MD3864C2

Cyanoanthranilamide compounds, compositions on base thereof and method for invertebrate pest control

Abstract

The invention relates to compounds of the formula (I), or to its derivatives in the form of N, N, N-diisopropylethylamine, and the like, oxides or salts thereof wherein: R1 represents Me, Cl, Br or F; R2 represents F, Cl, Br or C1 -C4 haloalkoxy; R3 represents F, Cl or Br; R4 represents H, C1 -C4 alkyl, C3 -C4 alkenyl, C 3 -C 4 alkynyl, C 3 -C 5 cycloalkyl, or C 4 -C 6 cycloalkylalkyl, each optionally substituted with one substituent selected from the group consisting of halogen, CN, SMe, S (O) Me, S (O) 2Me and OMe; R6 represents H, F or Cl and R7 represents H, F or Cl. The invention also relates to compositions based on cyanoanthranilamide and to a method for controlling invertebrate pests,containing a biologically effective amount of one of the above-mentioned compounds and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

MD3864C2, drawing sheet 1 — Sheet 1 of 34

Term

No projected expiry on record.

7 claims: 2 independent, 5 dependent

1
Compus cu formula I, N-oxid sau о sare a acestuia, in care:R 1 reprezintă Me, Cl, Br sau F;R 2 reprezintă F, Cl, Br sau C]-C 4 haloalcoxi;R 3 reprezintă F, Cl sau Br;R 4 reprezintă H, C]-C 4 alchil, C 3 -C 4 alchenil;C 3 -C 4 alchinil, C 3 -C 5 cicloalchil sau C 4 -C 6 cicloalchilalchil, fiecare substituit optional cu un substituent selectat din grupul constituit din halogen, CN, SMe, S(O)Me, S(O) 2 Me și OMe;R 5 reprezintă H sau Me;R 6 reprezintă H, F sau Cl și R 7 reprezintă H, F sau Cl.
2
Compus, conform revendicării 1, in care:R 1 reprezintă Me sau Cl;R 2 reprezintă Cl, Br, OCF 2 H, OCF 3 sau OCH 2 CF 3 și MD 3864 C2 2009.03.31 R 4 reprezintă H, Me, Et, z-Pr, /-Bu, CH 2 CN, CH(Me)CH 2 SMe sau C(Me) 2 CH 2 SMe.
3
Compus, conform revendicării 2, in care:R 2 reprezintă Cl, Br sau OCH 2 CF 3 ;R 4 reprezintă H, Me, Et sau z-Pr și R 5 reprezintă H.
4
Compozitie pentru combaterea dăunătorilor nevertebrați care conține о cantitate biologic efectivă de compus definit m revendicarea 1 și cel puțin un component adițional selectat din grupul constituit dintr-o substanță tensioactivă, un diluant solid și un diluant lichid.
5
Compozitie, conform revendicării 4, sub formă de compozitie lichidă pentru umectarea solului.
6
Procedeu de combatere a dăunătorilor nevertebrați, care include contactul dăunătorilor cu о cantitate biologic efectivă de compozitie definită în revendicarea 5, care umectează solul.
7
Compus cu formula 1, selectat din grupul constituit din:3-cloro-l-(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-[(metilamino)carbonil]fenil]-lH-pirazol-5-carboxamidă, 3-cloro-l-(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-(aminocarbonil)fenil]-lH-pirazol-5-carboxamidă, 3-bromo-1 -(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-[(metilamino)carbonil]fenil]-1 H-pirazol-5-carboxamidă, 3-bromo-l-(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-(aminocarbonil)fenil]-lH-pirazol-5-carboxamidă, 3-cloro-l-(3-cloro-2-piridinil)-N-[2-cloro-4-ciano-6-[(metilamino)carbonil]fenil]-lH-pirazol-5-carboxamidă, 3-bromo-N-[2-cloro-4-ciano-6-[[(l-metiletil)amino]carbonil]fenil]-l-(3-cloro-2-piridinil)-lH-pirazol-5-carboxamidă, 3-cloro-l-(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-[[(l-metiletil)amino]carbonil]feml]-lH-pirazol-5-carboxamidă, 3-bromo-l-(3-cloro-2-piridinil)-N-[4-ciano-2-metil-6-[[(l-metiletil)amino]carbonil]fenil]-lH-pirazol-5-carboxamidă, l-(3-cloro-2-piridinil)-N-[4-ciano-2-[(dimetilamino)carbonil]-6-metilfenil]-3-(2,2,2-trifluoroetoxi)-lH-pirazol-5-carboxamidă, l-(3-cloro-2-piridinil)-N-[4-ciano-2-[[(l,l-dimetiletil)amino]carbonil]-6-metilfenil]-3-(2,2,2-trifluoroetoxi)-lH-pirazol-5-carboxamidă, 3-cloro-l-(3-cloro-2-pmdinil)-N-[4-ciano-2-[(ciclopropilamino)carboml]-6-metilfeml]-lH-pirazol-5-carboxamidă, și 3-bromo-l-(3-cloro-2-piridiml)-N-[4-ciano-2-[[(ciclopropilmetil)amino]carbonil]-6-metilfenil]-lH-pirazol-5-carboxamidă.

Independent claims7

669 paragraphs in 44 sections, as filed

The invention relates to cyanoanthranylamide compounds, compositions based on it and a process for controlling invertebrate pests and can be used in agriculture and other fields.

Combating invertebrate pests is extremely important in order to achieve a high crop productivity. Damage caused by invertebrate pests to stored crops and those in the field can cause a considerable reduction in their productivity and may result in higher prices for the consumer. The control of invertebrate pests is also important in forestry, for greenhouse crops, decorative plants, seedlings, fibrous and stored food products, horned cattle, in the household, as well as for public and animal health. Many products are commercially available for these purposes, but the need for new compounds, more effective, less expensive, less toxic, environmentally pure or having different modes of action persists.

A-acylantranilic acid derivatives of formula I are known as anthropodicides.

i in which, inter alia, A and В independently represent О or S; J represents an optionally substituted phenyl ring, a 5- or 6-membered heteroaromatic ring, a naphthyl ring system, or an aromatic system of the 8, 9 or 10-membered heterobicyclic ring; R1 and R3 independently represents H or optionally substituted CrC6 alkyl; R2 represents H or C 1 -C 6 alkyl6, each R4 independently represents H, C 1 -C 6 alkyl, C 1 -C 1 haloalkyl, halogen or CN, and takes values from 1 to 4 [1].

The essence of the invention is that a compound of formula 1, N-oxide or о salt thereof is claimed,

in which:

R1 represents Me, Cl, Br or F;

R2 represents F, Cl, Br or C] -C4haloalkoxy;

R3 represents F, Cl or Br;

R4 represents H, CrC4 alkyl, C3-C4 alkenyl; C3-C4 alkynyl, C3-C5 cycloalkyl or C4-C6 cycloalkylalkyl, each optionally substituted with a substituent selected from the group consisting of halogen, CN, SMe, S (O) Me, S (O) 2Me and OMe;

R5 represents H or Me;

R6 represents H, F or Cl and

R7 represents H, F or Cl.

Compound, in which:

R1 represents Me or Cl;

R2 represents Cl, Br, OCF2H, OCF3 or OCH2CF3 and

R4 represents H, Me, Et, z-Pr, Г-Bu, CH2CN, CH (May) CH2EMS or C (Me)2CH2SME.

Compound, in which:

R2 represents Cl, Br or OCH2CF3;

R4 represents H, Me, Et or z-Pr and

R5 represents H.

Compound of formula 1, selected from the group consisting of: 3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1H -pyrazole-5-carboxamide, 3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1H-pyrazole-5-carboxamide, 3-Bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3-bromo- l- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -LH-pyrazole-5-carboxamide,

MD 3864 C2 2009.03.31

3-chloro-1- (3-chloro-2-pyridinyl) -N- [2-chloro-4-cyano-6 - [(methylamino) carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3-bromo- N- [2-chloro-4-cyano-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide, 3-chloro -I- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [[(1-methylethyl) aniino] carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3- bromo-l- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [[(l-methylethyl) amino] carbonyl] phenyl] -LH-pyrazole-5-carboxamide, l- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [(dimethylamino) carbonyl] -6-methylphenyl] -3- (2,2,2-trifluoroethoxy) -LH-pyrazole-5 carboxamide,

- (3-Chloro-2-pyridinyl) -N- [4-cyano-2 - [[((1,1-dimethylethyl) amino] carbonyl] -6-methylphenyl] -3- (2,2,2-trifluoroethoxy) - IH-pyrazole-5-carboxamide,

3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [(cyclopropylamino) carbonyl] -6-methylphenyl] -1H-pyrazole-5-carboxamide, and 3-bromo- l- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [[(cyclopropylmethyl) amino] carbonyl] -6-methylphenyl] -LH-pyrazole-5-carboxamide.

Composition for controlling invertebrate pests containing о effective biological amount of compound and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

Composition, in the form of a liquid composition for soil wetting.

A process for controlling invertebrate pests, which includes the contact of pests with о effective biological amount of composition defined in claim 5, which moistens the variety.

In the above listings, the term "alkyl", used either alone or in compound words, such as "alkylthio" or "haloalkyl", includes branched or straight chain alkyl, such as methyl, ethyl, n-propyl, z-propyl, or different butyl isomers. The term "halogen" either alone or in compound words, such as "haloalkoxy", includes fluorine, chlorine, bromine or iodine. Additionally, when used in compound words, such as "haloalkyl" or "haloalkoxy", the mentioned alkyl or alkoxy may be wholly or partially substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, CICH2, CF3CH2 and CF3CCI2. Examples of "haloalkoxy" include CF3O, HCF2O, CCI3CH2O, HCF2CH2CH2O and CF3CH2O.

One of skill in the art will recognize that not all nitrogen-containing heterocycles can form A-oxides, because nitrogen requires a solitary couple available for oxidation of the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles that can form A-oxides. One skilled in the art will also recognize that tertiary amines can form A-oxides. Synthetic methods for the preparation of tertiary N-oxides of heterocycles and amines are well known to one skilled in the art, including oxidation of tertiary heterocycles and amines with acid peroxides, such as m-chloroperbenzoic and peracetic acid (AMCPB), hydrogen peroxide, alkyl hydroperoxides such as Z-butyl hydroperoxide, sodium perborate and dioxirane, such as dimethyldioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see, for example: TL Gilchrist. Comprehensive Organic Synthesis, vol 7, pp. 748-750; SV Law, Ed. Pergamon Press; M. Tisler and В. Stanovnik. Comprehensive Heterocyclic Chemistry, vol. 3, pp. 18-20; AJ Boulton and A. McKillop, Pergamon Press Ed. MR Grimmett and В. RT Keene. Advances in Heterocyclic Chemistry, vol. 43, pp. 149-161; AR Katritzky, Ed. Academic Press; M. Tisler and В. Stanovnik. Advances in Heterocyclic Chemistry, vol. 9, pp. 285-291; AR Katritzky and AJ Boulton, Ed. Academic Press; and GW EL Cheeseman and ESG Werstiuk. Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392.

The compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One of skill in the art will recognize that a stereoisomer may be more active and / or exhibit beneficial effects when enriched than another (other) stereoisomer (s) or when separated from another (other) stereoisomer (s). Additionally, the person in the art knows how to separate, enrich and / or selectively prepare said stereoisomers. Accordingly, the present invention confines compounds selected from formula 1, A-oxides and salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers !, or as an optically active form.

The salts of the compounds according to the invention include addition salts with organic or inorganic acids, such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicyl, tartaric, 4- toluenesulfonic or valeric. In the compositions and methods of the present invention, the salts of the compounds of the invention are preferably favorable for the agronomic and non-agronomic uses described herein.

Important are compounds of formula 1, in which:

R4 represents H or C1-C4 alkyl optionally substituted with a substituent selected from the group consisting of CN, SMe and OMe; '

R5 represents H or Me;

R6 represents H and

R7 represents FI.

Preferred compounds due to their cost, ease of synthesis and / or biological efficiency are:

Preferable 1. Compounds of formula 1, wherein

R1 represents Me or Cl;

R2 represents Cl, Br, CF3, OCF2H, OCF3 or OCH2CF3 and

R4 represents H, Me, Et, / -Pr. t-Bu, CH2CN, CH (May) CH2EMS or C (Me)2SME.

Preferable 2. Compounds of formula 1, wherein

R2 represents Cl, Br, CF3, or ОСН2СЕ3;

R4 represents H, Me, Et or / -Pr and

R5 represents H.

Important are the compounds of Preferred 1 and Preferable 2, wherein R6 represents H; and R7 represents H.

Preferable compositions of the present invention are those which contain the above-mentioned preferable compounds. Preferable methods of use are those which include the preferable compounds mentioned above.

MD 3864 C2 2009.03.31

Compounds of formula 1 may be prepared by one or more of the following methods and variations, as described in Schemes 1-20. The definitions of R1, R ^, R3, R4 and R5 in the compounds of formulas 1-24 below are as given in the essence of the invention, unless otherwise provided.

Compounds of formula 1 may be prepared by reaction of benzoxazinones of formula 2 with о amine of formula HNR4R5, as shown in Scheme 1. This reaction may be solvent again! or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, dioxane, toluene, dichloromethane or chloroform with optimum temperatures ranging from room temperature to reflux temperature of the solvent. The general reaction of benzoxazinones with amines for the production of anthranilamides is well documented in the chemical literature. For a review of the chemistry of benzoxazinones see Jakobsen et. al. Biorganic and Medicinal Chemistry. 2000, 8, pp. 2095-2103 and the references cited. See also GM Coppola, J. Heterocyclic Chemistry. 1999, 36, pp. 563-588.

Scheme 1

Compounds of formula 1 may also be prepared from haloanthranyl diamides of formula 3 (wherein X represents halogen, preferably iodine or formula 3 with о metal cyanide (e.g. copper cyanide, zinc cyanide or potassium cyanide), optionally with or without a palladium catalyst (eg tetrakis (triphenylphosphine) palladium (0) or disclorobis (triphenylphosphine) palladium (II)) and optionally with or without metal halide (copper iodide, zinc iodide or potassium iodide) in a suitable solvent, such as acetonitrile, Ar, A-dimethylformamide or Л-methylpyrrolidinone. optionally at temperatures ranging from room temperature to reflux temperature of the solvent, it provides compounds of formula 1. The convenient solvent may also be tetrahydrofuran or dioxane when the palladium catalyst is used in the coupling reaction.

(X-halogen)

Cyanobenzoxazinones of formula 2 may be prepared by the method shown in Scheme 3. Reaction of a halobenzoxazinone of formula 4 (wherein X represents halogen, preferably iodine or bromine) with metal cyanide using a similar coupling method, as described above. top of Scheme 2 (optionally with or without a palladium catalyst and optionally with or without the presence of a metal halide), provides a compound of formula 2.

