fused 4-5-diamino-n,n-dihydro-pyrazol-3-one derivatives for use in composition for dyeing keratin fibres

The subject of the invention is a composition for dyeing keratin fibers, in particular human keratin fibers, such as hair, containing as oxidizable base at least one diamine-N, N-dihydropyrazolone derivative or one of its addition salts and a method using it. It also deals with amino-N, N-dihydropyrazolone derivatives as well as diamine-N, N-dihydropyrazolone derivatives or one of its addition salts as such and their preparation.

It is known to dye keratin fibers, and in particular human keratin fibers, such as hair, with dyeing compositions containing oxidative dye precursors, in particular ortho or para-phenylenediamines, heterocyclic compounds such as diaminopyrazole derivatives, pyrazolo derivatives [1,5-a] pyrimidines, pyrimidine derivatives, pyridine derivatives, 5,6-dihydroxyindole derivatives, 5,6-dihydroxyindoline derivatives, generally called oxidation bases. Oxidative dye precursors, i.e. oxidizable bases, are colorless or weakly colored compounds which, in combination with oxidizing products, can cause the formation of colored compounds or dyes through the oxidative condensation process.

It is also known that the shades obtained using these oxidizable bases can be changed by combining them with coupling agents or staining modifiers, the latter being selected in particular from meta-diphenylamines, meta-aminophenols, meta-hydroxyphenols and certain heterocyclic compounds such as for example. pyrazolo [1,5-b] -1,2,4-triazole derivatives, pyrazolo [3,2-c] -1,2,4 triazole derivatives, pyrazolo [1,5-a] pyrimidine derivatives, pyridine derivatives, pyrazole derivatives -5-on, indoline derivatives and indole derivatives.

The variety of molecules that can be considered when it comes to oxidizable bases and coupling agents allows a rich range of colors to be obtained.

The so-called "permanent" color obtained thanks to these oxidation dyes should also meet a certain number of requirements. Therefore, it should not present toxicological inconveniences, should allow to obtain shades of the desired intensity and show good resistance to external factors such as light, bad weather, washing, perm, sweating, friction.

Dyes should also allow gray hair to be covered and finally exhibit the least selectivity possible, i.e. allow the smallest possible color difference over the entire length of the same keratin fiber, which can be significantly differently sensitized (i.e. damaged) between its end and root. They should also show good chemical stability in preparations. They should show a good toxicological profile.

The use of an oxidizable base, such as derivatives of para-phenylenediamine and para-aminophenol, allows obtaining a fairly wide range of colors at alkaline pH, however, without achieving shades with good chromaticity while giving the hair fully excellent properties of color intensity, variety of shades, color uniformity and resistance to factors Outside.

The use of these bases at neutral pH is also ineffective for achieving a range of varied shades, in particular warm shades.

Patent DE 3843892 already proposed the use of certain diaminopyrazole derivatives, especially for shades of red to copper-red. However, this proposal does not allow

EP 1 550 656 to achieve good chromaticity, resistance to external factors such as washing and light. In addition, the range of shades is limited.

Furthermore, it is known from patent application EP 1 250 909 to use a pyrazole derivative, in particular 3,4-diamino-5-hydroxypyrazole as an oxidizable dye for hair dyeing.

Also known from patent application EP 0 873 745 is the use of 1-phenyl-3-carboxamido-4-aminopyrazol-5-one as an oxidizable base and 1-phenyl-3-naphthyl-pyrazol-5-one as a coupling agent for dyeing keratinous fibers.

Well, the applicant stated in a completely unexpected way that the new diamine-N, Ndihydropyrazolone compounds of formula (I) are suitable for use as oxidation dyeing precursors and allow obtaining color in varied, strong, chromatic, aesthetic shades, not very selective and very resistant to various aggressive factors that can be applied to the hair, such as shampooing, light, sweat and permanent deformation.

The applicant has also unexpectedly found that the colors obtained at neutral pH are intense.

The subject of the present invention is therefore a dyeing composition for keratin fibers, containing in an environment suitable for dyeing as an oxidizable base at least one diamine-N, N-dihydropyrazolone derivative of formula (I) or one of its addition salts:

ΝΗ

<img file="PL1550656T3_D0001.tif" />

wherein:

R1 and R2 form, with the nitrogen atoms to which they are attached, a saturated or unsaturated heterocyclic group containing 5 to 7 members, optionally substituted with one or more groups selected from the group formed by halogen, amino, di (C1-C4) -alkylamino groups , hydroxy, carboxy, carboxamido, C_rC2-alkoxy, CC, -alkyl groups optionally substituted by one or more hydroxy, amino, dialkylamino, alkoxy, carboxy, sulfonyl groups;

R3 and R4, identical or different, mean:

- a C1-C6-alkyl group, linear or branched, optionally substituted by one or more groups selected from the group formed by the group OR5, group NR6R7, carboxy group, sulfone group, carboxamido group CONR6R7, sulfonamido group SO2NR6R7, heteroaryl, aryl optionally substituted by CC, -alkyl, hydroxy, C_rC2-alkoxy, amino, di (C1-C2) -alkylamino;

- an aryl group optionally substituted by one or more CC, -alkyl, hydroxy, C1-C2alkoxy, amino, di (C1-C2) -alkylamino groups;

- a 5 or 6 membered heteroaryl group, optionally substituted with one or more groups selected from CC, -alkyl, C_rC2-alkoxy;

R3 and R4 may also be hydrogen;

R₅, R6 and R7, which are the same or different, represent a hydrogen atom; CC, -alkyl, linear or branched, optionally substituted with one or more groups selected from the group consisting of hydroxy, C1-C2-alkoxy, carboxamido CONR8R9, sulfonyl SO2R8, aryl optionally substituted with C_rC4-alkyl,

EP 1 550 656 hydroxy, C.₁-C2-alkoxy, amino, di (C₁C2) alkylamino; aryl optionally substituted with C.₁-C₄-alkyl, hydroxy, C_rC2-alkoxy, amino, di (C1-C2) -alkylamino;

R6 and R7, which are identical or different, may also be a carboxamido CONR group₈Rg, sulfonyl SO2R8;

R₈ and R9, which are identical or different, represent a hydrogen atom; C-C, -alkyl, linear or branched, optionally substituted with one or more hydroxy, C 1-4 alkoxy;

R3 and R₄ can form with the nitrogen atom to which they are attached a heterocyclic, saturated or unsaturated group containing 5 to 7 members, optionally substituted with one or more groups selected from the group formed by halogen atoms, amino, di (C1-C4) -alkylamino group, hydroxy, carboxy, carboxamido, C 1-6 alkoxy, CC, -alkyl groups optionally substituted by one or more hydroxy, amino, dialkylamino, alkoxy, carboxy, sulfonyl groups;

R3 and R4 can also form together with the nitrogen atom to which they are attached a heterocyclic, saturated or unsaturated group containing 5 to 7 members whose carbon atoms can be replaced by an optionally substituted oxygen or nitrogen atom.

In particular, the present invention makes it possible to obtain a permanent, lightfast and washable keratin color.

Another subject of the invention is a method for dyeing keratin fibers using the composition of the present invention, as well as the use of this composition for dyeing keratin fibers.

The invention also relates to new amino-N, N-dihydropyrazolone derivatives as well as diamine-N, N-dihydropyrazolone derivatives.

Finally, the invention relates to new methods for the synthesis of these diamine-N, Ndihydropyrazolone derivatives of the formulas (I ') and (I ") or their addition salts.

As stated previously, the composition contains at least one diamine-N, Ndihydropyrazolone derivative of formula (I) or one of its addition salts.

According to embodiments, R1 and R2 form, together with the nitrogen atoms to which they are attached, a 5 or 6 membered ring, saturated or unsaturated, optionally substituted.

Preferably, R1 and R2 form together with the nitrogen atoms to which they are attached a pyrazolidine, pyridazolidine ring, optionally substituted with a CC-alkyl, hydroxy, C1-C2alkoxy, carboxy, carboxyamido, amino, di (C1-C2) -alkylamino group.

Even more preferably, R1 and R2 form together with the nitrogen atoms to which they are attached a pyrazolidine, pyridazolidine ring.

As for the groups R3 and R4, the latter, which are the same or different, are more particularly selected from hydrogen; CC-alkyl, linear or branched, optionally substituted with one or more hydroxy, CC.-alkoxy, amino, di (C1-C2) -alkylamino; phenyl group optionally substituted by hydroxy, amino, CC.-alkoxy.

Preferably, the R3 and R4 groups, which are identical or different, are selected from hydrogen, methyl, ethyl, isopropyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, and 2-carboxyethyl. According to a specific embodiment, the R3 and R4 groups are hydrogen.

According to another embodiment, the R3 and R4 groups, together with the nitrogen atom to which they are attached, form a 5 or 7 membered ring selected from heterocyclic pyrrolidine rings,

EP 1 550 656 piperidine, homopiperidine, piperazine, homopiperazine; wherein said rings may be substituted by one or more hydroxy, amino, di (C₁-C2) -alkylamino, carboxy, carboxamido, C1-C₄-alkyl optionally substituted with one or more hydroxy, amino, di (C1-C2) -alkylamino groups.

