar, calcium carbonate, or sodium carbonate can also be added to improve the availability of the drug when the capsule is ingested.

Furthermore, when desired or necessary, suitable binders, lubricants, disintegrating agents and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose,

198 corn sweeteners, synthetic and natural gums such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose, polyethylene glycol, waxes and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like. Tablets are formulated, for example, by preparing a powder mixture, granulating or compressing, adding a lubricant and disintegrant and pressing on the tablets. A powder mixture is prepared by mixing the compound, suitably fractionated, with a diluent or base as described above, and optionally, with a binder such as carboxymethyl cellulose, an alginate, gelatin or polyvinylpyrrolidone, a retarding solution such as paraffin , a resorption accelerator such as a quaternary salt and / or an absorption agent such as bentonite, kaolin or dicalcium phosphate. The powder mix can be granulated by hydration with a binder such as a syrup, starch paste, acadia mucilage or solutions of cellulosic or polymeric materials and applying force through a sieve. As an alternative to granulation, the powder mix can be processed through the tablet machine and the result is imperfectly formed fragments broken into granules. The granules can be lubricated to prevent their adhesion to the tabletting molds by adding stearic acid, a stearate salt, talc or mineral oil. Mix

199 lubricated is then compressed into tablets. The compounds of the present invention can also be combined with a fluid inert carrier and compressed into tablets directly without undergoing the granulation or compression steps. A transparent or opaque protective coating consisting of a shellac seal coating, a sugar or polymeric material coating, and a polished wax coating can be provided. A coloring matter can be added to these coatings to distinguish different unit dosages.

Oral fluids such as solutions, syrups, and elixirs can be prepared in dosage unit form such that a given amount contains a predetermined amount of the compound. Syrups can be prepared by dissolving the compound in an aqueous solution with the proper flavor, while elixirs are prepared through the use of a non-toxic alcoholic vehicle. Suspensions can be formulated by dispersing the compound in a non-toxic vehicle. Solubilizers and emulsifiers such as ethoxylated isostearyl alcohols and polyoxyethylene sorbitol ethers, preservatives, flavor additives such as peppermint oil or natural sweeteners or saccharin or other artificial sweeteners and the like can also be added.

Where appropriate, dose unit compositions for oral administration can be microencapsulated. The formulation can also be prepared to prolong or sustain release, for example, by coating or embedding particulate matter in polymers, wax or

200 Similary.

The compounds of formula (I), and the salts, solvates, and physiological functional derivatives thereof, can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholine.

The compounds of formula (I) and the salts, solvates and physiological functional derivatives thereof can also be delivered by the use of monoclonal antibodies as individual carriers to which the composite molecules are associated. The compounds can also be associated with soluble polymers as addressable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylspartamidaphenol, or polyethylene oxidepolylysine substituted with palmitoyl residues. In addition, the compounds can be associated with a class of biodegradable polymers useful for achieving controlled release of a drug, for example, polylactic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates, and block copolymers o hydrogel amphiphatics.

Dosage forms for administration by inhalation can be conveniently formulated as aerosols or dry powders.

201

For compositions suitable and / or adapted for administration by inhalation, it is preferred that the compound or salt of formula (I) be in a reduced particle size form and more preferably the reduced size form is obtained or can be obtained by micronization .

The preferable particle size of the reduced size compound or salt or solvate (for example micronized) is defined by a D50 value of about 0.5 to about 10 microns (for example as measured using laser diffraction).

Aerosol formulations, for example for administration by inhalation, may comprise a solution or fine suspension of the active substance in a pharmaceutically acceptable aqueous or nonaqueous solvent. Aerosol formulations in single or multi-dose amounts can be presented sterilely in a sealed container, which can take the form of a cartridge or be refilled for use with an atomizing device or inhaler. Alternatively the sealed container may be a unitary dispensing device such as a single dose nasal inhaler or an aerosol dispenser equipped with a metering valve (metered dose inhaler) which is intended to be removed once the contents of the container are removed. have exhausted.

When the dosage form comprises an aerosol dispenser, it preferably contains a suitable propellant under pressure such as compressed air, carbon dioxide, or an organic propellant such as hydrofluorocarbon (HFC). Suitable HFC thrusters include

202

1,1,1,2,3,3,3-heptafluoropropane and 1,1,1,2-tetrafluoroethane. Aerosol dosage forms can also take the form of a pump atomizer. The pressure aerosol may contain a solution or a suspension of the active compound. This may require the incorporation of additional excipients for example co-solvents and / or surfactants to improve the dispersion and homogeneity characteristics of the suspension formulations. Solution formulations may also require the addition of co-solvents such as ethanol. Other excipient modifiers can also be incorporated to improve, for example, the stability and / or flavor and / or fine particle mass characteristics (amount and / or profile) of the formulation.

For pharmaceutical compositions suitable and / or adapted for administration by inhalation, it is preferred that the pharmaceutical composition is a composition for inhalation of dry powder. This composition may comprise a powder base such as lactose, glucose, trehalose, mannitol or starch, the compound of formula (I) or salt or solvate thereof (preferably in a reduced particle size form, for example in micronized form) and optionally a performance modifier such as L-leucine or other amino acid and / or metal salts of stearic acid such as magnesium or calcium stearate. Preferably, the dry powder inhalation composition comprises a mixture of lactose dry powder and the compound of formula (I) or salt thereof. Lactose is preferably lactose hydrate for example lactose monohydrate and / or is

203 preferably lactose for inhalation and / or fine quality. Preferably, the lactose particle size is defined because 90% or more (by weight or volume) of the lactose particles are less than 1000 microns in diameter (for example 10-1000 microns for example 30- 1000 microns) and / or 50% or more of the lactose particles are less than 500 microns (eg 10-500 microns) in diameter. More preferably, the lactose particle size is defined because 90% or more of the lactose particles are less than 300 microns (eg 10-300 microns eg 50-1000 microns) in diameter and / or 50% or more of the lactose particles less than 100 microns in diameter. Optionally, the lactose particle size is defined because 90% or more of the lactose particles are less than 100-200 microns in diameter and / or 50% or more of the lactose particles are less than 40-70 diameter micras. Most importantly, it is preferable that approximately 3 to approximately

30% (eg about 10%) (by weight or by volume) of the particles are less than 50 microns or less than 20 microns in diameter. For example, without limitation, a suitable lactose for inhalation is lactose E9334 (10% fines) (Borculo Domo Ingredients, Hanzeplein 25, 8017 JD Zwolle, The Netherlands).

Optionally, particularly for dry powder inhalation compositions, a pharmaceutical composition for administration by inhalation can be incorporated into a plurality of sealed dosing containers (eg, containing the

204 dry powder composition) mounted longitudinally on a strip or tape within a suitable inhalation device. The container can be broken or ripped open on demand and the dose of for example the dry powder composition can be administered by inhalation through the device such as the DISKUS® device (GlaxoSmithKIine). Other dry powder inhalers are well known to those skilled in the art, and many of these devices are commercially available, including representative Aerolizer® (Novartis), Airmax ™ (IVAX), ClickHaler® (Innovata Biomed), Diskhaler devices. ® (GlaxoSmithKIine), Accuhaler (GlaxoSmithKIine), Easyhaler® (Orion Pharma), Eclipse ™ (Aventis), FlowCaps® (Hovione), Handihaler® (Boehringer Ingelheim), Pulvinal® (Chiesi), Rotahaler® (GlaxoSmithKIine), SkyeHaler ™ or Certihaler ™ (SkyePharma), Twistaler (Schering-Plow), Turbuhaler® (AstraZeneca), Ultrahaler® (Aventis), and the like.

Dosage forms for ocular administration can be formulated as solutions or suspensions with excipients suitable for ophthalmic use.

Dosage forms for nasal administration can be conveniently formulated as aerosols, solutions, drops, gels, or dry powders.

Pharmaceutical compositions adapted for administration by inhalation include fine particulate sprays or powders, which can be generated by various types of aerosols

205 pressure metered dose, nebulizers or insufflators.

For pharmaceutical compositions suitable and adapted for intranasal administration, the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof can be formulated as a fluid formulation for delivery from a fluid dispenser.

These fluid dispensers may have, for example, a dispensing nozzle or a dispensing orifice through which a metered dose of the fluid formulation is delivered upon application of a force exerted by the user to a fluid dispenser pump mechanism. .

These fluid dispensers are generally provided with a reservoir of multiple metered doses of the fluid formulation, the doses being dispensable after sequential pump drives. The dispenser nozzle or orifice can be configured for insertion into the user's nostrils for spray delivery of the fluid formulation into the nasal cavity. A fluid dispenser of the aforementioned anes type is described and illustrated in WO-A-2005/044354, the entire contents of which is incorporated herein by reference. The dispenser has a housing that houses a fluid discharge device that has a container mounted compression pump to hold a liquid formulation. The housing has at least one finger operable side lever which is movable internally with respect to the housing to lift the container upwardly in the housing to cause the pump to compress and pump a measured dose of the formulation out of a

206 pump stem through a housing nozzle e. An especially preferred fluid dispenser is of the general type illustrated in FIGS. 30-40 of

WO-A-2005/044354.

The following are examples of representative dosage forms for the compounds of this invention:

Suspension for injection (IM) mq / ml

Compound of Formula la 10

Methylcellulose 5.0

Tween 80 0.5

Benzyl alcohol 9.0

Benzalkonium Chloride 1.0

Water for injection at a total volume of 1 ml

Mq tablet / tablet

Compound of Formula la 25

Microcrystalline cellulose 415

Providone 14.0

Pregelatinized starch 43.5

Magnesium stearate 2.5

500

Capsule mg / capsule

Compound of Formula la 25

Lactose powder 573.5

Magnesium stearate 1.5

600

Aerosol

Compound of Formula Lecithin, Liquid Concentrate of NF Trichlorofluoromethane, NF Dichlorodifluoromethane, NF

Per bottle mg 1.2 mg 4,025 gm 12.15 gm

207

It will be appreciated that when the compound of the present invention is administered in combination with other therapeutic agents normally administered by the inhalation, intravenous, oral, or intranasal routes, the resulting pharmaceutical composition can be administered by the same routes.

It should be understood that in addition to the ingredients particularly mentioned above, the compositions may include other agents conventional in the art regarding the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

A therapeutically effective amount of a compound of the present invention will depend on several factors including, for example, the age and weight of the animal, the precise condition requiring treatment and its severity, the nature of the formulation, and the route of administration, and ultimately will be at the discretion of the related physician or veterinarian however, an effective amount of a compound of formula (I) for the treatment of diseases or conditions associated with the inappropriate activity of Syk, will generally be in the range of 5pg to 100mg / kg of body weight of the container (mammal) per day and more generally in the range of 5pg to 10 mg / kg of body weight per day. This amount can be given in a single dose per day or more frequently in several (such as two, three, four, five or six) subdoses per day so that the total daily dose is the same. An effective amount of a salt can be determined or

208 solvate, thereof, as a proportion of the effective amount of the compound of Formula (I) per se.

The compounds of the present invention and their salts and solvates and physiologically functional derivatives thereof can be used alone or in combination with other therapeutic agents for the treatment of diseases and conditions associated with inappropriate Syk activity. Combination therapies according to the present invention thus comprise the administration of at least one compound of Formula (I) or a solvate or pharmaceutically acceptable salt thereof or a physiologically functional derivative thereof and the use of at least one pharmaceutically active agent. distinct asset. The compound (s) of Formula (I) and the other pharmaceutically active agent (s) can be administered together or separately and, when administered separately, can be produced simultaneously or sequentially in any order. The amounts of the compound (s) of Formula (I) and the other pharmaceutically active agent (s) and the relative timing of administration will be selected to achieve the desired combined therapeutic effect.

For the treatment of inflammatory diseases, rheumatoid arthritis, psoriasis, inflammatory bowel disease, COPD, asthma, and allergic rhinitis, a compound of Formula I may be combined with one or more other active agents such as: (1) TNF-α inhibitors such as infliximab (Remicade®), etanercept (Enbrel®), adalimumab (Humira®), certolizumab

209 pegol (Cimzia®), and golimumab (Simponi®); (2) non-selective COX-l / COX-2 inhibitors (such as piroxicam, diclofenac, propionic acids such as naproxen, flubiprofen, fenoprofen, ketoprofen, and ibuprofen, phenamate such as mefenamic acid, indomethacin, sulindac, etodolac, azapropazone, pyrazolones salicylates like aspirin); (3) COX-2 inhibitors (such as meloxicam, celecoxib, rofecoxib, valdecoxib, and etoricoxib); (4) other agents for the treatment of rheumatoid arthritis including methotrexate, leflunomide, sulfasalazine, azathioprine, cyclosporine, tacrolimus, penicillamine, bucillamine, actarit, mizoribine, lobenzarit, ciclesonide, hydroxychloroquine, u-penicillamine, aurotrothrine , cyclophosphamide, Lymphostat-B, BAFF / APRIL and CTLA-4-lg inhibitors or mimetics thereof; (5) leukotriene synthesis inhibitor, 5-lipoxygenase (5-LO) inhibitor, or 5-lipoxygenase activating protein (FLAP) antagonist such as zileuton; (6) LTD4 receptor antagonist such as zafirlukast, montelukast and pranlukast; (7) PDE4 inhibitor such as roflumilast, cilomilast, AWD-12-281 (Elbion), and PD-168787 (Pfizer); (8) antihistamine H1 receptor antagonists such as cetirizine, levocetirizine, loratadine, desloratadine, fexofenadine, astemizole, azelastine, levocabastine, olopatidine, metapyrilene, and chlorpheniramine; (9) a1- and a2-adrenoceptor agonist vasoconstrictive sympathomimetic agent, such as propylhexedrine, phenylephrine, phenylpropanolamine, pseudoephedrine, nafazoline hydrochloride, tetrahydrozoline hydrochloride, xylchlorohydrochloride; (10) anticholinergic agents

210 as ipratropium bromide, tiotropium bromide, oxypropium bromide, aclindinium bromide, glycopyrrolate, (R, R) -glycopyrrolate, pirenzepine, and telenzepine; (11) β-adrenoceptor agonists such as metaproterenol, isoproterenol, isoprenaline, albuterol, formoterol (particularly the fumarate salt), salmeterol (particularly the xinafoate salt), terbutaline, orciprenaline, bitolterol mesylate, phenoterol, and pirbuterol, or methylxantanines theophylline and aminophylline, sodium cromoglycate; (12) insulin-like type I growth factor (IGF-I) mimetic; (13) glucocorticosteroids, especially inhaled glucocorticoid with reduced systemic side effects, such as prednisone, prednisolone, flunisolide, triamcinolone acetonide, beclomethasone dipropionate, budesonide, fluticasone propionate, ciclesonide, and mometasone furoate; (14) kinase inhibitors as Janus kinase inhibitors (JAK 1 and / or JAK2 and / or JAK 3 and / or TYK2), p38 MAPK and IKK2; (15) B-cell targeting biologics such as rituximab (Rituxan®); (16) selective costimulation modulators such as abatacept (Orencia); (17) interleukin inhibitors, such as anakinra IL-1 inhibitor (Kineret) and tocilizumab IL-6 inhibitor (Actemra).

The present invention also provides so-called triple combination therapy, which comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof together with a beta2-adrenoreceptor agonist and an anti-inflammatory corticosteroid. This combination is preferably for the treatment and / or prophylaxis of asthma, COPD or allergic rhinitis. The beta2-adrenoreceptor agonist and / or the

211 anti-inflammatory corticosteroids can be as described before and / or as described in WO 03/030939 A1. Representative examples of such a triple combination are a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with the components of Advair® (salmeterol xinafoate and fluticasone propionate), Symbicort® (budesonide fumarate and formoterol), or Dulera® (mometasone furoate and formoterol). fumarate). salmeterol or a pharmaceutically acceptable salt thereof (eg salmeterol xinafoate) and fluticasone propionate.

For the treatment of cancer, a compound of Formula (I) can be combined with one or more than one anticancer agent. Examples of such agents can be found in Cancer Principles and Practice of Oncology by VT Devita and S. Hellman (editors), 6^th edition (February 15, 2001), Lippincott Williams &amp; Wilkins Publishers. A person of ordinary skill in the art could discern which combinations of agents would be useful based on the particular characteristics of the drugs and the cancer involved. Such anticancer agents include, but are not limited to, the following: (1) estrogen receptor modulator such as diethylstibestral, such as tamoxifen, such as raloxifene, such as idoxifene, such as

LY353381, as LY117081, as toremifene, as fluoxymester, and as

SH646; (2) other hormonal agents including aromatase inhibitors (eg aminoglutethimide, tetrazole anastrozole, letrozole and exemestane), luteinizing hormone releasing hormone (LHRH) analogs,

212 ketoconazole, goserelin acetate, leuprolide, megestrol acetate, and mifepristone; (3) androgen receptor modulator like finasterlde and other 5a-reductase inhibitors, like nilutamide, like flutamide, like bicalutamide, like liarozol, and like abiraterone acetate; (4) retinoid receptor modulator such as bexarotene, tretinoin, 13-cis-retinoic acid, acid

9-cis-retinoic, α-difluoromethylornitine, retinamide ILX23-7553, trans-N- (4'hydroxyphenyl), and retinamide Ν-4-carboxyphenyl; (5) antiproliferative agent such as antisense sense RNA and DNA oligonucleotides like G3139, like ODN698, like RVASKRAS, like GEM231, and INX3001, and antimetabolites like enocitabine, carmofur, tegafur, pentostatin, doxifluridine, trimetrexate, trimetrexate, trimetrexatin, trimetrexate, trimetrexate, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexatin, trimetrexate, trimetrexate, trimetrexate, trimetrexate, trimetretin cytarabine ophosphate, hydrated phosteabine sodium, raltitrexed, paltitrexid, emitefur, thiazofurin, decitabine, nolatrexed, pemetrexed, nelzarabine, N6- [4-deoxy-4- [N2- [2 (E), 4 (E) tetradecadienoyl] glycylamino] -L-gly-BL-manno-heptophanosyl] adenine aplidine, 2.15 deoxy 2'-methylidencytidine, 2'-fluoromethylene-2'-deoxycytidine, ecteinascidin, troxacitabine, aminopterin, 5-flurouracil, floxuridine, methotrexaoe, leucovarin, hydroxyurea, mercaptopurine cytarabine (6-MP), thioguanine, thioguanine, thioguanine, thioguanine, thioguanine, thioguanine, thioguanine). fludarabine, cladribine asparaginase (2-CDA), gemcitabine, alanosine, swainsonine, lometrexol, dexrazoxan, methioninase, and thiosemicarbazone 3-aminopyridin-2-carboxaldehyde; (6) inhibitor of prenyl protein transferase including farnesyl protein transferase (FPTase), geranylgeranyl protein of transferase I type (GGPTase-l) and geranylgeranyl protein of transferase type II (also called Rab GGPTase

