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

0001The subject of the invention is a composition for dyeing keratin fibers, and in particular human keratin fibers such as the hair, comprising at least one derivative of diamino-N, N-dihydropyrazolone or one of its addition salts as base oxidation and a process using it. It also relates to derivatives of amino-N, N-dihydropyrazolone as well as derivatives of diamino-N, N-dihydropyrazolone or one of its addition salts as such and their production.

0002It is known to dye keratin fibers, and in particular human keratin fibers such as the hair, with dye compositions comprising oxidation dye precursors, in particular ortho or para-phenylenediamines, ortho or para-aminophenols, heterocyclic compounds such as diaminopyrazole derivatives, pyrazolo [1,5-a] pyrimidine derivatives, pyrimidine derivatives, pyridine derivatives, 5,6-dihydroxyindole derivatives, 5,6-dihydroxyindoline derivatives generally called oxidation bases. The precursors of oxidation dyes, or oxidation bases, are colorless or weakly colored compounds which, associated with oxidizing products, can give rise, by an oxidative condensation process, to colored or coloring compounds.

0003We also know that we can vary the shades obtained with these oxidation bases by combining them with couplers or color modifiers, the latter being chosen in particular from meta-phenylenediamines, meta-aminophenols, meta-hydroxyphenols and certain heterocyclic compounds such as for example derivatives of pyrazolo [1,5-b] -1,2,4-triazoles, derivatives of pyrazolo [3,2-c] -1,2,4-triazoles, derivatives pyrazolo [1,5-a] pyrimidines, pyridine derivatives, pyrazol-5-one derivatives, indoline derivatives and indole derivatives.

0004The variety of molecules involved in the oxidation bases and couplers allows obtaining a rich palette of colors.

0005The so-called "permanent" coloring obtained by means of these oxidation dyes must moreover satisfy a certain number of requirements. Thus, it must be without drawbacks from the toxicological point of view, it must make it possible to obtain nuances in the desired intensity, to exhibit good resistance to external agents such as light, bad weather, washing, permanent undulations, sweating and rubbing.

0006The dyes must also make it possible to cover gray hair, and finally be the least selective possible, that is to say allow to obtain the smallest possible color differences throughout the same keratin fiber, which can be in fact differently sensitized (ie damaged) between its tip and its root. They must also have good chemical stability in the formulations. They must have a good toxicological profile.

0007The use of an oxidation base such as derivatives of para-phenylenediamine and para-aminophenol makes it possible to obtain a fairly wide range of colors at basic pH without however achieving nuances of good chromaticity while giving the hair excellent properties of color intensity, variety of shades, color uniformity and tenacity to external agents.

0008The use of these bases at neutral pH is moreover ineffective in reaching a range of varied shades, in particular for warm shades.

0009It has already been proposed in patent DE3843892 to use certain diaminopyrazole derivatives, in particular for the red to copper red shades. However, this proposal does not achieve good chromaticity properties, resistance to external agents such as washing and light. In addition, the extent of the range of shades is limited.

0010Now, the Applicant has discovered, completely surprisingly, that new diamino-N, N-dihydro-pyrazolone compounds of formula (I) are suitable for use as oxidation coloring precursors and make it possible to obtain coloring with shades. varied, powerful, chromatic, esthetic, not very selective and resistant well to the various aggressions that the hair can undergo such as shampoos, light, sweat and permanent deformations.

0011The Applicant has also surprisingly discovered that the colorings obtained at neutral pH are intense.