Particularly R3 and R groups₄ together with the nitrogen atom to which they are attached they form a 5 or 7 membered ring selected from pyrrolidine, 2,5-dimethylpyrrolidine, pyrrolidine-2-carboxylic acid, 3-hydroxypyrrolidine-2-carboxylic acid, 4-hydroxypyrrolidine-2- carboxylic, 2,4-dicarboxypyrrolidine, 3-hydroxy-2-hydroxymethylpyrrolidine, 2-carboxamidopyrrolidine, 3-hydroxy-2-carboxamidopyrrolidine, 2- (diethylcarboxamido) pyrrolidine, 2-hydroxymethylpyrrolidine, 3,4-hydroxyethyl-2-hydroxy-hydroxy-2-hydroxy 3-hydroxypyrrolidine, 3,4-dihydroxypyrrolidine, 3aminopyrrolidine, 3-methylaminopyrrolidine, 3-dimethylaminopyrrolidine, 4-amino-3-hydroxypyrrolidine, 3-hydroxy-4- (2-hydroxyethyl) aminopyrrolidine, piperidine, 2,6-dimethylpiperidine , 2-carboxamidopiperidine, 2-hddrossymethylpiperidine, 3-hddrossy-2-hydrossymethylpiperidine,

3-hydroxypiperidine, 4-hydroxypiperidine, 3-hydroxymethylpiperidine, homopiperidine, 2-carboxy-homopiperidine, 2-carboxamidomomopiperidine, homopiperazine, N-methyl homopiperazine, N- (2-hydroxyethyl) homopiper

Preferably, the R3 and R4 groups together with the nitrogen atom to which they are attached form a 5 or 7 membered ring selected from pyrrolidine, 3-hydroxypyrrolidine, 3-aminopyrrolidine, 3dimethylaminopyrrolidine, pyrrolidine-2-carboxylic acid, 3-hydroxypyrrolidine-2-carboxylic acid , piperidine, hydroxypiperidine, homopiperidine, diazepane, N-methyl homopiperazine, Nb-hydroxyethyl homopiperazine.

According to an even more preferred embodiment of the invention, R3 and R4 form together with the nitrogen atom to which they are attached a 5 membered ring such as pyrrolidine, 3-hydroxypyrrolidine, 3aminopyrrolidine, 3-dimethylaminopyrrolidine.

Compounds of formula (I) can optionally be converted into a salt with strong inorganic acids such as e.g. HCl, HBr, HI, H2SO4, H3PO4 or organic acids such as e.g. acetic, lactic, tartaric, citric or succinic, benzenesulfonic, para -toluenesulfonic, formic, methanesulfonic,

They may also be in the form of solvates, e.g. a linear or branched alcohol hydrate or solvate such as ethanol or isopropanol.

As examples of derivatives of formula (I), mention may be made of the compounds below or their addition salts.

2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3-methylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2- a] pyrazol-1-one

2-Amino-3-dimethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3-ethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3-izopropylooamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3- (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3- {2-hydroksypropyloo) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3-bis (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

EP 1 550 656

2-Amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3- (3-hydroxy-pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3- (piperidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2.3- Diamino-6-hydroxy-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 5 2,3-Diamino-6-methyl-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2.3- Diamino-6-dimethyl-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2.3- Diamino-5,6,7,8-tetrahydro-1H, 6H-pyridazine [1,2-a] pyrazol-1-one

2.3- Diamino-5,8-dihydro-1H, 6H-pyridazine [1,2-a] pyrazol-1-one

2.3- Diamino-6-hydroxy-6,7-dihydro-5H-pyrazolo [1,2-a] pyrazol-1-one, some of which are listed below for explanation of names by chemical structures:

<td>o: nk , Νχ Λ-mu / N ^ΝΗζ</td><td colspan="2">2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</td>

<td> 7</td><td>2-Amino-3-methylamino-6,7-dihydro-1 pyrazolo [1,2-a] pyrazol-1-one</td><td>H, 5H-</td>

<td> _/ ²</td><td>2-Amino-3-ethylamino-6,7-dihydro-1</td><td>H.5H-</td>

<td>Φ ".</td><td>pyrazolo [1,2-a] pyrazol-1-one</td><td></td>

<td>σ νη; V / ²</td><td colspan="2">2-Amino-3- (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-</td>

<td></td><td>pyrazolo [1,2-a] pyrazol-1-one</td><td></td>

<td>ΟΗ</td><td></td><td></td>

<td rowspan="2"></td><td colspan="2">2-Amino-3- (2-hydroxypropyl) amino-6,7-dihydro&gt; -1H, 5H</td>

<td>pyrazolo [1,2-a] pyrazol-1-one</td><td></td>

<td> - ^ν</td><td></td><td></td>

<td>ΟΗ</td><td></td><td></td>

<td rowspan="2">"Φ</td><td colspan="2">2-Amino-3-bis (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-</td>

<td>pyrazolo [1,2-a] pyrazol-1-one</td><td></td>

<td>OH</td><td></td><td></td>

EP 1 550 656

<td>C&gt; ΝΗ. y_ / ²</td><td>2-Amino-3-isopropylamino-6,7-dihydro-1H, 5H-</td>

<td></td><td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td>reef γ_ / 2</td><td>2-Amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-</td>

<td>cD</td><td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td></td><td>2-Amino-3- (3-hydroxypyrrolidin-1-yl) -6,7-dihydro-1H, 5H-</td>

<td>we*</td><td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td rowspan="2">O. ΝΗ, Ó / Ν n₂HO</td><td>2,3-diamino-6-hydroxy-6,7-dihydro-1H, 5H-</td>

<td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td> 4</td><td>2,3-diamino-6-methyl-6,7-dihydro-1H, 5H-</td>

<td>M</td><td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td> ?_/ ²</td><td>2,3-diamino-6-dimethyl-6,7-dihydro-1H, 5H-</td>

<td>.N- / NU &lt;N ^NHfrom 4</td><td>pyrazolo [1,2-a] pyrazol-1-one</td>

<td>Oh ΝΗ Ci / ²</td><td>2,3-Diamino-5,6,7,8-tetrahydro-1 H, 6H-</td>

<td> —</td><td>pyridazine [1,2-a] pyrazol-1-one</td>

<td> ^4</td><td>2,3-Diamino-5.8-dihydro-1H.6H-pyridazine [1,2-a] pyrazol-</td>

<td></td><td>1-one</td>

Among these compounds, particularly preferred diamine-N, N-dihydropyrazolone derivatives of formula (I) or their addition salts are:

2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a} pyrazol-1-one

2-Amino-3-ethylamino-6,7-dihydro-1H, 5H-pyrazolo {1,2-a] pyrazol-1-one

2-Amino-3-isopropylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 2-Amino-3- (pyrrolidin-1-yl) -6,7-dihydro -1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

EP 1 550 656

2-Amino-3- (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2-Amino-3-dimethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

2,3-Diamino-5,6,7,8-tetrahydro-1H, 6H-pyridazino [1,2-a] pyrazol-1-one

Each base or oxidizable bases of the invention are usually present in an amount of between 0.001 to about 10% by weight of the total weight of the dyeing composition, preferably between 0.005 and 6%.

The dyeing composition according to the invention may contain one or more coupling agents conventionally used for dyeing keratin fibers. Among these coupling agents, mention may in particular be made of meta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthalene coupling agents, heterocyclic coupling agents and their addition salts.

Examples include 2-methyl-5-aminophenol, 5-N- (b-hydroxyethyl) amino-2-methylphenol, 6-chloro-2-methyl-5-aminophenol, 3-aminophenol, 1,3-dihydroxybenzene, 1, 3-dihydroxy-2-methylbenzene, 4-chloro-1,3-dihydroxybenzene, 2,4-diamino-1- (b-hydroxyethyloxy) benzene, 2-amino-4- (bhydroxyethylamino) -1-methoxybenzene, 1,3-diaminobenzene , 1,3-bis- (2,4-diaminophenoxy) propane, 3ureidoaniline, 3-ureido-1-dimethylaminobenzene, sesamol, 1-b-hydroxyethylamino-3,4-methylenedioxybenzene, a-naphthol, 2-methyl-1-naphthol, 6-hydroxyindole, 4-hydroxyindole, 4-hydroxy-N-methylindole, 2-amino-3-hydroxypyridine, 6-hydroxybenzomorpholine, 3,5-diamino-2,6-dimethoxypyridine, 1-N- (b-hydroxyethyl) amino-3,4 -methylenedioxybenzene, 2,6-bis (bhydroxyethylamino) toluene and their acid addition salts.

In the composition of the present invention, each coupling agent or agents is usually present in an amount comprised between 0.001 and about 10% by weight of the total weight of the dyeing composition, preferably between 0.005 and 6%.

The composition of the present invention may further comprise one or more additional oxidizable bases conventionally used in oxidative dyeing, other than those previously described. For example, these additional oxidizable bases are selected from para-phenylenediamines, bisphenylalkylene diamines, para-aminophenols, bis-para-aminophenols, ortho-aminophenols, ortho-phenylenediamines, heterocyclic bases different from derivatives of formula (I) such as those previously defined and their salts addition.