213

GGPTase-ll); (7) HMG-CoA reductase inhibitor such as lovastatin, simvastatin, pravastatin, atorvastatin, fluvastatin, and rosuvastatin; (8) angiogenesis inhibitor such as Flt-1 tyrosine kinase receptor inhibitors (VEGFR1) and Flk-1 / KDR (VEGFR2) inhibitors, growth factors derived from epidermis, fibroblast derivatives, or platelets, inhibitors of MMP (matrix metalloprotease), integrin blockers, interferon-α, interleukin-12, erythropoietin), granulocyte-CSF (filgrastine), granulocyte, macrophage-CSF (sargramostim), pentosan polysulfate, cyclooxygenase inhibitors, sterloid anti-inflammatories, carboxyamidotriazole, combretastatin A-4, squalamine, Thalidomide, 6-0chloroacetylcarbonyl) -fumagilol, angiostatin, troponin-1, angiotensin II antagonists, heparin, carboxypeptidase U inhibitors, and VEG antibodies , to ukraine, to ranpyrnase, to IM862, to acetyldinanaline, to squalamine, 5-amino-1 - [[3,5-d-chloro-4- (415 chlorobenzoyl) phenil] methyl] -1 H-1, 2,3-triazol-4-carboxamide, CM101, combretastatin, to RPI4610, to NX31838, to sulfated mannopentaose phosphate, and to 3 - [(2,4-dimethylpyrrol-5-yl) methylene] -2-indolinone (SU5416); (9) PPAR-γ agonists, PPAR-δ agonists, thiazolidinediones (such as DRF2725, C-011, troglitazone, rosiglitazone, and pioglitazone), fenofibrate, gemfibrozil, clofibrate, GW2570, SB219994, JTT AR -50, -039 MCC-555, GW2331, GW409544, NN2344, KRP297, NP0110, DRF4158, NN622, GI262570, PNU182716, DRF552926, acid 2 - [(5,7-dipropyl-3-trifluoromethyl-1,2benzisoxazol-6-yl) - 2-methylpropionic (disclosed in USSN 09 / 782,856), and

214 (2R) -7- (3- (2-chloro-4- (4-fluorophenoxy) phenoxy) propoxy) -2-ethylchroman-2-carboxylic acid (disclosed in USSN 60 / 235,708 and 60 / 244,697); (9) Inherent multi-drug resistance inhibitor including P-glycoprotein (P-gp) inhibitors such as LY335979, XR9576, OC144-093, R101922, VX853 and PSC833 (valspodar); (10) inhibitor of cell proliferation and survival signaling such as EGFR inhibitors (eg gefitinib and erlotinib), ERB-2 inhibitors (eg trastuzumab), IGF1R inhibitors such as MK-0646 (dalotuzumab), inhibitors CD20 (rituximab), cell cycle receptor inhibitors, MET inhibitors, PI3K kinase family inhibitors (eg LY294002), serine / threonine kinase (including but not limited to Akt inhibitors as described in (WO 03/086404, WO 03/086403, WO 03/086394, WO 03/086279, WO 02/083675, WO 02/083139, WO 02 / 083140 and WO 02/083138), Raf kinase inhibitors (eg BAY-43-9006), MEK inhibitors (eg CI-1040 and PGDO-098059) and mTOR inhibitors (Wyet CCI-779 and Ariad AP23573); (11) a bisphosphonate such as etidronate, pamidronate, alendronate, risedronate, zoledronate, ibandronate, incadronate or cydronate, clodronate, EB-1053, minodronate, neridronate, pyridronate, and tiludronate; (12) inhibitors, (13) agents that intervene with tyrosine kinase receptors (RTKs) including C-kit, Eph, PDGF, Flt3, and CMET inhibitors; (14) agent that intervenes with a cell cycle checkpoint including inhibitors of ATR, ATM, Chk1 and kinaseChk2 and cdk, and inhibitors of cdc kinase and are specifically exemplified by 7215 hydroxystaurosporine, flavopyridol, CYC202 (Cyclacel ) and BMS-387032; (15) BTK inhibitors such as PCI32765, AVL-292, and AVL-101; (16) PARP inhibitors including iniparib, olaparib, AGO14699, ABT888 and MK4827; (16) ERK inhibitors; (17) mTOR inhibitors such as sirolimus, ridaforolimus, temsirolimus, everolimus; (18) cytotoxic / cytostatic agents.

"Cytotoxic / cytostatic agents" refer to compounds that cause cell death or inhibit cell proliferation by primarily directly intervening with the operation or inhibition of the cell or inhibiting or intervening with cell mitosis, including alkylating agents, tumor necrosis factors, intercalators, hypoxia activating compounds, microtubule inhibitors / microtubule stabilizing agents, mitotic kinesin inhibitors, histone deacetylase inhibitors, kinase inhibitors involved in mitotic progression, antimetabolites; biological response modifiers; hormonal / anti-hormonal therapeutic agents, hematopoietic growth factors, antibodies therapeutic agents targeting monoclonal antibodies, topoisomerase inhibitors, proteasome inhibitors, and ubiquitin ligase inhibitors.

Examples of cytotoxic agents include, but are not limited to, sertenef, cachectin, chlorambucil, cyclophosphamide, ifosfamide, mechloretamine, melphalan, uracil mustard, thiotepa, busulfan, carmustine, lomustine, streptozocin, tasonermin, lonidamine, carbonazol, procarbazine, prednimustine, dibromodulcitol, ranimustine,

216 Photemustine, Nedaplatin, Oxaliplatin, Temozolomide, Heptaplatin, Estramustine, Improsulfan Tosylate, Trophosphamide, Nimustine, Dibrospidium Chloride, Pumitepa, Lobaplatin, Satraplatin-Profiromycin, Cisplatin, Dexifosfine, Dexifosfine glufosfamide, GPX100, (trans, trans, trans d¡ar¡z¡d¡n¡lsperm¡na) -b¡s-mu- (hexan-1,6-diam¡na) -mu- [d¡am¡ naplatno (ll)] b¡s [d¡am¡na (chlorine) platio (ll) tetrachloride, arsenic trioxide, 1- (11-dodecylamino-10-hydroxyundecyl) -3,7-methylxantine, doxorubicin, daunorubicin, idarubicin, anthracenedione, bleomycin, mitomycin C, dactinomycin, plicatomycin, bisantrene, mitoxantrone, pyrarubin, mitoxantrone, pyrarubin , antineoplaston, 3'-deamino-3'-morpholin-13-deoxo-10-hydroxycarminomycin, galarubicin, elinafido, MEN10755, and 4-demethoxy-3-deamino-3-aziridinyl-4-methylsulfonyldaunorubicin.

An example of a compound susceptible to hypoxia activation is tirapazamine.

Examples of proteasome inhibitors include but are not limited to lactacystin and bortezomib.

Examples of microtubule inhibitors / microtubule stabilizing agents include vincristine, vinblastine, vindesine, vinzolidine, vinorelbine, vindesine sulfate, 3 ', 4'-didehydro-4'-deoxy8'-norvincaleukoblastine, (eg, etoposide (VP-16) and paclitaxel, tenipóido (VM-26)), docetaxol, rizoxina dolastatina isetionatode mivobulina

217 auristatin cemadotine RPR109881, BMS184476, vinflunine critofcina anhdrovinblastina N ^ -dimetil-L-valil-L-valil-N-methyl-L-valil-L-prolil-L-prolinatbutilamida, TDX258, epothilones (see for example US Pat. Nos. 6,284,781 and 6,288,237) and BMS188797.

Some examples of topoisomerase inhibitors are topotecan, hicaptamine, irinotecan, rubitecan, lurtotecan, 6-ethoxypropionyl-3 ', 4'O-exo-benzylidene-chartreusin, 7- [2- (N-isopropylamino) ethyl] - (20S) camptothecin, BNP1350, BNPI1100, BN80915, BN80942, etoposide phosphate, teniposide, sobuzoxane, 2'-dimethylamino-2'-deoxy-etoposide, GL331, asulacrine, N- [210 (dimethylamino) ethyl] -9 -hydroxy-5,6-dimethyl-6H-pyrido [4,3-b] carbazol-1carboxamide, 2,3- (methylenedioxy) -5-methyl-7-hydroxy-8-methoxy-benzo [c] phenanthridinium, 5- (3-aminopropylamino) -7,10-dihydroxy-2- (2-hydroxyethylaminomethyl) -6H-pyrazolo [4,5,1 -de] acridin-6-one, N- [1 - [2 (diethylamine) ethylamino] -7-methoxy-9-oxo-9H-thioxanthan-4-ylmethyl] formamide, N- (215 (dimethylamino) ethyl) acridine-4-carboxamide, 6 - [[2- (dimethylamino) ethyl] amino] -3hydroxy-7H-yndene [2,1-c] quinoline-n 7-one, and dimesna.

Examples of mitotic kinesin inhibitors include, but are not limited to KSP inhibitors, MKLP1 inhibitors, CENP-E inhibitors, MCAK inhibitors, Kif 14 inhibitors, Mphosphl inhibitors, and Rab6-inhibitors. KIFL.

Examples of histone deacetylase inhibitors include, but are not limited to, vorinostat, trichostatin A, oxamflatin, PXD101, MG98, valproic acid, and scriptaid.

218

Kinase inhibitors implicated in the progression of mitotic include, but are not limited to, aurora kinase inhibitors, Polo-Gusto kinase inhibitors (PLK; in particular inhibitors of PLK-1 inhibitors), bub-1 and bub-R1 inhibitors. An example of an aurora kinase inhibitor is VX-680.

Antiproliferative agents include antisense RNA and DNA oligonucleotides such as G3139, such as ODN698, such as RVASKRAS, such as GEM231, and such as INX3001, and antimetabolites such as enocitabine, carmofur, tegafur, pentostatin, doxifluridinae, trimetrexatin, fluimerazine, trimetrexatin, fluimerazine, trimetrexatin, fluimerazine cytarabine, hydrated phosteabine sodium, raltitrexed, paltitrexid, emitefur, tiazofurin, decitabine, nolatrexed, pemetrexed, nelzarabine, aplidine, N6- [4-deoxy-4- [N2- [2,4tetradecadienoyl] glycylamino] -L-glycero-BL-manno-heptopyranosyl] adenine, 2'deoxy-2'-methylidenecytidine, 2'-fluoromethylene-2 ​​' -deoxycytidine, ecteinascidin, troxacitabine, aminopterin, 5-flurouracil, floxuridine, methotrexate, leucovarin, hydroxyurea, cytarabine, mercaptopurine (6-MP), thioguanine (6TG), pentostatin, fludarabine, asparagine, asparagine, fluororabine, asparagine, 2-fluororabine, asparagines). gemcitabine, alanosine, swainsonin, lometrexol, dexrazoxane, methioninase, and thiosemicarbazone 3-aminopyridine-2-carboxaldehyde.

Non-limiting examples of convenient agents used in cancer therapy that can be combined with compounds of formula I include, but are not limited to, abarelix; aldesleukin; alemtuzumab; alitretinoin; allopurinol; altretamine; amifostine; anastrozole; trioxide

219 arsenic; asparaginase; azacitidine; bendamustine; bevacuzimab; bexarotene;

bleomycin bortezomib; busulfan; calusterono; Capecitabine; carboplatin;

carmustine; cetuximab; chlorambucil; cisplatin; cladribine; clofarabine;

cyclophosphamide; cytarabine; dacarbazine; dactinomycin, actinomycin D;

Dalteparin; darbepoetin esparto; dasatinib; daunorubicin; degarelix; Denileucine Diphitox; dexrazoxane; docetaxel; doxorubicin; dromostanolone propionate; eculizumab; Elliott B solution; eltrombopag; epirubicin; epoetin alfa; erlotinib; estramustine; etoposide phosphate; etoposide; everolimus; exemestane; filgrastim; floxuridine; fludarabine; fluorouracil;

fulvestrant; gefitinib; gemcitabine; ozogamicin, gemtuzumab; goserelin acetate; histrelin acetate; hydroxyurea; tiuxetan, ibritumomab;

idarubicin; ifosfamide; imatinib mesylate; interferon alfa 2a; interferon alfa2b; irinotecan, ixabepilone; lapatinib; lenalidomide; letrozole; leucovorin; leuprolide acetate; levamisole; lomustine; mechlorethamine, nitrogen mustard; megestrol acetate; melfalan, L-PAM; mercaptopurine; mesna; methotrexate; methoxsalen; mitomycin C; mitotane; mitoxantrone; Nandrolone Phenpropionate; nelarabine; nilotinib; Nofetumomab;

ofatumumab; oprelvecinan; oxaliplatin; paclitaxel; palifermin; pamidronat; panitumumab; pazopanib; glue stick pegaspargasa; Pegfilgrastim;

pemetrexed disodium; pentostatin; pipobroman; plerixafor; plicamycin, mithramycin); porfimer sodium; pralatrexate; procarbazine; quinacrine; Rasburicase; raloxifene hydrochloride; Rituximab; romidepsin; romiplostim; sargramostim; sargramostim; satraplatin; sorafenib; streptozocin; maleate

220 from sunitinib; tamoxifen; temozolomide; temsirolimus; teniposide; testolactone; thioguanine; thiotepa; topotecan; toremifene; tositumomab; trastuzumab;

tretinoin; uracil mustard; valrubicin; vinblastine; vincristine; vinorelbine;

vorinostat; and zoledronate.

It will be clear to a person skilled in the art that, when appropriate, the other or other therapeutic ingredients can be used in the form of salts, for example as an alkali metal or amine salts or as acid addition salts or prodrugs or as esters, for example lower alkyl esters or as solvates, for example hydrates, to optimize the activity and / or stability and / or physical characteristics, such as solubility, of the therapeutic ingredient. It will also be clear that, where appropriate, the therapeutic ingredients can be used in pure optical form.

The aforementioned combinations may conveniently be presented for use in the form of a pharmaceutical composition and therefore pharmaceutical compositions comprising a combination as defined above together with a pharmaceutically acceptable diluent or carrier represent a further aspect of the invention. These combinations are of particular interest in respiratory diseases and are suitably adapted for inhalation or intranasal delivery.

The individual compounds of such combinations can be administered sequentially or simultaneously in separate or combined pharmaceutical compositions. Preferably the compounds

221 Individuals will be administered simultaneously in a combined pharmaceutical composition. Appropriate doses of known therapeutic agents will be readily appreciated by those skilled in the art.

The compounds of this invention can be made by a variety of methods, including standard chemistry. Any previously defined variable will continue to have the previously defined meaning unless otherwise indicated. Synthetic, general and illustrative methods are outlined below and then specific compounds of the invention are prepared in the Examples.

The compounds of general formula (I) can be prepared by methods known in the art of organic synthesis as set forth in part by the following synthesis schemes. In all the schemes described below, it is well understood that protection groups for sensitive or reactive groups are used when necessary in accordance with general principles of chemistry. Protection groups are handled according to conventional organic synthesis methods (TW Green and PGM Wuts (1991) Protecting Groups in Organic Synthesis, John Wiley &amp; Sons). These groups are removed at a convenient stage of compound synthesis using methods that are readily apparent to those skilled in the art. The selection of protection groups as well as the reaction conditions and order of the reaction steps should be consistent with the preparation of compounds of Formula (I). Those of skill in the art will recognize whether there is a stereocenter in compounds of Formula

222 (I). Accordingly, the present invention includes all possible stereoisomers and includes not only mixtures of stereoisomers (such as racemic compounds) but also the individual stereoisomers. When a compound is desired as a single enantiomer, it can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Resolution of the final product, an intermediate, or a starting material can be accomplished by any suitable method known in the art. See, eg, Stereochemistry of Organic Compounds by EL Eliel, SH Wilen, and LN Mander (Wiley-lnterscience, 1994).

The following abbreviations are used in the schemes and examples: Ac = Acetyl; AcOH = Acetic Acid; Bn = benzyl; Boc (t-Boc) = tbutyloxycarbonyl; BOP = (Benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate; DAST = sulfuric (Dietolamino) trifluoride;

dba = dibenzylidene ketone; DCE = 1,2-dichloroethane; DCM = Dichloromethane;

Dibal / Dibal-H = Diisobutylaluminum hydride;

DIPEA / DIEA = Diisopropylethylamine; DMAP = N, N-dimethylaminopyridine; DME = 1,2dimethoxyethane; DMF = Dimethyl formamide; DMSO = Dimethylsulfoxide; Dppf = 1,1'Bis (diphenylphosphino) ferrocene; EDC = N- (3-Dimethylaminopropyl) -N'-ethylcarbodiimide; EtOAc = ethyl acetate; HATU = N, N, N ', N'-Tetramethyl-O- (7-azabenzotriazol-120 µl) uron or hexafluorophosphate; HMDS = Hexamethyldisilazane; HOBT = 1Hydroxybenzotriazole; IPA = isopropyl alcohol; LDA = lithium diisopropylamide; mCPBa = Meta-chloroperoxybenzoic acid; Ms = Methanesulfonyl (mesyl); MTBE = Methyl t-butyl ether; NBS = N-bromosuccinimide; Ph = phenyl; TBAF = fluoride

223 of t-butylammonium; TBDMS / TBS = t-butyl dimethylsilyl;

TFA = Trifluoroacetic / trifluroacetate; THF = Tetrahydrofurani;

TLC = thin layer chromatography; TMS = Trimethylsilyl; Ts = Toluensulfonyl (tolyl); TSA = p-toluenesulfonic acid. Abbreviations for alkyl / cycloalkyl groups:

Me = methyl, Et = ethyl, nPr = N-propyl, ¡Pr = isopropyl, nBu = N-butyl, T-Bu = tert-butyl, cPr = cyclopropyl, cBu = cyclobutyl, cPen = cyclopentyl, cHex = cyclohexyl, cHept = cycloheptyl.

In the following Schemes, A and B are the appropriate groups as defined for R5 in Formula (I), and may be for example, optionally substituted alkyl, or A, B and the carbon to which they are attached form a carbocyclyl group or optionally substituted heterocyclyl.

224

SCHEME 1

<img file="MX2012007154A_D0008.tif" />

Suzuki coupling

ID

<img file="MX2012007154A_D0009.tif" />

The compounds of formula (I) can be prepared by Suzuki coupling of boronic esters (1) with thiazole bromides (2). Boronic esters (1) can be obtained by reacting 2-chloropyrimidines (3) and 3-bromoanilines (82) to form the corresponding A / - (3-bromophenyl) -pinm¡d¡ne-2-amines (83) followed by coupling

225

Miyaura with bis (pinacolato) diboro. The compounds of formula (I) can also be obtained by reacting 2-chloropyrimidines (3) and thiazole-substituted anilines (4) in the presence of a Pd catalyst or alternatively a SwAr reaction. The thiazol-substituted anilines (4). In turn, they can be formed under Suzuki coupling conditions using a bromothiazole and nitrophenyl boronic ester, followed by reduction of the nitro group to give an amino group using known conventional conditions to reduce nitroaromatic compounds in anilines, such as Pd catalyzed hydrogenation. The compounds of formula (I) can also be formed by the Heck reaction between bromo-substituted anilines (83) with substituted thiazoles (84). Bromine-substituted anilines (83) can be prepared by reacting 8νΑγ between 2-chloropyrimidines (3) and bromine-substituted anilines (82).

226

SCHEME 2

<img file="MX2012007154A_D0010.tif" />

(5)

1) Base, A-CO₂Et

2) NaBH₄

Base,

CK _ZN ^ B

T

<img file="MX2012007154A_D0011.tif" />

<img file="MX2012007154A_D0012.tif" />

TO

<img file="MX2012007154A_D0013.tif" />

TO

Oxidizer _RIts)

ΛΛΛ.

P)

Oh

<img file="MX2012007154A_D0014.tif" />

The compounds of formula (I) can also be prepared from compounds (5). Thiazole (5) is treated with a strong base such as LDA, and then with ketones or aldehydes to provide alcohols (6); with esters followed by NaBH₄ to give secondary alcohols (7); with sulfimines to provide sulfinamides (9), which can be dissociated under acidic conditions to give amines (10). The alcohols (7) can be further oxidized, for example with Dess-Martin periodinanu, to give the corresponding ketones (8).