MD 3864 C2 2009.03.31

Scheme 3

The cyanobenzoxazinones of formula 2 can also be prepared by the method described in detail in Scheme 4 by coupling a pyrazolcarboxylic acid of formula 5 with a cyanoantranilic acid of formula 6. This reaction includes the successive addition of methanesulfonic chloride in the presence of a tertiary amine, such as triethylamine or pyridine to a pyrazolcarboxylic acid of formula 5, followed by the addition of cyanoantranilic acid of formula 6, followed by the secondary addition of tertiary amine and methanesulfonic chloride.

Scheme 4

4) MeS (O)2Cl

NH2

ООзН râ

Scheme 5 describes another method for the preparation of benzoxazinones of formula 2 which includes coupling an isotonic anhydride of formula 7 with az chlorazole of pyrazolic acid of formula 8. Solvents, such as pyridine or pyridine / acetonitrile, correspond to this reaction. The acid chlorides of formula 8 are available from the acids suitable for formula 5 by known methods, such as thionyl chloride or oxalyl chloride.

Scheme 5

As shown in Scheme 6, haloantranyl diamides of formula 3 can be prepared by the reaction of benzoxazinones of formula 4, wherein X represents halogen, with о amine of formula HNR4R5 using о similar method, as described above for Scheme 1. The conditions for this reaction are similar to those specified in Scheme 1.

Scheme 6

R2

X - halogen 3

As shown in Scheme 7, the halobenzoxazinones of formula 4 (wherein X represents halogen) can be prepared by directly coupling a carboxylic pyridylpyrazole of formula 5 with a haloantranyl acid of formula 9 (wherein X

MD 3864 C2 2009.03.31 represents halogen) by a similar method, as described above for Scheme 4. This reaction includes the successive addition of methanesulfonic chloride in the presence of a tertiary amine, such as ft triethylamine or pyridine, to a pyrazolcarboxylic acid. of formula 5, followed by the addition of a haloantranilic acid of formula 9, followed by the secondary addition of tertiary amine and methanesulfonic chloride. This method generally provides good yields of benzoxazinone.

Scheme 7

4) MeS (O) 2

As shown in Scheme 8, halobenzoxazinone of formula 4 may also be prepared by coupling an isatoic anhydride of formula 10 (wherein X represents halogen) with о chlorazole of pyrazolic acid of formula 8 by a similar method, as has been described above for Scheme 5.

Cyanoanthranyl acids of formula 6 may be prepared from haloanthranyl acids of formula 9, as shown in Scheme 9. Reaction of a haloantranilic acid of formula 9 (wherein X represents halogen) with о metal cyanide using the same coupling procedure described above. for Scheme 2 (optional with or without the presence of a metal halide) it provides a compound of formula 6.

Scheme 9

X - halogen

As illustrated in Scheme 10, cyanoisathic anhydrides of formula 7 may be prepared from cyanoantranyl acids of formula 6 by reaction with phosgene (or an equivalent phosgene, such as trifosgene) or an alkylchloroformate (e.g. methylchloroformate) in a solvent. accordingly, such as toluene or tetrahydrofuran.

MD 3864 C2 2009.03.31

Scheme 10

As shown in Scheme 11, haloantranyl acids of formula 9 can be prepared by direct halogenation of an unsubstituted anthranilic acid of formula 11 with N-chlorosuccinimide (NCS), A-bromosuccinimide (NBS) or Niodosuccinimide (NIS), respectively, in solvents, such as Α, Α-dimethylformamide (DMF), to produce the halogenated acid corresponding to formula 9.

Scheme 11

As illustrated in Scheme 12, haloisatoic anhydrides of formula 10 can be prepared from haloantranyl acids of formula 9 by reaction with phosgene (or an equivalent phosgene, such as trifosgene) or an alkylchloroformate, e.g. methylchloroformate, in a suitable solvent, such as toluene or tetrahydrofuran.

The carboxylic pyridylpyrazole acids of formula 5 can be prepared by the method described in Scheme 13. The reaction of pyrazole 12 with 2-halopyridine of formula 13 in the presence of a suitable base, such as potassium carbonate, in a solvent such as Α, Α -dimethylformamide or acetonitrile, provides good yields of 1-pyridylpyrazole 14 with good specificity for desirable regiochemistry. Metallization 14 with lithium diisopropylamide (DAL) followed by quenching the lithium salt with carbon dioxide gives pyrazolcarboxylic acid of formula 5.

Scheme 13

R2

1) DAL, THF

2) CO2

Pyrazoles 12, wherein R2 represents CF3, Cl or Br are known compounds. Pyrazole 12, wherein R2 represents CF3, can be prepared by the procedures described in the literature (J. Fluorine Chem. 1999, 53 (1), 61-70). Pyrazoles 12, wherein R2 represents Cl or Br, can also be prepared by the procedures described in the literature (H. Reimlinger and A. Van Overstraeten. Chem. Ber. 1966, 99 (10), 3350-7). О useful alternative method for the preparation of pyrazoles 12, wherein R2 represents Cl or Br, is described in Scheme 14. Metallization of sulfamoyl pyrazole 15 with α-butyllithium followed by direct halogenation of the anion with either hexachlorethane (for R2 being Cl) or with 1,2-dibromotetrachlorethane (for R2 being Br) offers halogenated derivatives 16 (wherein R2 represents Cl or Br). Removal of the sulfamoyl group with trifluoroacetic acid (ATF) at room temperature produces solvents and in good yield to obtain pyrazoles 12, wherein R2 represents, respectively, Cl or Br.

MD 3864 C2 2009.03.31

Scheme 14

1) n-BuLi, solvent

ZJI & XbCChR2

ATF i> 12

SOtNMc *)

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids of formula 5, wherein R2 represents CF3, also can be prepared by the method described in Scheme 15. Reaction of a compound of formula 17 (wherein R8 represents C 1 -C 6 alkyl4) with a suitable base in a suitable organic solvent provides the cyclized product of formula 18 after neutralization with an acid, such as acetic acid.

Scheme 15

The corresponding base may be, for example, but not limited to, sodium hydride, potassium t-butoxide, sodium dimsil (CH3S (O) CH2-N / A+), alkali metal hydroxides or carbonates (such as lithium, sodium or potassium), tetraal chi-lammonium hydroxides or fluorides (such as methyl, ethyl or butyl), or 2- / c77-butylimino-2-diethylamino-1.3 dimethyl-perhydro-1,3,2diazafosfonina. The convenient organic solvent may be, for example, but not limited to, acetone, acetonitrile, tetrahydrotane, dichloromethane, dimethylsulfoxide, or / V, A'-dimethylformamide. The cyclization reaction is usually performed within a temperature range of about 0 to 120 ° C. The effects of solvent, base, temperature and time are all interdependent, and the choice of reaction conditions is important for minimizing the formation of by-products. The preferred base is tetrabutylammonium fluoride.

Dehydration of the compound of formula 18 to obtain the compound of formula 19, followed by the hydrolysis of the carboxylic ester group of the carboxylic acid into the carboxylic acid, provides the compound of formula 5. The dehydration is accomplished by treating a suitable acid with a catalytic amount. This catalytic acid may ft, for example, but not limited to, sulfuric acid. The reaction is usually conducted using an organic solvent. As one of ordinary skill in the art will understand, dehydration reactions can be conducted in a wide variety of solvents, for example acetic acid, in a temperature range generally between about 0 and 200 ° C, more preferably between about 0 and 100 ° C. Carboxylic esters of formula 19 can be converted to carboxylic acids of formula 5 by numerous methods including nucleophilic decomposition into anhydrous condices or hydrolytic methods including the use of etheric bases or acids (see TW Greene and PGM Wuts. Protective Groups in Organic Synthesis. Ed. 2nd, John Wiley & Sons, Inc., New York, 1991, pp. 224-269 for a review of methods). For Scheme 15, the base-catalyzed hydrolytic methods are preferable. Suitable bases include alkali metal hydroxides (such as lithium, sodium or potassium). For example, the ester may be dissolved in a mixture of water and alcohol, such as ethanol. When treated with sodium hydroxide or potassium hydroxide, the ester is saponified to obtain the carboxylic acid sodium or potassium salt. Acidification with a strong acid, such as hydrochloric acid or sulfuric acid, generates carboxylic acid of formula 5.

Compounds of formula 17, wherein R2 represents CF3, can be prepared by the method described in Scheme 16. Treatment of a hydrazine compound of formula 20 with о ketone of formula CH3CHOIR2 In a solvent, such as water, methanol or acetic acid, it produces hydrazone of formula 21.

Scheme 16

wherein R2 represents CF3 and R8 represents C 1 -C 6 alkyl4.

MD 3864 C2 2009.03.31

One skilled in the art will recognize that this reaction may require catalysis by an optional acid and may also require elevated temperatures depending on the molecular substituent structure of hydrazone of formula 21. Reaction of hydrazone of formula 21 with an alkylchlorooxalate in an organic solvent Conveniently, such as, for example, but not limited to, dichloromethane or tetrahydrofuran in the presence of an acid neutralizer, such as triethylamine, generates the compound of formula 17. The reaction is usually conducted at a temperature of about 0 to 100 ° C. Hydrazine compounds of formula 20 may be prepared by standard methods, such as by reaction of the corresponding halopyridine of formula 13 with hydrazine.

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids! of formula 5, wherein R2 represents Cl or Br, can also be prepared by the method described in Scheme 17. Oxidation of the compound of formula 22, optionally in the presence of acid, provides the compound of formula 19, wherein R2 represents Cl or Br. Hydrolysis of the function of the carboxylic ester in the carboxylic acid generates the compound of formula 5.

Scheme 17

22 19 5 wherein R8 represents C 1 -C 4 alkyl.

The oxidizing agent for converting a compound of formula 22 into a compound of formula 19 may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate (for example Oxonium®) or permanganate. potassium. In order to obtain the complete conversion, at least one equivalent of the oxidizing agent against a compound of formula 22 should preferably be used between one or two equivalents. This oxidation is typically carried out in the presence of a solvent. The solvent may be an ether, such as tetrahydrofuran, p-dioxane and the like, an organic ester, such as ethyl acetate, dimethylcarbonate and the like, or a polar aprotic organic solvent such as / V, / V-dimethylformamide, acetonitrile and the like. Suitable acids for use in the oxidation phase include inorganic acids such as sulfuric acid, phosphoric acid and the like, and organic acids such as acetic acid, benzoic acid and the like. From one to five equivalents of acids can be used. Preferably the oxidant is potassium persulfate, and the oxidation of sulfuric acid is preferably carried out in the presence of sulfuric acid. The reaction can be conducted by mixing the compound of formula 22 in the solvent and, if used, the desired acid. The oxidant can then be added at a convenient percentage. The reaction temperature typically ranges from as low as possible from about 0 ° to the boiling point of the solvent to obtain a reasonable reaction time for completion of the reaction. Suitable methods for converting the ester of formula 19 into the carboxylic acid of formula 5 are already described for Scheme 15.

Compounds of formula 22, wherein R2 represents halogen and R8 represents C 2 -C 4 alkyl, can be prepared from the corresponding compounds of formula 23, as shown in Scheme 18.

Scheme 18

22 wherein R8 represents C 1 -C 6 alkyl4.

Treating a compound of formula 23 with a halogenating reagent, usually in the presence of a solvent, provides the corresponding halocompound of formula 22. Halogenating reagents that may be used include phosphoric oxyhalides, phosphoric trihalogens, phosphorous pentahalogens, thionyl chloride, dihalotrialkylphosphorylphenylphosphorylans, , oxalyl chloride and phosgene. Phosphoric oxyhalogens are preferable. In order to achieve complete conversion, at least 0.33 equivalents of phosphoric oxyhalide against the compound of formula 23 should preferably be used between about 0.33 and 1.2 equivalents. In order to achieve the complete conversion, at least 0.20 equivalents of phosphoric pentahalogenide against the compound of formula 23 should preferably be used between about 0.20 and 1.0 equivalents. Typical solvents for this halogenation include halogenated alkanes, such as dichloromethane, chloroform, chlorobutane and

MD 3864 C2 2009.03.31 Other aromatic solvents such as benzene, xylene, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, and polar aprotic solvents such as acetonitrile , N, Ndimethylformamide and the like. Optionally, an organic base such as triethylamine, pyridine, N, N-dimethylaniline or the like may be added. Adding a catalyst, such as Ν, Ν-dimethylformamide, is also an option. Preferably it is the process in which the solvent is acetonitrile and lacks a base. Typically, no base and no catalyst is required when using the acetonitrile solvent. The preferred process is carried out by mixing the compound of formula 23 in acetonitrile. The halogenate reagent is then added at a convenient time and the mixture is then maintained at the desired temperature until the reaction is complete. The reaction temperature typically varies between 20 ° C and the boiling point of acetonitrile, and the reaction time is typically less than 2 hours. The reaction mass is then neutralized with an inorganic base, such as sodium bicarbonate, sodium hydroxyl and the like, or an organic base, such as sodium acetate. The desired product of formula 22 can be isolated by methods known to those skilled in the art, including crystallization, extraction and distillation.

Alternatively, compounds of formula 22, wherein R2 represents Br or Cl, can be prepared by treating the corresponding compounds of formula 22, wherein R2 represents a different halogen (for example, Cl for obtaining formula 22, wherein R2 represents Br) or a group of sulfonates, such as э-toluenesulfonate, benzenesulfonate and methanesulfonate, respectively, with hydrogen bromide or hydrogen chloride. By this method the halogen R2 or the sulphonate substituent in the compound of formula 22 is replaced by Br or Cl from hydrogen bromide or hydrogen chloride, respectively. The reaction is conducted in a suitable solvent, such as dibromethane, dichloromethane, acetic acid, ethyl acetate or acetonitrile. The reaction may occur at or near atmospheric pressure or above atmospheric pressure in a pressure vessel. The halogenate reagent may be added as a gas to the reaction mixture which confines the solvent and the compound of formula 2. When R2 In the initial compound of formula 22 represents a halogen, such as Cl, the reaction is preferably carried out in such a way that the sprayer or other suitable means to remove the hydrogen halide generated from the reaction. Alternatively, the halogenate reagent may first be dissolved in an inert solvent in which it is highly soluble (such as acetic acid) until contact with the compound of formula 23 is either solvent-free or in solution. The reaction may be between about 0 and 100 ° C, most conveniently close to ambient temperature (for example, about 10 to 40 ° C), and more preferably between about 20 and 30 ° C. Addition of a Lewis acid catalyst (such as aluminum tribromide for the preparation of formula 22, wherein R2 represents Br) may facilitate the reaction. The product of formula 22 is isolated by ordinary methods known to those skilled in the art, including by extraction, distillation and crystallization.

The initial compounds of formula 22, wherein R2 represents a group of sulfonates, can be prepared from the corresponding compounds of formula 23 by standard methods, such as treatment with sulfonyl chloride (for example, / Molensulfonyl chloride) and base, such as tertiary amine (e.g. (triethylamine) in a suitable solvent, such as dichloromethane.