Among the para-phenylenediamines, for example, para-phenylenediamine, paratoluene diamine, 2-chloro-para-phenylenediamine, 2,3-dimethyl-para-phenylenediamine, 2,6-dimethyl-para-phenylenediamine, 2,6-diethyl-para-phenylenediamine, 2,5-dimethyl-para-phenylenediamine, N, N-dimethyl-para-phenylenediamine, N, N-diethyl-para-phenylenediamine, N, N-dipropyl-para-phenylenediamine, 4-aminoN, N-diethyl-3-methylaniline, N, N-bis (beta-hydroxyethyl-para-phenylenediamine, 4-N, N-bis (bhydroxyethyl) amino-2-methylaniline, 4-N, N-bis- (b-hydroxyethyl) amino-2-chloroaniline, 2-βhydroxyethyl-para-phenylenediamine, 2-fluoro-para-phenylenediamine , 2-isopropyl-para-phenylenediamine, N- (b-hydroxypropyl) -para-phenylenediamine, 2-hydroxymethyl-para-phenylenediamine, N, N-dimethyl-3-methyl-para-phenylenediamine, N, N- (ethyl, b- hydroxyethyl) para-phenylenediamine, N- (b, gdihydroxypropyl) para-phenylenediamine, N- (4'-aminophenyl) para-phenylenediamine, N-phenyl-para-phenylenediamine, 2-b-hydroxyethyloxy-para-phenylenediamine, 2-b-acetylaminoethyloxy-para-phenylenediamine, N- (b-methoxyethyl) -para-phenylenediamine, 4-aminophenylpyrrolidine, 2-thienyl-para EP 1 550 656 phenylenediamine, 2-b-hydroxyethylamino 5-aminotoluene, 3-hydroxy-1- (4'-aminophenyl) pyrrolidine and their acid addition salts.

Of the para-phenylenediamines mentioned above, paraphenylenediamine, para-toluene diamine, 2-isopropyl-para-phenylenediamine, 2-b-hydroxyethyl-phenylenediamine, 2-b-hydroxyethyloxy-para-phenylenediamine, 2,6-dimethyl-para-phenylenediamine are particularly preferred , 2,6-diethyl-para-phenylenediamine, 2,3-dimethyl-para-phenylenediamine, N, N-bis (b-hydroxyethyl) paraphenylenediamine, 2-chloro-para-phenylenediamine, Sp-acetylaminoethyloxy-para-phenylenediamine and their salts acid addition.

Among the bisphenylalkylene diamines, for example N, N'-bis (- hydroxyethyl) -N, N'bis (4'-aminophenyl) -1,3-diaminopropanol, N, N'-bis (b-hydroxyethyl) -N, N'-bis (4'aminophenyl) ethylenediamine, N, N'-bis (4-aminophenyl) tetramethylenediamine, N, N'-bis (b-hydroxyethyl) N, N'-bis (4-aminophenyl) tetramethylenediamine, N, N'-bis (4-methylaminophenyl) tetramethylenediamine, N, N'bis (ethyl) -N, N'-bis (4'-amino, 3'-methylphenyl) ethylenediamine, 1,8-bis (2,5-diaminophenoxy) -3,6-dioxaoctane and their acid addition salts.

Among the para-aminophenols, for example, para-aminophenol, 4-amino-3-methylphenol, 4-amino-3-fluorophenol, 4-amino-3-hydroxymethylphenol, 4-amino-2-methylphenol, 4-amino-2-hydroxymethylphenol, 4-amino -2-methoxymethylphenol, 4-amino-2-aminomethylphenol, 4-amino-2- (bhydroxyethylaminomethyl) phenol, 4-amino-2-fluorophenol and their acid addition salts.

Among the ortho-aminophenols, for example, 2-aminophenol, 2-amino-5-methylphenol, 2 amino-6-methylphenol, 5-acetamido-2-aminophenol and their acid addition salts can be mentioned.

Examples of heterocyclic bases include pyridine derivatives, pyrimidine derivatives and pyrazole derivatives.

Among the pyridine derivatives, mention may be made of the compounds described e.g. in GB 1 026 978 and GB 1 153 196, such as 2,5-diaminopyridine, 2- (4-methoxyphenyl) amino-3-aminopyridine, 2,3-diamine-6-methoxypyridine, 2- (b-methoxyethyl) amino-3-amino-6-methoxypyridine, 3,4-diaminopyridine and their acid addition salts.

Other pyridine oxidizable bases useful in the present invention are 3-aminopyrazolo [1,5-a] pyridine oxidation bases or their addition salts described, e.g., in patent application FR 2 801 308. For example, pyrazolo [1,5-a] pyridin-3-ylamine; 2acetyloaminopirazolo [1,5-a] pyridin-3-ylamine; 2-morpholin-4-yl- pyrazolo [1,5-a] pyridin-3-ylamine; 3-amino-pyrazolo [1,5-a] pyridine-2-carboxylic acid; 2-methoxypyrazolo [1,5-a] pyridin-3-ylamine; (3aminopirazolo [1,5-a] pyridin-7-yl) methanol; 2- (3-amino-pyrazolo [1,5-a] pyridin-5-yl) ethanol; 2- (3aminopirazolo [1,5-a] pyridin-7-yl) ethanol; (3-amino-pyrazolo [1,5-a] pyridin-2-yl) methanol; 3,6diaminopirazolo [1,5-a] pyridine; 3,4-diaminopirazolo [1,5-a] pyridine; pyrazolo [1,5-a] pyridine-3,7-diamine; 7-morpholin-4-yl- pyrazolo [1,5-a] pyridin-3-ylamine; pyrazolo [1,5-a] pyridine-3,5-diamine; 5-morpholin-4-yl- pyrazolo [1,5-a] pyridin-3-ylamine; 2 - [(3-amino-pyrazolo [1,5-a] pyridin-5-yl) (2-hydroxyethyl) amino] ethanol; 2 - [(3-amino-pyrazolo [1,5-a] pyridin-7-yl) (2-hydroxyethyl) amino] ethanol; 3-amino-pyrazolo [1,5-a] pyridin-5-ol; 3-amino-pyrazolo [1,5-a] pyridin-4-ol; 3-amino-pyrazolo [1,5-a] pyridin-6-ol; 3-amino-pyrazolo [1,5-a] pyridin-7-ol; as well as their acid or base addition salts.

Among the pyrimidine derivatives, mention may be made of the compounds described, for example, in DE 23 59 399; JP 88-169571; JP 05-63124; EP 0 770 375 or in a patent application

EP 1 550 656

WO 96/15765, like 2,4,5,6-tetraaminopyrimidine, 4-hydroxy-2,5,6-triaminopyrimidine, 2-hydroxy-4,5,6 triaminopyrimidine, 2,4-dihydroxy-5,6-diaminopyrimidine, 2,5,6-triaminopyrimidine and pyrazolopyrimidine derivatives such as those mentioned in patent application FR-A-2 750 048 and of which pyrazolo [1,5-a] pyrimidine-3,7-diamine may be mentioned; 2,5-dimethyl-pyrazolo [1,5-a] pyrimidine-3,7diaminę; pyrazolo [1,5-a] pyrimidine-3,5-diamine; 2,7-dimethyl-pyrazolo [1,5-a] pyrimidine-3,5-diamine; 3aminopirazolo [1,5-a] pyrimidin-7-ol; 3-amino-pyrazolo [1,5-a] pyrimidin-5-ol; 2- (3-aminopyrazolo [1,5a] pyrimidin-7-ylamino) ethanol, 2- (7-aminopyrazolo [1,5-a] pyrimidin-3-ylamino) ethanol, 2 - [(3aminopyrazolo [1,5- a] pyrimidin-7-yl) (2-hydroxyethyl) amino] ethanol, 2 - [(7-aminopyrazolo [1,5-a] pyrimidin-3-yl) (2-hydroxyethyl) amino] ethanol, 5,6-dimethylpyrazolo [ 1,5-a] pyrimidine-3,7-diamine, 2,6-dimethylpyrazolo [1f5-a] pyrimidine-3,7-diamine, 2,5-N7, N7-tetramethylpyrazolo [1,5-a] pyrimidine-3, 7diaminę, 3-Amino-5-methyl-7-imidazolylpropylaminopyrazolo [1,5-a] pyrimidine and their acid addition salts and their tautomeric forms when tautomeric equilibrium exists.