227

SCHEME 3

X

<img file="MX2012007154A_D0015.tif" />

X is H or optionally substituted alkyl as provided in Formula (I).

Treatment of tlazoles (5) with a strong base such as LDA followed by carbon dioxide provides acids (26), which can be converted to amides using conventional coupling methodologies. Treatment of tlazoles (5) with a strong base such as LDA followed by dimethylformamide provides formylated compounds (27), which can be converted to bromides (29) through the primary alcohol (28). Bromides (28) can react with various nucleophilic species to

228 providing compounds of type (30). Treatment of tlazoles (5) with a strong base such as LDA followed by bromine provides bromides (31). The aldehydes (27) can be converted to the corresponding olefins (85) by Wittig reaction. The olefins (85) can then be hydrogenated with

H₂ and Pd / C to provide compounds saturated (86) or dihydroxylated by the action of OsO₄ and NMO to provide diols (87).

SCHEME 4

<img file="MX2012007154A_D0016.tif" />

229

Various functionalized thiazole compounds in the above Schemes can be further elaborated. Alcohols (6) can be fluorinated using a fluorinating agent such as DAST or deoxofluor to provide compounds (11a), or treated with triethylsilane / TFA to provide deoxygenated compounds (11). Ketones (8) can be converted to trifluoromethyl alcohols (12) by treatment with TMSCF₃ and TBAF. The reductive amination of ketones (8) provides the amines (13).

SCHEME 5

B

N

<img file="MX2012007154A_D0017.tif" />

NHSO2NH2 (14)

HNSOqNH

2ΙΝΠ 2 _R5(¡)

N

<img file="MX2012007154A_D0018.tif" />

B

<img file="MX2012007154A_D0019.tif" />

NHC (O) NH₂

KNCO.AcOH (15)

KNCO.AcOH

<img file="MX2012007154A_D0020.tif" />

N _ / ^ NHC (O) NHC (O) NH₂ y of) ^ 0 (0) 0 or CO2H

TO.

B

<img file="MX2012007154A_D0021.tif" />

N- ^ 'NHC (O) R^to

(17)

230

The amines (10) can be treated (a) with sulfamide to provide compounds (14); (b) with potassium cyanate in the presence of acetic acid to provide ureas (15), as well as compounds (16); (C) with acylating agents such as acid chlorides and carboxylic acids with a coupling agent to provide amides (17).

SCHEME 6

<img file="MX2012007154A_D0022.tif" />

<img file="MX2012007154A_D0023.tif" />

(19)

231

Ketals (18), prepared from compounds (5) and 1,4-dioxaspiro [4.5] decane-8-one, can be treated with HCI to provide ketones (19), which can then be reduced with sodium borohydride or treated with methyl Grignard to provide the diols (20) or (22), respectively. Alternatively, ketals (18) or ketones (19) are treated with sodium azide and methanesulfonic acid to provide the rearranged lactam (21). Ketones (19) can be reacted with tetramethyl guanidine and triethylphosphite to give phosphonate esters (88). Acetone (19) can also be reacted with hydroxylamine to form oximes (89). Alternatively, ketones (19) can be reacted with 1-chloro2- [iodine (dimethyl) -4-sulfanyl] ethane to give spirocycles (91) and (92) after reduction of sodium borohydride. The alkylation of the compounds (21) followed by deprotection of the intermediate silyl ether produces the alcohols (90).

232

SCHEME 7

<img file="MX2012007154A_D0024.tif" />

<img file="MX2012007154A_D0025.tif" />

Negishi's coupling of bromides (31) with alkylzinc halides provides the esters (32), which can be hydrolyzed to provide the acids (33). Acids (33) can react with amines or acylhydrazines to provide amides (34) or hydrazides (35),

233 respectively. Compounds (35) can be heated with Burgess reagent to produce 1,3,4-oxadiazoles (36). The addition of Grignard reagents to the esters (32) provides access to the tertiary alcohols (37).

SCHEME 8

<img file="MX2012007154A_D0026.tif" />

Compounds (4) can be prepared from 2-amino-1 (3-nitrophenyl) ethanone (23). Coupling of amide with an acid provides compounds (24), which are treated with Lawesson's reagent, resulting in the formation of nitrophenyls (25). Palladium-mediated reduction of nitroarenes (25) with hydrogen produces anilines (4).

234

SCHEME 9 a; b '' S (38) —ge 1, i-PrMgCI 2. A'C (O) B '

VS (39)

<img file="MX2012007154A_D0027.tif" />

Oh

<img file="MX2012007154A_D0028.tif" />

HS CO₂I

Znl₂, D

<img file="MX2012007154A_D0029.tif" />

Br (48)

235

Various functionalized bromothiazoles can be prepared as shown in Scheme 8, starting from 2-bromothiazole (38). Grignard thiazole formation and addition to various ketones provides the alcohols (39). The joking of (39) with Br₂ gives bromothiazoles (40), which are reacted with methyl 3-mercaptopropionate under acidic Lewis conditions to provide (41). Radical bromination of 5-bromo-2-methylthiazole (42) gives (43), followed by reaction with methyl 3-mercaptopropionat provides compound (44). The oxidation of (41) and (44) to their respective sulfones (45) is followed by conversion to either the primary sulfonamide (47) (with hydroxylamine-O-sulfonic acid) or sulfone (46) (with alkyl halides via sulphinate following the method as described in Baskin, JM, Wang, Z. Tetrahedro Lett, 2002, 43, 8479. Further elaboration of (47) with acetic anhydride gives access to acyl sulfonamides (48).

SCHEME 10

<img file="MX2012007154A_D0030.tif" />

MVu \, (49) (93)

236

Ring "A" is an optionally substituted carbocycle or heterocycle as defined in formula (I)

Dehydration of compounds (49) with Eaton's reagent provides cycloalkenes (50), which provides saturated compounds (51) or diols (93) following hydrogenation or dihydroxylation, respectively.

<img file="MX2012007154A_D0031.tif" />

<td></td><td colspan="2">R^toNCO</td><td></td><td></td><td colspan="2">R^toC (O) CI</td>

<td> 20</td><td></td><td>_RS (¡)</td><td>R⁵</td><td>R¹</td><td>_RS (¡),</td><td>R⁵</td>

<td></td><td rowspan="2">K r, A Λ tr</td><td></td><td></td><td colspan="2">2 an i^R\ Λ J</td><td>Cl</td>

<td></td><td>N ' H</td><td>^^^ \ IHC (O) NH₂</td><td>N</td><td>N H</td><td>NHC (O) R</td>

(57) (56)

237

Suzuki coupling of a thiazole bromide (2) with (3-amino-5-nitrophenyl) boronic acid (52) provides biaryl compounds (53). Palladium catalyzed coupling of compounds (53) with chloropyrimidines provides nitroarenes (54), which are reduced to provide anilines (55). Acylation with acyl chlorides provides amides (57), and isocyanate reactions provide ureas (56).

SCHEME 12

R⁵_R, 1.

Br

2 _! _ 'N

<img file="MX2012007154A_D0032.tif" />

9-BBN dimer -&gt;

two. NaOH

3. Pd (PPh₃)₄ &lt;K7)

R²-n

<img file="MX2012007154A_D0033.tif" />

1. —

-TMS

Hunig Pd Base (PPh₃)₄, Cul

2.ΤΒΛΡ

<img file="MX2012007154A_D0034.tif" />

<img file="MX2012007154A_D0035.tif" />

The bromides (67) undergo Sonogashira coupling with TMS-acetylene and subsequently the deprotection of the silyl produces the

238 acetylene compounds (69), which are reduced to produce the compounds (70). Palladium-mediated coupling of (67) with cyclopropylboronate (prepared according to the literature; see: JA; Huertas, R .; Leon-Colon, G. Tetrahedron Lett. 2000, 41, 4251-4255) provides the cyclopropyl compound (68 ).

SCHEME 13

O2N

<img file="MX2012007154A_D0036.tif" />

(58) (59)

Br

NR₂ (60)

OjN

Br

<img file="MX2012007154A_D0037.tif" />

2) H_2l PD / C (61)

NO,

H₂N

<img file="MX2012007154A_D0038.tif" />

(62)

<img file="MX2012007154A_D0039.tif" />

NBS

<img file="MX2012007154A_D0040.tif" />

DAST (64)

CHO OjN

<img file="MX2012007154A_D0041.tif" />

(65)

CHF₂^{Fe, NH4C}'H₂N

<img file="MX2012007154A_D0042.tif" />

(66)

CHF,

The preparation of various aniline building blocks are exemplified in Scheme 12. Compounds (58) can be prepared as disclosed in Sil. PCT Int. W02008104754. Compounds (58) are transformed into boronic ester (59) by a reaction

239 Palladium-mediated Miyaura coupling with bis (pinacoloto) diboro. The Suzuki coupling reaction of boronic esters (59) and bromides (2), followed by reduction of the nitro group provides the anilines (60). Commercially available 1-bromo-3,5-dinitrobenzene (61) is reduced in the presence of iron to produce 5-bromobenzene-1,3-diamine (62); reductive amination with trifluoroacetaldehyde provides compound (63). Commercially available 3-nitrobenzaldehyde (64) is fluorinated with DAST to provide compound (65); bromination of nitroarene (65) and subsequent reduction of the nitro group provides aniline (66).

SCHEME 14, heterocycle 'N (76)

RMgCI

Faith (acac)₃

OR

ROH í ~ | i base Sl ^ CI _s31 &lt;»2&gt;

SAci («) heterocyclyl-OH 4 C SjC O 3 ^Cl R-BfOH),, Suzuki Jv.

^RIT ϊ -^RIT II

SAci ⁵⁵⁰ SAc.

(71) &lt;W)

EtOC (= CH j) Sn (Bu)₃PdCI¡ (dppf) -DCM adduct

BF_toK PdCb (dppf) t

C (O) CH₃

CH = CHi r'-L

- ^N (MJ

R²-L

A (75)

R is for example alkyl, lower cycloalkyl

240

The preparation of 2-chloropyrimidine building blocks starting with 2,4-dichloropyrimidines (71) is illustrated in Scheme 13. Functionalization of pyrimidine through Suzuki coupling produces substituted 2-chloropyrimidines (73), while a reaction of Substituted alcohol nucleophile-based SuAr provides ethers (72). Reaction of compounds (71) with commercially available vinyl potassium trifluoroborate provides olefin adducts (75). Stille coupling of compounds (71) with commercially available tributyl (1-ehoxyethenyl) stannane provides ketones (74). Compounds (71) are transformed into compounds (74) through an iron catalyzed Grignard addition, and into compounds (77) by the action of an alcohol and base. Compounds (76) are prepared with an iron promoted coupling of Grignard reagents with compounds (71).

SCHEME 15

<img file="MX2012007154A_D0043.tif" />

mCRBA

<img file="MX2012007154A_D0044.tif" />

<img file="MX2012007154A_D0045.tif" />

241

Coupling of compounds (4) with 2-chloro-4 (methylsulfanyl) pyrimidine (78) provides the anilines (79), which are oxidized to sulfones (8) by mCPBA. Displacement of the sulfone moiety with alcohols or thiols under basic conditions provides the compounds (81).

SCHEME 16

<img file="MX2012007154A_D0046.tif" />

NK4OHCI K₂CO₃ / hl'V

R 'is H or Me; x and Y are independently a bond, CH2, CH (CH₃) or C (CH₃)₂

OR- &lt;¹⁰°)

242

The saponification of esters (94) produces acids (95) and lactones (96). The reaction of the acids (94) with hydrazine carboxamide produces the 1,3,4-oxadiazoles (97). Alternatively, coupling of amide with acids (94) produces amides (98). Dehydration of the amides (98) with a sulfamoyl salt produces the nitriles (99). Delation of nitriles (99) with ammonium hydroxide produces 1,2,4-oxadiazoles (100).

SCHEME 17

<img file="MX2012007154A_D0047.tif" />

(103)

243

The alkylation of bromolactams (101) with 1- (bromomethyl) -4methoxybenzene gives Iso compounds (102). The deprotonation of thiazole (5) with LDA followed by the addition of 3-bromo azepanones (102) gives (103) after deprotection under acidic conditions.

<img file="MX2012007154A_D0048.tif" />

<img file="MX2012007154A_D0049.tif" />

(104) X, Y = CHo N

The carbonylation of (104) in the presence of carbon monoxide and a palladium catalyst produces (105).

244

SCHEME 19

<img file="MX2012007154A_D0050.tif" />

The primary alcohols (106) are activated with MsCI and the resulting methanesulfonates are displaced with azide to produce azides (107). Reduction of azides (107) with triphenylphosphine gives the corresponding amines (108). Amide coupling of (108) by the action of an amine and an appropriate coupling reagent gives the amides (109). Reaction of amines (108) with potassium cyanide gives the ureas (110).

245

SCHEME 20

<img file="MX2012007154A_D0051.tif" />

<img file="MX2012007154A_D0052.tif" />

(112)

<img file="MX2012007154A_D0053.tif" />

<img file="MX2012007154A_D0054.tif" />

H₂NOC \ _ / R (1)

Suzuki r coupling

<img file="MX2012007154A_D0055.tif" />

(114)

In Scheme 20 the two R groups and the carbon to which they are attached represent a ketal such as 1,3-dioxolane. The 2-chlorothiazole is reacted with (111) in the presence of NaHMDS followed by bromination to provide (112). Suzuki's coupling of (1) with (112) produces (113). Hydrolysis of (113) gives (114). Nitrile (113) is reduced with DIBAL to give the amine (115) or reacted with hydrochloric acid to give the cyclohexyl compound (116). The ketal can be converted to the ketone,

246 which can be further elaborated into appropriate functional groups.

SCHEME 21

<img file="MX2012007154A_D0056.tif" />

(117) (117)

Reaction of amines (117) with acid chloride (118) gives lactams (119).

247

SCHEME 22

<img file="MX2012007154A_D0057.tif" />

two. NaN₃, MsOH (122)

Ketone (120) is reacted with t-butyl sulfonamide in the presence of titanium ethoxide to provide (121). The deprotonation of compound (5) with LDA followed by the addition of (121) and then expansion of the ring by the action of acid and azide gives (122).

The compounds of formula (I), as well as the intermediates for their syntheses, can be prepared according to the procedures described in the Schemes, Preparation of intermediates and Examples herein, using appropriate materials and are further illustrated by the following intermediates and specific examples. The illustrated compounds are representative of the invention, and should not be construed as limiting the scope of the invention in any way. The examples further illustrate details for the preparation of those of the compounds of the present invention. Those of skill in the art will appreciate

248 Easily known variations of protecting groups, of reagents, as well as of the conditions and procedures of the following preparative procedures can be used to prepare intermediates and compounds of the present invention. It will also be appreciated that when a chemical reagent is not commercially available, such a chemical reagent can be readily prepared by those skilled in the art by following or adapting the known methods described in the literature. All temperatures are degrees Celsius unless otherwise indicated. Mass spectra (MS) were measured by electrospray ionization-mass spectroscopy (ESI) or by atmospheric pressure chemical ionization mass spectroscopy (APCI).

PREPARATION OF INTERMEDIARIES

Intermediate it 1: 1- (5-bromo-1,3-t¡azol-2-¡l) cilobutanol

<img file="MX2012007154A_D0058.tif" />

The isopropyl magnesium chloride / lithium chloride complex (1.3

M in THF, 582 mL, 756 mmol) was cooled to 0 OC. Thiazole (53.2 ml, 749 mmol) was added over 15 minutes, resulting in an orange / red solution. Stirred for 20 min at 0 OC, then stirring the bath

249 cooling and allowed to warm to rt. Stirred another 2h, then re-cooled to 0 OC. Cyclobutanone (53.3 ml_, 713 mmol) was added over 50 min. The cooling bath was removed and allowed to warm to rt and stirred 20 min at that temperature. The reaction mixture was cooled to 0 OC and saturated aqueous ammonium chloride was slowly added. The reaction mixture was diluted with EtOAc, the phases were separated, and the organic portion was washed with water. The aqueous phase was washed with ethyl acetate. The combined organic portions were dried over MgSO4 and concentrated in vacuo to provide 127.5 g of material containing 1- (1,3-thiazol-2-yl) cyclobutanol, which was used without further purification.

Step 2:

The product from Step 1 (171.9 g, 1,107 moles) was dissolved in DMF (860 mL) and cooled to 0 OC. NBS added (236 g, 1,327 moles) and stirred 1 h at 0 OC. It was removed from the cooling bath and allowed to warm to rt. LC analysis was continued until the starting material was consumed. The solution was poured into the cooled water (2 L) containing Na2SO3 (30 g), washing with MTBE (1 L). The mixture was stirred for 10 min and then diluted with MTBE (1.5 I) and water (500 mL). The layers were separated and the organic portion was washed with water (2 I). The aqueous portions were washed with MTBE (2 I). The combined organic extracts were dried over MgSO4 and concentrated in vacuo to provide an orange oil. Diluted in hexanes at 50 OC (1 L). They were stirred while allowing to cool slowly. I know

250 they added seed crystals, and crystallization started around 35 OC. Stirred overnight at rt. Cooled to -20 OC and stirred for 20 min. Filtered, washed with hexane at -20 OC. Dried in a nitrogen atmosphere to provide 1- (5-bromo-1,3-thiazol-2-yl) cyclobutanol (172.9 g, 739 mmol,

67%). The filtrate and all the remaining material in the flask was diluted in

CH2CI2 and concentrated in vacuo. Hexane was added, concentrated to a volume of ~ 300 ml cooled to rt and seminal crystals were added. It began to crystallize. Cooled to -10 OC and filtered, washed with hexane to -10 OC. A second crystal culture was allowed to air dry, yielding 110 (5-bromo-1,3-thiazol-2-yl) cyclobutanol (38.8 g, 166 mmol, 15%). The mother liquor from the second filtration was concentrated, purified by column chromatography on silica gel (Biotage EtOAc / Hex) and then dried in vacuo to provide 1- (5-bromo-1,3-thiazol-2-yl ) cyclobutanol (10.6 g, 45 mmol, 4%). In total, 1- (5-bromo-1,3-thiazol-215 yl) cyclobutanol (222 g, 948 mmol, 86%) was obtained.¹H NMR (400 MHz, CDCb): δ 7.58 (s, 1H); 3.56 (br s, 1H); 2.69-2.60 (m, 2H); 2.47-2.36 (m, 2H); 2.09-1.87 (m, 2H).

Intermediary

N- (3-Bromo-5-methylphenyl) -420 (tr¡fluoromethyl) p¡rim¡d¡n-2-amína

Br

<img file="MX2012007154A_D0059.tif" />

NNH

251

A solution of 3-bromo-5-methylaniline (162.5 g, 873.66 mmol) in 1,4-dioxane (2 L) was prepared, and 2-chloro-4 (trifluoromethyl) pyrimidine (182 g, 994.54 mmol) and methanesulfonic acid (97.5 g, 1.02 mol) were added sequentially. The resulting solution was heated under reflux overnight. The resulting mixture was cooled and concentrated in vacuo. The residue was diluted with 2 L of water, then adjusted to pH 7-8 with aqueous sodium bicarbonate solution, followed by extraction with EtOAc (2x2 L). The organic layers were combined, washed with water (2x 2 L), dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in N- (3-bromo-5-methylphenyl) -4 (trifluoromethyl) pyrimidin-2-amine (200g, 602mmol, 69%) as a light yellow solid. MS (ESI): [M + H] + 334.0. Ή NMR (400 MHz, CDCI₃): δ 8.68 (d, J = 4.9 Hz, 1H); 7.79 (s, 1H); 7.30 (s, 2H); 7.10-7.06 (m, 2H); 2.36 (s, 3

H).