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids of formula 5, wherein R2 represents haloalkoxy, can also be prepared by the method described in Scheme 19. A compound of formula 23 is oxidized into a compound of formula 24. The reaction conditions for this oxidation are those described for the conversion of the compound of formula 22 into the compound of formula 19 in Scheme 17.

Scheme 19

wherein R2 represents haloalkoxy and R8 represents C 1 -C 6 alkyl4.

The intermediate of formula 24 is then alkylated to form a compound of formula 19 (wherein R2 represents haloalkoxy) by reaction with a suitable haloalkylating agent, such as a sulfonate or haloalkyl halide.

The reaction is conducted in the presence of at least one equivalent of a base. Suitable bases include inorganic bases such as alkali metal hydrides, hydroxides and carbonates (such as lithium, sodium or potassium) or organic bases such as triethylamine, diisopropylethylamine and l, 8-diazabicyclo [5.4.0] undec- 7-ene. The reaction is generally carried out in a solvent which may contain alcohols, such as methanol and ethanol, halogenated alkanes, such as dichloromethane, aromatic solvents, such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and solvents. polar apricots such as acetonitrile, Α, Α-dimethylformamide and the like. Alcohols and polar aprotic solvents are preferable for use with inorganic bases. Potassium carbonate as a base and Λ ', Λ-dimethilibmamide or acetonitrile as a solvent are more preferred. The reaction is generally conducted between 0 and 150 ° C, most typically between ambient temperature and 100 ° C. The ester of formula 24 can then be converted to carboxylic acid of formula 5 by the methods already described for converting a compound of formula 19 into a compound of formula 5 in Scheme 15.

MD 3864 C2 2009.03.31

Compounds of formula 23 may be prepared from compounds of formula 20, as described in Scheme 20. In this method, a hydrazine compound of formula 20 may react with a compound of formula 25 (a fumaric ester or a maleic ester or a mixture thereof may be used) in the presence of a base or solvent.

Scheme 20

wherein R8 represents C4-C4 alkyl.

The base used in Scheme 20 represents alco alkoxide metal salt, such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium Zert-butoxide, lithium Zert-butoxide and the like. Polar aprotic organic and polar protic solvents such as alcohols, acetonitrile, tetrahydrofuran, N, N-dimethylformamide, dimethylsulfoxide and the like may be used. Preferred solvents are alcohols, such as methanol and ethanol. In particular, it is preferred that the alcohol be similar to that which forms the maleic or fumaric ester and the base of the alkoxide. The reaction is typically conducted by mixing the compound of formula 20 and the solvent base. The mixture may be heated or cooled to the desired temperature and the compound of formula 25 may be added after a period of time. Typically, the reaction temperatures vary between 0 ° C and the boiling point of the solvent used. The reaction may be conducted at a pressure greater than atmospheric pressure to increase the boiling point of the solvent. Temperatures between about 30 and 90 ° C are generally preferable. The reaction may then be acidified by the addition of an organic acid, such as acetic acid and the like, or an inorganic acid, such as hydrochloric acid, sulfuric acid and the like. The desired product of formula 23 can be isolated by methods known to those skilled in the art, such as crystallization, extraction or distillation.

It has been recognized that certain reagents and reaction conditions described above for the preparation of compounds of formula 1 may not be compatible with certain functional groups present in intermediates. In these cases, incorporating the protection / deprotection sequences or the interconversions of the functional group in the synthesis will help to obtain the desired products. The use and choice of protecting groups will be evident to those skilled in the art in chemical synthesis (see, for example, TW Greene and PM Wuts. Protective Groups in Organic Synthesis, 2nd ed .; Wiley, New York, 1991 ). The person skilled in the art will recognize that, in some cases, after the introduction of a given reagent, as described in each scheme, it may be necessary to perform additional regulated synthetic stages, not described in detail, to complete the synthesis of compounds of formula 1. The person skilled in the art will also recognize that it may be necessary to combine the stages illustrated in the above schemes in a different order than that suggested by the particular sequence presented for the preparation of compounds of formula 1.

It is considered that a person skilled in the art, using the description, further elaboration, may use the present invention in its entirety. The following examples should therefore be considered as illustrative and in no case should they limit the description. The stages in the following examples illustrate how many procedures for each stage in a synthetic transformation are generated, and the reference material for each stage does not necessarily have to be prepared by a particular preparation process, the procedure of which is described in other examples or stages. . The ratios are by mass, except for the mixtures of the chromatographic solvent or if indicated otherwise. The parts and ratios for the chromatographic solvent mixtures are volumetric, unless the invention provides otherwise. NMR spectra are reported in ppm relative to tetramethylsilane; s means singlet, d - doublet, t - triplet, q - quartet, m - multiplet, dd - doublet of doubles, dt - doublet of triplets, and br s - wide singlet.

EXAMPLE 1

Preparation of I- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1/7-pyrazole-5-carboxamide

Stage A: Preparation of 2-amino-3-methyl-5-iodobenzoic acid

To the solution of 2-amino-3-methylbenzoic acid (Aldrich, 5 g, 33 mmol) in M / V-dimethylformamide (30 mL) was added A-iodosuccinimide (7.8 g, 34.7 mmol) and the mixture The reagent was incubated overnight in a greased bath at 75 ° C.

After cooling, the reaction mixture was slowly poured into ice water (100 mL) for precipitation. The ash-light solid obtained was filtered and washed four times with water and then placed overnight in a vacuum oven at 70 ° C for drying. The desired intermediate was isolated as an ash-light solid substance (8.8 g).

1 H NMR (DMSO-4): δ 7.86 (d, 1H), 7.44 (d, 1H), 2.08 (s, 3H). '

Stage B: Preparation of 3-chloro-2- [3- (trifluoromethyl) -1 / 7-pyrazol-1-yl] pyridine

To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and 3- (trifluoromethyl) -pyrazole (83 g, 0.61 mol) in N, dry dimethylformamide (300 mL) was added carbonate. potassium (166.0 g, 1.2 mol) and the reaction was then heated to 11O ... 125 ° C for 48 hours. The reaction was cooled to 100 ° C and filtered through a Celite® diatomic filtration medium to remove solids. VN-dimethylformamide and dichloropyridine surplus were removed by distillation under reduced pressure. The distillation of the product under reduced pressure (mp 139 ... 141 ° C, 7 mm) provided 113.4 g of intermediate desired as a light-yellow oil.

MD 3864 C2 2009.03.31

NMR (CDC1)3): δ 8.45 (d, 1H), 8.15 (s, 1H), 7.93 (d, 1H), 7.36 (t, 1H), 6.78 (s, 1H).

Stage C: Preparation of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H-pyrazole-5-carboxylic acid

To a solution of 3-chloro-2- [3- (trifluoromethyl) -1 / 7-pyrazol-1-yl] pyridine (which is the product of stage B pyrazole) (105.0 g, 425 mmol) in dry tetrahydrofuran ( 700 mL) at -75 ° C was added via a cannula о lithium diisopropylamide solution at 30 ° C (425 mmol) in dry tetrahydrofuran (300 mL). The dark-red solution was stirred for 15 min, after which the carbon dioxide was bubbled at -63 ° C until the solution turned to a pale yellow and the exothermicity ceased. The reaction was further stirred for 20 min and then quenched with water (20 mL). The solvent was removed under reduced pressure, and the reaction mixture was separated into ether and 0.5 N aqueous sodium hydroxide solution. The aqueous extracts were washed with ether (3x), filtered through a Celite® diatomic filter to remove the residual solids, and then acidified to a pH of about 4, in which an orange oil was formed. The aqueous mixture was stirred vigorously and additional acid was added to reduce the pH to 2.5 ... 3. The orange oil coagulated in a granular solid that was filtered, washed successively with water and A-hydrochloric acid and dried in vacuo at 50 ° C to obtain 130 g of title product as a not-white solid. The product of another reaction obtained by a similar procedure melted at 175 ... 176 ° C. '' '' H NMR (DMSO - d6): δ 7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d, 1H).

Step D: Preparation of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1,7-pyrazol -5-yl] -6-iodo-8-methyl-4 // -3 , 1-benzoxazine-4-onei

To the solution of methanesulfonyl chloride (291 mL, 37.74 mmol) in actonitrile (50 mL) was added dropwise a mixture of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -65- pyrazole-5-carboxylic acid (which is the product of stage C carboxylic acid) (10.0 g, 34.31 mmol) and triethylamine (4.78 mL, 34.31 mmol) in acetonitrile (50 mL) at -5 ° C . The reaction temperature was then maintained at 0 ° C during successive addition of the reagents. After stirring for 20 min, 2-amino-3-methyl-5-iodobenzoic acid (which is the product of stage A) (9.51 g, 34.31 mmol) was added and stirring continued for another 10 min. A solution of triethylamine (9.56 g, 68.62 mmol) in acetonitrile (15 mL) was then added dropwise, and the reaction mixture was stirred for 30 min, followed by the addition of methanesulfonyl chloride (2.91 mL). (37.74 mmol). The reaction mixture was heated to room temperature and stirred for 2 hours. The solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to give 8.53 g of the above-mentioned title compound as a yellow solid.

1 H NMR (CDCl3): δ 8.59 (dd, 1H), 8.35 (d, 1H), 7.97 (ddJH), 7.86 (d, 1H), 7.49 (m, 2H) ), 1.79 (s, 3H).

Stage E: Preparation of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1 H -pyrazol5-yl] -6-cyano-8-methyl-4 / 7-3.1 -benzox azin-4-onei

To the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4Z7-3, benzoxazine-4-one (i.e., stage D benzoxazinone product) (500 mg, 0.94 mmol) in tetrahydrofuran (10 mL) copper (I) iodide (180 mg, 0.094 mmol), tetrakis (triphenylphosphine) palladium was added (0) (5.4 mg, 0.047 mmol) and copper cyanide (I) (420 mg, 4.7 mmol) sequentially at room temperature. After heating the reflux mixture overnight with the additional reactant mixture, copper cyanide (I) (107 mg, 0.56 mmol) and tetrakis (triphenylphosphine) palladium (0) (325 mg, 0.28 mmol) were added and reflux continued. 1 hour. The reaction mixture changed its color, at which point the thin layer chromatography on the silica gel confirmed the completion of the reaction. The reaction mixture was then diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO4) and concentrated under reduced pressure to obtain о yellow crude solid.

1 H NMR (CDCl 3): δ 8.59 (dd, 1H), 8.33 (d, 1H), 8.03 (dd, 1H), 7.95 (d, 1H), 7.56 (m, 2H), 1.88 (s, 3H).

Stage F: Preparation of 1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1 / 7-pyrazole5-carboxamide

To the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1,7-pyrazol-5-yl] -6-cyano-8-methyl-4 / 7-3, 1-benzoxazine-4-one (ie, the product of stage E cyanobenzoxazinone) (200 mg, 0.46 mmol) in tetrahydrofuran (5 mL) was added dropwise ammonium hydroxide (0.5 mL, 12.8 mmol) to room's temperature. The reaction mixture was stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain 620 mg of the title compound, a compound of the present invention, as the melting solid at 200 ... 202 ° C. '']H NMR (CDC1)3): δ 10.65 (s, lH), 8.43 (dd, lH), 7.9 (dd, lH), 7.67 (s, lH) , 7.63 (s, lH), 7, 45 (m, 1H), 7.25 (s, 1H), 6.21 (bs, 1H), 5.75 (bs, 1H), 2.26 (s, 3H).

EXAMPLE 2

Preparation of 1 - (3-Chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -imazazole-5-carboxamide

Stage A: Preparation of 1- (3-Chloro-2-pyridinyl) -A- [4-iodo-2-methyl-6 [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -lf7-pyrazole-5- carboxamide

To the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl-1,7-pyrazol-5-yl)] - 6-iodo-8-methyl-4Z7-3, benzoxazin-4-one (i.e., the benzoxazinone product of Example 1, step D) (500 mg, 0.94 mmol) m tetrahydrofuran (15 mL) was added dropwise methylamine (2.0 M solution in THF, 1.4 mL (2.8 mmol) and the reaction mixture was stirred for 3 hours, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel to give 400 mg of the above-mentioned title compound as a yellow solid.

1 H NMR (CDCl 3): δ 10.25 (s, lΗ), 8.45 (dd, lH), 7.85 (dd, lH), 7.55 (s, lH), 7.50 (s, 1H), 7.46 (s, 1H), 7.40 (s, 1H), 6.15 (d, 1H), 2.93 (d, 3H), 2.12 (s, 3H).

MD 3864 C2 2009.03.31

Stage B: Preparation of 1- (3-chloro-2-pyridinyl) -V- [4-cyano-2-methyl-6 - [(methylarmno) carbonyl] phenyl] -3- (trifluoromethyl) -1-pyrazole- 5-carboxamide

To the solution of 1- (3-chloro-2-pyridinyl) -V- [4-iodo-2-methyl-6 - [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -1 H -pyrazole5- carboxamide (i.e., the product of stage A diamide) (410 mg, 0.72 mmol) in tetrahydrofuran (8 mL) was added copper (I) iodide (24 mg, 0.126 mmol), tetralds (triphenylphosphine) palladium (0) ( 70 mg, 0.060 mmol) and copper cyanide (I) (640 mg, 7.2 mmol) sequentially at room temperature. The reaction mixture was heated at reflux for 4.5 hours. Thin layer chromatography on silica gel confirmed the end of the reaction. The reaction mixture was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO4) and concentrated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain 114 mg of the above-mentioned title compound, a compound of the present invention, as a white solid which melts at 214. 216 ° C.

]H NMR (CDC1)3): δ 10.70 (s, lH), 8.46 (dd, lH), 7.87 (dd, lH), 7.57 (s, 2H), 7.45 (m, lH), 7, 31 (s, 1H), 6.35 (d, 1H),

2.98 (d, 3H), 2.24 (s, 3H).

EXAMPLE 3

Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 [(methylamino) carbonyl] phenyl] -1,7-pyrazole-5-carboxamide

Stage A: Preparation of 3-chloro-A, A-dimethyl-1 H -pyrazol-1-sulfonamide

To a solution of A-dimethylsulfamoylpyrazole (188.0 g, 1.07 mol) in dry tetrahydrofuran (1500 mL) at -78 ° C was added dropwise to a 2.5 M «-butyl-lithium solution (472 mL, 1.18 mol) in hexane keeping the temperature below -65 ° C. At the end of the addition, the reaction mixture was maintained at -78 ° C for an additional 45 minutes, after which a solution of hexachlorethane (279 g, 1.18 mol) in tetrahydrofuran (120 mL) was added dropwise. The reaction mixture was maintained for 1 hour at -78 ° C, heated to -20 ° C and then quenched with water (1 L). The reaction mixture was extracted with methylene chloride (4 x 500 mL); The organic extracts were dried over magnesium sulfate and concentrated. The crude product was then purified by chromatography on silica gel using methylene chloride as eluent to obtain 160 g of the above-mentioned title compound as a yellow oil.