Among the pyrazole derivatives, the compounds described in patents DE 38 43 892, DE 41 33 957 and patent applications WO 94/08969, WO 94/08970, FR-A-2 733 749 and DE 195 43 988, such as 4,5- diamino-1-methylpyrazole, 4,5-diamino-1- (b-hydroxyethyl) pyrazole, 3,4-diaminopyrazole,

4.5- diamino-1- (4'-chlorobenzyl) pyrazole, 4,5-diamino-1,3-dimethylpyrazole, 4,5-diamino-3-methyl-1-phenylpyrazole, 4,5-diamino-1-methyl-3- phenylpyrazole, 4-amino-1,3-dimethyl-5-hydrazinopyrazole, 1-benzyl4.5-diamino-3-methylpyrazole, 4,5-diamino-3-tert-butyl-1-methylpyrazole, 4,5-diamino 1-tert-butyl-3-methylpyrazole, 4,5-diamino-1- (b-hydroxyethyl) -3-methylpyrazole, 4,5-diamino-1-ethyl-3-methylpyrazole, 4,5-diamino-1-ethyl-3- (4'-methoxyphenyl) pyrazole, 4,5-diamino-1-ethyl-3-hydroxymethylpyrazole, 4,5-diamino-3-hydroxymethyl-1-methylpyrazole, 4,5-diamino-3-hydroxymethyl-1-isopropylpyrazole, 4,5-diamino-3-methyl-1-isopropylpyrazole, 4-amino-5- (2'-aminoethyl) amino-1,3-dimethylpyrazole, 3,4,5-triaminopyrazole, 1-methyl-3,4,5-triaminopyrazole, 3,5-diamino-1-methyl-4-methylaminopyrazole, 3,5-diamino-4- (bhydroxyethyl) ) amino-1-methylpyrazole and their acid addition salts.

Each base or oxidizable bases present in the composition of the invention are generally in an amount comprised between 0.001 to about 10% by weight of the total weight of the dyeing composition, preferably between 0.005 and 6%.

In general, the addition salts of oxidizable bases and coupling agents suitable for use in the context of the invention are especially selected from acid addition salts such as hydrochlorides, hydrobromides, sulfates, citrates, succinates, tartrates, lactates, tosylates, benzenesulfonates, phosphates and acetates and base addition salts such as sodium hydroxide, potassium hydroxide, ammonia water, amines or alkanolamines.

The dyeing composition according to the invention may furthermore contain one or more direct dyes, which can be chosen in particular from nitro dyes from the benzene series, direct azo dyes, direct methine dyes. These direct dyes may be nonionic, anionic or cationic in nature.

A dyeing medium also called a paint substrate is a cosmetic medium usually formed by water or a mixture of water and at least one organic solvent to dissolve compounds that are not sufficiently water soluble. As the organic solvent, lower C1-C4-alkanols such as ethanol and isopropanol may be mentioned; polyols and polyol ethers, such as 2-butoxyethanol, propylene glycol, glycol monomethyl ether

EP 1 550 656 propylene, monoethyl ether and diethylene glycol monomethyl ether, as well as aromatic alcohols such as benzyl alcohol or phenoxyethanol, and mixtures thereof.

The solvents are preferably present in amounts preferably between 1 and about 40% by weight based on the total weight of the dyeing composition and even more preferably between 5 and about 30% by weight.

The dyeing composition according to the invention may also contain various adjuvants conventionally used in hair dye compositions, such as anionic, cationic, nonionic, amphoteric, zwitterionic or mixtures thereof, anionic, cationic, nonionic, amphoteric, zwitterionic or mixtures thereof, inorganic or organic thickeners, in particular thickeners, which are associations of anionic, cationic, nonionic and amphoteric polymers, antioxidants, penetrating agents, masking agents, flavors, buffers, dispersing agents, conditioning agents such as, for example, volatile or non-volatile silicones, modified or unmodified, film-forming agents, ceramides, preservatives, opacifiers.

The above adjuvants are usually present in an amount for each of them between 0.01 and 20% by weight based on the weight of the dyeing composition.

Of course, the skilled person will ensure that this optional complementary compound or compounds are selected such that the beneficial properties essentially associated with the oxidative dyeing composition according to the invention do not deteriorate, or at least substantially, as a result of the additive or additives under consideration.

The dyeing composition according to the invention has a pH of generally between 3 and about 12, preferably between 5 and about 11. They can be brought to the desired size using acidifying or alkalizing agents usually used in dyeing keratin fibers or also using conventional buffer systems.

Among the acidifying agents, for example, inorganic or organic acids, such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids, such as acetic acid, tartaric acid, citric acid, lactic acid, sulfonic acids.

Among the alkalizing agents, for example, ammonia water, alkaline carbonates, alkanolamines such as mono-, di- and triethanolamines and their derivatives, sodium or potassium hydroxide and compounds of the following formula (II):

^R. \ Λ

N -WN zx

<img file="PL1550656T3_D0002.tif" />

wherein W is a propylene residue optionally substituted with a hydroxyl group or a C1-C4alkyl group; R_and, Rb, R_c and Rd, which are identical or different, represent a hydrogen atom, a CC-alkyl or hydroxy-C1-C4-alkyl group.

The dyeing composition of the invention may be in a variety of forms, such as in the form of lotions, creams, gels, or in any other form suitable for dyeing keratin fibers, especially human hair.

EP 1 550 656

The method of the present invention is a method in which the composition of the present invention as previously defined is applied to the fibers and the color is developed with an oxidant. Color may be developed at acidic, neutral or alkaline pH, and the oxidant may be added to the composition of the invention at the time of use, or may be used with an oxidizing composition containing it, applied simultaneously or sequentially with the composition of the invention.

According to a particular embodiment, the composition of the present invention is mixed, preferably at the time of use, with a composition comprising, in a dyeing environment, at least one oxidant, said oxidant in an amount sufficient to develop color. The resulting mixture is then applied to keratin fibers. After a break period of 3 to about 50 minutes, preferably 5 to about 30 minutes, the keratin fibers are rinsed, washed with shampoo, rinsed again and then dried.

The oxidant typically used for the oxidative dyeing of keratinous fibers is e.g. hydrogen peroxide, urea peroxide, alkali metal bromates, peroxides such as perborates and persulphates, peracids and oxidase enzymes, including peroxidases, 2-electron oxidoreductases, such as uricase and oxidase 4 electrons, like laccase. Hydrogen peroxide is particularly preferred.

The oxidizing composition may also include various adjuvants conventionally used in hair dye compositions as previously defined.

The oxidizing composition containing the oxidant exhibits such a pH that, when mixed with the dyeing composition, the pH of the resulting composition applied to keratin fibers varies preferably between 3 and about 12, and even more preferably between 5 and 11. They can be brought to the desired size by means of acidifying or alkalizing usually used in dyeing keratin fibers as previously defined.

The ready-to-use composition, which is finally applied to keratin fibers, can be in a variety of forms, such as in the form of lotions, creams, gels or in any other form suitable for dyeing keratin fibers, especially human hair.

The invention also relates to a device with several compartments or a "dye" kit, in which the first compartment contains the dyeing composition of the present invention as defined above, and the second compartment contains the oxidizing composition. The device may be provided with a system that allows the desired mixture to be delivered to the hair, such as devices described in FR-2 586 913 on behalf of the applicant.

With this device, it is possible to dye keratin fibers, starting from a method which involves mixing a dyeing composition containing at least one oxidation base of formula (I) with an oxidant and applying the resulting mixture to keratin fibers for a period of time sufficient to produce the desired color.

The present invention also relates to the use for oxidative dyeing of keratin fibers, and in particular human keratin fibers, such as hair, a diamine-N, N-dihydropyrazolone derivative of formula (I) or one of its addition salts as previously defined.

EP 1 550 656

Another object of the present invention is the amino-N, N-dihydropyrazolone derivatives of the following formula (I ') and their addition salts:

<img file="PL1550656T3_D0003.tif" />

formula in which:

Rj, R'2, R'3 and R'4 have the same meanings as R, respectively₁, R2, R3 and R4, provided that • R'13 is not Ar-N = N- when R'3 and R'4 are both hydrogen;

R'13 is a nitro, nitroso or arylazo group Ar-N = N-, wherein the aryl group Ar is optionally substituted by a C1-C4-alkyl, amino, di (C1-C4) -alkylamino, C1-C2-alkoxy group, sulfone, carboxy, halogen.

Everything previously mentioned regarding the preferred definitions of groups R1, R2, R3 and R4 is valid for R'1, R'2, R'3 and R'4 and will not be repeated in this part of the text.

Another object of the present invention are also diamine-N, Ndihydropyrazolone derivatives having the following formula (I ") and their addition salts:

<img file="PL1550656T3_D0004.tif" />

formula in which R'j, R "2, R'3 and R" 4 have the same meanings as previously given in the text for R'1,

R'2, R'3, R'4.

Also, everything previously mentioned regarding the preferred definitions of groups R'1, R'2, R'3 and R'4 is important for R "_1f R ”2, R'3 and R” 4 and will not be repeated in this part of the text.

Amino-N, N-dihydropyrazolone and diamino-N, N-dihydropyrazolone derivatives according to the invention and in which R'3 and R'4 on one side and R "3 and R" 4 on the other are hydrogen can be obtained from intermediates and synthetic routes described in the literature and especially in the following references:

J. Het. Chem., 2001, 38 (3), 613-616, Helvetica Chimica Acta, 1950, 33, 1183-1194, J. Org. Chem., 23, 2029 (1958), J. Am. Chem. Soc, 73, 3240 (1951), J. Am. Chem. Soc., 84, 590 (1962), Justus Liebig Ann. Chem., 686, 134 (1965), Tetrahedron, Lett., 31.2859-2862 (1973), patents US 4128425 and US 2841584 and references cited.