Intermediary_3; _N- [3-methyl-5- (4,4.5.5-tetramethyl-1,3,2-dioxaborolan-2-yl) phen¡l1-4- (trifluoromethyl) p¡r¡midin-2- amyna

<img file="MX2012007154A_D0060.tif" />

252

To a solution of Intermediary 2 (250 g, 753.01 mmol,) in

1,4-dioxane (3 L) was added 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1,3, 2-doxaboronol (225 g, 885.83 mmol), KOAc (225 g, 2.30 mol) and Pd (dppf) CI2 (19 g, 25.23 mmol). The resulting solution was heated under reflux overnight. The solid was filtered. The filtrate was discolored by passing through a column of silica gel. The fractions were collected and concentrated in vacuo. This resulted in 110 g of pure product and 150 g of crude product. The crude product was decolorized with activated carbon to provide an additional 125 g of pure product. This resulted in N- [3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] -4- (trifluoromethyl) pyrimydin-2-amine (235g, 620mmol, 82%) as a white solid. MS APCI: [M + H] + m / z 380.¹H NMR (400 MHz, CDCb, ppm): 1,350 (12H, la s), 2,386 (3H, la s), 6,993-7,006 (1H, D, J = 5.2

Hz), 7,385-7,427 (2H, s,), 7,636 (1H, s), 7,753 (1H, s), 8,608-8,621 (1H,

D, J = 5.2Hz).

Intermediary_4l

N- | 3-methyl-5- (1,3-thiazol-5-yl) fenin-4 (trifluoromethyl) p¡r¡m¡d¡n-2-amina

<img file="MX2012007154A_D0061.tif" />

253

To a solution of Intermediate 3 (80 g, 211.08 mmol) in 1,4-dioxane (800 mL) was added 5-bromo-1,3-thiazole (28 g, 171.78 mmol), Pd (dppf) CI2 (8 g, 10.62 mmol) and a solution of sodium carbonate (44.7 g, 421.70 mmol) in water (447 mL). The resulting solution was heated under reflux for 1 hour. Then it was allowed to cool and concentrated in vacuo. The residue was diluted with EtOAc (500 mL) and filtered. The filtrate was washed with brine (2 x 300 mL) and water (2 x 300 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was recrystallized from EtOAc: DCM in the ratio of 1: 5 to get 34 g of product. The mother liquor was used on a column of silica gel and eluted with dichloromethane / ethyl acetate (2: 1). This resulted in N- [3-methyl5- (1,3-thiazol-5-yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (42 g, 125 mmol, 73%) as a pale yellow solid . MS APGI: [M + H] + m / z 337.¹H NMR (400 MHz, CD3COCD3, ppm): 2,413 (3H, s), 7,250-7,263 (2H, m), 7,636 (1H,

s), 8.204-8.213 (2H, m), 8.834-8.846 (1H, d, J = 4.8Hz), 8.970 (1H, s), 9.210 (1H, br). RhSYK = +++ activity.

Intermediate 5: N- (3-Bromophenyl) -4- (tr¡fluoromethyl) p¡r¡midın-2amina

Br

<img file="MX2012007154A_D0062.tif" />

254

A solution of 3-bromoaniline (250 g, 1.46 mol) in 1,4-dioxane (2.5 L) was prepared, and 2-chloro-4- (trifluoromethyl) pyrimidine (267 g, 1.47 mol) and methanesulfonic acid (155 g, 1.61 moles) were added sequentially. The resulting solution was heated to 100 OC overnight. The resulting mixture was cooled and concentrated in vacuo. The residue was adjusted to pH 7-8 with an aqueous solution of sodium bicarbonate. The solid was filtered, and the filtrate was extracted with EtOAc (4x500 mL). The organic layers were combined, washed with water (2x 2 L), dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in N- (3-bromophenyl) 4- (trifluoromethyl) pyrimidin-2-amine (200g, 629mmol, 43%) as a light yellow solid. MS APCI: [M + 3] + m / z 319.¹H NMR (500 MHz, CDCI₃): 8.68 (D, J = 4.9 Hz, 1H); 7.95 (s, 1H); 7.53-7.50 (M, 1H); 7.44 (br s, 1H); 7.22 (M, 2H); 7.08 (D, J = 4.9 Hz, 1H).

Intermediate 6: N- [3- (4,4,5.5-Tetramethyl-1,3,2-dioxaborolan-2l) phenyl1-4- (trifluoromethyl) pyridine-2- amyna

<img file="MX2012007154A_D0063.tif" />

O /

B

CF

To a solution of Intermediate 5 (200 g, 631 mmol,) in 1,4-dioxane (2 L) was added 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-1,3 , 2,255 dioxaborolan-2-yl) -1,3,2-dioxaborolane (177 g, 697 mmol), KOAc (187 g, 1.91 mol) and Pd (dppf) CI2 (24 g, 32 mmol). The resulting solution was heated to 100 OC for 2H. The reaction was allowed to cool, and the solid was filtered. The filtrate was concentrated in vacuo. The residue was applied to a column of silica gel and eluted with ethyl acetate / petroleum ether (1:10). This resulted in Λ / - [3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (140 g, 384 mmol) , 61%) as a white solid. MS APCI: [M + H] + m / z 366.¹H NMR (400 MHz, ppm DMSOd₆): 1,300 (12H, s), 7,237-7,249 (1H, m), 7,331-7,342 (2H, m), 7,882-7,910 (1H, m), 8,000 (1H, s), 8,796-8.806 (1H, m) ), 10.130 (1H, s).

Intermediary_1 \ _N- [3- (1,3-thiazol-5-yl) phenyl-1-4 (trifluoromethyl) pyridine-2-amine

<img file="MX2012007154A_D0064.tif" />

Pd (dppf) CI₂ (1.01 g, 1.23 mmol) and Intermediate 6 (9.0 g, 25 mmol) were combined in a flask and were evacuated and filled with nitrogen (x3). 2-Me THF (90 mL), 5-bromothiazole (4.45 g, 27.1 mmol) and aqueous sodium carbonate (24.7 mL, 49.3 mmol) were added sequentially. The flask was sealed and heated at 80 OC for 15H. The brown solution was allowed to cool to rt, then diluted with water and EtOAc. The layers

256 they were separated and the aqueous portion was extracted with EtOAc (2x). The combined organic portions were washed with saturated aqueous NaHCO3, then with brine, then dried over Na2SO4 and concentrated in vacuo. Trituration with CH2CI2 and collection of the beige solid through filtration provided 5.94 g of the desired product. The mother liquor was concentrated in vacuo and subsequent purification through silica gel column chromatography (CH2CI2-40% EtOAc: CH2CI2) provided another 1.41 g of the desired product. In total, N- [3- (1,3-thiazol-5-yl) phenyl] -4- (trifluoromethyl) pyrimidin2-amine (7.35 g, 22.8 mmol, 93%) was isolated as a beige solid . MS

APCI: [M + H] + m / z 323. ¹H NMR (600 MHz, DMSO-D₆, ppm) δ 10.32 (s, 1H), 9.06 (s, 1H), 8.82 (d, J = 4.8, 1H), 8.20 (d, J = 8.2, 1H), 8.20 (s, 1H), 7.64 (d , J = 7.5.1 H), 7.40 - 7.31 (m, 2H), 7.27 (d, J = 4.9, 1H). RhSYK = ++ activity.

Intermediary 8: 4- (3-vodo-5-n¡trofenil) morpholine

<img file="MX2012007154A_D0065.tif" />

Morpholine (3.26 mL, 37.5 mmol) was added to a solution of 1-fluoro-3-iodo-5-n -trobenzene (4.0 g, 15 20 mmol) in DMSO (7.5 mL), and the mixture (which became instantly purple) was heated at 130 ° C for 30 min in the microwave. Purification was attempted by directly loading the mixture onto a column of silica gel (80 g; pure loading

257

P / CH2CI2 rinse; 100: 0 to 60:40 hexanes: EtOAc for 35 minutes) but the mixture crashed on top of the column and not all of the mixture could be loaded. However, after an initial spike in pressure, purification was possible, and the residual material was purified in a second purification (24 g; CH2CI2 charge w / CH of charge: 100: 0 to 60:40 hexanes: EtOAc for 20 minutes). Concentration of the combined fractions from the two purifications provided 4- (3-iodo-5-nitrophenyl) morpholine (4.01 g, 12.0 mmol, 80%) as a bright yellow solid. Ή NMR (400 MHz, CDCI₃): δ 7.99 (s, 1H); 7.67 (s, 1H); 7.47 (s, 1H); 3.89 (m, 4H); 3.26 (m, 4H).

Intermediate 9: N- [3- (2-Bromo-1,3-t¡azol-5-yl) -5-methylphenin-4 (tr¡fluoromethyl) p¡r¡m¡d¡n-2- amyna

<img file="MX2012007154A_D0066.tif" />

Lithium diisopropyl ml (1.8 M in THF / heptane / ethylbenzene, 11.4 mL, 20.5 mmol) was cooled to -70 OC. Intermediate 4 (2.3 g, 6.8 mmol) in THF (23 mL) was added slowly over 15 minutes, keeping the temperature at -65 ° C. The reaction was allowed to stir for 30 minutes after addition, and then bromine (0.53 mL, 10.3 mmol) was added. The reaction was stirred for 30 minutes, then quenched with 20 ml of water and warmed to rt. The reaction was diluted with EtOAc

258 (50 mL). The layers were separated and the organic portion was washed with Na2SO3 (10% aqueous), brine, dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (ISCO, dry loading with silica gel, hexane-50% EtOAc: hexane) provided N- [3- (2-bromo-1,35 thiazol-5-yl) -5-methylphenyl] -4- (trifluoromethyl) pyrimin-2-amine (1.88 g, 4.53 mmol, 66%). MS APCI: [M + H] + m / z 414.8, 416.8.¹H NMR (600 MHz, CDCI₃) δ 8.64 (d, J = 4.9, 1H), 7.88 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.05 (t, J = 6.4, 1H), 7.01 (s, 1H) ), 2.38 (s, 3H).

Intermediate 10: N-f3-Bromo-5- (4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-il) fenyl-4- (trifluoromethyl) pyrmmdin-2-amine

<img file="MX2012007154A_D0067.tif" />

Br

Step 1:

To a solution of 3,5-dibromoanaline (4.47 g, 17.8 mmol) and 2-chloro-4- (trifluoromethyl) pyrimidine (2.36 mL, 19.6 mmol) p20 toluenesulfonic acid (4.06 g, 21.4 mmol) was added, resulting in the formation of a thick suspension. This mixture was heated to 100 ° C overnight, during which it became a deep red solution. The mixture was diluted with 200 mL EtOAc and washed with 200 mL of NaHCO3 (ac)

259 sat and 200 mL of brine. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification by chromatography on silica gel (220 g; loading w / toluene; 100: 0 to 85:15 hexanes: EtOAc for 45 min) provided N (3,5-dibromophenyl) -4- (trifluoromethyl) pyrimidin- 2-amine (5.85 g, 14.7 mmol,

83%) as a light yellow solid. MS APCI: [M + H] + m / z 397.8.¹H NMR (400 MHz, CDCI₃): δ 8.72 (d, J = 4.9 Hz, 1H); 7.84 (s, 2H); 7.39 (s, 1H); 7.34 (s, 1H); 7.14 (d, J = 4.9 Hz, 1H).

Step 2:

To a solution of the product from Step 1 (2.0g, 5.0 mmol) in

DMSO (10.1 mL) were added 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1,3,2 -dioxaborolane (1.4 g, 5.5 mmol), KOAc (1.48 g, 15.1 mmol) and Pd (dppf) CI2 (123 mg, 0.151 mmol), and the mixture was heated at 125 ° C for 30 minutes in the microwave. The mixture was diluted with 100 mL EtOAc and washed with 2 X 100 mL 1: 1 H₂O: brine. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification by Chromatography on silica gel (80 g; load w / CH2CI2; 100: 0 to 70:30 hexanes: EtOAc for 40 min) provided N- [3-bromo-5- (4,4,5, 5tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (755 mg, 1.70 mmol, 34%) as an off-white solid.¹H NMR (500 MHz, DMSO-d₆) δ 8.86 (d, J = 4.9, 1H), 8.25 (s, 1H), 7.96 (s, 1H), 7.36 (s, 1H), 7.32 (d, J = 4.9, 1H), 1.34 (s, 12H ).

260

Intermediary_11: _N- [3-Bromo-5- (1,3-thiazol-5-yl) phenyl-4 (trifluoromethyl) pyrimidin-2-amine

<img file="MX2012007154A_D0068.tif" />

A solution of Pd (OAc) 2 (19 mg, .085 mmol) and di-1adamantyl butyl phosphine (61 mg, 0.18 mmol) in THF (12.8 ml_) was stirred for 15 min. Intermediate 10 (755 mg, 1.70 mmol), 5-bromo-1,3-thiazole (760 μΙ_, 8.50 mmol), potassium fluoride (296 mg, 5.10 mmol), and water (4.25 mL) were then added, and the mixture was heated to 75 ° C overnight. After cooling to rt, the mixture was diluted with 100 ml of EtOAc and washed with 100 ml of brine. A bright yellow solid remained undissolved on the walls of the settling funnel, thereby rinsing with 100 ml of THF. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Purification by Chromatography on silica gel (40 g; dry load; 100: 0 to 50:50 hexanes: EtOAc for 25 min) provided N- [3-bromo-5- (1,3-thiazol-5- yl) phenyl] -4 (trifluoromethyl) pyrimidin-2-amine (449 mg, 1.12 mmol, 66%) as an off-white solid. MS APCI: [M + H] + m / z 403.0. ¹H NMR (400 MHz, (CD₃)₂CO): δ 9.46 (s, 1H); 9.03 (s, 1H); 8.89 (d, J = 4.9 Hz, 1H); 8.32-8.26 (m, 2H); 8.16 (s, 1H); 7.59 (s, 1H); 7.33 (d, J = 4.9 Hz, 1H). RhSYK = ++ activity

261

Intermediary_12: _N- [3-N¡tro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) fenin-4- (trifluoromethyl) pyr¡m¡d¡n -2-amine

<img file="MX2012007154A_D0069.tif" />

A solution of 3-nitro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) aniline (9.09 g, 34.4 mol) and 2-chloro-4- (trifluoromethyl) pyrimid, na (6.1 g, 33.4 mmol) in 1,4-dioxane (67 mL) was prepared. Methanesulfonic acid (2.17 mL, 33.4 mmol) was added. The resulting solution was heated to 110 OC overnight. The resulting mixture was cooled, and aqueous sodium bicarbonate solution was added. It was extracted with EtOAc. It was washed with brine, dried over anhydrous sodium sulfate, filtered through a plug of silica gel, and concentrated in vacuo. The resulting brown solid was ground with hexanes, and the solid was filtered and dried in a vacuum oven for two days to provide N- [3-nitro-5- (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2l) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (11.7 g, 28.5 mmol, 85%). MS APCI: [M + H] + m / z 411.1.¹H NMR (600 MHz, CDCI₃) δ 9.00 (t, J = 2.2 Hz, 1H), 8.71 (d, J = 4.9 Hz, 1H), 8.32 (d, J = 1.9 Hz, 1H), 8.01 (d, J = 1.7 Hz, 1H),

7.55 (s, 1H), 7.11 (d, J = 4.9Hz, 1H), 1.35 (s, 12H).

262

Intermediate 13 N- [3- (4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) 5- (trifluoromethyl) phenyl-4- (trifluoromethyl) p! r¡midın-2-am¡na

<img file="MX2012007154A_D0070.tif" />

Step 1:

To a solution of 2-chloro-4-trifluoromethylpyrimidine (1,224 g, 6.1 mmol) and 3-bromo-5- (trifluoromethyl) aniline (1.4 g, 5.83 mmol) in dioxane (20 mL) was added p-toluenesulfonic acid monohydrate ( 1,220 g, 6.42 mmol). An immediate white suspension formed. The tube was sealed and the sludge was shaken and heated at 100 ° C for 24H. The now clear solution was diluted with ethyl acetate and diethyl ether and washed with saturated NaHCO3 (aq). The organic fraction was dried over MgSO4 and concentrated in vacuo. The product was then purified by column chromatography on silica gel, eluting with ethyl acetate / hexane with a 0-30% gradient to provide N- [3-bromo-5- (trifluoromethyl) phenyl] -4 (trifluoromethyl ) pyrimidin-2-amine (2,252 g, 87%) as a light beige solid. MS APCI: [M + H] + m / z 386.0. Ή NMR (400 MHz, CDCI₃): δ 8.75 (d, J = 4.9 Hz, 1

H); 8.09 (s, 1H); 7.94 (s, 1H); 7.52-7.43 (m, 2H); 7.17 (d, J = 4.9 Hz, 1H).

RhSYK = + activity.

263

Step 2:

PdCI2 (dppf), 4,4,4 ', 4', 5,5,5 ', 5'-octamet was added to a solution of the product from Step 1 (790 mg, 2,046 mmol) in degassed DMSO (9.0 ml_) L-2,2'-bi-1,3,2-dioxaborolane (572 mg, 2,251 mmol) and potassium acetate (602 mg, 6.14 mmol). Nitrogen was bubbled through the mixture for 2 min and then the tube was sealed and heated to 125 ° C in the microwave. The reaction mixture was diluted with ethyl acetate and water. The layers were separated, and the aqueous fraction was extracted with ethyl acetate. The combined organic fractions were washed with water, brine, and dried over MgSO4. The product was further purified by column chromatography on silica gel, eluting with ethyl acetate / hexane with a 0-50% gradient to provide- [3- (4,4,5,5-tetramethyl1,3,2 -dioxaborolan-2-yl) -5- (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (886 mg, 80%) as a solid.¹H NMR (400 MHz, CDCb): δ 8.70 (d, J = 4.9

Hz, 1H); 8.41 (s, 1H); 7.93 (d, J = 2.2 Hz, 1H); 7.79 (s, 1H); 7.43 (s, 1H); 7.10 (d, J = 4.9 Hz, 1H); 1.38 (s, 12H).

Intermediate 14: 1- (5-Bromo-1,3-thiazol-2-yl) -2,2-difluoroethanol

N

Oh

Br

<img file="MX2012007154A_D0071.tif" />

F

F

Step 1:

264

This procedure is based on literature, see: Krasovskiy, A .; Krasovskaya, V .; Knochel, P. Angew. Chem. Fnt. Ed. 2006, 45, 2958. Thiazole (5.7 ml_, 80 mmol) in THF (100 mL) was added to a stirred, cooled (0 ° C) solution of isopropylmagnesium chloride-lithium chloride (1.18 M in

THF, 74.9 mL, 88 mmol) in THF (75 mL) then the mixture was stirred at room temperature for 1 hour. Then the solution was cooled to 20 ° C and ethyl difluoroacetate (9.29 ml, 88 mmol) was added. The mixture was stirred for 10 minutes at -20 ° C, then 10 minutes at room temperature. The mixture was diluted with ethyl acetate (200 mL), washed with aqueous ammonium chloride (saturated, 200 mL), dried (MgSO4), filtered, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chromatography on silica gel, 0-90% ethyl acetate in hexanes) to give 2,2-difluoro-1- (1,3thiazol-2 -il) ethanone (12 g, 73.6 mmol, 92% yield) as a yellow oil. MS ESI: [M + H] + m / z 164.0.