1 H NMR (CDCl 2): δ 7.61 (s, 1H), 6.33 (s, 1H), 3.07 (d, 6H).

Stage B: Preparation of 3-chloropyrazole

To tri-fluoroacetic acid (290 mL) was added dropwise 3-chloro-A, A-dimethyl-1/7-pyrazol-1-sulfonamide (i.e., the product of stage A chloropyrazole) (160 g), the reaction mixture was stirred at room temperature for 1.5 hours, after which it was concentrated under reduced pressure. The residue was added to hexane, the insoluble solids were filtered, and the hexane was concentrated to obtain the crude product as an oil. The crude product was subsequently purified by silica gel chromatography using ether / hexane (40:60) as eluent to obtain 64.44 g of the product with the aforementioned title as a yellow oil.

1 H NMR (CDCl 2): δ 6.39 (s, 1H), 7.66 (S, 1H), 9.6 (brs, 1H).

Stage C: Preparation of 3-chloro-2- (3-chloro-1H-pyrazol-1-yl) pyridine

To a mixture of 2,3-dichloropyridine (92.60 g, 0.629 mol) and 3-chloropyrazole (i.e., the stage B product) (64.44 g, 0.629 mol) in ALV-dimethylformamide (400 mL) was added potassium carbonate (147.78 g, 1.06 mol), then the reaction mixture was heated at 100 ° C for 36 hours, cooled to room temperature and slowly poured into ice water. The precipitated solids were filtered and washed with water. The solid filtrate was introduced into ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographed on silica gel using 20% ethylacetate / hexane as eluent to obtain 39.75 g of the product with the aforementioned title as a white solid.

1 H NMR (CDCl 2): δ 6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H), '8.41 (d , H).

Step D: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -lf / -pyrazole-5-carboxylic acid

To a solution of 3-chloro-2- (3-chloro-1 H -pyrazol-1-yl) pyridine (i.e., the C-product pyrazole product) (39.75 g, 186 mol) in dry tetrahydrofuran (400 mL) at -78 ° C was added dropwise to a solution of 2.0 M lithium diisopropylamide (93 mL, 186 mmol) in tetrahydrofuran. The carbon dioxide was bubbled through amber solution for 14 minutes, after which the solution became brownish-yellow. The reaction was made basic with IN aqueous sodium hydroxide solution and extracted with ether (2x500 L). The aqueous extracts were acidified with 6N hydrochloric acid, followed by extraction with ethylacetate (3x500 mL). The extracts of ethyl acetate were dried over magnesium sulfate and concentrated to give 42.96 g of the product with the aforementioned title as a not even white solid. The product of another reaction obtained by the same procedure melted at 198 ... 199 ° C. '' '' H NMR (DMSO-4s): δ 6.99 (s, 1H), 7.45 (m, 1H), 7.93 (d, 1H), 8.51 (d, 1H).

Step E: Preparation of 2- [3-chloro-1- (3-chloro-2-pyridiml) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4 // -3,1 benzoxazin-4-one

To the solution of methanesulfonyl chloride (0.63 mL, 8.13 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1 (3-chloro-2-pyridinyl) -1 H 7-pyrazole-5-carboxylic acid (ie, the product of stage D carboxylic acid) (2.0 g, 7.75 mmol) and triethylamine (1.08 mL, 7.75 mmol) in acetonitrile (5 mL) at 0 ° C. The reaction mixture was stirred for 15 min at 0 ° C. Thereafter, 2-amino-3-methyl-5-iodobenzoic acid (i.e., the product of Example 1, stage A) (2.14 g, 7.75 mmol) was added and stirring continued for 5 min. A solution of triethylamine (2.17 mL, 15.15 mmol) in acetonitrile (5 mL) was added dropwise at a temperature below 5 ° C. The reaction mixture was stirred for 40 min at 0 ° C, then methanesulfonyl chloride (0.63 mL, 8.13 mmol) was added, warmed to room temperature and stirred overnight. It was then diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (1x20 mL), dried (MgSO4) and concentrated to obtain 3.18 g of the product with the aforementioned title as о yellow crude solid.

1 H NMR (CDCl 2): δ 8.55 (dd, 1H), 8.33 (s, 1H), 7.95 (dd, 1H), 7.82 (d, 1H), 7.45 (m, 1H), 7.16 (s, 1H), 1.77 (s, 3H).

MD 3864 C2 2009.03.31

Step F: Preparation of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 // -3-l benzoxazin-4-one

To the solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4 // -3, benzoxazin-4-one (i.e., the product of stage E benzoxazinone) (600 mg, 1.2 mmol) in tetrahydrofuran (15 mL) was added copper (I) iodide (137 mg, 0.72 mmol), tetrakis ( triphenylphosphine) palladium (0) (416 mg, 0.36 mmol) and copper cyanide (I) (860 mg, 9.6 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight. The reaction became black in color, at which point the thin layer chromatography on the silica gel confirmed the completion of the reaction. The reaction was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO4) and concentrated under reduced pressure to obtain 397 mg of the title compound as о yellow crude solid.

1 H NMR (CDCl 3): δ 8.50 (q, 1H), 8.22 (d, 1H), 7.90 (dd, 1H), 7.67 (d, 1H), 7.45 (m, 1H), 7.15 (s.lH), 1.79 (s, 3H).

Stage G: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (methylamino) carbonyl] phenyl] -1 H -pyrazole-5-carboxamide

To a solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 H -3-benzoxazine -4-one (eg, C-stage cyanobenzoxazinone product) (100 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine solution (2.0 M solution in THF, 0.5 mL) (1.0 mmol) and the reaction mixture was stirred for 5 minutes, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain the title compound, a compound of the present invention, as a white solid (52 mg), which was decomposed into a device for melting at temperatures above 140 ° C.

Ή NMR (CDC13): δ 10.55 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.55 (d, 2H), 7.40 (m, lH), 6, 97 (d, 1H), 6.30 (d, 1H),

2.98 (d, 3H), 2.24 (d, 3H).

EXAMPLE 4

Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (arninocarbonyl) phenyl] -1H-pyrazole-5-carboxamide

To the solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 // -3- benzoxazin-4-one (ie, the product of cyanobenzoxazinone from Example 3, stage F) (100 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was added dropwise ammonium hydroxide (0.5 mL, 12.8 mmol) ) at room temperature. The reaction mixture was then stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain 55 mg of the above-mentioned title compound, a compound of the present invention, as a white solid which decomposes in an apparatus. for melting at temperatures above 255 ° C.

NMR (CDCl3): δ 10.50 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.66 (d, lH), 7.61 (s, lH) , 7.41 (m, 1H), 6.95 (s, 1H), 6.25 (bs, 1H), 5.75 (bs, 1H), 2.52 (s, 3H).

EXAMPLE 5

Preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6 [(methylamino) carbonyl] phenyl] -1,7-pyrazole-5-carboxamide

Stage A: Preparation of 3-bromo- / V, / V-dimethyl-1/7-pyrazole-1-sulfonamide

To a solution of ΑζΝ-dimethylsulfamoylpyrazole (44.0 g, 0.251 mol) in dry tetrahydrofuran (500 mL) at -78 ° C was added dropwise to a solution of w-butyllithium (2.5 M in hexane, 105.5 mL). , 0.264 mol) with a temperature lower than -60 ° C, as a result of the о thick solid substance was formed. After completion of the addition, the reaction mixture was maintained for a further 15 min, after which a solution of 1,2-dibromo-tetrachlorethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) was added dropwise with a temperature below -70. ° C. The reaction mixture was transformed into a pure orange; stirring was further continued for 15 min. The bath at -78 ° C was removed and the reaction was quenched with water (600 mL). The reaction mixture was extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride-hexane (50:50) as eluent to obtain 57.04 g of the product with the above-mentioned title as a colorless pure oil.

1 H NMR (CDCl 3): δ 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

Stage B: Preparation of 3-brompirazole

To trifluoroacetic acid (70 mL) was slowly added 3-bromo-A-A-dimethyl -] // - pyrazole-1-sulfonamide (ie, the product of stage A brompirazole) (57.04 g). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The residue was introduced into hexane, the insoluble solids were filtered, and the hexane was evaporated to obtain the crude product as an oil. The crude product was subsequently purified by chromatography on silica gel using ethylacetate / dichloromethane (10:90) as eluent to obtain an oil. The oil was introduced into dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with methylene chloride (3x), dried over magnesium sulfate and concentrated to afford 25.9 g of the product with the above-mentioned title as a solid substance. white, mp 61 .. .64 ° C.

1 H NMR (CDCl 2): δ 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H). '

Stage C: Preparation of 2- (3-bromo-1 H -pyrazol-1-yl) -3-chlorpyridine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-brompirazole (i.e., the stage B product) (25.4 g, 176 mmol) in dried A / A'-dimethylformamide (88 mL) potassium carbonate (48.6 g, 352 mmol) was added and the reaction mixture was heated at 125 ° C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 mL). A precipitate formed. The precipitated solids were stirred for 1.5 hours, filtered and washed with water (2x100 mL). The solid filter check was introduced into methylene chloride and washed successively with water, IN hydrochloric acid, saturated aqueous sodium bicarbonate solution and salt solution. The organic extracts were then dried over sulfate

MD 3864 C2 2009.03.31 magnesium and concentrated to obtain 39.9 g of pink solid. The crude solid was passed into hexane and stirred vigorously for 1 hour. The solids were filtered, washed with hexane and dried to obtain the product with the aforementioned title as a not even white powder (30.4 g) determined to be> 94% pure by NMR. This material was used without further purification in stage D.

Ή NMR (CDC13): δ 6.52 (s, lH), 7.30 (dd, lH), 7.92 (d, lH), 8.05 (s, lH), 8.43 (d, lH).

Stage D: Preparation of 3-Bromo-1- (3-chloro-2-pyridinyl) -1 H -pyrazole-5-carboxylic acid

To a solution of 2- (3-bromo-1 H -pyrazol-1-yl) -3-chlorpyridine (i.e., the C-stage pyrazole product) (30.4 g, 118 mmol) in dry tetrahydrofuran (250 mL ) at -76 ° C a solution of lithium diisopropylamide (118 mmol) in tetrahydrofuran was added dropwise in such a ratio to maintain temperatures below -71 ° C. The reaction mixture was stirred for 15 minutes at -76 ° C and carbon dioxide was then bubbled for 10 minutes, causing heating to -57 ° C. The reaction mixture was heated to -20 ° C and quenched with water, concentrated and placed in water (1 L) and ether (500 mL), after which aqueous sodium hydroxide solution (IN, 20 mL) was added. The aqueous extracts were washed with ether and acidified in hydrochloric acid. The precipitated solids were filtered, washed with water and dried to obtain 27.7 g of the product with the aforementioned title as a brownish-yellow solid. The product from another reaction using the similar procedure melted at 200 .. .201 ° C.

1 H NMR (DMSO 4): δ 7.25 (s, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.56 (d, 1H).

Step E: Preparation of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4Z / -3-yl. benzoxazin-4-one

To the solution of methanesulfonyl chloride (0.54 mL, 6.94 mmol) in acetonitrile (15 mL) was added dropwise a mixture of 3-bromo-1 (3-chloro-2-pyridinyl) -17 ¥ - pyrazole-5-carboxylic acid (ie, the product of stage D carboxylic acid) (2.0 g, 6.6 mmol) and triethylamine (0.92 mL, 6.6 mmol) in acetonitrile (5 mL) at 0 ° C . The reaction mixture was stirred for 15 min at 0 ° C. Thereafter, 2-amino-3-methyl-5-iodobenzoic acid (ie, the product of Example 1, stage A) (1.8 g, 6.6 mmol) was added and stirring continued for a further 5 min. Then a solution of triethylamine (1.85 mL, 13.2 mmol) in acetonitrile (5 mL) was added dropwise, keeping the temperature below 5 ° C. The reaction mixture was stirred for 40 min at 0 ° C, followed by methanesulfonyl chloride (0.45 mL, 6.94 mmol). The reaction mixture was then warmed to room temperature and stirred overnight, then diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (1x20 mL), dried (MgSO4) and concentrated to obtain 2.24 g of the product with the aforementioned title as о yellow crude solid.

1 H NMR (CDC 13): δ 8.55 (dd, lH), 8.33 (d, 1H), 7.95 (dd, lH), 7.85 (s, lH), 7.45 (m, lH), 7, 25 (s, 1H), 1.77 (s, 3H).

Stage F: Preparation of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 H -3,3-l benzoxazin-4-one

To a solution of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4 H -3, benzoxazine-4-one (i.e., stage E benzoxazine product) (600 mg, 1.1 mmol) in tetrahydrofuran (15 mL) copper (I) iodide (126 mg, 0.66 mmol), tetrakis ( triphenylphosphine) palladium (0) (382 mg, 0.33 mmol) and copper cyanide (I) (800 mg, 8.8 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight. The reaction became black in color, at that point the thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction mixture was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% sodium bicarbonate solution and о with salt solution. The organic extract was dried (MeSO4) and concentrated under reduced pressure to obtain 440 mg of the compound with the above-mentioned title as a yellow crude solid.

'Ή NMR (CDCl3): δ 8.55 (m, 1H), 8.31' (d, 1H), 7.96 (dd, 1H), 7.73 (s, 1H), 7.51 (m , 1H), 7.31 (s, 1H), 1.86 (s, 3H).

Stage G: Preparation of 3-Bromo-1- (3-chloro-2-pyridinyl) -A, A-cyano-2-methyl-6 [(methylamino) carbonyl] phenyl-1 H -pyrazole-5-carboxamide

To a solution of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -17-pyrazol-5-yl] -6-cyano-8-methyl-4 H -3-benzoxazine -4-one (i.e., the product from stage F) (100 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol) and the reaction mixture was stirred for 5 min, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to afford the title compound, a compound of the present invention, as a white solid (41 mg), which was decomposed into an apparatus. for melting above 180 ° C.

Ή NMR (CDC13): δ 10.55 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.57 (s, 2H), 7.37 (m, 1H), 7, 05 (s, 1H), 6.30 (d, 1H),

2.98 (d, 3H), 2.24 (s, 3H).

EXAMPLE 6

Preparation of 3-Bromo-1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1 H -pyrazol-5-carboxamide In a solution of 2- [3-bromo-l- (3-chloro-2-pyridinyl) -l // - pyrazol-5-yl] -6-cyano-8-methyl-4 // - 3, l-benzoxazin-4- An ion (i.e., the cyanobenzoxazinone product of Example 5, stage F) (100 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added dropwise to ammonium hydroxide (0.5 mL, 12.8 mmol) at room temperature. . The reaction mixture was then stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to afford the above-mentioned compound, a compound of the present invention, as a white solid (36 mg) with a melting point. above 255 ° C.

1 H NMR (CDCl 3): δ 10.52 (s, 1H), 8.45 (dd, 1H), 7.85 (dd, 1H), 7.65 (s, 1H), 7.60 (s, lH), 7.40 (m, lH), 7.05 (s, lH), 6.20 (bs, lH), 5.75 (bs, lH), 2.25 (s, 3H).