According to these references, compounds of formula (I) containing R groups₃ and R₄ representing hydrogen atoms can be obtained by the synthesis shown below in Scheme A:

EP 1 550 656 ^R1 N "

Μ^ΝΉ a

EtO

ΝΉ,

COJEt b

Η, Ν, Ν. /

R2 Ν ι

rl

NaNO2, AcOH

<img file="PL1550656T3_D0005.tif" />

H or Na2S2O4 and

Η, Ν_NO ou NO "A

rl

Scheme A

Compounds according to the invention and in which the R and R groups₂ together they form a ring with 5 members and in which the R groups₃ and R₄ are hydrogen atoms can be obtained, inspired by the method described in J. Het. Chem., 2001, 38 (3), 613-616 (scheme D):

tBuCOOC-N-N-COOtBo HH

<img file="PL1550656T3_D0006.tif" />

Diagram D.

According to the new method, the compounds of formula (I) can be obtained according to the synthesis explained in Scheme E:

R.HN-NHR, ą +

NH,

EtO

COjEl

<img file="PL1550656T3_D0007.tif" />

<img file="PL1550656T3_D0008.tif" />

Diagram E

According to this new method, the following steps are used:

a) etaal: ppdddje się; reactive relationship with

EP 1 550 656

R 1 N-NHR; a

with compound b:

<img file="PL1550656T3_D0009.tif" />

to obtain the 5-amino-1,2-dihydropyrazol-3-one compound from:

<img file="PL1550656T3_D0010.tif" />

b) etaaP: ppoddjee iareeakjitaatrzep start with soybean salt (Ar-NH2, NaNO 2, H +) to obtain the azo compound f:

<img file="PL1550656T3_D0011.tif" />

h) eeaaS: provisionally or inadvertently to the primary salt group of the primary amine of the retained azo compound, to obtain the following compound g:

<img file="PL1550656T3_D0012.tif" />

d) eetaa: araudiaiaeenisation of the ligamente ęuuazę ę fwa ube cg abb arazzmaa, aoppwieenio, amine compound e or h:

<img file="PL1550656T3_D0013.tif" />

The optional step of introducing a functional group into the primary amine group in position 5 to obtain the secondary and tertiary amine HR3R4, to obtain g compounds, is performed according to clasical methods of organic synthesis (alkyl halide, alkyl O-oligonate, compound

For trialkylammonium alkyl, reductive amination etc. see e.g. Advanced Organic Chemistry, 3rd Edition, 1985, J. March., Willey Interscience).

The reduction of the azo group leads to the compounds e and e according to the invention.

The reduction step is carried out in a classical manner, e.g. by conducting a hydrogenation reaction by heterogeneous catalysis in the presence of Pd / C, Pd (II) / C, Ni / Ra, etc ... or by performing a reduction reaction with a metal, e.g. zinc, iron, tin etc. (see Advanced Organic Chemistry, 3rd edition, J. March, 1985, Willey Interscience and Reduction in Chemistry, M. Hudlicky, 1983, Ellis Horwood Series Chemical Science).

According to the new process, 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one and 2,3-diamino-5,6,7,8-tetrahydro derivatives 1H, 6H-pyridazine [1,2-a] pyrazol-1-one according to formula (I) is obtained according to the synthesis explained in scheme F:

<img file="PL1550656T3_D0014.tif" />

a5 a6 »7

Diagram F

According to this method, the following steps are used:

a) step 1: the following compound al is reacted:

<img file="PL1550656T3_D0015.tif" />

with compound a2:

EP 1 550 656

<img file="PL1550656T3_D0016.tif" />

To obtain a3 relationship:

<img file="PL1550656T3_D0017.tif" />

in which:

group R₁₀ is hydrogen, carboxy; carboxamido; group C₁-C₄-alkyl, optionally substituted with one or more hydroxy, amino, dialkylamino, alkoxy, carboxy, sulfonyl;

the groups R11 and R12 are independently of each other hydrogen, halogen; amino groups; di (C₄) alkylamino; hydroxy; carboxy; carboxamido; Ci-C2-alkoxy; Ci-C group₄-alkyl, optionally substituted with one or more hydroxy, amino, dialkylamino, alkoxy, carboxy, sulfonyl;

X is halogen or alkylsulfonate. r is an integer between 1 and 3;

b) Step 2: reacting compound a3 with an amine of formula NHR3R4 to obtain compound aZ:

<img file="PL1550656T3_D0018.tif" />

c) etaap: the reaction of the compound 4 with cc at least one haloogn α-alkylsulfonyl, arylsulfonyl or perfluoroalkylsulfonyl R-O2S-X1 (R is alkyl, aryl or perfluoroalkyl, oznacza1 is halogen), in a solvent with a boiling point of 60 ° C. To obtain a5:

<img file="PL1550656T3_D0019.tif" />

d) step 4: the obtained compound a5 is then heated in a solvent with a boiling point comprised between 60 ° C and 190 ° C to obtain compound a6:

EP 1 550 656

<img file="PL1550656T3_D0020.tif" />

e) step 5: The obtained compound a6 is reduced to obtain compound a7 of formula (III) below:

about

NH

R io

R

<img file="PL1550656T3_D0021.tif" />

aZ formula (lll)

More particularly according to this method 3,5-dibromo-4-nitropyrazole a1, obtained e.g. according to the method described in DE 4234885, reacts with reagent a2, preferably in a solvent with a boiling point comprised between 60 ° C and 190 ° C. For example, pentanol, dimethylformamide, N-methylpyrrolidine may be mentioned. More particularly, the reaction is carried out in the presence of an organic or inorganic base, such as, for example, sodium carbonate, sodium hydroxide, sodium acetate, or triethylamine. The temperature of the reaction medium is preferably maintained between 60 ° C and 160 ° C, preferably between 80 ° C and 120 ° C.

1-Hydroxyalkyl-3,5-dibromo-4-nitropyrazole a3 is preferably isolated by precipitation or crystallization after adding ice to the reaction medium.

In step 2, derivative a3 is reacted with the amine NHR3R4, preferably in a solvent with a boiling point comprised between 60 ° C and 190 ° C, such as, for example, butanol, pentanol, dimethylformamide. The temperature is more particularly between 60 ° C and 160 ° C, preferably between 80 ° C and 120 ° C. After the reagents have been consumed, the 5-amino-4-nitro-3-bromo-1-hydroxyalkylpyrazole a4 compound is isolated by precipitation or crystallization with water.

According to step 3, derivative a5 is obtained by reacting alcohol a4 and alkylsulfonyl, arylsulfonyl or perfluoroalkylsulfonyl halide. The reaction takes place preferably in an aprotic solvent such as, for example, tetrahydrofuran, dioxane. The reaction takes place preferably at a temperature comprised between -20 ° C and 60 ° C, preferably between 0 ° C and 25 ° C. In addition, this step occurs in the presence of an organic or inorganic base, such as potassium carbonate, triethylamine, N-methylmorpholine, for example. After the disappearance of the reagents, compound a5 is separated by precipitation or crystallization from water.

The sulfonate a5 obtained from step 3 is converted in step 4 into a solution or dispersion in a solvent with a boiling point comprised between 60 ° C and 190 ° C, preferably between 90 ° C and 140 ° C. The temperature of the reaction medium is then adjusted between 90 ° C and 140 ° C, preferably between 105 ° C and 125 ° C, until complete consumption of the sulfonate a5. After returning to ambient temperature, the perhydropyrazolo [1,2-a] pyrazol-1-one compound (r = 1), perhydropyridazine [1,2-a] pyrazol-1-one (r = 2) or

EP 1 550 656 perhydrodiazepino [1,2-a] pyrazolone (r = 3) a6 crystallizes and is separated by classical organic synthesis methods.

The final compound a7 according to the invention is obtained during step 5 by reduction of the nitro derivative a6, the reduction methods used being e.g. hydrogenation by heterogeneous catalysis in the presence of Pd / C, Pd (II) / C, Ni / Ra, etc ... or also a metal reduction reaction, e.g. by zinc, iron, tin, etc., (see Advanced Organic Chemistry, 3rd Edition, J. March, 1985, Willey Interscience and Reduction in organic Chemistry, M. Hudlicky, 1983, Ellis Horwood Series Chemical Science).

The examples which follow serve to illustrate the invention.

EXAMPLES

Example 1: Synthesis of 2,3-diamino-6,7-dihydro-1H.5H-pyrazol-1.2alpyrazol-1-one dihydrochloride

<img file="PL1550656T3_D0022.tif" />

- Step 1: Synthesis of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol 1

Into a 500 ml three-necked flask, 0.369 mol of sodium acetate is introduced into a solution of 0.184 mol of dibromonitropyrazole in 250 ml of N-methylpyrrolidone, and the reaction medium is heated to 80 ° C.

0.369 mol of 3-bromopropanol is added dropwise at this temperature. This temperature is maintained for 5 hours.

After cooling to ambient temperature, the environment is poured onto ice with stirring. 3- (3,5-Dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol 1 precipitates. It is pressed off, dried and obtained in 75% yield.