Step 2:

To a solution of the product from Step 1 (3 g, 18.39 mmol) in chloroform (90 mL) and methanol (22.5 mL) at 0 ° C, sodium borohydride (3.53g, 18.49 mmol) was added, per portion. The reaction was then allowed to warm to room temperature and was diluted with a saturated aqueous sodium bicarbonate solution (200 mL). The aqueous layer was extracted with diethyl ether (2 X 100 mL) and the combined organic fractions were

265 dried (Na2TAN4), filtered and the solvent was evaporated under reduced pressure. 2,2-Difluoro-1- (1,3-thiazol-2-yl) ethanol was carried forward as an oil without further purification in the next step. MS ESI: [M + H] + m / z

166.0.

Step 3:

Bromine (7.58 mL, 147 mmol) was added dropwise to a stirred mixture of the Step 2 product (3.04 g, 18.39 mmol) and sodium acetate (15.10 g, 184 mmol) in acetic acid (92 mL) and the mixture was Stirred at 80 ° C for 12 Hours and then the weekend at room temperature. The solvent was removed by evaporation (Na trap₂S₂O3). The residue was diluted with water: brine (1: 1) and the aqueous phase was extracted 3x with ethyl acetate. The combined organics were washed with brine, dried (Na₂SW₄) and were concentrated. The resulting residue was purified by column chromatography on silica gel (chromatography on silica gel, 0-70% ethyl acetate in hexanes) to give 1- (5-bromo-1,3-thiazole- 2yl) -2,2-difluoroethanol (1.4 g, 5, .4 mmol, 31.2% yield). Ή NMR (500 MHz, CDCI₃): δ 7.73 (s, 1H); 6.04 (td, J = 55.0, 3.3 Hz, 1H); 5.15-5.09 (m, 1H).

266

Intermediate 15: 1- [5- (3-amino-5-methylphenyl) -1,3-thiazol-2-ylcyclobutanol h₂n zt-n

Step 1:

Dioxane (720 mL) in a three neck round bottom flask was degassed for 30 min. 3-Bromo-5-methylaniline (60g, 193mmol), (bispinacholate) diboro (96g, 377mmol), potassium acetate (42.7g, 435mmol), X-Phos (8.3g, 17.41mmol) and Pd₂dba3 (3.99 g, 4.35 mmol) were added to the solvent degassed under N₂(g). After stirring for 10 min at room temperature, the reaction mixture was heated to an internal temperature of 80 ° C. After ca. 4 hours, the heating mantle was removed and replaced with an ice-water bath. The reaction mixture was cooled to 30 ° C and then filtered through a pad of celite (washing with 500 ml of MTBE). It was transferred to a settling funnel containing 500 ml of phosphate buffer at pH 8, 500 ml of brine and 500 ml more of MTBE. The layers were separated and the organic product was washed with 1 I of a 1: 1 mixture of brine and water. The aqueous layers were combined and re-extracted sequentially with a second 500 ml portion of MTBE. The combined organics were treated with 100 g of MgSO₄ and the resulting mixture was stirred for 20 min. This was then filtered and concentrated in vacuo. The resulting residue is

267 purified by chromatography on silica gel (Biotage, 025% ethyl acetate in hexanes) to yield 3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline ( 66 g, 255 mmol, 88%) as a light orange solid. MS APCI: [M + H] + m / z 234.2.

Step 2:

2-Methyl THF (720 mL) and an aqueous sodium carbonate solution (2M, 367 mL, 734 mmol) were added to a 500 mL three-neck round bottom flask. The solution was degassed for 30 min. The product of Step 1 (90 g, 367 mmol), Intermediary 1 (86 g, 367 mmol) and PdCI₂(dppf) (8.05 g, 11 mmol) were added to the degassed solution under N₂(g). The resulting mixture was stirred for 5 min at room temperature and was then heated to 80 ° C. After ca. 9 hours, the heating mantle was removed and the reaction was cooled to 30 ° C. The reaction mixture was filtered through a SolkaFloc pad that uses water (500 mL) and ethyl acetate (500 mL) to complete the transfer. . The filtrate was then transferred to a settling funnel, using an additional 500 ml of ethyl acetate and 250 ml of brine to complete the transfer. The layers were separated, the organic product was washed with a mixture of water and brine (500 ml and 250 ml, respectively), and then the aqueous product was again extracted with ethyl acetate (400 mL). The organics were combined, dried over MgSO₄ (100 g), filtered, and concentrated in vacuo to produce a brown crystalline solid. This material was recrystallized from

268 hot ethyl acetate (250 ml at 60 ° C), using hexanes in the form of a counter-solvent (750 mL) to produce 1- [5- (3-amino-5-methylphenyl) -1,3-thiazol-2-yl-cyclobutanol (88 g, 338 mmol, 92%). MS APCI: [M + H] + m / z 261.2.¹H NMR (500 MHz, DMSO-D₆) δ 7.87 (s, 1H), 6.59 (s, 1H), 6.58 (s, 1H), 6.45 (s,

1H), 6.34 (s, 1H), 5.14 (s, 2H), 2.52 - 2.48 (m, 2H), 2.31 (q, J = 9.3, 2H), 2.17 (s, 3H), 1.93-1.80 (m, 2H).

Intermediate 16: 3-methyl-5- (1,3-t¡azol-5-yl) an¡l¡na

<img file="MX2012007154A_D0072.tif" />

3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline (20.98 g, 90 mmol), of 5-bromothiazole (8.85 mL, 99 mmol), and sodium carbonate (90 mL, 180 mmol) were combined in a flask. 2-methyl-THF (326 mL) was added and the flask was degassed with N₂ for 1.5 H before the 1, r-bis (diphenylphosphino) ferrocene-palladium (ll) dichloride dichloromethane complex (3.67 g, 4.50 mmol) was added. The reaction was heated to 100 ° C overnight, and then cooled to room temperature. The reaction mixture was filtered through a Celite pad, washing with ethyl acetate. The layers were separated and the aqueous layer back-extracted with ethyl acetate, dried over Na₂SW₄, and concentrated. The residue was purified by chromatography (0-40% ethyl acetate in hexanes). 3-Methyl-5- (1,3269 thiazol-5-yl) aniline was isolated as a yellowish-brown solid (15.33 g, 81 mmol, 90%). Step 4: [M + H] + m / z 191.1.¹H NMR (500 MHz, CDCI₃) δ 8.71 (s, 1H), 8.02 (s, 1H), 6.80 (s, 1H), 6.71 (s, 1H), 6.50 (s, 1H), 3.71 (s, 2H), 1.79 (s, 3H) .

Intermediary 17: 2- [5- (3-amino-5-methelonyl) -1.3-t¡azol-2-¡l1-1,1,1trifluoropropan-2-ol

<img file="MX2012007154A_D0073.tif" />

To diisopropylamine (18.73 ml, 131 mmol) in THF (263 mL) at 78 ° C was added N-butyl lithium (2.5M in hexanes, 54.7 ml, 137 mmol). The reaction was aged for 30 minutes at -40 ° C before cooling to -78 ° C. Intermediate 16 (10g, 52.6mmol) was added as a solution in 5mL of THF at -78 ° C and was then heated at 0 ° C for 2 hours. The reaction was cooled once again to -78 ° C before adding 1,1,1-trifluoroacetone (14.85 mL, 158 mmol) as a solution in 5 mL THF at 78 ° C. The reaction was allowed to warm to room temperature slowly, and was diluted with water and DCM. The layers were separated and the organic layer was dried over sodium sulfate and concentrated in vacuo. The resulting residue was purified on silica gel (0-30% ethyl acetate in hexanes) to produce a yellow oil that solidified in hexanes overnight. The yellow to off-white solid was sonicated and filtered to

270 produce 2- [5- (3-amino-5-methylphenyl) -1,3-thiazol-2-yl] -1,1,1-trifluoropropan-2-ol (11.69 g, 38.7 mmol, 73.6%) . MS APCI: [M + H] + m / z 303.0.¹H NMR (500 MHz, CDCI₃) δ 7.85 (s, 1H), 6.76 (s, 1H), 6.67 (s, 1H), 6.52 (s, 1H), 4.53 (br s, 2H), 2.29 (s, 3H), 1.83 (s, 3H ).

Intermediate 18: 4-methyl-N- [3-methyl-5- (4.4,5,5-tetramethyl-1,3,2d¡oxaborolan-2-l) fen¡llpir¡m¡d¡ n-2-amine

<img file="MX2012007154A_D0074.tif" />

Step 1:

Acetic acid (0.234 ml, 4.08 mmol) was added to 2-chloro-4-methylpyrimidine (0.5 g, 3.89 mmol) and 3-bromo-5-methylaniline (1,096 g, 3.89 mmol) suspended in dioxane (7.78 ml_). The reaction was heated to 120 ° C overnight. The reaction was then cooled to room temperature and directly purified by silica gel column chromatography eluting with ethyl acetate / ethyl hexanes to give N- (3-bromo-5methylphenyl) -4-methylpyrimidin-2-amine (1.08 g, 3.89 mmol, quant) as a white solid. MS ESI; [M + H] + m / z 278.0 and 280.0.

271

Step 2:

A 40 mL bottle was loaded with the product from Step 1 (500 mg, 1,798 mmol), bis (pinacolate) diboro (502 mg, 1,977 mmol), 1, T-bis (diphenylphosphine) ferrocene-palladium (ll) dichloride complex dichloromethane (44.0 mg,

0.054 mmol) and potassium acetate (529 mg, 5.39 mmol). The solid mixture was dissolved with DMSO (7.19mL) and heated to 120 ° C. After stirring for 2H, the mixture was cooled to room temperature. The reaction was diluted with ethyl acetate, washed with a saturated aqueous solution of

NaHCO3 and brine. The organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with ethyl acetate in hexanes to give 4-methyl-N- [3-methyl-5- (4,4,5,5-tetramethyl1,3,2- dioxaborolan-2-yl) phenyl] pyrimidin-2-amine (331 mg, 1018 mmol, 56.6% yield) as an orange oil. MS ESI: [M + H] + m / z 326.2.¹H

NMR (500 MHz, DMSO-D₆) δ 9.40 (s, 1H), 8.31 (d, J = 5.0 Hz, 1H), 7.77 (s, 2H), 7.07 (s, 1H), 6.70 (d, J = 5.0 Hz, 1H), 2.33 (s , 3H), 2.26 (s, 3H), 1.27 (s, 12H).

Intermediary_19: _4-methyl-N- [3-methyl-5- (1,3-thiazol-520 yl) phenylpyr¡m¡din-2-amine

<img file="MX2012007154A_D0075.tif" />

272

A microwave bottle was loaded with Intermediate 18 (218 mg, 0.670 mmol), 5-bromo-1,3-thiazole (59.9 μΙ_, 0.670 mmol), Pd₂(dba) 3 (30.7 mg, 0.034 mmol), X-Phos (32.0 mg, 0.067 mmol) and cesium carbonate (437 mg, 1,341 mmol). The system was purged and flushed four times with Ar (g) before adding dioxane (918 µΙ_) and water (92 µΙ_). Again, the system was purged and cleaned five times before sealing the bottle and heating to 100 ° C. LCMS showed ~ 60% desired product, ~ 35% boron product, and starting material that remained unreacted. The reaction mixture was diluted with ethyl acetate, filtered through a pad of celite, and concentrated.

The resulting residue was purified by column chromatography on silica gel (Biotage, 0-20% ethyl acetate in hexanes) to provide 4-methyl-N- [3-methyl-5- (1,3-thiazole -5-yl) phenyl] pyrimidin-2-amine (105mg, 0.372mmol, 55.5%). MS ESI: [M + H] + m / z 283.0.¹H NMR (500

MHz, DMSO-De) δ 9.60 (s, 1H), 9.04 (s, 1H), 8.35 (d, J = 6.6, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.54 (s, 1H), 7.10 (s, 1H), 6.75 (d, J = 6.3, 1H), 2.37 (s, 3H), 2.30 (s, 3H).

Intermediate 20: 4-methoxy-N-í3-methyl-5- (4,4,5,5-tetramethyl-1,3,220 d¡oxaborolan-2-yl) fen¡np¡r¡m¡d¡n-2 -amine

<img file="MX2012007154A_D0076.tif" />

m

Step 1:

A 10-20 ml microwave bottle was loaded with 2-chloro-4-methoxypyrimidine (0.835 g, 5.78 mmol), 3-bromo-5-methylaniline (1,075 g, 5.78 mmol), acetic acid (0.347 ml, 6.06 mmol), and dioxane (11.55 mL). The system was purged and flushed with Ar (g) three times before shutting down and heating at 120 ° C for 3 hours. The mixture was cooled and stirred overnight. The light brown solids were collected by filtration and dried in a vacuum oven overnight to produce N- (3-bromo5-methylphenyl) -4-methoxypyrimidin-2-amine (1.7 g, 5.78 mmol, 100% yield) as a brown solid. MS ESI: [M + H] + m / z 296.0.

Step 2:

A 10-20 mL microwave bottle was loaded with the product from Step 1 (1.6 g, 5.44 mmol), diboro bisplnacolate (1,519 g,

5.98 mmol), 1,1'-bis (diphenylphosphino) ferrocene-palladium (ll) dichloride-dichloromethane complex (0.133 g, 0.163 mmol), potassium acetate (1602 g, 16.32 mmol) and DMSO (10.88 mL). The system was flushed extensively and purged five times with Ar (g) before sealing the vial and heating at 120 ° C for 1 hour. The reaction was then cooled to room temperature, diluted with ethyl acetate, filtered through a pad of celite, and concentrated to dryness. The resulting residue was purified by column chromatography on silica gel (Biotage, 5-60% ethyl acetate in hexanes) to provide 4-methoxy-N- [3-methyl-5- (4,4,5 , 5274 tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] pyrimidin-2-amine (900 mg, 2.64 mmol, 48.5% yield) as a brown solid. MS ESI: [M + H] + m / z 342.1.¹H NMR (500 MHz, DMSO-d₆) δ 9.46 (s, 1H), 8.17 (d, J = 5.8, 1H), 8.04 (s, 1H), 7.62 (s, 1H), 7.06 (s, 1H), 6.25 (d, J = 5.8, 1H ), 3.92 (s, 3H),

2.26 (s, 3H), 1.26 (s, 12H).

Intermediate 21: 4- methoxy-N- [3-methyl-5- (1,3-t¡azol-5yl) phen¡l1pirim¡din-2-amína

<img file="MX2012007154A_D0077.tif" />

To a round bottom flask were added 2-chloro-4methoxypyrimidine (1.58g, 10.93mmol), Intermediate 20 (2g, 10.51mmol), cesium carbonate (6.85g, 21.02mmol) and degassed dioxane (105ml_). The system was flushed extensively, purged with Ar (g), and palladium (II) acetate (0.236 g, 1.051 mmol) and Xantphos (0.912 g, 1.577 mmol) were added. The system was flushed, purged three times with Ar (g) again, and then heated at 90 ° C for 2 hours. The reaction was cooled to room temperature and the solvent was removed under reduced pressure and the residue was directly purified by column chromatography on silica gel (0 to 100%, 10: 1 ethyl acetate: methanol in hexanes) to provide 4-methoxy-N- [3-methyl-5- (1,3-thiazol-5-yl) phenyl] pyrimidin-2-amine (3.1

275 g, 10.39 mmol, 99%). MS ESI: [M + H] + m / z 299.1.¹H NMR (600 MHz, CDCI₃) δ 8.72 (s, 1H), 8.13 (d, J = 5.7, 1H), 8.06 (s, 1H), 7.91 (s, 1H), 7.29 (s, 1H), 7.25 (s, 1H), 7.05 ( s, 1H), 6.21 (d, J = 5.7, 1H), 3.98 (s, 3H), 2.37 (s, 3H).

Intermediate 22: 1- (5- (3-amino-5-n-trophenyl) -1.3-t-acezol-2 and 1-cyclobutanol

<img file="MX2012007154A_D0078.tif" />

To a solution of commercially available (3-amino-5-nitrophenyl) boronic acid (18 g, 99 mmol) and Intermediate 1 (25.5 g, 109 mmol) in DME (360 mL) were added tetraks (triphenylphosphine) palladium (0) (5.72 g, 4.95 mmol) and Na₂CO₃ 2M (aq) (148 mL, 297 mmol), and the mixture was degassed and then heated at 85 ° C for 5 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (500 mL) and filtered through Celite (ethyl acetate rinse). The filtrate was washed with brine (300 mL), dried (Na₂SW₄) and concentrated under vacuum. The impure material was split into two batches, and each was purified by chromatography on silica gel (70:30 to 0: 100 hexanes: ethyl acetate) then the product fractions from the two purifications were combined and concentrated to the vacuum to provide 26.53 g (91 mmol, 92%) of 1- (5- (3 amino-5- nitrophenyl) -1,3-thiazol-2-yl] cyclobutanol as a green solid MS ESI: [M + H] + m / z 292.0.¹H NMR (DMSO-d₆): δ 8.15 (1 H, s), 7.54 (1 H, s), 7.33 (1

276

H, s), 7.14 (1 Η, s), 6.58 (1 Η, s), 6.00 (2 Η, s), 2.56-2.47 (2Η, m), 2.39-2.29 (2

H, m), 1.95-1.83 (2 H, m).

Intermediate 23: 1-f5- (3-aminophenyl) -1,3-thiazol-2-yl1ethanol

<img file="MX2012007154A_D0079.tif" />

Step 1.

To a solution of 2-acetylthiazole (3.0 mL, 28.9 mmol) in ethanol (50 mL) at room temperature, under nitrogen, triethyl orthoformate (48.2 mL, 289 mmol) and p-TSA (550 mg, 2.89 mmol) were added. The mixture was stirred at reflux for 18H to give 90% conversion. Additional p-TSA (4.73 g, 24.87 mmol) was added so that the reaction was refluxed for an additional 5 hours until completion. The reaction mixture was cooled to room temperature and poured into 500 mL of NaHCO₃ saturated aqueous. The aqueous layer was extracted with ethyl acetate (3x). The combined organics were washed with NaHCO₃ saturated aqueous and brine, dried (sodium sulfate) and concentrates to give an amber liquid (13.2 g). Chromatography on silica gel (CombiFlash, 5-20% ethyl acetate in hexanes) provided 2- (1,1-diethoxyethyl) -1,3-thiazole (3.54 g,

17.59 mmol, 60.8% yield) as a colorless liquid.

277

Step 2:

To a solution of the product from Step 1 (3.54 g, 17.59 mmol) in THF (60 mL) at -78 ° C, under nitrogen, N-butyllithium (1.6 M, 11.54 mL, 18.47 mmol) was added by dripping at such speed that the internal temperature was kept below -65 ° C (addition for 15 min). The mixture was stirred at -78 ° C for 30 min and a solution of carbon tetrabromide (6.42 g, 19.35 mmol) in THF (20 mL) was added dropwise at such a rate that the internal temperature was kept below -65 ° C (addition for 15 min). After 30 min at -78 ° C, the temperature was allowed to reach 0 ° C and the reaction was quenched by the addition of NH₄Saturated aqueous IC after 30 min. The aqueous layer was extracted with ethyl acetate (3x). The combined organics were washed with water and brine, dried (sodium sulfate) and concentrated to give a pale yellow liquid (8 g). Chromatography on silica gel (chromatography on silica gel, 5-30%, ethyl acetate in hexanes) gave 5-bromo-2- (1,1-diethoxyethyl) -1,3-thiazole (989 mg , 3.53 mmol, 20.07% yield) as a colorless liquid.