MD 3864 C2 2009.03.31

EXAMPLE 7

Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -A- [2-chloro-4-cyano-6 [(methylamino) carbonyl] phenyl] -1,7-pyrazole-5-carboxamide!

Stage A. Preparation of 2-amino-3-chloro-5-iodobenzoic acid

To the solution of 2-amino-3-chloro-5-iodobenzoic acid (Aldrich, 5 g, 29.1 mmol) in Α, Α-dimethylformamide (30 mL) was added A-iodosuccinimide (5.8 g, 26 mmol ) and the reaction mixture was heated overnight at 60 ° C. The heating was removed and the reaction mixture was then slowly poured into ice water (100 mL) to clarify the nozzle о light brown solid. It was filtered and washed 4 times with water and then placed in a vacuum oven at 70 ° C for overnight drying. The desired intermediate was isolated as a brownish-light solid (7.2 g).

1 H NMR (DMSO-d): δ 7.96 (d, 1H), 7.76 (t, 1H). '

Step В: Preparation of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 / 7-pyrazol-5-yl] -6-iodo-4 // -3, 1 benzoxazin-4-one

To the solution of methanesulfonyl chloride (0.31 mL, 4.07 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1 (3-chloro-2-pyridinyl) -1 / / -pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Example 3, step D) (1.0 g, 3.87 mmol) and triethylamine (0.54 mL, 3.87 mmol) in acetonitrile (5 mL) at 0 ° C. The reaction mixture was then stirred for 15 min at 0 ° C. Thereafter, 2-amino-3-chloro-5-iodobenzoic acid (i.e., the product from stage A) (1.15 g, 3.87 mmol) was added and stirring continued for another 5 min. The triethylamine solution (1.08 mL, 7.74 mmol) in acetonitrile (5 mL) was added dropwise at a temperature below 5 ° C. The reaction mixture was stirred for 40 minutes at 0 ° C, after which methanesulfonyl chloride (0.31 mL, 4.07 mmol) was added. It was then warmed to room temperature and stirred overnight, further diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (11x20 mL), dried (MgSO4) and concentrated under reduced pressure. The residual solid was purified by chromatography on silica gel to obtain 575 g of the above-mentioned title compound as a crude yellow solid.

1 H NMR (CDC 13): δ 8.55 (q, lH), 8.39 (d, lH), 8.04 (d, lH), 7.94 (dd, lH), 7.45 (m, lH), 7, 19 (s, 1H).

Step C: Preparation of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -65-pyrazol-5-yl] -6-cyano-4 / 7-3, benzoxazine 4-one

In the solution of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 / 7-pyrazol-5-yl] -6-iodo-4 / 7-3, benzoxazine-4-one (i.e., the product of stage V benzoxazine) (575 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper (I) iodide (840 mg, 0.4 mmol), tetrakis ( triphenylphosphine) palladium (0) (255 mg, 0.22 mmol) and copper cyanide (I) (550 mg, 5.5 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight. The reaction turned black, at this point the thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о salt solution. The organic extract was dried (MgSO4) and concentrated under reduced pressure to obtain 375 mg of the title compound as о crude yellow solid.

H NMR (CDC13): δ 8.55 (q, 1H), 8.36 (d, 1H), 7.95 (m, 2H), 7.5 (m, 1H).

Step D: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -A- [2-chloro-4-cyano-6 [(methylamino) carbonyl] phenyl] -imazazole-5-carboxamide

In the solution of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1/7-pyrazol-5-yl] -6-cyano-4 / 7-3, benzoxazin-4-one (i.e., C-stage cyanobenzoxazinone product) (187 mg, 0.446 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol) and the reaction mixture was stirred for 5 min, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to contain 49 mg of the above-mentioned title compound, a compound of the present invention, as a white solid which melted at 197. .200 ° C.

1 H NMR (CDCl 2): δ 10.05 (bs.lH), 8.45 (q, lH), 7.85 (dd, lH), 7.70 (dH), 7.59 (d, 1H), 7.38 (m, 1H), 7.02 (s, 1H), 6.35 (d, 1H), 2.94 (d, 3H).

By the procedures described here, together with the methods known in the art, the compounds inserted in Table 1. can be prepared. The following abbreviations are used in the following tables: t means tertiary, 5 - secondary, n - normal, i iso, Me - methyl, Et - ethyl, Pr - propyl, z - Pr - isopropyl, Bu - butyl and CN - cyano.

Table 1

R2

MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31

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<td>Вт</td><td>Вг</td><td>CHfMeJCi ^ SMe</td><td>H</td><td>а</td><td>Вг</td><td>Вг</td><td>CH (Me) CH2SMe</td><td>H</td>

<td>CF3</td><td>а</td><td>OMe ^ CHoSMe</td><td>H</td><td>а</td><td>CF3</td><td>а</td><td>C (Me) 2CH2SMe</td><td>H</td>

<td>OCF2H</td><td>F</td><td>H</td><td>H</td><td>а</td><td>OCFjH</td><td>F</td><td>H</td><td>H</td>

MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31 κΐ

MD 3864 C2 2009.03.31

Table 3 к?

MD 3864 C2 2009.03.31

The compounds of the present invention will generally be used as a formulation or composition with a convenient carrier for agronomic or non-agronomic use containing at least one of the liquid diluents, a solid diluent or a surfactant. The ingredients of the formulation or composition are selected to correspond to the physical properties of the active ingredient, the mode of application and environmental factors, such as the type of variety, humidity and temperature. Useful formulations include liquids, such as solutions (including concentrated emulsifiers), suspensions, emulsions (including microemulsions and / or suspensions) and the like, which can optionally be thickened in gels. Useful formulations also include solid substances, such as powders, powders, granules, tablets, pills, films and the like that can be dispersible in water or soluble in water. The active ingredient can be (micro) encapsulated and subsequently formed into a suspension or solid formulation; alternatively the total formulation of the active ingredient may be capsulated (or "coated"). Capsulation can control or delay separation of the active ingredient. The sprayable formulations can be dissolved in convenient environments and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further preparation.

The formulations will typically contain effective amounts of the active ingredient, diluent and surfactant in the quantities indicated, which together constitute up to 100% by mass.

Percentage by mass

<td></td><td>Active ingredient</td><td>thinner</td><td>Surfactant</td>

<td>Water-soluble powders, tablets and granules</td><td> 5...90</td><td> 0...94</td><td> 1...15</td>

<td>dispersible in water</td><td></td><td></td><td></td>

<td>Suspensions, emulsions (including concentrates)</td><td> 5...50</td><td> 40...95</td><td> 0...15</td>

<td>emulsifiable)</td><td></td><td></td><td></td>

<td>powders</td><td> 1...25</td><td> 70...99</td><td> 0...5</td>

<td>Granules and pills</td><td> 0,01...99</td><td> 5...99,99</td><td> 0...15</td>

<td>Highly resistant compositions</td><td> 90...99</td><td> 0...10</td><td> 0...2</td>

Typical solid diluents are described in Watkins et al. Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, inserts surfactants and recommended uses. All formulations may contain minor amounts of additions to reduce foaming, baking, corrosion, microbiological growth, etc., or thickeners to increase viscosity.

Subsurface surfactants include, for example, polyethoxyl alcohol, alkylphenol polyethoxylphen, sorbitan fatty acid esters, polyethoxylaphthes, dialkylsulfosuccinaphs, alkyl sulfaphs, alkylbenzenesulfonaphs, organosilicones, N, N-dialkylthyraphenes, ligninsulfonates, ligninsulfones . Solid diluents include, for example, clays, such as bentonite, montmorillonite, atapulgite and kaolin, starch, sugar, silica, talc, diatomic soil, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, ΝΜ, Ν-dimethylformamide, dimethylsulfoxide, Nalkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzene, alkylnaphthalene, olive oil, castor, flax seed, porcinium, ground flax, porridge cotton, soybean, raspberry and coconut, fatty acid esters, ketones, such as 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexane, decanol and tetrahydrofurfuryl alcohol.

MD 3864 C2 2009.03.31

The solutions, which include emulsifiable concentrates, can be prepared by simple mixing of the ingredients. The powders and powders can be prepared by blending and usually milled such as in a hammer mill or a fluidized mill. Suspensions are usually prepared by wet grinding; see, for example, US 3,060 084. Granules and pills can be prepared by spraying the active material on preformed granular carriers or by agglomeration techniques (see Browning "Agglomeration", Chemical Engineering, December 4, 1967, pp. 147-148, Perry's Chemical Engineer's Handbook, 4th Edition). a, McGraw-Hill, New York, 1963, pages 8-57 and WO 91/13546). The pills can be prepared as described in US 4,172,714. Water-soluble and water-dispersible granules can be prepared as described in US Pat. No. 4,144,050, U.S. Patent No. 3,944,442, and US $ 3,246,493. Tablets may be prepared as described in US Pat. US 5 208 030. Films can be prepared as described in GB 2 095 558 and US 3 299 566.

For more information on the form field, see TS Woods. The Formulator's ToolboxProduct Forms for Modern Agriculture. Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and TR Roberts. Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also US 3 235 361, col. 6, row 43 of col. 7, row 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166,167, and 169-182; US 2 891 855, col. 3, row 66 et al. 5, row 17 and examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp. 81-96; and Hance et. al. Weed Control Handbook. 8th ed., Blackwell Scientific Publications, Oxford, 1989.

In the following examples all the percentages are by mass and all the solutions are prepared by traditional procedures. The numbers of the compounds refer to the compounds in Index Table A.

Example A

Wettable powder

<td>Compound 1 sodium dodecylphenol ether polyethylene glycol ligninsulphonate sodium silicoaluminate sodium montmorillonite (calcined)</td><td colspan="2"> 65,0% 2,0% 4,0% 6,0% 23,0%</td>

<td>Granulate Compound 1</td><td>Example В</td><td> 100%</td>

<td>granules of atapulgite (low volatile material,</td><td>0.71 / 0.30 mm; USS No. 25-</td><td> 90,0%</td>

<td>50 sites) Extruded Pill Compound 1</td><td>Example C</td><td> 25,0%</td>

<td>crude sodium sulfate</td><td></td><td> 10,0%</td>

<td>sodium ligninsulphate</td><td></td><td> 5,0%</td>

<td>sodium alkylnaphthalenesulfonate</td><td></td><td> 1,0%</td>

<td>magnesium / calcium bentonite</td><td></td><td> 59,0%</td>

<td>Emulsifiable concentrate Compound 1</td><td>Example D</td><td> 20,0%</td>

<td colspan="2">mixture of oil-soluble sulphonates and polyoxyethylene ethers</td><td></td>

<td>isophorone</td><td></td><td> 10,0% 70,0%</td>

<td>Granule Compound 1</td><td>Example E</td><td> 0,5%</td>

<td>cellulose</td><td></td><td> 2,55</td>

<td>lactose</td><td></td><td> 4,0%</td>

<td>cornmeal</td><td></td><td> 93,0%.</td>

The compounds of the present invention are characterized by the residual characteristics of favorable metabolism and / or soil and manifest activity of combating a spectrum of agronomic invertebrate pests! and non-agronomic ones. The compounds of the present invention are also characterized by favorable foliar systemicity and / or applied by soil in plants, exercising translocation to protect the foliage and other parts of plants that have not directly contacted the insecticidal compositions containing the compounds present. (In the context of this description, "fighting invertebrate pests" means inhibiting the development of invertebrate pests (including mortality) that cause food shortage or other damage or damage caused by pests; rooted expressions are similarly defined.) As described, the term "invertebrate pests" includes arthropods, gastropods and nematodes of importance! The term "arthropod" includes insects, ticks, spiders, scorpions, chilopods, myrrhpods, baboon dogs (scorpions) and scolopendrons. The term "gastropod" includes snails, snails and other stylomatophores. The term "nematode" includes all helminths, such as; phytophagous nematodes and nematodes, trematodes, acantocephalics and parasitic worms in the form of ribbon (Cestodele). Those skilled in the art will recognize that not all compounds are equally effective against pests. The compounds of the present invention manifest activity against economically important agronomic and non-agronomic pests. The term "agronomic" refers to the production of field crops, such as for food and fiber, and includes the growth of cereal crops (eg, wheat, oats, barley, rye, rice, corn), soybean crops, vegetable crops.