The mass of the expected compound C6H7Br2N8O3 is detected by mass spectrometry.

^ANDnaNz^{y NMR} (¹HI ^{400 MH}from ^{and 13c1}°0,^{61 MH}from D^{MSO d6}) p^and from^gabout^dne from wait^and structure.

- Step 2: Synthesis of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propan-1-ol 2

0.135 moles of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol 1 are dispersed in a 500-ml three-necked flask containing 150 ml of ethanol, heated to 60 ° C, then 0.825 mol of benzylamine is added over 30 minutes.

After 6 hours at 60 ° C, the reaction medium is cooled to ambient temperature.

EP 1 550 656

3- [5- (Benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propan-1-ol 2 precipitates by pouring the reaction medium into 1 liter of ice while stirring. After pressing and drying under reduced pressure in the presence of P2O5, compound 2 is isolated in a yield of 90%.

AnaNz^s NMR (^{1h 400 MH}from ^{and 13}C ^{100.61 MH}from DMS^At6) p^and ZGO^dne with being prepared^and structure.

Elemental analysis:

Theory: C 43.96 H 4.26 N 15.77 O 13.51 Br 22.50

Measurement: C 44.09 H 4.22 N 15.44 O 14.37 Br 21.50

- Step 3: Synthesis of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate

Into a 500 ml three-necked flask containing 200 ml THF, 0.126 mole of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propan-1-ol is introduced with stirring. 2 and 15.82 ml triethylamine. The resulting mixture is then cooled to 5 ° C and 0.126 mol of mesyl chloride is poured over 45 minutes.

The reaction medium is maintained at this temperature for 2 hours, then 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 3 precipitates by pouring the reaction medium into 800 ml of ice.

After filtration, the solid is washed thoroughly with water and diisopropyl ether. Drying is carried out under reduced pressure in the presence of P2O₅. The yield of this stage is 94%.

Mass of expected Ci4HvBrN4O compound₅S is detected by mass spectrometry.

^ANDnaNz^{y NMR} (^{1h 400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure.

Elemental analysis:

Theory: C 38.81 H 3.96 N 12.93 O 18.46 S 7.40 Br 18.44

Measurement: C 39.03 H 3.91 N 12.83 O 18.52 S 7.29 Br 18.26

- Step 4: Synthesis of 3- (benzylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 4

In a 500 ml three-necked flask containing 300 ml of pentanol, 0.1 mole of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 3 is dispersed under stirring and heated the environment reaction at 130 ° C for 2 hours.

After cooling to ambient temperature, the solid formed is sintered, washed with diisopropyl ether and dried in vacuo in the presence of P2O₅. 3- (Benzylamino) 2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 4 is obtained in a yield of 86%.

^ANDnaNz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected C6H11N4O compound is detected by mass spectrometry.

Elemental analysis:

Theory: C 56.72 H 5.49 N 20.36 O 17.44

Measurement: C 56.68 H 5.13 N 20.38 O 17.69

- Step 5: Synthesis of 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride

20 g of 3- (benzylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 4 and 4 g are introduced into the 1 liter autoclave, containing 800 ml of ethanol. 5% palladium on carbon. The reduction is then carried out under 8 bar hydrogen pressure and a temperature between 50 ° C and 100 ° C (mixing between 1000 and 2500 rpm).

After 4 hours of reaction, there is no more hydrogen consumption and the environment is cooled to 20 ° C.

EP 1 550 656

The catalyst is removed under a nitrogen atmosphere by filtration; then hydrogen chloride saturated ethanol is added to the filtrate. The crystallized product is drained, washed with diisopropyl ether, then dried under reduced pressure in the presence of P2O5. 2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride is obtained in a yield of 89%.

The mass of the expected compound is detected by mass spectrometry.

AnaNz^{y NMR} (¹IH 400 ^MHfrom ^{and 13}C 100.61 ^MHfrom D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure.

Elemental analysis:

Theory: C 31.73 H 5.33 N 24.67 O 7.07 Cl 31.22

Measurement: C 31.45 H 5.20 N 24.62 O 7.24 Cl 30.86

Example 2: Synthesis of 2-amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a-pyrazol-1-one dihydrochloride 9

<img file="PL1550656T3_D0023.tif" />

- Step 2: Synthesis of 3- [3-bromo-5- (ethylamino) -4-nitro-1H-pyrazol-1-yl] propan-1-ol 6

15 millimoles of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol in 30 ml of ethanol are introduced into the three-necked flask with stirring. The homogeneous environment is heated to 75 ° C, then 93 mmol of ethylamine are added dropwise and stirring is maintained for four hours.

After cooling to ambient temperature, the medium is poured onto ice and 3- [3-bromo-5 (ethylamino} -4-nitro-1H-pyrazol-1-yl} propan-1-ol 6 precipitates.

The yellow solid is squeezed out, then washed thoroughly with water and diisopropyl ether. Drying is carried out under reduced pressure in the presence of P2O5. The obtained weight is 3.6 g.

^ANDnaNz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected compound C8H13BrN4O3 is detected by mass spectrometry.

- Step 3: Synthesis of 3- [5- {ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 7

11.2 millimoles of 3- [3-bromo-5- (ethylamino) -4-nitro-1H-pyrazol-1-yl] propan-1- are introduced into a 100 ml three-necked flask containing 30 ml THF with stirring. olu 6 and 1.6 ml triethylamine. The resulting homogeneous orange mixture is cooled to 0 ° C and poured with 1.44 ml of mesyl chloride over 20 minutes.

EP 1 550 656

The reaction medium is maintained at this temperature for 2 hours, then 3- [5 (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 7 precipitates by pouring the reaction medium on 500 ml of ice.

The yellow solid is squeezed out, then washed thoroughly with water and diisopropyl ether; drying is carried out under reduced pressure in the presence of P2O5. The obtained weight is 3.1 g.

AnaNz^s NMR (^{1h 400} mk ^{and 13}C ^100,61 Mk DMS^At6) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected CgHi5BrN4O5S compound is detected by mass spectrometry.

- Step 4: Synthesis of 3- (ethylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 8

In a 50 ml three-necked flask containing 20 ml of pentanol, 8 millimoles of 3- [5- (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 7 are dispersed under stirring and heated the reaction medium in 130 ° C in 2 hours.

After cooling to ambient temperature, the solid formed is filtered off, then washed with diisopropyl ether.

After drying under reduced pressure in the presence of P2O5, 1.46 g of 3- (ethylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 8 are obtained.

anahz^{y NMR} (^{1h 400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gohhhhhhhhhhhhhhhhh^and structure

The mass of the expected compound is detected by mass spectrometry.

- Step 5: Synthesis of 2-amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2a] pyrazol-1-one dihydrochloride 9

1.45 g of 3- (ethylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 8 and 300 are introduced into a 300 ml autoclave containing 200 ml of ethanol. mg 5% palladium on carbon. The reduction is carried out under 8 bar hydrogen pressure at 60 ° C (mixing at 1700 rpm).

After 2 hours of reaction, there is no more hydrogen consumption and the environment is cooled to 20 ° C.

The catalyst is removed by filtration under a nitrogen atmosphere and the filtrate is diluted with 100 ml of hydrogen chloride saturated isopropyl ether.

The pale yellow solution is evaporated to dryness, then an ethanol / isopropyl ether mixture is added to the solid. 2-Amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride dihydrochloride 9; it is pressed and after drying under reduced pressure in the presence of P2O5, 1.18 g of 2-amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2a] pyrazol-1-one dihydrochloride is obtained. 9.

^ANDnaNz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected C8H14N4O compound is detected by mass spectrometry.

Example 3: 2-Amino-3- (isopropylamino) -6,7-dihydro-1H.5H-pyrazol-1.2alpyrazol-1-one dihydrochloride

EP 1 550 656

<img file="PL1550656T3_D0024.tif" />

- Step 2: 3- [3-Bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-yl-propan-1-ol

15 millimoles of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol in 30 ml of ethanol are introduced into the three-necked flask with stirring. The homogeneous environment is heated to 75 ° C, then 93 millimoles of isopropylamine are added dropwise while maintaining stirring for four hours.

After cooling to ambient temperature, the medium is poured into ice, then neutralized with hydrochloric acid. 3- [3-Bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-yl-propan-1-ol is extracted with dichloromethane.

After drying the organic phase over sodium sulfate and removing the solvent by evaporation under reduced pressure, 4.37 g of 3- [3-bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-yl] propan-1-ol are obtained. 10.

AnaNz^s NMR ('^{H 400 MH}from ^{and 13}C ^{100.61 MH}with DMSO ^d6 s^and from^gabout^dne with being prepared^and structure.

The mass of the expected Cd-tBrN / .O; compound is detected by mass spectrometry.

- Step 3: Synthesis of 3- [5-isopropylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 11

Into a 50 ml three-necked flask containing 20 ml THF, 13.7 mmol 3- [3-bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-ylolpropan-1-ol are introduced with stirring. 10 and 1.94 ml triethylamine. The homogeneous orange mixture thus obtained is cooled to 0 ° C and poured with 1.76 ml of mesyl chloride over 20 minutes.