Step 3:

To a solution of the product from Step 2 (981 mg, 3.50 mmol) in dichloromethane (4 mL) at room temperature, under nitrogen, trifluoroacetic acid (6,204 mL, 81 mmol) and water (208 pL, 11.55 mmol) were added. The mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane

278 and it was washed with 5% aqueous sodium bicarbonate (3x) and the brine, dried (sodium sulfate) and concentrated to give 1- (5-bromo-1,3-thiazol-2yl) ethanone (654 mg, 3.17 mmol) 91% yield) as a yellow solid that was used without further purification.

Step 4:

The product from Step 3 (300 mg, 1,456 mmol), 3aminophenylboronic acid monohydrate (271 mg, 1,747 mmol), tetrakis (triphenylphosphine) palladium (0) (84 mg, 0.073 mmol), DME (9 mL) and Sodium carbonate (2M, 2,184 mL, 4.37 mmol) were successively introduced into a 10-20 mL reaction flask under nitrogen. The mixture was stirred under microwave irradiation at 140 ° C for 20 min, cooled to room temperature, and diluted with water. The aqueous layer was extracted with ethyl acetate (3x). The combined organics were washed with water and brine, dried (sodium sulfate) and concentrated to give a beige solid (419 mg). Chromatography on silica gel (CombiFlash, 5-25% ethyl acetate in dichloromethane) gave 1- [5- (3-aminophenll) -1,3-t¡azol-2¡Ijetanone (252 mg, 1,155 mmol) 0.79% yield) as a yellow solid.

Step 5:

To a solution of the product from Step 4 (179 mg, 0.820 mmol) in THF (3 mL) and methanol (1 mL) at 0 ° C, under nitrogen, sodium borohydride (62.1 mg, 1,640 mmol) was added. The mixture was allowed to heat

279 at room temperature and was stirred for 1 H, before being warmed by the addition of 25% NH₄OAc aqueous. The aqueous layer was extracted with ethyl acetate (3x). The combined organics were washed with water and brine, dried (Na₂SW₄) and concentrates to give a colorless gum (177 mg). Chromatography on silica gel (CombiFlash, 40-90% ethyl acetate in dichloromethane) provided 1- [5- (3-aminophenyl) -1,3-thiazol-2-yl] ethanol (151 mg, 0.685 mmol) , 84% yield) as a white solid.¹H NMR (400 MHz, CDCI₃): δ 7.84 (s, 1H); 7.20 (t, J = 7.8 Hz, 1H); 6.97 (d, J = 7.7 Hz, 1H); 6.88 (s, 1H); 6.68 (dd, J = 8.0, 2.2 Hz, 1H); 5.20-5.12 (m, 1H); 3.78 (s, 2

H); 2.96 (d, J = 4.6 Hz, 1H); 1.69 (d, J = 6.5 Hz, 3H).

Intermediate 24: methyl 2,2-dimethyl-4-oxocyclohexanecarboxylate

Step 1:

Methyl 3-oxobutanoate (232g, 2.00mol) and paraformaldehyde (30g, 999.00mmol) were combined, and piperidine (10g, 117.44mmol) was added to the mixture. The resulting solution was stirred for 2H at 0 ° C. The solution was heated at 60 ° C for 2 h. Extracted with Et₂O (3x), and the organic layers were combined and dried Na₂SW₄. Filtered and concentrated under vacuum. This resulted in 370 g (crude) of dimethyl 2-methyl-6280 oxocyclohex-1-ene-1,3-dicarboxylate as a brown oil. MS: [M + H] + m / z 227.

Step 2:

To a solution of sodium methanolate (90 g, 1.67 mol) in methanol (300 mL), the product from Step 1 (150 g, 663.04 mmol) in methanol (150 mL) was added by dripping with stirring for 30 min. The resulting solution was heated at 80 ° C for 30 min. and the mixture was concentrated in vacuo. The reaction mixture was then quenched by the addition of H₂O / ice (120 mL), then diluted with acetic acid (130 mL). The resulting solution was extracted with Et₂O (3x), and the organic layers were combined and dried over Na₂SW₄, filtered and concentrated under vacuum. The final product was purified by distillation under reduced pressure (5 Mm Hg) and the fraction was combined at 110 ~ 120 ° C. This resulted in 100 g (88%) of methyl 2-methyl-4-oxocyclohex-2-enecarboxylate as a yellow oil. MS: [M + H] + m / z 169.

Step 3:

Copper iodide (121.8 g, 639.54 mmol) was added to Et₂O (800 mL). Methylithium (1.6 M in diethyl ether, 800 mL, 1.28 mol) was added dropwise at -40 ° C over 3 H. A solution of the product from Step 2 (53.8 g, 319.88 mmol) was added in Et₂Or (400 mL) at -40 ° C for 2 min. The resulting solution was stirred 5H at -20 ° C. It was inactivated by adding

281 saturated aqueous ammonium chloride (2.5 I). It was extracted with EtOAc (3x2 I). The combined organic extracts were dried on Ña₂SO4, filtered, and concentrated in vacuo. The residue was purified by eluting through a silica gel column with a 1:20 EtOAc / PE solvent system. This resulted in 45 g (73%) of methyl 2,2-dimethyl-4-oxocyclohexanecarboxylate as a yellow oil. MS: [M + H] + m / z 185.¹H NMR (600 MHz, CDCI₃) δ 3.49 (s, 3H), 2.43 - 2.40 (m, 1H), 2.35 - 2.29 (m, 1H), 2.21 - 2.17 (m, 1H), 2.11 - 2.04 (m, 1H), 2.00 - 1.96 (m , 1H), 1.91 - 1.85 (m, 1H), 0.85 (s, 3H), 0.77 (s, 3H).

Intermediate 25 C / s -methyl 4- (5-bromo-1,3-thiazol-2-yl) -4-hydroxy2,2-dimethylcyclohexanecarboxylate racemic

OR

<img file="MX2012007154A_D0080.tif" />

Step 1:

N-Butyl lithium (2.2 mL, 5.5 mmol, 2.5 M solution in hexanes) was added dropwise over 12 minutes to a solution of thiazole (0.515 g, 6.05 mmol) in tetrahydrofuran (15 mL) at -78 ° C. After 30 minutes, the opaque yellow suspension was transferred for 5 minutes through a cannula cooled on dry ice to a solution of Intermediate 24 (1,013 g, 5.5 mmol) in tetrahydrofuran (15 mL) at -78 ° C. The resulting yellow solution was kept at -78 ° C for 1 hour, moved to a 0 ° C bath for 15

282 minutes, and then cooled again to -78 ° C. The saturated aqueous ammonium chloride solution (10 mL) was added and the mixture was allowed to warm to room temperature. The biphasic mixture was partitioned between ethyl acetate (50 mL) and water (5 mL); the layers were separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography (Biotage 100g SNAP column, 90:10 to 65:35 hexane: ethyl acetate) to provide cis-methyl-4-hydroxy-2,2-dimethyl-410 ( Racemic 1,3-thiazol-2-yl) cyclohexanecarboxylate as a white solid (1.08 g, 73% yield). MS APCI: [M + H] + m / z 270.1.

Step 2:

To a solution of the product from Step 1 (0.35 g, 1.3 mmol) in

Ν, Ν-dimethylformamide (1.9 mL) was added N-bromosuccinimide (0.254 g, 1,429 mmol). After three hours an additional portion of Nbromosuccinimide (0.046 g, 0.258 mmol) was added. After an additional hour, the reaction mixture was partitioned between ethyl acetate (25 mL), saturated aqueous sodium thiosulfate (10 mL), and water (5 mL). The layers were separated, and the organic layer was washed with water (3x5 mL) and brine (10 mL), dried over sodium sulfate, filtered, and concentrated. The crude reaction was purified through silica gel chromatography (Biotage 100g SNAP column, 95: 5 to 75:25 hexane: ethyl acetate) to provide cis283 methyl 4- (5-bromo-1,3-thiazol-2 -L) -4-hydroxy-2,2-dimethyl cyclohexanecarboxylate as a white solid (286.8 mg, 63% yield). MS APCI: [M + H] + m / z 348.0, 350.0. Ή NMR (500 MHz, CDCI₃): δ 7.58 (s, 1H); 3.69 (s, 3H); 2.45 (s, 1H); 2.36 (m, 1H); 2.21 (m, 1H); 1.94 (m, 3H); 1.75 (m,

2H); 1.19 (s, 3H); 1.06 (s, 3H).

Intermediate 26 5-Bromo-2- (1-methoxychlorobutyl) -1,3-thiazole

<img file="MX2012007154A_D0081.tif" />

Sodium hydride (60% dispersion in mineral oil) (47.0 mg, 1,175 mmol) was added at 0 ° C to a solution of Intermediate 1 (250 mg, 1,068 mmol) in DMF (3 mL) and THF (3 mL ) and the mixture was allowed to react for 1 hour. Methyl iodide (0.080 ml, 1,281 mmol) was added and the mixture was further reacted for 2 hours. The reaction mixture was poured into NH₄Aqueous CI diluted and extracted twice with diethyl ether. The organic fraction was concentrated and the residue was passed through a silica plug eluting with 1:10 ethyl acetate: hexane to produce 2-bromo-5- (1-methoxycyclobutyl) -1,3-thiazole (225 mg, 85% ).¹H NMR (500 MHz, (CD₃)₂CO): δ 7.73 (s, 1H); 3.19 (s, 3H); 2.54-2.40 (m, 4H);

1.92-1.82 (m, 2H).

284

Intermediary 27: 2-chloro-4-et¡lp¡rim¡d¡na

Ethylmagnesium Bromide (1.0 M in THF, 71.4 mL, 71.4 mmol) was added dropwise at -78 ° C to a solution of 2,4-dichloropyrimidine (10 g, 67.1 mmol) in THF (125 mL). After stirring for 1 h, NH₄Saturated aqueous CI was added at -78 ° C and the reaction was allowed to reach room temperature with stirring. Then, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with NaHCO₃saturated aqueous, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with ethyl acetate and hexanes to provide 2-chloro-4-ethylpyrimidine (5,031 g, 18.70 mmol, 27.9%) as a regioisomeric 53:47 mixture.

Intermediate 28: 2-chloro-4- (methylsulfanil) p¡r¡mid¡na

Sodium thiomethoxide (5.18 g, 73.8 mmol) was added slowly portionwise through a powder addition funnel to a stirred solution of 2,4-dichloropyrimidine (10 g, 67.1 mmol) in THF (150 mL) at room temperature. After stirring overnight, the reaction was taken in ethyl acetate, washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with ethyl acetate and hexanes to give 2-chloro-4- (methylsulfanyl) pyrimidine (10.127g, 47.3mmol, 70.4%) as a white solid.

285

Intermediary 29: 2-chloro-4-cyclopropylpyrididine

2,4-Dichloropyrimidine (15 g, 101 mmol), cyclopropylboronic acid (8.65 g, 101 mmol), PdChidppfJ-CFkCh adduct (8.22 g, 10.07 mmol), and potassium phosphate (53.4 g, 252 mmol) were combined in a 1L round bottom flask. THF (503 mL) was added and the suspension was heated under reflux with stirring overnight. The reaction was then cooled to room temperature, concentrated to ~ 100 mL under reduced pressure, extracted with ethyl acetate, washed with

NaHCO₃ saturated aqueous, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with ethyl acetate in hexanes to give 2-chloro-4-cyclopropylpyrimidine (10,124 g, 58.3 mmol, 57.9%) as an 89:11 mixture of regioisomers.

Intermediary 30: N-f3-Fluoro-5- (4.4.5.5-tetramethyl-1,3.2d¡oxaborolan-2-¡l) phen¡l1-4- (tr¡fluorometíl) pyrmidine-2 -amine

<img file="MX2012007154A_D0082.tif" />

To a flask containing 3-fluoro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) anline (3.3 g, 14.00 mmol) and 2-chloro-4 (trifluoromethyl ) pyrimidine (2.94 g, 16.10 mmol) were added dioxane (44

286 mL) and methanesulfonic acid (1.55 g, 16.10 mmol) and the reaction was heated to 100 ° C overnight. The reaction was quenched, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce N- [3-fluoro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] -4 (trifluoromethyl) pyrimidine -2-amine (4.10 g, 10.70 mmol, 76% yield). MS ESI: [M + H] + m / z 384.¹H NMR (500 MHz, DMSO-d₆) δ 10.41 (s, 1H), 8.85 (d, J = 4.9, 1H), 7.92 (dt, J = 2.3, 12.1, 1H), 7.77 (d, J = 1.5, 1H), 7.32 (d, J = 4.9, 1H), 6.98 (dd, J = 2.2, 8.4, 1H), 1.28 (s, 12H).

Intermediate 31: 5-fluoro-4-methoxy- / V- [3-methyl-5- (4,4,5.5tetramethyl-1,3,2-dioxaborolan-2-l) phen¡Hpir¡ midin-2-am¡na

<img file="MX2012007154A_D0083.tif" />

To a flask containing 2-chloro-5-fluoro-4-methoxypyrimidine (0.32 g, 1.97 mmol) and 3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl ) aniline (0.40 g, 1.72 mmol) were added dioxane (17 mL) and methanesulfonic acid (0.13 mL, 1.97 mmol). The reaction was heated to 100 ° C overnight. The reaction was then cooled to room temperature, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Ultrafast chromatography was used

287 for purification to produce 5-fluoro-4-methoxy-N- [3-methyl-5- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] pyrimidin-2 -amine (0.31 g, 0.86 mmol, 50% yield). MS ESI: [M + H] + m / z 360.¹H NMR (500 MHz, DMSOd₆) δ 9.51 (s, 1H), 8.27 (d, J = 3.2, 1H), 8.00 (s, 1H), 7.57 (s, 1H), 7.07 (s, 1H),

4.01 (s, 3H), 2.25 (s, 3H), 1.26 (s, 12H).

Intermediate 32: 4- methyl-N- [3- (4,4,5_l5-tetramethyl-1,3,2d¡oxaborolan-2-l) phen¡Hp¡r¡mid¡n-2-am¡na

<img file="MX2012007154A_D0084.tif" />

To a flask containing 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline (1.50 g, 6.85 mmol) and 2-chloro-4-methylpyrimidine (1.01 g, 7.87 mmol) ) Dioxane (69 mL) and methanesulfonic acid (0.51 mL, 7.87 mmol) were added. The reaction was heated to 100 ° C overnight. The reaction was then cooled to room temperature, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Ultra-fast chromatography was used for purification to produce 4-methyl-N- [3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] pyrimidin2-amine (1.23 g, 3.95 mmol, 58% yield). MS ESI: [M + H] + m / z 312.¹H NMR (500 MHz, DMSO-d₆) δ 9.48 (s, 1H), 8.30 (d, J = 5.0, 1H), 7.98

288 (d, J = 8.0, 1H), 7.95 (s, 1H), 7.29-7.20 (m, 2H), 6.71 (d, J = 5.0, 1H), 2.33 (s, 3H), 1.28 (s, 12H) .

Intermediary 33: 4- (2-methoxyethoxy¡) - / V- [3-methyl-5- (4.4,5.5tetramethyl-1,3,2-dioxaborolan-2-¡l) fen¡llpir¡m¡d¡n -2-amine

<img file="MX2012007154A_D0085.tif" />

2-chloro-4- (2-methoxyethoxy) p¡r¡m¡d¡na (91 mg, 0.485 mmol) and 310 methyl-5- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) aniline (113 mg, 0.485 mmol) were dissolved in Dioxane (4 mL), and methanesulfonic acid (0.033 mL, 0.509 mmol) was added. The mixture was heated at 100 ° C for 18H. The mixture was allowed to cool to room temperature, quenched with saturated aqueous sodium bicarbonate, and extracted with EtOAc (2x). The combined organics were dried over Na₂SW₄, filtered and concentrated in vacuo to obtain 4- (2-methoxyethoxy) - / \ / - [3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) Phenyl] pyrimidine-2-amine (160 mg, 86%) as a brown solid. MS APCI: [M + H] + m / z 386.¹H NMR (500 MHz, CDCI₃) δ 8.08 (d, J = 5.8, 1H), 7.93 (s, 1H), 7.48 (s, 1H), 7.34 (s, 1H), 6.26 (d, J = 6.0, 1H), 4.58 (m, 2H ), 3.77 (m, 2H), 3.42 (s 3H), 2.37 (s, 3H), 1.34 (s, 12H).

289

Intermediary 34: 4- (3-methoxypropoxy) - / V- [3-methyl-5- (4,4,5,5tetramethyl-1,3,2-d-oxoborolan-2-¡ l) fen¡llpir¡m¡d¡n-2-amina

<img file="MX2012007154A_D0086.tif" />

Step 1:

2,4-Dichloropyrimidine (250 mg, 1,678 mmol), 3-methoxy-1-propanol (0.193 ml, 2,014 mmol), and cesium carbonate (929 mg, 2.85 mmol) were combined in DMF (5 mL). The suspension was heated at 80 ° C for 15H. The mixture was allowed to cool to room temperature, diluted with brine and extracted with EtOAc (3x). The organic layer was dried over Na₂SW₄ and concentrated in a vacuum. Purification by flash chromatography (5-15% EtOAc: Hexanes) gave 2-chloro-4- (315 methoxypropoxy) pyrimidine (112 mg, 33%) as a colorless oil. MS ESI: [M + H] + m / z 203.

Step 2:

The product from Step 1 (107 mg, 0.528 mmol) and 3-methyl-520 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline (123 mg, 0.528 mmol) were dissolved in Dioxane (4 mL), and methanesulfonic acid (0.036 ml, 0.554 mmol) was added. The mixture was heated to 100 ° C for 18 H. The mixture was allowed to cool to room temperature, tempered with bicarbonate

290 aqueous saturated with sodium and extracted with EtOAc (2x). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to provide 4- (3-methoxypropoxy) - / \ / - [3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl) phenyl] pyrimidin-2-amine (165 mg, 78%) as a brown solid. MS ESI: [M + H] + m / z 400.¹H NMR (500 MHz, CDCI₃) δ 8.09 (d, J = 5.8, 1H), 7.82 (s, 1H), 7.59 (s, 1H), 7.32 (s, 1H), 6.17 (d, J = 4.4, 1H), 4.48 (t, J = 5.8, 2H), 3.53 (t, J = 5.5, 2H), 3.34 (s, 3H), 2.37 (s, 3H), 2.05 (dd, J = 3.3, 9.4, 2H), 1.34 (s, 12H) .