MD 3864 C2 2009.03.31 (eg, green salad, cabbage, tomatoes, beans), potatoes, sweet potatoes, mackerel, cotton, and fruits (eg, seed poems, peach fruits and citrus fruits). The term "non-agronomic" refers to other fruit plants (eg forest, greenhouse, nursery or ornamental plants that are not grown in the field), lawns (commercial, golf, residential, recreational, etc.), wood products, human and animal health, commercial and domestic structure, household, and pest or stored product applications. Due to the spectrum of combating invertebrate pests and the economic importance, the protection (against damage or damage caused by the invertebrate pests) of agricultural crops of cotton, corn, soybean, rice, vegetable crops, potato, sweet potato, pumice and fruit by the fighters Examples of embodiment of the invention are preferred. Agronomic pests! or non-agronomic include larvae from the order of Lepidopterans, such as owls, butterfly-owls, quail-butterflies, and from the nocturnal butterfly family Noctuidae (eg, Spodoptera fugipedra JE Smith), buha-mica (Spodoptera exigua Hubner), butterfly ipsilon (Agrotis ipsdon Hufnagel), buha-cabbage (Trichoplusia ni Hubner), omida-tobacco (Heliothis virescens Fabricius); minions, moles, mints, spiders, worms and worms that skeletonize the leaves of the Piralidae family (eg, butterflies (Ostrinia nubilalis Hubner), Walker butterflies (Amyelois transitella), (Crambus caliginosellus) (Herpetogramma Ucarsisalis Walker)); tortricides, cigarettes, seed worms and fruit worms in the Tortricidae family (eg, apple worms (Cydia pomonella Linnaeus), pyrotechnics (Endopiza viteana Clemens), omida-oriental-peach (Grapholita molesta Busck) and many more other economically important lepidoptera (eg, moth-cabbage (Plutella xylostella Linnaeus), pink-worm-cotton (Pectinophora gossypiella Saunders), hairy-oak (Lumantria dispar Linnaeus)); adult nymphs and insects of the Blatod order, including beetles from the Blatelidae and Blatidae families (eg, the black-throated beetle (Blatta oriental is Linnaeus), the Asian-cockroach (Blatella asahinai Mizukubo), the red-tailed beetle (Blatella-de-bucatella) germanica Linnaeus), the beetle (Supella longipalpa Labricius), the American beetle (Periplaneta americana Linnaeus), the beetle-brown (Periplaneta brunnea Burmeister), the beetle-de-Madeira (Leucophaea maderae Labricius)); adult larvae and insects feeding on the leaves of the Coleoptera, including the caterpillars in the families of Antribids, Bruchids and Curculionids (eg, cottonseed (Anthonomus grandis Boheman), water-borne (Lissorgilustrus) (Sitophilus granarius Linnaeus), the mackerel (Sitophilus oryzae Linnaeus); ground fleas, leaf cockroaches, Colorado cockroaches, potato fleas and miners in the Chrysomelid family (eg, Colorado beetle) (Say Leptinotarsa decemlineata Say), western worm roots corn (Diabrotica virgilera virgifera LeConte); beetles and other beetles of the Scarabaeidae family (eg, Japanese-beetle (Popillia japonica Newman) and European beetle (Rhizotrogus majalis Razo-umowsky)); the beetles of the skin of the Dermestide family; wire worms from the family of Elaterides; bark beetles from the Scolithite family and beetles from the Tenebrionid family. In addition, agronomic and non-agronomic fish include: adult insects and larvae of the order of Dermaptera, including the earworms of the Forficulidae family (eg, the common earworm (Forficula auricularia Linnaeus), the black-eared eagle (Chelisoches morio Fabricius); adult insects and nymphs in the orders of Hemiptera and Homoptera, such as: herbs from the family of Miridas, cicadas from the family of Cicadas, cicadas (eg, Empoasca spp.) from the family of Cicadelides, cicadas from the families of Fulgoroids and Delfacids, chicory-bites from the family of Membracides, psyllids from the family of Psilids, aleirod family Aleirodids, aphids in the family of aphids, phylloxera in the family of phylloxerids, lice in the Pseudococcid family, lice in the Coccid family, Diaspidids and Margarodids, Fingid family breams, Pentatomid family bream cereals, North American wheat bean bites (eg, Blissus spp.) And other seed bites from the Ligaeididae family, Bleeding bean from the Cormorant family , and the red-and-red-and-red-cotton-bunnies of the Pirrocorid family. They are also included as agronomic pests! and non-agronomic adult insects and larvae of the mites (mites), such as: common spiders of the Tetranicide family (eg, spider-red-spider (Panonychus ulmi Koch)), spider-spider (Tetranychus urticae Koch), McDaniel tick (Tetranychus mcdanieli McGregor), flat claws Tenuipalpid (eg, citrus-clove (Brevipalpus lewisi McGregor), vine-clippers and moss-clippers from the family of Eriophiids and other mites that feed on leaves and mites important for human and animal health, that is, the clamps of the Epidermoprid family, the eels of the Demodicide family, the ticks of the Glycifagidae family, the ticks of the Ixodidae (eg, the cap-ixoda-de-deer (Ixode scapularis Say)), the tick-ticks of the Ixodex-Isoxysalus of the Austro-Ixodus. Neumann), the dog tick (Dermacentor variabilis Say), the dog tick (Ambyomma americanum Linnaeus), and the ticks of the families of Psoroptids, Piemotids and Sarcoptids; adult and immature insects on the order of Orthoptera, including brambles, locusts and crickets (eg, buggies (e.g., Melanoplus sanguinipes Fabricius, M.) differential is Thomas), American grasshoppers (eg, American schistocerca Drury), wild locust (Schistocerca gregaria Forskal), traveling locust (Locusta migratoria Linnaeus), shrub locust (Zonocerus spp.), greyhound -from-house (Acheta domestricus Linnaeus), coropișnițele (Gryllotalpa spp.)); adult and immature insects on the order of Dipteres, including miners, moths, drosophile flies (Tefritids), Swedish-flies (eg, Oscinella frit Linnaeus), larvae-apodes-ground, house-flies (de eg, Musca domestica Linnaeus), small-house flies (eg, Fannia canicularis Linnaeus, F. Stein's femoralis), common flies (e.g., Stomoxys calcitrans Linnaeus), autumn flies, blue flies (e.g., Chrysomya spp., Phormia spp.) and other flying pests, horsehair (e.g. , Tabanus spp.), Narrow-gastric larvae (eg, Gastrophilus spp., Oestrus spp.), Calf strains (e.g., Hypoderma spp.), Reindeer (e.g., Chrysops spp.) .), ticks (e.g., Melophagus ovinus Linnaeus) and other Brachychids, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), Molluscs (eg, Prosimulium spp., Simulium spp.), Biting-flies, mosquitoes, sciarids and other Nematocides; adult and immature insects of the Tisanoptera, including tobacco thrips (Thrips tabaci Lindeman), wheat thrips (Frankliniella spp.) and other leaf-feeding thrips; harmful insects in the order of Hymenopterans, including ants (eg, red-bellied-feathers of Pennsylvania (Camponotus ferrugineus Fabricius), red-bellies of Pennsylvania (Camponotus pennsylvanicus De Geer), house-ferns (Monomorius ponis) , ant-vasmania (Wasmannia

MD 3864 C2 2009.03.31 Roger auropunctata), ant-solenopsis {Solenopsis geminata Fabricius), red-ant-Richter ant (Solenopis invicta Buren), Argentine ant {Iridomyrmex humilis Mayr), ant {Paratrechina longicornis Latreille), meadow ant {Tetramorium caespitum Linnaeus), American ant {Lasius alienus Forster), ant {Tapinoma sessile Say)), bees (including moss bees), wasps, bumblebees and wasps {Neodiprion spp., Cephas spp. ) harmful insects in the order of Isoptera, including termites {Reticulitermes flavipes Kollar), {Reticulitermes hesperus Banks), {Coptotermes formosanus Shiraki), {Incisitermes immigrans Snyder) and other isotopes of economic importance; harmful insects in the order of the Tizanura, such as {Lepisma saccharina Linnaeus) and (Thermobia domestica Packard); harmful insects in the order of Malophages, including head lice {Pediculus humanus capitis De Geer), body lice {Pediculus humanus humanus Linnaeus), malophagus {Menacanthus stramineus Nitszch), dog lice {Trichoder canis) , lice {Goniocotes gallinae De Geer), ticks {Bovicola ovis Schrank), lice {Haematopinus eurysternus Nitzsch), long-nosed-horned-lice {Linognathus vituli Linnaeus) and other parasitic lice that are blood-sucking and ruminant-attacking humans and animals; harmful insects in the order of Siphonopterans, including rat fleas {Xenopsylla cheopis Rothschild), cat fleas {Ctenocephalides felis Bouche), deciduous fleas {Ctenocephalides canis Curtis), chicken fleas {Ceratophyrankllus gallinae (Ceratophyrankllus gallinae) -vouse {Echidnophaga gallinacea West wood), fleas {Pulex irritans Linnaeus) and other lice that affect mammals and birds. Invertebrate pests additionally included: spiders of the order Araneae, such as the spider {Loxosceles reclusa Gertsch & Mulaik) and the spider-weaver-black {Eatrodectus mactans Fabricius), and centipedes of the order Scutigeromorphs, such as Scorpion mackerel, Common scallop { ). The compounds of the present invention also have action on members of the classes of Nematodes, Cestodes, Trematodes and Acantocephalics, including members of economic importance in the orders of Strongilides, Ascaridides, Oxiurides, Roots, Spirurids and Enoplids, such as, but not limited to, agricultural fish. economic (that is, Gallic nematodes of the genus Meloidogyne, harmful nematodes of the genus Pratylenchus, nematodes of the genus Trichodorus, etc.) and fish that affect the health of humans and animals (ie all trematodes, worms and worms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofdaria immitis Leidy in dogs, Anoplocep horses; Eadciola hepatica Linnaeus in ruminants, etc.).

The compounds of the invention possess particular high activity against pests of the Lipidoptera (e.g., Alabama argillacea Hubner (American-buha), Archips argyrospila Walker (butterfly-omitted), A. rosana Linnaeus (European caterpillar), and other species Archips, Chilo suppressalis Walker (paratus), Cnaphalocrosis medinalis Guenee (buha-rice), Crambus caliginosellus Clemens (butterfly moth), Crambus teterrellus Zincken (butterfly), Cydia pomerier Lineae apples), Earias insulana Boisduval (omida-thorns), Earias vitella Fabricius (worms-spotted), Helicoverpa armigera Hubner (American worm), Helicoverpa zea Boddie (buhabumbacului), Heliothis virescens Fabricius (tobacco moth), Herpetogramma Ucarsisalis Walker (butterfly), Lobesia botrana Denis & Schiffermuller (pear-vines), Pectinophora gossypiella Saunders (worm-pink-cotton-worm), Phyllocnistis citrella Straer (moth) citrus fruits), Pieris brassicae Linnaeus (white-cabbage), Pieris rapae Linnaeus (white-cabbage), Plutella xylostella Linnaeus (moth-cabbage), Spodoptera exigua Hubner (buha-mica), Spodoptera litura Fabricius (butterfly, omida-clusters), Spodoptera frugiperda JE Smith (buha-grass), Trihoplusia ni Hubner (buha ni) and Tuta absolut Meyrick (tomato-miner)).

The compounds of the invention also possess important commercial activity on the members of the Homoptera order, including: Acyrthisiphon pisum Harris (aphea peas), Aphis craccivora Koch (black-beet-lice), Aphis fabae Scopoli (black-beet-lice), Aphis gossypii Glover (cotton-lice, cotton-louse, Deer-louse) (apples-green-lice), Aphis spiraecola Patch (lice-tavolgian), Aulacorthum solani Kaltenbach (lice-lice), Chaetosiphon fragaefolii Cockerell (lice-strawberry), Diuraphis noxia Kurdjumov / Mordvilko-lice-Russia ) Dysaphis plantaginea Paaserini (lice-verdeal-rose), Eriosoma lanigerum Hausmann (lice-woolly), Hyalopterus pruni Geoffrey (lice-hay-prunus), Lipaphis erysimi Kaltenbach (louse), Metopolophium dirruchrose Macerealum (Walker) (potato-leaf lice), Myzus persicae Sulzer (artichoke-peach-leaf-lice, green-peach lice), Nasonovia ribisnigri Mosley (salad-leaf lice), Pemphigus spp. (Root lice and tubercle lice), Rhopalosiphum maidis Fitch (leaf lice), Rhopalosiphum padi Linnaeus (lice), Schizaphis graminum Rondani (lice-seedlings) wheat), Therioaphis maculata Buckton (Lucerne-lice), Toxoptera aurer Bayer de Fonscolombe (bitter-black-orange-flea), and Kirkaldy Toxoptera citricida (citrus lice); Adelges spp. (Adelgide); Phylloxera devastatrix Pergande (phylloxera), Bemisia tabaci Gennadius (tobacco aleroidide, sweet potato aleroidide), Bemisia argentifolii Bellows & Perring (white-magnolia), Dialeurodes citri Ashmead (white-citrus) and Trwoodurodes albarbiorum; Empoasca fabae Hanis (potato-chicory), Laodelphax striatellus Fallen (small-coffee-chicory), Macrolestes quadrilineatus Forbes (turkey-eyed-chicory), Nephotettix ciniceps Uhler (green-cicada), Nephotettix nigropictus Nalori (cicada) lugens Sial, Peregrinus maidis Ashmead, Sogatella furcifera Horvath, Sogatodes orizicola Muir, Typhlocyba pomaria McAtee (apple coriander), Erythroneoura spp. (Succories-vine); Magicidada septendecim Linnaeus (17-year-old chicory); Icerya purchasi Maskell (turtle-shaped-lice-of-Australia), Quadraspidiotus perniciosus Comstock (San-Jose-lice); Pianococcus citri Risso (lice-flour-vines); Pseudococcus spp. (Another complex of turtle lice); Cacopsylla pyricola Foerster (honey-flea-flea), Ashmead Trioza diospyri (honey-flea-flea). These compounds also possess action on the members of the order of the Hemiptera, including: Acrosternum hilare Say (ploșnița-scutar), Anasa tristis De Geer (ploșnița-rhomboid), Blissus leucopterus Say (ploșniţa-earth), Corythuca gossșii (Corythuca gossșii) , Dysdercus suturellus Herrich-Schaffer (red-bellied plum), Euchistus servus Say (brown-plutin-brown), Euchistus variolarius Palisot de Beauvois (plutniţa-scutar-cuo-pat), Graptosthetus spp. (seed-bite complex), Leptoglossus cor-culus Say (pine-seed bite),

MD 3864 C2 2009.03.31

Lygus lineolaris Palisot de Beauvois (meadow), Nezara viridula Linnaeus, Oebalus pugnax Fabricius (meadow), Oncopeltus fasciatus Dallas (meadow Dallas), Pseuda-tomoscelis seriatus Reuter (meadow). Other orders of insect wiped out by the compounds of the invention include ordinal Tisanoptera (eg, Frankliniella occidentalis Pergande (flower thrips), Moulton Scirthothrips (thrips-citrus), Sericothrips variabilis Beach (soybean thrips), and Thrips Lindeman tobacco (onion thrips); and ordinarily Coleoptera (eg, Leptinotarsa decemlineata Say (Colorado cockroach), Epilachna varivestis Malsant (Mexican-a-bobcat) and worms from the genus Agriotes, Athous san Limonius).