The reaction medium is maintained at this temperature for 2 hours, then 3- [5 (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-ylpropylmethanesulfonate 11 precipitates by pouring the reaction medium onto 500 ml of ice.

The yellow solid is squeezed out, then washed thoroughly with water and petroleum ether, drying is carried out under reduced pressure in the presence of P2O5. The obtained weight is 4.2 g.

^ANDnaNz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^godne with preparations^and structure.

The mass of the expected compound is detected by mass spectrometry.

- Step 4: Synthesis of 3- (isopropylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-alpirazol-1-one 12

EP 1 550 656

In a 50 ml three-necked flask, 10 millimoles of 3- [5- (isopropylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate 11 in 20 ml of pentanol are dispersed under stirring and heated at 130 ° C in 2 hours.

After cooling to ambient temperature, the solid obtained is sintered and washed with diisopropyl ether.

After drying under reduced pressure in the presence of P2O5, 1.71 g of 3- (isopropylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1one 12 are obtained.

AnaNz^s NMR (^{1H 400 MH}from ^{and 13}C ^{100.61 MH}from DMS^{At d6}) p^and from^godne with preparations^and struttura

The mass of the expected compound C9H14N4O3 is detected by mass spectrometry.

- Step 5: Synthesis of 2-amino-3- (isopropylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2a] pyrazol-1-one dihydrochloride

1.70 g 3 (isopropylaminoamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1r2-a] pyrazol-1-one 12 and 300 are introduced into a 300 ml autoclave containing 200 ml ethanol. mg 5% palladium on carbon. The reduction is carried out at a temperature of 60 ° C and a hydrogen pressure of 6 bar (mixing at 2000 rpm).

After 2 hours of reaction, there is no more hydrogen consumption and the environment is cooled to 20 ° C. The catalyst is removed by filtration under a nitrogen atmosphere after cooling to ambient temperature and hydrogen chloride saturated isopropyl ether is added.

The pale yellow solution is evaporated to dryness, then 50 ml of diisopropyl ether saturated with hydrochloric acid are added to the solid, a precipitate is obtained by pressing. After drying under reduced pressure in the presence of P2O5, 1.5 g of 2-amino-3- (isopropylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride are isolated. .

^ANDnaNz^{y NMR} (¹I4 ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure

The mass of the expected C9H16N4O compound is detected by mass spectrometry.

Example 4: 2-Amino-3- (pyrrolidin-1-yl) -6.7-dihydro-1H, 5H-pyrazol-1.2alpyrazol-1-one dihydrochloride

<img file="PL1550656T3_D0025.tif" />

- Step 2: 3- (3-Bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propan-1-ol 14

EP 1 550 656

15 millimoles of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol in 20 ml of isopropanol are added to the three-necked flask with stirring. The homogeneous environment is heated to 75 ° C, then 90 millimoles of pyrrolidine are added dropwise and stirring is maintained for two hours.

After cooling to ambient temperature, the environment is poured onto ice and neutralized with hydrochloric acid. 3- (3-Bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propan-1-ol 14 is extracted with dichloromethane.

After drying the organic phase over sodium sulfate and distilling off the solvent by evaporation under reduced pressure, 4.8 g of 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propane are obtained. -1-olu 14.

AnaNz^s NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}with DMSO ^d6) are from^gabout^dAD with a pre-fabricated structure.

The mass of the expected compound C ^ H ^ Br ^ O is detected by mass spectrometry.

- Step 3: Synthesis of 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propylmethanesulfonate

Into a 100 ml three-necked flask containing 50 ml THF, 30 millimoles of 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propane are introduced with stirring. -1-ol 14 and 4.25 ml triethylamine. The resulting homogeneous orange mixture is cooled to 0 ° C. and 2.32 ml of mesyl chloride are poured over 20 minutes.

The reaction medium is maintained at this temperature for 2 hours, then 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propylmethanesulfonate precipitates, pouring the reaction medium on ice .

The solid is filtered off, then dried under reduced pressure in the presence of P2O₅. The obtained weight is 9.3 g.

^ANDnaHz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d}g) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected compound CnH ^ Br ^ OaS is detected by mass spectrometry.

- Step 4: Synthesis of 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolol-1,2-a-pyrazol-1-one 16

Into a 250 ml three-necked flask, 22.5 mmol of 3- (3-bromo-4-nitro-5 (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propylmethanesulfonate in 100 ml of pentanol are introduced under stirring. . The medium thus obtained is heated at 130 ° C. for 2 hours.

After cooling to ambient temperature, 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 16 is extracted with dichloromethane.

After drying the organic phase over sodium sulfate and distilling off the solvent under reduced pressure, 1.2 g of 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2a] pyrazole are obtained. -1-on 16.

^ANDnaNz^{y NMR} (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) p^and from^gabout^dne with being prepared^and structure..

The mass of the expected compound C ^ h ^ n ^ O is detected by mass spectrometry.

- Step 5: Synthesis of 2-amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2a1-pyrazol-1-one dihydrochloride

1.1 g of 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a) pyrazol-1 are introduced into a 300 ml autoclave containing 200 ml of ethanol. -one 16 and 300 mg 5% palladium on carbon. The reduction is carried out by mixing at 2000 rpm, 60 ° C and 6 bar hydrogen pressure.

After 2 hours of reaction, there is no more hydrogen consumption and the environment is cooled to 20 ° C.

EP 1 550 656

The catalyst is removed by filtration under a nitrogen atmosphere after cooling to ambient temperature and hydrogen chloride saturated isopropyl ether is added.

The pale yellow solution is evaporated to dryness, then 50 ml of diisopropyl ether saturated with hydrochloric acid are added to the solid, a precipitate is obtained by pressing. After drying under reduced pressure in the presence of P2O5, 1.5 g of 2-amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a} pyrazol- dihydrochloride is isolated. 1-on 5 17.

AnaNz^s NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from DMS^{At d6}) p^and from^gabout^dne with being prepared^and structure.

The mass of the expected compound C10H16N4O is detected by mass spectrometry.

Example 5: Synthesis of 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolofl, 2alpyrazol-1-one dimethanesulfonate

<img file="PL1550656T3_D0026.tif" />

3

Synthesis of 3-amino-2-nitroso-6,7-dihydro-1H, 5H-pyrazolo [1,2-a1-pyrazol-1-one: 2

In a 500 ml three-necked flask, 43 g (0.245 mol) of 3-amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a-pyrazol-1-one hydrochloride are dissolved in a mixture with stirring at ambient temperature ml of water and 35 ml of 35% hydrochloric acid.

It is cooled to 0 ° C and a solution of 17.3 g sodium nitrite (0.25 mol) in 20 ml water is added dropwise over 30 minutes. The temperature of the reaction medium is maintained between 0 and + 5 ° C throughout the addition and during one hour after the addition.

The reaction medium is adjusted to pH 8 by the addition of sodium hydroxide while stirring, maintaining the temperature between 0 and 5 ° C. 3-Amino-2-nitroso-6,7-dihydro-1H, 5H-pyrazolo [1,2a] pyrazol-1-one 2 is precipitated as an orange-red solid, which is filtered through sintered glass No. 4, earns a minimum of 2-propanol, washed with diisopropyl ether and dried under reduced pressure in the presence of phosphorus pentoxide. 35 g of a red-orange product are obtained in this way (yield: 85%).

^INand^dIt has ^NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) ^and mass p^and from^gabout^dne with being prepared^andstructure 2.

Synthesis of 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a1-pyrazol-1-one dimethanesulfonate: 3

33.6 g (0.2 mol) of 3-amino-2-nitroso-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 2,500 ml are introduced into the autoclave of 1 liter. ethanol and 6 g 5% palladium on carbon containing 50% water. The medium is purged three times with nitrogen, then three times with hydrogen, and the temperature of the mixture is raised to 40 ° C.

The reduction is carried out in two hours at a pressure of 8 bar. This reduction is exothermic and the temperature itself reaches 70 ° C.

The temperature is allowed to drop to 50 ° C, then the catalyst is filtered off with a pressure filter under a nitrogen stream.

EP 1 550 656

The filtrate is poured into a mixture of 50 ml ethanol and 40 ml methanesulfonic acid under cooling to 0 ° C. 2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dimethanesulfonate 3 crystallizes in the form of a light yellow solid, which is pressed onto sintered glass No. 4, washed with diisopropyl ether then with petroleum ether and finally dried under reduced pressure in the presence of phosphorus pentoxide. 43 g of a light yellow solid are obtained in this way (yield: 65%).

wi^dhas NMR ('^{H 400 MH}from ^{and 13}C ^{100.61 MH}from DMS^{At d6}) ^and mass p^and from^gabout^dne with being prepared^andstructure 3.

Elemental analysis:

Theory: C 227.74 H 5.23 N16.17 O 32.33 S 18.51

Measurement: C27J6 H 5.22 Ν1,, 33 O 32.81 S 18.64

Example 6: Synthesis of 2.3-diamino-5.6.7.8-tetrahydro-1H-pyrazol-1.2alpyridazin-1-one hydrochloride

<img file="PL1550656T3_D0027.tif" />

Synthesis of di-tert-butyl tetrahydropyridazine-1,2-dicarboxylate: A.