Intermediate 35: 4-ethyl-N- [3-methyl-5- (4,4,5,5-tetramethyl-1,3,2d¡oxaborolan-2-yl) fenillpir¡m¡din-2 -amine

<img file="MX2012007154A_D0087.tif" />

Step 1:

In a 1 I 3-neck flask containing 3-bromo-5-methylaniline (60 g, 290 mmol), bis (pinacholate) diboro (96 g, 377 mmol), 2-dicyclohexylphosphine-2 ', 4', 6'-triisopropylbiphenyl ( 8.3 g, 17.4 mmol), dibenzylidene acetone palladium (3.99 g, 4.35 mmol) and potassium acetate (42.7 g, 435 mmol) 1,4-dioxane (720 mL) which had been degassed by nitrogen spray was added over 30 minutes. After washing the flask abundantly with nitrogen for 2 minutes, the reaction was heated to

291 an internal temperature of 80 ° C for 4 hours. With cooling, the reaction mixture was filtered through a pad of Celite, and then the

Celite was washed with methyl tert-butyl ether (500 mL). The resulting solution was diluted with methyl tert-butyl ether (500 mL), pH 8 phosphate buffer (500 mL), and brine (500 mL). The layers were separated and the organic layer was washed with a semi-saturated brine solution (1 I). The aqueous layers, which were maintained separately, were sequentially back-extracted with methyl tert-butyl ether (500 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel (0-90% ethyl acetate / hexanes) and the resulting light orange solid was dried overnight under a nitrogen atmosphere to give 3-methyl-5 - (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) aniline (67.7 g, 255 mmol, 88% yield, 90% purity). MS ESI: [M + H] + m / z 234.1.

Step 2:

A solution of 2-chloro-4-ethyl pyrimidine (0.98g, 7.00mmol), the product from Step 1 (1,794g, 7.70mmol) and methanesulfonic acid (0.50ml, 7.70mmol) in 1,4-dioxane (30mL ) was hermetically sealed in a pressure flask with a 100 ml screw cap and heated at 110 ° C for 15 hours. The flask was cooled, an additional portion of 2-chloro-4-ethyl pyrimidine (0.145 g, 1.05 mmol) was added, the flask was resealed, and heated for an additional 6.5 hours. The reaction mixture was cooled,

292 diluted with ethyl acetate (70 mL), washed with a saturated aqueous solution of sodium bicarbonate (25 mL) and brine (25 mL), dried over sodium sulfate, filtered, and concentrated. The resulting reddish brown solid of 4-ethyl-N [3-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] pyrim¡d¡n-2 -amine (3.44 g as an 80:20 w / w mixture with 1,4-dioxane) was used without further purification. MS ESI: [M + H] + m / z 340.1

Intermediary 36: / V- [3-cyclopropyl-5- (4.4₁5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl -4-methylpyrimidin-2-amine

<img file="MX2012007154A_D0088.tif" />

A solution of 3,5-dibromoaniline (2.93 g, 11.67 mmol), 2-chloro-4-methyl pyrimldine (1.5 g, 11.67 mmol) and acetic acid (0.701 ml, 12.25 mmol) in 1,4-dioxane (23.5 mL) is hermetically sealed in a pressure vessel under an argon atmosphere and heated at 120 ° C for 17 hours. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (100 mL) and a saturated aqueous solution of sodium bicarbonate (40 mL). The layers were separated and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Flash chromatography on silica gel (10% to 30% acetate

293 ethyl / hexanes) provided N- (3,5-dibromophenyl) -4-methylpyrimidin-2-amine (3. g, 9.7 mmol, 85% yield, 95% purity) as a light yellow solid. MS ESI: [M + H] + m / z 343.8.

Step 2:

A mixture of 1,4-dioxane (40 mL) and aqueous sodium carbonate (2M, 10.50 mL, 20.99 mmol) was sprayed with argon for 15 minutes and then poured into a flask containing the product from Step 1 (3.6 g , 9.97 mmol, 85% yield, 95% purity) and PdCI adduct₂(dppf) 10 CH₂CI₂ (0.686 g, 0.840 mmol). Cyclopropylboronic acid (1037g, 12.07mmol) was added followed by a condenser and the entire system was placed under argon by five cycles of vacuum / flush with argon. The reaction mixture was heated under reflux for 18 hours and then cooled to room temperature and diluted with ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (45-80% acetonitrile / water with 0.10% TFA buffer). Fractions containing the desired product were diluted with ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated to give N- (3-bromo-5-cyclopropylphenyl) -4-methylpyrimidin-2-amine (443.6 mg, 1.31 mmol, 13% yield) as a brown oil . MS ESI: [M + H] + m / z 306.0.

294

Step 3:

A solution of the product from Step 2 (443.6 mg, 1,458 mmol), Bis (pinacolloate) diboro (407 mg, 1,604 mmol), PdCI adduct₂(dppf) CH₂CI₂ (119 mg, 0.146 mmol), and potassium acetate (429 mg, 4.37 mmol) in dimethyl sulfoxide was heated under argon in a microwave for 10 minutes at 150 ° C. The reaction mixture was diluted with diethyl ether (40 mL) , ethyl acetate (40 mL), and saturated aqueous sodium bicarbonate solution (30 mL) and then filtered to remove any solid that did not dissolve. The layers were separated and the organic layer was washed with water (3 x 25 mL) and brine (25 mL), dried over sodium sulfate, filtered, and concentrated. The resulting crude product was purified through silica gel chromatography (5-30% ethyl acetate / hexanes) to provide A / - [3-cyclopropyl5- (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2-yl) phenyl] -4-methylpyrimidin-2-amine (186.1 mg, 0.53 mmol, 36% yield, approximately 75% pure) as a white solid. The material was used in later stages in this crude form. MS ESI: [M + H] + m / z 352.2.

Intermediate 37: N-f3- (Methoxymethyl) -5- (4.4,5,5-tetramethyl-1,3,2-dioxaborolan-2l) phenyl-4- (trifluoromethyl) pyrimidin -2-amine

<img file="MX2012007154A_D0089.tif" />

.0.

295

Step 1.

Iodomethane (0.40 mL, 6.46 mmol) was added to a solution of (3-bromo-5-nitrophenyl) methanol (500 mg, 2,155 mmol) in DMF (7.2 mL). The solution was cooled to 0 ° C before NaH ( 60% dispersion in mineral oil, 172 mg, 4.31 mmol) was added. The reaction was stirred at 0 ° C and allowed to reach room temperature. After 2 hours the reaction was quenched with water and ethyl acetate then added The extraction was done with ethyl acetate (3X). The combined organic layer was dried over magnesium sulfate and then filtered. Ethyl acetate was then removed in vacuo to provide 1-bromo-3- (methoxymethyl) -5-nitrobenzene (470 mg, 1,910 mmol, 89% yield) as a yellow solid.¹H NMR (500 MHz, DMSO-d₆) δ 8.25 (s, 1H), 8.13 (s, 1H), 7.96 (s, 1H), 4.53 (s, 2H), 3.33 (s, 3H).

Step 2:

To a solution of the product from Step 1 (470 mg, 1,910 mmol) in (EtOH / Water) (8.5 mL mL / 4.2) were added iron (533 mg, 9.55 mmol) and ammonium chloride (51 mg, 0.955 mmol). The reaction was stirred at 90 ° C for approximately 4 hours. The reaction was then allowed to reach room temperature and diluted with ethyl acetate. The solution was then filtered through Celite and organic solvent was then removed under vacuum. Flash chromatography (ethyl acetate / hexane: 70/30) was used for purification to provide 3-bromo-5- (methoxymethyl) aniline

296 (258 mg, 1,194 mmol, 62.5% yield). MS ESI: [M + H] + m / z =

216.0.

Step 3:

To a solution of the product from Step 2 (258 mg, 1,194 mmol) in dioxane (3.8 mL) were added 2-chloro-4- (trifluoromethyl) pyrimidine (251 mg, 1,373 mmol) and methanesulfonic acid (0.07 mL, 1,015 mmoles). The reaction was then stirred overnight at 100 ° C. The reaction was then cooled, diluted with ethyl acetate, and then washed with brine solution. The organic layer was combined, dried over magnesium sulfate, and then filtered. The ethyl acetate was then removed in vacuo. Flash chromatography (ethyl acetate / hexane: 70/30) was used for purification to provide N- [3-bromo-5- (methoxymethyl) phenyl] -4 (trifluoromethyl) pyrimin-2-amine as an off-white solid (314 mg, 0.867 mmol, 72.6% yield). MS ESI: [M + H] + m / z = 362.0.

Step 4:

To a solution of the product from Step 3 (200 mg, 0.552 mmol) in dioxane (2.8 mL) were added Bis (pinacolato) diboro (210 mg, 0.828 mmol), potassium acetate (108 mg, 1,105 mmol), X-Phos (26.5 mg, 0.055 mmol) and palladium (II) acetate (6.20 mg, 0.029 mmol). Nitrogen was bubbled into the reaction for approximately 5 minutes and the reaction was then sealed and stirred overnight at 90 ° C. The reaction then was

297 cooled to room temperature and diluted with ethyl acetate. The solution was then filtered through Celite and the organic solvent was removed in vacuo to provide N- [3- (methoxymethyl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2yl ) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine as a brown oil. 100% yield was assumed and no further purification was done on this material. MS ESI: [M + H] + m / z = 410.2.

Intermediary 38: (5-Fluoro-4-met¡lp¡rim¡d¡n-2-¡l) - [3-met¡l-5 (4.4,5,5-tetramethyl- [1,3, 2] d¡oxaborolan-2-il) -fen¡ll-am¡na

<img file="MX2012007154A_D0090.tif" />

To a solution of 2-chloro-5-fluoro-4-methylpyrimidine (4.00 g, 27.3 mmol) and 3-methyl-5- (4,4,5,5-tetramethyl- [1 , 3.2] dioxaborolan-2-yl) -phenylamine (8.27 g, 35.5 mmol) in dioxane (40.7 mL) methanesulfonic acid (1.77 mL, 27.3 mmol) was added dropwise during which the reaction became exothermic at 15.7 ° C. Subsequently, the reaction mixture was heated to 100 ° C and allowed to stir over the weekend. The mixture was cooled to room temperature and was diluted with NaHCO₃ aqueous saturated and extracted with ethyl acetate. The organic extracts were washed with brine and dried over MgSO₄, filtered and concentrated under vacuum. Purification by flash chromatography provided (5-fluoro-4-methyl298 pyrimidin-2-yl) - [3-methyl-5- (4,4,5,5-tetramethyl- [1,3,2] d Oxaborolan-2-yl) -phenyl] -amine (5.87 g, 17.1 mmol) MS ESI: [M + H] + m / z 344.1.¹H NMR (500 MHz, DMSO-de) δ 9.50 (s, 1H), 8.38 (d, J = 1.6, 1H), 7.81 - 7.62 (m, 2H), 7.07 (s, 1H), 2.36 (d, J = 2.3, 3H), 2.26 (s, 3H), 1.27 (s, 12H).

Intermediary 39: (4-D¡fluoromet¡lp¡rim¡d¡n-2-¡l) - [3-met¡l-5 (4.4,5_l5-tetramethyl- [1,3₁21d¡oxaborolan-2-¡l) -fenin-am¡na

<img file="MX2012007154A_D0091.tif" />

Step 1:

To a solution of difluoroacetic anhydride (50 g, 287 mmol) in CH2CI2 (300 mL) cooled to -20 ° C was added DMAP (0.351 g, 2.87 mmol) followed by the addition of vinyl ethyl ether (13.8 mL, 144 mmol) ) at such a speed that the internal temperature did not exceed -10 ° C. When completed, the flask was shaken at 0 ° C for 12H before slowly warming to room temperature over the next 6H. Water along with CH₂CI₂The separated layers were added, and the organic layer was washed sequentially with saturated aqueous NaHCO3 and then brine. The organic layer was dried with MgSO₄, filtered, concentrated in vacuo. The residue was subsequently taken up in EtOH (162 mL), immersed in an ice-water bath, and then urea (17.25 g, 287 mmol) followed by conc. HCI. (43 mL)

299 They were added at such a rate that the internal temperature did not exceed 20 ° C. When the addition was complete, the cooling bath was removed and the resulting mixture was stirred for 18H before concentration in vacuo. EtOH was added and the mixture was concentrated a second time, then repeated twice with EtOAc. The residue was diluted with EtOAc (100 mL), the heterogeneous mixture stirred for 10 min, and then the solvent was decanted. This was repeated two more times then the light brown solid was dried under vacuum for 48 H before dilution with phosphorous oxychloride (215 mL, 2310 mmol). The resulting suspension was heated at 105 ° C for 90 min during which time it was observed to become homogeneous. The reaction mixture was cooled to room temperature, carefully poured into a 4 I chilled flask containing 2 I of ice and a temperature probe. The mixture was stirred for 1 H until the exotherm ceased at which time the content was transferred to a separating funnel with CH₂CI₂ additional.

The layers were cut, the aqueous layer was extracted with CH₂CI₂ (2x), then the combined organics were dried with MgSO₄, filtered and concentrated in vacuo (200 Torr, 40 ° C) to an orange oil. The product was placed under vacuum for 1 min to produce 2-chloro-4-difluoromethyl-pyrimidine (31 g, 62.5% by weight of solution in CH₂CI₂ for 1H

NMR, 118 mmol). ¹H NMR (600 MHz, CDCI₃) δ 8.82 (d, J = 5.0, 1H), 7.57 (d, J = 5.0, 1H), 6.51 (t, J = 54.4, 1H).

300

Step 2:

The product from Step 1 (4.75 g, 23 mmol) and 3-bromo-5-methylaniline (5.59 g, 30 mmol) was diluted with dioxane (33 mL) to which AcOH (1.32 mL, 23 mmol) was added. The resulting mixture was heated under reflux and maintained with stirring for 30 H after which it was re-cooled to room temperature, diluted with CH2CI2 and absorbed into the silica prior to purification by flash chromatography to provide / V- (3-bromo- 5methylphenyl) -4- (difluoromethyl) pyrimidin-2-amine (5.2 g, 16.6 mmol).¹H NMR (600 MHz, CDCI3) δ 8.58 (d, J = 4.9, 1H), 7.75 (s, 1H), 7.32 (s, 1H), 7.21 (s,

1H), 7.06-6.92 (m, 2H), 6.50-6.27 (m, 1H), 2.30 (s, 3H).

Step 3:

The product from Step 2 (0.5g, 1.6mmol), bis (pinacholate) diboro (0.465g, 1.83mmol), potassium acetate (0.469g, 4.78mmol) and PdCl2 adduct (dppf) -CH2CI₂ (0.065 g, 0.08 mmol) were diluted with degassed dioxane (3.5 mL) and heated under reflux for 2 H then re-cooled to room temperature. The mixture was diluted with CH2CI2 and water was added. The layers were cut, the organic dried with MgSO4, filtered and concentrated in vacuo, and in the crude residue purified by flash chromatography to provide (4-difluoromethyl-pyrimidin-2-yl) - [3methyl-5- (4, 4,5,5-tetramethyl- [1,3,2] dioxaborolan-2-yl) -phenyl] -amine (550 mg, 1.52 mmol) MS ESI: [M + H] + m / z 362.1. ¹H NMR (600 MHz, CDCI₃) δ 8.56 (d, J

301 = 4.1, 1Η), 7.74 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.35 (s, 1H), 6.94 (d, J = 4.2, 1H), 6.38 (t, J = 55.0, 1H), 2.36 (s, 3H), 1.33 (s, 12H).

Intermediary_40: _2- [3- (1.3-thiazol-5-yl) -5 - {[45 (trifluorometyl) pyrimidin-2-l1amino) phenyllpropan-2-ol

<img file="MX2012007154A_D0092.tif" />

Step 1:

To a flask containing methyl 3-amino-5-iodobenzoate (500 mg, 1.81 mmol) was added a solution of 2-chloro-4 (trifluoromethyl) pyrimidine (379 mg, 2.08 mmol) in dioxane (5.6 mL). Methanesulfonic acid (199 mg, 2.08 mmol) was added and the reaction was heated to 100 ° C overnight. The reaction was quenched, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce methyl 3-iodo-5 - {[4- (trifluoromethyl) pyrim¡din-2-yl] amino} benzoate (538 mg, 1.27 mmol, 71% yield) . MS ESI: [M + H] + m / z

424.0.

302

Step 2:

To a flask containing the product from Step 1 (538 mg, 1.27 mmol), (bispinacholate) diboro (646 mg, 2.54 mmol), tricyclohexylphosphine (36 mg, 0.13 mmol), Pd₂(dba)₃ (29 mg, 0.03 mmol) and potassium acetate (200 mg, 2.03 mmol) was previously added to degassed dioxane (12 mL). The solution was evacuated and then purged with argon 5 times and then heated at 95 ° C overnight. The reaction was quenched, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -5 - {[4 (trifluoromethyl) pyrimidin-2-yl] Methyl amino} benzoao (391 mg, 0.92 mmol, 73% yield). MS ESI: [M + H] + m / z 424.1.

Step 3:

To a flask containing the product from Step 2 (391 mg, 0.92 mmol), dicyclohexyl [2 ', 4', 6'-tri (propan-2-yl) biphenyl-2-yl] phosphane (44 mg, 0.092 mmol), Pd₂(dba)₃ (42 mg, 0.046 mmol), cesium carbonate (602 mg, 1.85 mmol), a solution of 5-bromothiazole in a degassed mixture of dioxane (8.4 mL) and water (840 pL) was added. The solution was evacuated and then purged with argon 5 times and then heated at 90 ° C overnight. The reaction was quenched, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce methyl 3- (1,3-thiazol-5-yl) -5303 {[4- (trifluoromethyl) pyrimidin-2-yl] amino} benzoate (254 mg, 0.67 mmol, 72% yield). MS ESI: [M + H] + m / z 381.0.

Step 4:

THF (6.7 mL) was added to a flask containing the product from Step 3 (254 mg, 0.7 mmol). The solution was cooled to 0 ° C and then methylmagnesium chloride (3.0M in Et₂O, 1.1 mL, 3.3 mmol) was added and the reaction was stirred for one hour. After one hour, more methylmagnesium chloride (3.0M in Et₂O, 1.1 mL, 3.3 mmol) was added and the reaction was stirred for 30 minutes. The reaction was then diluted with ethyl acetate and carefully quenched with water and then diluted with water. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce 2- (3- (1,3-thiazol-5-yl) -5 - {[4- (trifluoromethyl) pyrimidin-215 yl] amino} phenyl] propan-2-ol (188 mg, 0.49 mmol, 74% yield). MS ESI: [M + H] + m / z 381. ¹H NMR (500 MHz, DMSO-d₆) δ 10.26 (s, 1H), 9.07 (s, 1H), 8.82 (d, J = 4.8, 1H), 8.20 (s, 1H), 8.03 (s, 1H), 7.79 (s, 1H), 7.45 ( s, 1H), 7.28 (d, J = 4.9, 1H), 5.12 (s, 1H), 1.46 (s, 6H).

304

Intermediate 41: N- [3-cyclopropyl-5- (1,3-thiazol-5-yl) pheniH-4 (trfluoromethyl) prmmdin-2-amine

<img file="MX2012007154A_D0093.tif" />

A / - [3- (Bromomethyl) -5- (1,3-thiazol-5yl) phenyl] -4- (trifluoromethyl) pyrimin-2-amine (523 mg, 1.30 mmol), acid was added to a flask. cyclopropyl boronic (336 mg, 3.91 mmol), potassium phosphate (968 mg, 4.56 mmol), Pd (OAc)₂ (15 mg, 0.07 mmol) and tricyclohexylphosphine (37 mg, 0.13 mmol). Degassed toluene (10 mL) and water (0.5 mL) were added and the solution was evacuated and then purged 5 times with argon. The mixture was then microwaved at 130 ° C for 30 minutes. The reaction was diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce N- [3-cyclopropyl-5- (1,3-thiazol-5yl) phenyl] -4- (trifluoromethyl) pyrimidin-2-amine (384 mg, 1.06 mmol, 81% performance). MS ESI: [M + H] + m / z 363.¹H NMR (500 MHz, DMSO-d₆) δ 10.23 (s, 1H), 9.06 (s, 1H), 8.83 (d, J = 4.8, 1H), 8.23 ​​(s, 1H), 7.92 (s, 1H),

7.41 (s, 1H), 7.28 (d, J = 4.9, 1H), 7.12 (s, 1H), 2.03 - 1.80 (m, 1H), 1.05 0.92 (m, 2H), 0.78-0.61 (m, 2H) .