The compounds of the present invention may also be admixed as a blood anal with several other biologically active compounds, including insecticides, nematocides, bactericides, acaricides, growth regulators, such as root stimulants, chemostyrenes, repellents, semiochemists, entomopathogenic food stimulants, fungus viruses for the form of a rhombicomponent pesticide that gives equal broad spectrum of agronomic and non-agronomic utility. Thus, the present invention also relates to о composition containing о effective biological amount of the compound n1 as the formal 1 and о effective amount of the patin nna compass without additional biologically active agent and saplimentary may contain at least о surfactant, a solid dilaant year the blood dilaant fluid. Examples of these compounds without biologically active agents such that the compounds of the present invention can be formulated are: insecticides, such as abamectin, azadirectin, azinfosmethylnl, bifentril, bifenazatnl, bistriflnronnl, bnprofezinnl, carbofuran, chlorophenapinyl, chlorofnaznronnl, chlorpyrifosnl, chlorpyrifos-metilnlthran, , deltamethrin, diafentinronnl, diazinone, diflnbenznronnl, dimetoatnl, dinotefurannl, diophenolannl, emamectin, endosnlfannl, esfenvaleratnl, etiprolnl, phenoticabnl, phenoxycarbone, fenpropatrine, fenvaleratnl, fipronilal, flonicamide, flncitrinatnl, taa-flavalinatal, flnfenerime (UR-50701), flnfenoxaronal, gamma-calotrine, halofenoside, hexafhimnronnl, imidaclopridal, indoxacarlone, , metoprennl, methoxychloro, methoxyphenozide, metoflntrine, monochrotrophosal, methoxyphenozide, novalnronnl, novilflamnronal (XDE-007), oxamylal, parationnl, parationmethylnl, permethrin, foratnl, phosalonal, fosmetnl, fosfamidonnl, pyrimicarbnl, profenofosnl, proflntrine, protrifenbntnhil, pimetrozine, pyridiall, pyripro-xifen, rotenone, S1812 (Valent) spinozadnl, spiromezifennl (BSN 2060), teflprofnl thiamethoxamnl, thiodicarbnl, thiosaltapsodial, tolfenpiradnl, tralometrine, trichlorfonal and triflnmaronal; phimgicides, such as acibenzolar, S-methyl, azoxistrobinal, benalazi-M, bentia-valicarbal, benomilal, blasticidin-S, mixing Bordeaax (tribasic copper snlfatnl), boscalidal, bromnconazolal, bntiobatal, carpropamal, carpropamal, carpropamal, carpropamal, chloroebnl, chlorothaloniln, clotrimazolal, oxycornorn capne, capnite salts, cimoxanilal, ciazofamide, cifenfenamide, ciproconazolnl, ciprodinilnl, diclocimetnl, diclomezine, dichloranal, diphenoconazomorph, dimethane dimoxistrobinnl, diniconazolnl, diniconazolnl-M, dodine, edifenfosnl, epoxiconazolnl, etaboxamnl, famoxadone, fenoxamilnl, fenpiclonilnl, fenpropidin, fenpropimorftil, fentinacetatnl, fentinhidroxidnl, flaazinamal, flndioxonilnl, flnmorful, flnoxastrobinal, flachinconazolal, flarilazolal, flutolamilul, fhichinconazolnl, flazilazolnl, flntolanilal, flntriafolnl, folpetal, fozetilalnminial, furalaxilal, fnrametapinil, gaazatin, hexaconazolal, himexazolnl, imazalilal, imibenconazolnl, iminoctadine, ipconazole, iprobenfosal, iprodione, iprovalicarb, isoconazole, isoprothiolane, kasagamicina, kresoximmetihil, mancozebnl, maneb, mefenoxamnl, mepanapirimal, mepronilnl, metalaxyl, metconazolnl, metominostrobin / fenominostrobina, metrafenone, miconazole, myclobutanil, neoazozina (metanarzonatul ferric), nuarimol, orizastrobin, oxadixil, oxpoconazole, penconazole, pencicurone, picobenzamide, picoxistrobin, probenazolnl, procloraz, propamocarbon, propiconazole, proquinazid, prothioconazole, pyraclostrobin, pyrimethanil, pyrifenox, pirochilonnl, chinoxifennl, siltiofamal, simeconazolnl, sipconazolnl, spiroxamine, Salf, tebaconazolnl, tetraconazole, tiadinil, thiabendazole, tiflnzamida, tiofanatmetilnl, thiram, tolilflaanida, triadimefon, triadimenolnl, triarimolnl, tricyclazole, trifloxystrobin, triflnmizolal, triforinnl, triticonazolal, nniconazolal, validamycin, vinclozolinnl, and zoxamide; nematocides, such as aldicarbal, oxamylal and fenamifos; bactericides, such as streptomycin; acarides, such as amitraz, quinometionate, chlorobenzylate, chhexatin, dicofol, dienocloml, ethoxazole, phenazachine, fenbutatin oxide, fenproppatrin, fenpiroxymate, hexitiazox, propargite, pyridaben and tebufenpirad; and biological agents, such as Bacillus thuringiensis, including ssp. aizawai and kurstaki, endotoxin delta Bacillus thuringiensis, baculovirus, and entomopathogenic bacteria, virus and fungi. The compounds of the present invention and their compositions may be applied to genetically transformed plants to express toxic proteins for invertebrate pests (such as Bacillus thuringiensis toxin). The effect of the compounds of the present invention for controlling exogenously applied invertebrate pests may be synergistic with the expressed toxins proteins.

The general reference to these agricultural protectors is The Pesticide Manual. 12th Edition, CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2000.

Preferred insecticides and acaricides for mixing with the compounds of the present invention include pyrethroids, such as acetamipride, cyhalothrin, ciflutrin, beta-cyylutrine, sphenvaleratn, fenvaleratn and talometrine; carbamates, such as phenotricarb, methomyl, oxamylal and thiodicarb; neonicotinoids, such as clotianidine, imidaclopridal and thiacloprid; neuronal sodium channel blockers, such as indoxacarbal; insecticidal macrocyclic lactones, such as spinozad, abamectin, avermectin and emamectin; γ-aminobutyric acid (GABA) antagonists, such as endosulfan, etiprol and fipronilal; insecticidal ureas, such as flufenoxiron and triflumuron; juvenile hormone imitators, such as diophenolannl and pyriproxifene, pimetrozine and amitraza. Preferred biological agents for mixing with the compounds of the present invention include Bacillus thuringiensis and the endotoxin delta Bacillus thuringiensis, as well as naturally occurring and genetically modified viral insecticides, including members of the Baculovirid family, as well as entomophagous fungi.

Most preferred mixtures include a mixture of a compound according to the present invention with chlhalothrin, a mixture of a compound according to the present invention with beta-ciflutrine; a mixture of a compound of the present invention with sphenvalerate; a mixture of a compound of the present invention with methomyl; a mixture of a compound of the present invention with imidacloprid; a mixture of a compound of the present invention with thiacloprid; a mixture of a compound of the present

MD 3864 C2 2009.03.31 inventions with indoxacarb; a mixture of a compound of the present invention with abamectin; a mixture of a compound of the present invention with endosulfan; a mixture of a compound of the present invention with etiprol; a mixture of a compound of the present invention with fipronil; a mixture of a compound of the present invention with flufenoxuron; a mixture of a compound of the present invention with pyriproxifene; a mixture of a compound of the present invention with primetrozine; a mixture of a compound of the present invention with amitrazone; a mixture of a compound of the present invention with Bacillus thuringiensis uizawai or Bacillus thuringiensis hurstaki, and a mixture of a compound of the present invention with Bacillus thuringiensis delta endotoxin.

In some cases, combinations with other agents or compounds to combat invertebrate pests having a similar spectrum of control, but a different mode of action, will be particularly advantageous for enhancing resistance. Thus, the compositions of the present invention may additionally contain at least biologically effective amount of at least one additional agent or compound for controlling invertebrate pests, having a similar spectrum of control, but a different mode of action. Contact of a genetically modified plant to express a plant protection compound (eg, protein) or plant site with о effective biological amount of a compound of the invention may also provide a broad spectrum of plant protection and may be advantageous for intensification of resistance.

Invertebrate pests are controlled in agronomic and non-agronomic applications by applying one or more compounds of the present invention, in ο effective amount, in the environment of pests, including the place of agronomic and / or non-agronomic infection, on the land to be protected, or directly to the pests to be fought. Thus, the present invention further includes a method of controlling Hebrew green in agronomic and / or non-agronomic applications, which includes non-green Hebrew contact with them or their environment with an effective biological quantity of one or more compounds of the invention; or with a composition containing at least one such compound or a composition containing at least one such compound and an effective amount of at least one additional biologically active agent or compound. Examples of suitable compositions containing a compound of the invention and an effective amount of at least one additional biologically active agent or compound include granular compositions wherein the additional biologically active compound is present in the same granule as the compound according to the invention or in separate granules thereof. of the compound of the present invention.

The preferred method of contact is spraying. Alternatively, a granular composition which confines a compound of the invention may be applied to the leaves of the plant or to the soil. The compounds of the present invention are effectively used by plant absorption, by contact with the plant with о composition which confines a compound of the present invention applied by impregnating the soil with о liquid solution, о granular solution in the soil, by treating the nursery or through a transplant bath. The compounds are also effective by topically applying a composition that confines a compound of the present invention instead of the infestation. Other methods of contact include the introduction of a compound or composition according to the invention by direct or subsequent spray solutions, aerial spraying solutions, gels, fattening of seeds, microcapsulation, systemic absorption, baits, label fixation, pills (food cocoons). , aerosol sprayers, fumigants, aerosols, dusts and more. The compounds of the present invention may also be impregnated in the materials for making devices for the control of invertebrates (eg, insect nets).

A compound of the present invention can be incorporated into a bait composition that is consumed by an invertebrate pest or used in devices such as traps, bait traps and the like. This bait composition may be in the form of granules containing (a) an active ingredient, namely a compound of formula 1, an N-oxide, or its salt, (b) one or more nutritional substances, (c) optionally an attractant, and (d) optional to one or more moisturizers. It should be noted that the pellets or the compositions of bait containing about 0.001 ... 5% of active ingredient, about 40 ... 99% of nutritious and / or attractive substance, and optionally about 0.05 ... 10% of moisturizers they are effective in combating soil invertebrate pests in very low application ratios, particularly in active ingredient doses that are lethal by injection rather than by direct contact. It should be noted that some nutritious substances will function both as a source of food and as an attractant. Nutritional substances include carbohydrates, proteins and lipids. Examples of nutritious substances are plant flour, sugar, starch, animal fat, vegetable oil, yeast extracts and dry milk. Examples of attractants are odorant and flavoring agents, such as plant or fruit extracts, parfiim, or other plant or animal component, pheromones or other known agents that attract an invertebrate pest. Examples of humidifiers, which are humidity refining agents, are glycols and other polyols, glycerine and sorbitol. Important is the bait composition (and method of using this bait composition) used to combat invertebrate pests that include, or in combination with, the animals, termites and cockroaches. A device for combating invertebrate pests may contain the present bait composition and a slot provided for the location of the bait composition, the housing having at least one orifice executed so as to allow invertebrate pests to enter through it and gain access to the bait composition. place outside the place, and where the housing is additionally provided to be located in or near the place of possible or known activity of invertebrate pests.

The compounds of the present invention may be applied in a pure state, but most commonly, a solution including one or more compounds with convenient carriers, diluents and surfactants and possibly in combination with a food product depending on the intended use is applicable. Preferable method of application includes spraying an aqueous dispersion or a refined oil solution of the compounds. Combinations with spray oils, concentrations of spray oils, adhesives, adjuvants, other solvents, and synergists, such as piperonyl butoxide, often increase the effectiveness of the compounds. For non-economical uses, these spray solutions may be applied from spray containers, such as a tin box, a bottle or other container either through a pump or by releasing them from an airtight container, e.g. о tin box with hermetic spray solution. Thus, these spray compositions may have various forms, for example, sulfates, aerosols, foam, fumes or nape. These spray compositions may additionally include explosive substances, foams, etc. as the case. Important is a spray composition that confines a compound or composition of the present invention and an explosive substance. Representative explosive substances include, but are not limited to, methane, ethane, propane, isopropane, butane, isobutane, butene, pentane, isopentane,

MD 3864 C2 2009.03.31 neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, methyl ether and mixtures thereof. Important is a spray composition (and a method of using this spray composition from a spray container) used to combat invertebrate pests that include, individually or in combination, mosquitoes, molluscs, black lice, autumn mites, reindeer mites horse mates, wasps, buzzards, ticks, spiders, ants, etc.

The application rule required for effective control (eg, effective biological quantity) will depend on factors for controlling invertebrate species, such as the life cycle of pests, life stage, size, location, time of year, host animal or host plant, appetite behavior, mating behavior, environmental humidity, temperature, etc. Under normal circumstances, the introduction rules of about 0.01 ... 2 kg of active ingredient per hectare are sufficient to combat pests in agronomic ecosystems, but at least 0.0001 kg / hectare may be sufficient or at most 8 kg / hectare may be necessary. For non-agronomic applications, the effective use standards will range from about 1.0 to 50 mg / m2, but at least 0,1 mg / m2 may be sufficient or at most 150 mg / m2 may be necessary. The person skilled in the art can easily determine the effective biological quantity required for the desired level of combat of invertebrate pests.

The following tests demonstrate the effectiveness of combating the compounds of the present invention at specific pests. Combating efficacy is the inhibition of the development of invertebrate pests (including mortality) that cause considerably reduced feeding. However, the pest control offered by the compounds is not limited to these species. See index table А, В and C for descriptions of compounds. The following abbreviations are used in the index tables below: i represents iso, t - tertiary, Me - methyl, Et - ethyl, Pr - propyl, z - Pr - isopropyl, c - Pr - cyclopropyl, Bu butyl and CN.

INDEX TABLE A

Λ 1+ RMD 3864 C2 31.03.2009

<td>Compound</td><td>Bl</td><td> 12</td><td>Bl</td><td> 21</td><td>к!</td><td></td>

MD 3864 C2 2009.03.31

<td>Compound</td><td>. Bl</td><td>B *</td><td>Bl</td><td>Bi</td><td>Bl</td><td></td>

<td> 64</td><td>Xie</td><td>of</td><td>of</td><td>CHCCH ^ O ^ SMe</td><td>H</td><td> 193...194</td>

MD 3864 C2 2009.03.31

<td>Compound</td><td>Bl</td><td>Bl</td><td>Bl</td><td>Bi</td><td>Bi</td><td>* · Ρ · (* α</td>

<td> 69</td><td>Me</td><td>c₽3</td><td>of</td><td>(CHjJjOMe</td><td>H</td><td> 206-207</td>

<td> 72</td><td>Me</td><td>br</td><td>of</td><td>(CHjJjOMe</td><td>я</td><td> 216-217</td>

<td> 83</td><td>Me</td><td>of</td><td>of</td><td>СЩСНзХСН ^ ЗСОгМе</td><td>Η</td><td> 186-187</td>

<td> 84</td><td>Me</td><td>br</td><td>of</td><td>ещензхен ^ дагМе</td><td>Η</td><td> 182-183</td>

See index table C for MRI data

MD 3864 C2 2009.03.31

<td>Compound</td><td>Bl</td><td></td><td>в *</td><td>Fd</td><td>в!</td><td>B *</td><td>sZ</td><td></td>

INDEX TABLE C

Nr. Compound Data 'H NMR (in CDCI3 solution, unless otherwise indicated) (CDCI3) 10.55 (s, IB), 8.45 (d, 1H), 7.85 (dd, 1H), 7.55 ( s, 2B), 7.40 (dd, 1H), 6.97 (s, IB), 6.30 (bq, .lH), 2.98 (d, 3B), 2.24 (s, 3H) (CDQ3) 10.55 (β, IB), 8.45 (d, IB), 7.85 (dd, IB), 7.57 (ш, 2B), 7.37 (dd, IE), 7.05 ( s, IB), 630 (bq, IB) 2.98 (d, 3H), 2.24 (s, 3H) (CDCI3) 10.10 (br s, IB), 8.38 (d, IB), 7.75 (s, 1H), 7.65 (s, IB), 7.60 (m, IB), 7.34 (ш, IB), 7.10 (s, IB), 6.58 (bq , IB) 2 ^ 6 (s, 3B) (00 (¾) 10.12 (s, 1H), 8.56 (d, 1H), 7.85 (d, IB), 7.58 (m, 2H) ), 7.40 (dd, IB), 6.97 (s, 1H), 6.00 (bd, IB) 4.22 (m, IB), 2.25 (s, 3H), 126 (d, 6H) (CDCI3) 10.60 (s, 1H), 8.47 (d, IB), 7.85 (dd, IB), 7.56 (s, 2H), 7.39 (dd, IB), 7.06 (S, IB), 6.04 (bd, IB) 4.20 (m, IB), 2.24 (s, 3B), 1.26 (s, 6B)

Nr. Compound Data 'H NMR (in CDC1 solution3, unless otherwise indicated)

MD 3864 C2 2009.03.31 (CMj) 10.60 ft IE), 8.45 (d, IE), 7.85 (d, 1H), 7.58 ft 2H), 7.39 (m,

1H), 6.97 ft 1H), 6.20 (bt, IE) 3.46 (m, 2H), 2225 ft 3H), 1.25 ft 3H) (CDCl3) 10.60 ft 1H), 8, 46 (d, 1H), 7.85 (d, 1H), 7.57 ft 2H), 7 »38 (m, IE), 7.05 (s, IE), 6.25 (bt, 1H) 3 »46 (m, 2H), 2.24 ft 3H), 1.25 (ζ 3H) 41 (CDCI3) 10.40 ft 1H), 8.47 (d, 1H), 7.85 (d, 1H), 7.50 ft 2H), 7.37 (dd,

1H), 6.63 ft IE), 5.97 ft IE) 4.68 (q, 2H), 1.42 ft 9H)

BIOLOGICAL EXAMPLES OF THE INVENTION

TESTULA

For the evaluation of the control of the cabbage moth (Plutella xylostella) the test model consisted of an open container with о radish plant of 12 ... 14 days inside. It was preliminary infested with 10 ... 15 newborn larvae on an insect fragment by using a probe for sampling m inside the fixed insect fragment, m developing larvae and transferring the sample with larvae to the test device.