Into a 250 ml three-necked flask equipped with a condenser, thermometer and dropping funnel, 50 ml of toluene, 5 g (21.5 mmol) of N, N'-di-tert-butoxycarbonyl hydrazide, 680 mg of tetraethylammonium bromide and 25 ml are added with mechanical stirring. 50% sodium hydroxide.

The heterogeneous environment is heated to 100 ° C, then 1,4-dibromobutane is added dropwise over 15 minutes.

The reaction medium is heated at 100 ° C. for 3 days. After cooling, 100 ml of ethyl acetate are added and transferred to a separatory funnel. The organic phase is washed 4 times with 70 ml aqueous saturated sodium carbonate solution, then 4 x 70 ml water and finally 4 x 70 ml brine. The organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure. A colorless oil is obtained which crystallizes into a white solid.

A weight of 6.1 g is obtained (yield: 99%).

^INand^dIt has ^NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) ^and mass p^and from^gabout^dne with being prepared^andstructure A.

Synthesis of hexahydropyridazine dihydrochloride: B

5.9 g of compound A in 50 ml of a 3/1 mixture of dioxane and 35% hydrochloric acid are introduced into the 100 ml three-necked flask equipped with a condenser and a thermometer.

EP 1 550 656

The resulting colorless solution is stirred at ambient temperature for 3 hours, then the reaction medium is diluted with diisopropyl ether. The solvents are evaporated off under reduced pressure. An ether / ethanol mixture is added to the resulting pasty residue. 1.39 g of a white solid are obtained after filtration of the solid and drying under reduced pressure.

wi^dhas NM^R (¹H 400 MHz ^{and 13}C ¹00^,6¹ MHz DMS^ABOUT &lt;1θ) ^and mass p^and from^gabout^dne with being prepared^andstructure B.

Synthesis of 3-amino-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a1-pyridazin-1-one: C

7.5 ml ethanol, 1.5 ml triethylamine and 0.73 ml 3-amino-3-ethoxyacrylic acid are introduced into the 25 ml three-necked flask equipped with a condenser and a thermometer. Then 500 mg hexahydropyridazine dihydrochloride (compound B) is added and stirred for 3 hours at ambient temperature.

Insoluble parts are filtered off and the solvent is distilled off under reduced pressure. A minimum amount of water is added to the solid, filtered and dried under reduced pressure. 0.9 g of a slightly yellow powder is obtained in this manner.

^INand^dIt has ^NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) ^and mass p^and from^gabout^dne with being prepared^andstructure C.

Synthesis of 3-amino-2-nitroso-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a1-pyridazin-1-one: D

Into a 50 ml three-necked flask equipped with a condenser and a thermometer, 20 ml 35% hydrochloric acid and 1 g 3-amino-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a] pyridazine -1-on (compound C).

It is cooled to 0 ° C and a solution of 675 mg sodium nitrite in 5 ml water is poured, maintaining this temperature. The color of the reaction mixture changes from yellow to orange and a precipitate begins to form.

Within 30 minutes, the reaction is complete and the orange solid is filtered off on sintered glass No. 4, washed with water, then dried under reduced pressure. The yield is 78.3%.

^INand^dIt has ^NMR (¹IH ^{400 MH}from ^{and 13}C ^{100.61 MH}from D^{MSO d6}) ^and mass p^and from^gabout^dne with being prepared^andD. structure

Synthesis of 2,3-diamino-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a1-pyridazin-1-one hydrochloride: E

Into a 300 ml autoclave containing 250 ml ethanol, 1.3 g 3-amino-2-nitroso-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a] pyridazin-1-one (compound D) and 250 mg 5% palladium on carbon. The reduction is carried out by mixing at 2000 rpm, 60 ° C and 6 bar hydrogen pressure.

After 2 hours of reaction, there is no more hydrogen consumption and the environment is cooled to 20 ° C.

The catalyst is removed by filtration under a nitrogen atmosphere after cooling to ambient temperature and the solution is poured into 75 ml of hydrogen chloride saturated dioxane.

The solution thus obtained is evaporated until a slightly yellow powder is obtained, which is added to diisopropyl ether.

A solid is obtained by filtration. After drying under reduced pressure in the presence of phosphorus pentoxide, 1.1 g of 2,3-diamino-5,6,7,8-tetrahydro-1H-pyrazolo [1,2a] pyridazin-1-one dihydrochloride is obtained.

EP 1 550 656

NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO όθ) and mass are consistent with the expected structure of E.

PAINT EXAMPLES

Examples 1 to 3: Dyeing in an acid medium, starting from 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolof1,2-alpirazol-1-one

The following dyeing compositions are prepared:

<td>Example</td><td> 1</td><td> 2</td><td> 3</td>

<td>2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride</td><td>¹⁰"³ can^land</td><td>¹⁰"³ can^land</td><td>¹⁰"³ can^land</td>

<td>5-Amino-2-methylphenol</td><td>¹⁰"³ can^land</td><td></td><td></td>

<td>2- (2,4-diaminophenoxy) ethanol hydrochloride</td><td></td><td>¹⁰"³ can^land</td><td></td>

<td>3-Amino-2-chloro-6-methylphenol hydrochloride</td><td></td><td></td><td>¹⁰"³ can^land</td>

<td>Paint base (2)</td><td> (*)</td><td> (*)</td><td> (*)</td>

<td>Demineralized water qsad</td><td>100 g</td><td>100 g</td><td>100 g</td>

(*): paint base (1) pH 7

<td>96 ° ethyl alcohol</td><td></td><td>20.8 g</td><td></td>

<td>Sodium metabisulphite in 35% aqueous solution</td><td>0.23 g sa</td><td></td><td></td>

<td>Diethylenetriaminepentaacetic acid pentasodium salt</td><td></td><td></td><td></td>

<td>in 40% aqueous solution</td><td></td><td>0.48 g</td><td>are</td>

<td>C₈-C10-Alkylpolyglucoside in 60% aqueous solution</td><td>3.6 g sa</td><td></td><td></td>

<td>Benzyl alcohol</td><td></td><td>2.0 g</td><td></td>

<td>Polyethylene glycol with 8 ethylene oxide groups 3.0 g</td><td></td><td></td><td></td>

<td>On₈HPO 4</td><td></td><td></td><td>0.28 g</td>

<td>KH2PO4</td><td></td><td></td><td>0.46 g</td>

At the time of use, each composition is mixed with an equal weight of hydrogen peroxide with 20 volumes (6% by weight). A final pH of 7 is obtained.

Each mixture obtained is applied to strands of gray, 90% white hair. After a 30-minute break, the strands are rinsed, washed with a standard shampoo, rinsed again, and dried.

The resulting shades are in the following table:

<td>Example</td><td> 1</td><td> 2</td><td> 3</td>

<td>Observed shade</td><td>orange chromatic</td><td>chromatic red intense</td><td>orange chromatic</td>

Examples 4 to 6: Dyeing in an alkaline environment. starting from 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolof1,2-alpirazol-1-one

The following dyeing compositions are prepared:

EP 1 550 656

<td>Example</td><td> 4</td><td> 5</td><td> 6</td>

<td>2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride</td><td>¹⁰"³ can^land</td><td>¹⁰"³ can^land</td><td>¹⁰"³ can^land</td>

<td>5-Amino-2-methylphenol</td><td>¹⁰"³ can^land</td><td></td><td></td>

<td>2- (2,4-diaminophenoxy) ethanol hydrochloride</td><td></td><td>¹⁰"³ can^land</td><td></td>

<td>3-Amino-2-chloro-6-methylphenol hydrochloride</td><td></td><td></td><td>¹⁰"³ can^land</td>

<td>Paint base (1)</td><td> (*)</td><td> (*)</td><td> (*)</td>

<td>Demineralized water qsad</td><td>100 g</td><td>100 g</td><td>100 g</td>

(*): paint substrate (1) pH 9.5

96 ° ethyl alcohol

Sodium metabisulphite in a 35% aqueous solution of 0.23 g sa

Diethylenetriaminepentaacetic acid pentasodium salt in 40% aqueous solution

C₈-C10-Alkylpolyglucoside in a 60% aqueous solution of 3.6g sa

Benzyl alcohol

Polyethylene glycol with 8 ethylene oxide groups 3.0 g

20.8 g

0.48 g sa

2.0 g

NH4Cl 4.32 g

Ammonia water with 20% NH3 2.94g

At the time of use, each composition is mixed with an equal weight of hydrogen peroxide with 20 volumes (6% by weight). A final pH of 9.5 is obtained.

Each mixture obtained is applied to strands of gray, 90% white hair. After a 30-minute break, the strands are rinsed, washed with a standard shampoo, rinsed again, and dried.

The resulting shades are in the following table:

<td>Example</td><td> 4</td><td> 5</td><td> 6</td>

<td>Observed shade</td><td>orange chromatic</td><td>chromatic red</td><td>orange chromatic</td>

EP 1 550 656