305

Intermediary 42: A / 43 - ({fter-butíl (d¡metíl) s¡l¡l1ox¡) metíl) -5- (1,3thiazol-5-il) fenín-4- (trifluoromethyl) p¡r¡m¡d¡n-2-am¡na

<img file="MX2012007154A_D0094.tif" />

Step 1:

THF (9.0 mL) was added to a flask containing methyl 3-amino-5-iodobenzoate (250 mg, 0.90 mmol). The solution was cooled to 0 ° C and lithium aluminum hydride (1.0M in THF, 1.8 mL, 1.8 mmol) was added slowly and the reaction was allowed to warm to room temperature. Once complete on TLC, the reaction was carefully quenched with water and then diluted with ethyl acetate. The organic layer was extracted, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce [3 (aminomethyl) -5-iodophenyl] methanol (109mg, 0.44mmol, 49% yield). MS ESI: [M + H] + m / z 250.0.

Step 2:

A solution of 2-chloro-4- (trifluoromethyl) pyrimidine (92 mg, 0.50 mmol) in dioxane (1.4 mL) was added to a flask containing the product from Step 1 (109 mg, 0.44 mmol). Methanesulfonic acid was added (0.02 mL, 0.37 mmol) and the reaction was heated to 100 ° C by the

306 night. The reaction was then cooled to room temperature, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography was used for purification to produce (3-iodo-5 - {[4- (trifluoromethyl) pyrimidin-25 yl] amino} phenyl) methanol (90mg, 0.23mmol, 52% yield). MS ESI: [M + H] + m / z 396.0.

Step 3:

Ter-butyldimethylsilyl chloride (1.60 g, 10.59 mmol), imidazole (0.96 g, 14.12 mmol) and DMAP (86) were added to a flask containing the product from Step 2 (2.79 g, 7.06 mmol) in DMF (71 mL). mg, 0.71 mmol). After two hours, the reaction was diluted with water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. Column chromatography on silica gel was used for purification to produce N- [3 - ({[terbutyl (dimethyl) silyl] oxy} methyl) -5-iodophenyl] -4- (trifluoromethyl) pyrimidin-2 -amine (3.46 g, 6.79 mmol, 96% yield). MS ESI: [M + H] + m / z 510.0.

Step 4:

The product from Step 3 (3.46 g, 6.79 mmol), (bispinacholate) diboro (2.59 g, 10.19 mmol), d¡ciclohexil [2 ', 4', 6'tri (propan-2-il) was added to a flask biphenyl-2-yl] phosphane (324 mg, 0.68 mmol), Pd (OAc)₂ (76 mg, 0.34 mmol) and potassium acetate (1.33 g, 13.59 mmol) was added

307 above to degassed dioxane (68 mL). The solution was evacuated and then purged with argon 5 times and then heated to 85 ° C overnight. The solution was cooled, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Ultra-fast chromatography was used for purification to produce N- [3 - ({[terbutyl (dimethyl) silyl] oxy} methyl) -5- (4,4,5,5-tetramethyl-1,3, 2-doxaboronol-2-yl) phenyl] -4 (trifluoromethyl) pyrimidin-2-amine (2.75 g, 5.40 mmol, 79% yield). MS ESI: [M + H] + m / z 510.2.

Step 5:

To a flask containing the product from Step 4 (750 mg, 1.47 mmol), dicyclohexyl [2 ', 4', 6'-tri (propan-2-yl) biphenyl-2-yl] phosphane (70 mg, 0.15 mmol) ), Pd2 (dba) 3 (67 mg, 0.074 mmol), cesium carbonate (959 mg, 2.94 mmol), a solution of 5-bromothiazole in a degassed mixture of dioxane (2.7 mL) and water (270 pL) was added. The solution was evacuated and then purged with argon 5 times and then heated at 90 ° C overnight. The reaction was quenched, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Ultra fast chromatography was used for purification to produce N- [3 - ({[ter20 butyl (dimethyl) silyl] oxy} methyl) -5- (1,3-thiazol-5-yl) phenyl] -4 - (trifluoromethyl) p¡r¡m¡d¡n-2amina (414 mg, 0.89 mmol, 60% of yield). MS ESI: [M + H] + m / z 381.¹H NMR (500 MHz, DMSO-d₆) δ 10.38 (s, 1H), 9.07 (s, 1H), 8.81 (d, J =

308

4.9, 1 Η), 8.17 (s, 1 Η), 8.09 (s, 1 Η), 7.69 (s, 1 Η), 7.28 (d, J = 4.9, 1H), 7.26 (s, 1H), 4.72 ( s, 2H), 0.91 (s, 9H), 0.09 (s, 6H).

Intermediary_43: _4-cyclopropyl - f3-methyl-5- (1,3-t-acezol-55 yl) phenipyrpyridine-2-amine

<img file="MX2012007154A_D0095.tif" />

To a solution of 4-cyclopropyl- / V- (3-methyl-5- (4,4,5,5-tetramethyl10 1,3,2-dioxaborolan-2-yl) phenyl) pyrimidin-2-amine (750 mg , 2.14 mmol) in 2-methyl tetrahydrofuran (10.7 mL) 5-bromothiazole (406 mg, 2.35 mmol), RdCI was added₂(dppf) -CH₂Cl2 (87 mg, 0.11 mmol), and aqueous sodium carbonate (2 M, 2.14 mL). The reaction was sealed and purged with N2 for 5 minutes. The reaction was stirred at 80 ° C for 16h and cooled to room temperature. Water was added and extracted with EtOAc (x 3). The combined organic layers were dried (magnesium sulfate), concentrated, and purified by flash chromatography to provide 4- cyclopropyl-N- [3-methyl-5- (1,3-thiazol-5-yl) phenyl] pyrimidine- 2-amine (600 mg, 1.95 mmol, 91% yield) as a whitish solid. MS ESI: [M + H] + m / z 309.1. iH NMR (500 MHz, DMSO-d₆) δ 9.49 (s, 1H), 9.06 (s, 1H), 8.26 (d, J = 5.0, 1H), 8.19 (s, 1H), 8.04 (s, 1H), 7.43 (s, 1H), 7.10 ( s, 1H), 6.82 (d, J = 5.0, 1H), 2.29 (s, 3H), 2.00 (m, 1H), 1.17 - 0.93 (m, 4H).

309

<img file="MX2012007154A_D0096.tif" />

To a solution of 4-isopropyl-N- (3-methyl-5- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) phenyl) pyrimidin-2-amine (500 mg, 1.42 mmol) in tetra h id non-2-methyl breakdown (7.1 mL) 5-bromothiazole (318 mg, 1.84 mmol), PdCl2 (dppf) -CH were added₂Cl2 (58 mg, 0.07 mmol), and aqueous sodium carbonate (2 M, 1.42 mL). The reaction was sealed and purged with N2 for 5 minutes. The reaction was stirred at 80 ° C for 16h and cooled to room temperature. Water was added and extracted with EtOAc (x 3). The combined organic layers were dried over magnesium sulfate, concentrated in vacuo, and purified by flash chromatography to give 415 isopropyl-A / - (3-methyl-5- (thiazol-5-yl) phenyl) pyrimidin-2-amine ( 366 mg, 1.18 mmol, 83% yield) as an off-white solid. MS ESI: [M + H] + m / z 311.1.¹H NMR (500 MHz, DMSO-d₆) δ 9.59 (s, 1H), 9.05 (s, 1H), 8.38 (d, J = 4.7, 1H), 8.19 (s, 1H), 8.13 (s, 1H), 7.51 (s, 1H), 7.11 ( s, 1H), 6.77 (d, J = 5.1, 1H), 2.87 (m, 1H), 2.30 (s, 3H), 1.25 (d, J = 6.8, 6H).

310

Intermediate 45: 2-U3-methyl-5- (1,3t¡azol-5-l) phenol-1-amino) pyryrine-4-carboxylic acid trifluoroacetate

<img file="MX2012007154A_D0097.tif" />

To a solution of 2-chloropyrimidine-4-carboxylic acid (417 mg, 2.6 mmol) and 3-methyl-5- (1,3-thiazol-5-yl) aniline (500 mg, 2.6 mmol) in 1,4 dioxane degassed (11 mL) were added Pd (OAc)₂ (59 mg, 0.26 mmol), Xantphos (228 mg, 0.39 mmol) and C₂CO₃ (2.6 g, 7.9 mmol) and the reaction was heated at 100 ° C for 30 minutes. After cooling, the reaction was partitioned between 100 mL each of dichloromethane and buffer pH 1. The layers were separated and the organic phase was dried over MgSO₄ anhydrous, filtered, and concentrated under reduced pressure. Reverse phase HPLC purification (35-70% acetonitrile gradient using 0.1% trifluoroacetic acid buffer water) yielded 2 - {[3-methyl-5- (1,3-thiazole-) trifluoroacetate 5-yl) phenyl] amino} pyrimidine-4-carboxylic (20 mg, 1.8%) as a colorless oil. MS ESI: [M + H] + m / z

313.0.

311

Intermediate 46: 3-methyl-N- [3- (pentafluoroethyl) phenIl1-5- (1,3-thiazol5-il) aniline

<img file="MX2012007154A_D0098.tif" />

To a solution of 2-chloro-4- (pentafluoroethyl) pyrimidine (61 mg, 0.26 mmol) and 3-methyl-5- (1,3-thiazol-5-yl) aniline (50 mg, 0.26 mmol) in 1, Degassed 4-dioxane (1.1 mL) Xantphos (23 mg, 0.039 mmol), Pd (OAc) were added₂ (5.9 mg, 0.026 mmol) and C₂CO₃ (172 mg, 0.53 mmol) and the reaction was heated at 100 ° C for 30 minutes. After a cooling period, the reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous phase was extracted with EtOAc (10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (10 mL), dried over

MgSO₄ anhydrous, filtered and concentrated under reduced pressure. Purification on silica (20-60% ethyl acetate in hexanes) provided 3-methyl-N- [3- (pentafluoroethyl) phenyl] -5- (1,3-thiazol-5-yl) aniline (13 mg, 13% ) as a colorless foam. MS ESI: [M + H] + m / z 387.0.

312

Intermediary 47: 4- [1- (4-methoxybenzyl) -1 / 7-1,2,3-triazol-4-yl1- / V- [3methyl-5- (1.3-t¡azol-5-yl ) pheninpyrimidin-2-amine

<img file="MX2012007154A_D0099.tif" />

Step 1:

To a solution of 2-chloro-4-ethynylpyrimidine (200 mg, 1. 4 mmol) and 1- (azidomethyl) -4-methoxybenzene (0.5 M in f-butanol, 2.9 mL, 1.44 mmol) in 1: 1 water fBuOH (7.2 mL) was added copper (II) sulfate pentahydrate (36 mg, 0.14 mmol) and sodium ascorbate (143 mg, 0.72 mmol) and the reaction was stirred at room temperature for 2 hours. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous phase was extracted once with EtOAc (50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO₄ anhydrous, filtered, and concentrated under reduced pressure. Purification on silica (30-50% ethyl acetate in hexanes) provided 2-chloro-4- [1 - (4-methoxybenzyl) -1 A7-1,2,3-triazol-4-yl] pyrimidine (256 mg, 59%) as a white solid.

313

Step 2:

To a solution of 3-methyl-5- (1,3-thiazol-5-yl) aniline (63 mg, 0.33 mmol) and the product from Step 1 (100 mg, 0.33 mmol) in degassed 1,4-dioxane ( 1.3 mL) were added Pd (OAc)₂ (7.4 mg, 0.033 mmol),

Xantphos (29 mg, 0.050 mmol) and C₂CO₃ (216 mg, 0.66 mmol) and the reaction was heated at 100 ° C for 30 minutes. After cooling, the reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate (10 mL). The phases were separated and the aqueous phase was extracted with EtOAc (10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (10 mL), dried over MgSO₄ anhydrous, filtered, and concentrated under reduced pressure. Purification on silica (30-70% ethyl acetate in hexanes) provided 4- [1- (4-methoxybenzill) -1H-1,2,3triazol-4-yl] -N- [3-methyl-5 - (1,3-thiazol-5-yl) phenyl] pyrimidin-2-amine (50 mg, 33%) as a colorless foam. MS ESI: [M + H] + m / z 456.1.

Intermediary_48: _5-chloro-N- [3-methyl-5- (1,3-thiazol-5¡l) phen¡Hpir¡m¡d¡n-2-am¡na

<img file="MX2012007154A_D0100.tif" />

A flask containing 2,5-dichloropyrimidine (2 g, 13.42 mmol), 3-methyl-5- (1,3-thiazol-5-μl) anline (2.55 g, 13.42 mmol), PdOAc₂

314 (0.603 g, 2.68 mmol), Xantphos (2,330 g, 4.03 mmol), and cesium carbonate (8.75 g, 26.8 mmol) was degassed for 5 min. Dioxane (89 mL) was added and argon was bubbled through the mixture for 15 min. The temperature was raised to 110 ° C and the reaction was stirred for 14 H at that temperature.

The cooled reaction was diluted with brine and water and extracted three times with CH₂CI₂. The organic layer was concentrated under reduced pressure and purified by flash chromatography (0-70% EtOAc: Hexanes) to give 5- chloroN- [3-methyl-5- (1,3-thiazol-5-yl) phenyl] pyrimidin-2-amine (2.95 g, 73%) as a white solid. MS ESI: [M + H] + m / z 303.¹H NMR (500 MHz, CDCI₃) δ 8.75 (s, 1H), 8.37 (s, 2H), 8.08 (s, 1H), 7.71 (s, 1H), 7.33 (s, 1H), 7.09 (s, 1H), 2.40 (s, 3H) . RhSYK = + + activity.

Intermediate 49: 5-Fluoro-4-methyl-A / - [3-methyl-5- (1.3-t¡azol-5yl) phenyl1p¡r¡m¡din-2-amína

<img file="MX2012007154A_D0101.tif" />

2-chloro-5-fluoro-4-methylpyrimidine (500 mg, 3.41 mmol), 3-methyl20 5- (1,3-thiazol-5-yl) aniline (649 mg, 3.41 mmol), PdOAc₂ (77 mg, 0.341 mmol), Xantphos (296 mg, 0.512 mmol), and cesium carbonate (2223 mg, 6.82 mmol) were combined in a flask and degassed with Argon. Dioxane (12 mL) was added and the solution was degassed with Argon for 5

315 min. The mixture was heated to 100 ° C for 2H and then allowed to cool to room temperature. The mixture was diluted with Brine and EtOAc. The layers were separated and the aqueous portion was re-extracted with EtOAc. The combined organic layers were dried over Na₂SW₄ and concentrated in a vacuum. Purification by flash chromatography on silica gel (040% EtOAc: CH2CI2) provided 5-fluoro-4-methyl- / V- [3-methyl-5- (1,3-thiazol-5yl) phenyl] pyrimidine- 2-amine (588 mg, 57%) as a solid beige solid. MS ESI: [M + H] + m / z 301.¹H NMR (500 MHz, CDCI₃) δ 8.75 (s, 1H), 8.33 (s, 2H), 8.09 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.08 (s, 1H), 2.40 (s, 3H) . RhSYK = + ++ activity.

Intermediary_50: _5-Fluoro-N- [3-methyl-5- (1,3-thiazol-5yl) phen¡np¡r¡m¡din-2-am¡na

<img file="MX2012007154A_D0102.tif" />

2-chloro-5-fluoropyrimidine (0.443 ml, 3.58 mmol), 3-methyl-5- (1,3-thiazol-5-yl) aniline (682 mg, 3.58 mmol), PdOAc₂ (80 mg, 0.358 mmol),

Xantphos (311 mg, 0.538 mmol), and cesium carbonate (2336 mg, 7.17 mmol) were combined in a flask and degassed with Argon. Dioxane (12 mL) was added and the mixture was degassed with Argon for 5 min. The mixture was then heated to 100 ° C for 2H. The reaction was cooled to

316 room temperature, diluted with brine and EtOAc. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organics were dried over Na₂SW₄, filtered and concentrated under vacuum. Purification via flash chromatography of silica gel (0-40% EtOAc: CH₂CI₂) provided 5-fluoro-N- [3-methyl-5- (1,3-thiazol-5yl) phenyl] pyrimidin-2-amine (947 mg, 92%) as a beige solid. MS ESI: [M + H] + m / z 287. Activity of rhSYK = ++.

Intermediate 51: 4-cyclopropyl-5-fluoro- / V- [3-methyl-5- (1,3-thiazol-510, Dphenylpyrimidin-2-amine

<img file="MX2012007154A_D0103.tif" />

Step 1:

5-Fluoro-2,4-dichloropyrimidine (5 g, 29.9 mmol), cyclopropyl boronic acid (2.57 g, 29.9 mmol), tribasic potassium phosphate (15.89 g, 74.9 mmol) and PdCI adduct₂(dppf) -dichloromethane (1.22 g, 1,497 mmol) were added to a dry flask. The flask was degassed with argon and then tetrahydrofuran (150 mL) was added. The reaction mixture was degassed with argon for five minutes, and then heated to 67 ° C. After 12 hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (1000 mL), washed with

317 brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by ultra-fast chromatography on silica gel (the EtOAc / hexane gradient) to provide 2-chloro-4-cyclopropyl-5fluoropyrimidine (4.1 g, 23.8 mmol, 79% yield). MS ESI: [M + H] + m / z 172.9.¹H NMR (500 MHz, DMSO-d₆) δ 8.66 (d, J = 2.0 Hz, 1H); 2.34-2.26 (m, 1H); 1.26-1.20 (m, 2H); 1.12-1.08 (m, 2H).

Step 2:

3-methyl-5- (1,3-thiazol-5-yl) aniline (0.250 g, 1.31 mmol), the 10 product from Step 1 (0.227 g, 1.31 mmol), palladium (II) acetate (0.0295 g, 0.131 mmol), Xantphos (0.114 g, 0.197 mmol), and cesium carbonate (0.856 g, 2.63 mmol) were added to a dry flask. The flask was degassed with argon and then dioxane (4.4 mL) was added. The reaction mixture was degassed with argon for 5 minutes, and then heated to 100 ° C. After 2 hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (the gradient of

EtOAc / dichloromethane) to provide 4-cyclopropyl-5-fluoro-N- [3-methyl-520 (1,3-thiazol-5-yl) phenyl] pyrimidin-2-amine (0.390 g, 1.20 mmol, 91% of performance). MS ESI: [M + H] + m / z 326.8.¹H NMR (500 MHz, DMSO-d₆)

9.59 (s, 1H); 9.06 (s, 1H); 8.38 (d, J = 2.5 Hz, 1H); 8.19 (s, 1H); 7.94 (s, 1H); 7.39 (s, 1H); 7.10 (s, 1H); 2.29 (s, 3H); 2.28-2.23 (m, 1H); 1.18-1.14 (m, 4H).

318