The test compounds were made using a solution containing 10% acetone, 90% water and 300 ppm non-ionic surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries Inc., Greeley, Colorado, USA). Obfinufi compounds were introduced into 1 mL of liquid through a customized 1/8 JJ body spray capsule (Spraying Systems Co., Wheaton, Illinois, USA) positioned 127 cm (0.5 inches). above the top of each test model. Tofi experimental compounds! in these tests were sprayed at 50 ppm and replicated 3 times. After spraying the obtained test compound, each test device was left to dry for 1 hour and afterwards a black protective cap was placed on the top. The test models were finished 6 days in a growth chamber at 25 ° C and the relative humidity of 70%. The damage caused to the plant by feeding was visually evaluated on the basis of the leaves consumed.

From the following test compounds have provided levels of protection of the plants from very good to excellent (a damage by feeding of 20% or more): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 88, 89, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 106, 108, 109, 110, 111 and 112.

TEST В

For the evaluation of the control of the butterfly-moth (Spodoptera frugiperda) the test model consisted of a small open container with о maize plant of 4 ... 5 days inside it. It was preliminary infested (using о core sample) with 10 ... 15 larvae at 1 day old per о piece of insect raft.

Test compounds were made and sprayed at 50 ppm as described for Test A. The applications were replicated 3 times. After spraying, the test models were stained in a growth chamber and then visually evaluated as described for Test A.

From the test compounds, the following have provided excellent levels of plant protection (damage by feeding

20% or more): ί, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 24 , 25, 26, 27, 28, 29, 30, 31,

32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 63, 64, 65, 66, 67, 68, 70,

73, 74, 76, 78, 88, 91, 92, 94, 95, 96, 98, 99, 100, 101, 102, 103, 106, 109, 110, 111 and 112.

TEST С

In order to evaluate the control of the green-peach louse (Myzys persioae) by systemic and / or contact means, the test model consisted of a small open container with an о radish plant of 12 ... 15 days inside. This was infested by placing on the French о plant the test plant of 30 ... 40 aphids on the о piece of leaf cut from the о culture plant (the method of cutting the French). The larvae moved to the test plant immediately after cutting the leaf peel. After preliminary infestation, the variety in the test model was covered with a layer of sand.

Test compounds were made using о solution containing 10% acetone, 90% water and 300 ppm non-ionic surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries , Inc.). Compounds were introduced into 1 mL of liquid through an SUI2 spray capsule with a 1/8 JJ custom-made body (Spraying Systems Co.) positioned 127 cm (0.5 inches) above the top edge of each device. Testing. After spraying the formed test compound, each test model was left to dry for 6 days in a growth chamber at 19 ... 21 ° C and relative humidity of 50 ... 70%. Each test model was then visually assessed for insect mortality.

From the test compounds, the following resulted in mortality of at least 80%: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, Tl, 28, 29, 30, 31, 32, 33, '34, 35, 36, 37, 38, 40, 41, 43 , 44, 46, 47,48,49, 50,51, 52, 53, 55, 56, 63, 65, 66, 67, 68, 69, 70, 73, 74, 76, 78, 88, 89, 90 , 91, 92, 94, 95, 96, 98, 99, 100, 101, 102, 103, 106, 108, 109, 110, 111 and 112.

TEST D

For the evaluation of the control of the potato cicorife (Empoasca fabae Harris) by systemic and / or contact means, the test model consisted of a small open container with a о Longio bean plant (sprouted leaves) inside. Above the ground was added white sand and one of the initial leaves was cut down to the introduction. The test compounds were made and sprayed at 250 ppm and replicated 3 times, as described for Test C. After spraying, the test models were left to dry for 1 hour, before being infested with 5 cicorifes (adult insects from 18 to 21 days). A black protective cap was placed above the cylinder. The test models have

MD 3864 C2 2009.03.31 were kept for 6 days in a growth chamber at a temperature of 19 ... 21 ° C and a relative humidity of 50 ... 70%. Each test model was then visually evaluated for insect mortality.

From the test compounds, the following resulted in at least 80% mortality: 1, 3, 4, 5, 6, 8, 10, 12, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 33, 34, 35, 37, 38, 40, 41, 43, 44, '46, 47, 48, 49, 50, 51, 52, 53, 54 , 55, 56, 63, 66, 67, 68, 70, 73, 76, 88, 89, 90, 94, 95, 98, 99,101, 103, 106, 108, 109, 110, 111 and 112.

testu

For the control of evaluation of cotton-and-cucumber lice (Aphis gossypii) by systemic and / or contact means, the test model consisted of a small open container with о cotton plant of 6 ... 7 days in inside. It was preliminary infested with 30 ... 40 insects per о leaf piece according to the leaf cutting method described for Test C, and the soil in the test model was covered with a layer of sand.

The test compounds formulated and sprayed at 250 ppm, as described for Test D. The applications were replicated 3 times. After spraying, the test models were stained in a growth chamber and then visually evaluated, as described for Test D.

Of the test compounds, the following resulted in mortality of at least 80%: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 , 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 32, 33, 34, 35, 36, '37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56, 63, 69, 71, 72, 74, 76, 78, 79, 81, 84, 88, 89, 90, 91, 92, 95, 96, 97, 98, 99, 100, 101, 102, 103, 106, 108, 109,110, 111 and 112.

TEST F

For the evaluation control (Peregrinus maidis) by systemic and / or contact means, the test model consisted of a small open container with maize (spike) plant 3 to 4 days inside. White sand was added to the soil surface until applied. The test compounds were made up and sprayed at 250 ppm and replicated 3 times, as described for Test C. After spraying, the test models were left to dry within 1 hour until their preliminary infestation with 10 ... 20 insects (nymphs at the age of 18 ... 20 days) sprinkling them on the sand using a salt sprinkler device. A black protective cap was placed above the cylinder. The test models were maintained for 6 days in a growth chamber at 19 .. .21 ° C and the relative humidity of

50 .. .70%. Each test model was then visually evaluated for insect mortality. Of the test compounds, the following resulted in mortality of at least 80%: 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 18, 20, 24, 25, 26 , 27, 28, 29, 32, 33, 35, 37, 38, 39, 40, 41, 43, 45, 46, 47, 48.49, 50, 51, 53, 56, 88, 89, 90, 91 , 94, 95, 108 and 109.

TEST G

For the control of the Bermisia tabacia evaluation, the test model was made up of a plant of a mackerel of

14 .. .21 days grown on Redi-earth® (Scotts Co.) media with at least two true leaves infested with stage nymphs of age 2 and 3 on the dorsal side of the leaves.

The test compounds were made up of no more than 2 mL of acetone and then diluted with water to 25 ... 30 mL. The composite compounds were introduced using о flat spray jet capsule (Spraying Systems 122440) at 10 psi (69 kPa). The plants were sprayed to the surface with a rotary sprayer. Tofi experimental compounds! in this sieve were sprayed at 250 ppm and replicated 3 times. After spraying the test compound, the test patterns were maintained for 6 days in a growth chamber at 28 ° C by day and 24 ° C by night and relative humidity of 50 .. .60%. Then the leaf e were removed and the living and dead nymphs were counted to calculate the mortality rate.

Of the test compounds, the following resulted in mortality of at least 80%: 2, 3, 4, 5, 7, 8, 9, 10, 24, 25, 26, 27, 28, 30, 32, 33, 34 , 35, 38, 41, 46, 48, 49, 51, 52, 53, 66, 67, 70, 73, 88, 92 and 98.

TESTULH

For the evaluation of the displacement of the compounds in plants and of the control of the green-peach louse (Myzus persicae) and of the potato chicory (Empoasca fabae) after the foliar movement of the compound through the plant, the test model consisted of a small open container with о radish plant of 12 ... 15 days (for testing the lice-green-alpiersic) or о Longio bean plant of 5 ... 6 days (for testing the cicorife-potato).

Test compounds were made using о solution containing 10% acetone, 90% water and 600 ppm surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries, Be.). Compounds were applied in 20 µL through a pipette to 2 larger photosynthetic active leaves. Tofi experimental compounds from this sieve were applied at 1000 ppm, and the tests were replicated 3 times. After the introduction of the test compounds made. The variety in this test model was covered with a layer of sand and each test model was left to dry for 1 hour, after which a black protective cap was placed over it. The test models were kept in a growth chamber at a temperature of about 20 ° C and a relative humidity of 50 ... 70%.

Over 2 days, the treated leaves were covered on all the edges with a fine plastic screen, but with the leaf stem intact and attached to the plant to allow normal vascular movement and photosynthesis. The plants were then infested with 20 ... 30 aphids (radish) or 20 cicorife (beans) and kept in a growth chamber for 8 days. Each test device was then visually evaluated for estimating insect mortality, which contacted and fed the untreated plant's tissues.

The results of green-peach-lice mortality (% M PVP) and potato-cicorife mortality (% M CC) are listed in Table A.

MD 3864 C2 2009.03.31

TABLE A

Percentage of insect mortality

<td>Compound</td><td>% MCC</td><td>% M PVP</td>

TEST I

For the evaluation of the displacement of the compounds in plants and the control of the green-peach louse (Myzus persicae) and the potato chicory (Empoasca fabae) after the xylene movement of the compound from the soil to the leaves through the roots, the test model was consisting of a small open container with о radish plant of 12 ... 15 days (for testing the lice-green-of-peach) or о bean plant of Longio of 5 ... 6 days (for testing of cicorifeicartof).

The test compounds were made using о solution containing 10% acetone, 90% water and 600 ppm non-ionic surfactant X-77® Spreader LO-Foam Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries , Inc.). Compounds were applied in 20 µL of solution through a pipette into the soil at the base of the plant. All experimental compounds in this sieve were applied at 1000 ppm, and the tests were replicated 3 times. After the introduction of the test compounds formed, each test model was left to dry for 1 hour. The variety of each model was covered with a layer of sand and then a black protective cap was placed above. The test models were kept in a growth chamber at a temperature of about 20 ° C and a relative humidity of 50 ... 70%.

Over 2 days, the plants were infested with 20 ... 30 aphids (radish) or 20 cicorife (beans) and kept in a growth chamber for 5 days. Each test model was then visually evaluated for insect mortality, which contacted and fed on untreated plant tissues.

The results regarding the mortality of the green-peach lice (% M PVP) and the mortality of the cicorife-potato (% M

<td>CC) are inserted in table B.</td><td colspan="2">TABLE В Percentage of insect mortality</td>

<td>Compound</td><td>% MCC</td><td>% M PVP</td>

Contents44

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Citations
Document	Relation	Office	Cited during
WO0170671A2	Cites	World Intellectual Property Organization (WIPO)	Search report
WO0170671A2	Cites	World Intellectual Property Organization (WIPO)	Search report
WO03015518A1	Cites	World Intellectual Property Organization (WIPO)	Search report
WO03015519A1	Cites	World Intellectual Property Organization (WIPO)	Search report
WO03024222A1	Cites	World Intellectual Property Organization (WIPO)	Search report

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Priority claims
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44325603	United States of America	P	2003-01-28
2004003568	United States of America	W	2004-01-21

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AU2004207848A1	Australia	A1	2004-08-12
CA2512242A1	Canada	A1	2004-08-12
WO2004067528A1	World Intellectual Property Organization (WIPO)	A1	2004-08-12
WO2004067528B1	World Intellectual Property Organization (WIPO)	B1	2004-10-07
TW200505897A	Taiwan Province of China	A	2005-02-16
AR042943A1	Argentina	A1	2005-07-06
MXPA05007924A	Mexico	A	2005-09-30
HRP20050745A2	Croatia	A2	2005-10-31
MA27622A1	Morocco	A1	2005-11-01
EP1599463A1	European Patent Office (EPO)	A1	2005-11-30
MD20050219A	Republic of Moldova	A	2005-11-30
BRPI0406709A	Brazil	A	2005-12-20
RU2005127049A	Russian Federation	A	2006-01-27
JP2006028159A	Japan	A	2006-02-02
PL378413A1	Poland	A1	2006-04-03
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JP3770500B2	Japan	B2	2006-04-26
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JP2006515602A	Japan	A	2006-06-01
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TNSN05182A1	Tunisia	A1	2007-06-11
US7247647B2	United States of America	B2	2007-07-24
RS20050582A	Serbia	A	2007-09-21
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NZ541112A	New Zealand	A	2008-01-31
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2022-06-30	Change/correction in patent specificationCHANGE/CORRECTION IN INID 73TH4A	TH4A
2019-01-31	Change of proprietorship (patent for invention)PD4A	PD4A
2018-12-31	Change/correction in patent specificationCHANGE/CORRECTION IN INID 73TH4A	TH4A
2013-12-31	Restoration of lapsed patent for inventionLapsedNF4A	NF4A
2013-08-31	Patent for invention lapsed due to non-payment of fees (with right of restoration)LapsedKA4A	KA4A
2009-11-30	Patent for invention issuedFG4A	FG4A

Abstract

Term

MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31

R2

MD 3864 C2 2009.03.31

R2

1) DAL, THF

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MD 3864 C2 2009.03.31

EXAMPLE 1

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EXAMPLE 2

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EXAMPLE 3

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EXAMPLE 4

EXAMPLE 5

EXAMPLE 6

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EXAMPLE 7

R2

MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31

FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFE19

MD 3864 C2 2009.03.31

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MD 3864 C2 2009.03.31

INDEX TABLE A

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MD 3864 C2 2009.03.31

MD 3864 C2 2009.03.31

INDEX TABLE C

BIOLOGICAL EXAMPLES OF THE INVENTION

TESTULA

TEST D

TEST F

TEST G

TESTULH

MD 3864 C2 2009.03.31

TABLE A

TEST I

Priority claims2

Members71

Over the term

Events

Numbers

Titles3

Classification