0012The subject of the present invention is therefore a dye composition for keratin fibers comprising, in an appropriate dyeing medium, as oxidation base, at least one derivative of diamino-N, N-dihydro-pyrazolone of formula (I) or one of its addition salts:<chemistry id="chem0001" num="0001"><img file="EP1550656A1_D0001.tif" /></chemistry> in which :<ul id="ul0001" list-style="none"><li>R₁, R₂, R₃ and R₄, identical or different, represent:<ul id="ul0002" list-style="dash" compact="compact"><li>a C 1 alkyl radical₁-VS₆ linear or branched optionally substituted by one or more radicals chosen from the group consisting of an OR radical₅, a radical NR₆R₇, a carboxy radical, a sulfonic radical, a carboxamido CONR radical₆R₇, a sulfonamido SO radical₂NR₆R₇, a heteroaryl, an aryl optionally substituted by a group (C₁-VS₄) alkyl, hydroxy, C alkoxy₁-VS₂, amino, (di) alkyl (C₁-VS₂) amino;</li><li>an aryl radical optionally substituted by one or more (C₁-VS₄) alkyl, hydroxy, C alkoxy₁-VS₂, amino, (di) alkyl (C₁-VS₂) amino;</li><li>a 5 or 6-membered heteroaryl radical, optionally substituted by one or more radicals chosen from (C₁-VS₄) alkyl, (C₁-VS₂) alkoxy;</li></ul></li><li>R₃ and R₄ may also represent a hydrogen atom;</li><li>R₅, R₆ and R₇, identical or different, represent a hydrogen atom; a linear or branched C alkyl radical₁-VS₄ optionally substituted by one or more radicals chosen from the group consisting of hydroxy, C alkoxy₁-VS₂, a CONR carboxamido₈R₉, a sulfonyl SO₂R₈, an aryl optionally substituted by a (C₁-VS₄) alkyl, hydroxy, C alkoxy₁-VS₂, amino, (di) alkyl (C₁-VS₂) amino; an aryl optionally substituted by a (C₁-VS₄) alkyl, hydroxy, C alkoxy₁-VS₂, amino, (di) alkyl (C₁-VS₂) amino;</li><li>R₆ and R₇, identical or different, can also represent a carboxamido radical CONR₈R₉ ; SO sulfonyl₂R₈ ;</li><li>R₈ and R₉, identical or different, represent a hydrogen atom; C 1 alkyl radical₁-VS₄ linear or branched optionally substituted by one or more hydroxy, C alkoxy₁-VS₂ ;</li><li>R₁ and R₂ on the one hand, and R₃ and R₄ on the other hand can form with the nitrogen atoms to which they are attached, a saturated or unsaturated heterocycle, comprising 5 to 7 members, optionally substituted by one or more radicals chosen from the group consisting of halogen atoms, the radicals amino, (di) alkyl (C₁-VS₄) amino, hydroxy, carboxy, carboxamido, (C₁-VS₂) alkoxy, C alkyl radicals₁-VS₄ optionally substituted by one or more hydroxy, amino, (di) -alkylamino, alkoxy, carboxy, sulfonyl radicals;</li><li>R₃ and R₄ may also form, together with the nitrogen atom to which they are attached, a 5 or 7-membered heterocycle whose carbon atoms may be replaced by an oxygen or nitrogen atom which may be substituted.</li></ul>

0013The present invention makes it possible in particular to obtain a tenacious coloring of keratin fibers, resistant to light and to washing.

0014Another subject of the invention is a process for dyeing keratin fibers using the composition of the present invention, as well as the use of this composition for dyeing keratin fibers.

0015A subject of the invention is also new amino-NN-dihydropyrazolone derivatives, as well as diamino-N, N-dihydro-pyrazolone derivatives.

0016Finally, the invention relates to new methods for the synthesis of these (di) amino-N, N-dihydropyrazolone derivatives of formulas (I ') and (I' ') or their addition salts.

0017As indicated above, the composition comprises at least one diamino-N, N-dihydro-pyrazolone derivative of formula (I) or one of its addition salts.

0018More particularly, in formula (I) the radicals R₁ and R₂, identical or different, are chosen from<ul id="ul0003" list-style="dash" compact="compact"><li>a C 1 alkyl radical₁-VS₄ optionally substituted by a hydroxy, a (C₁-VS₂) alkoxy, amino, (di) alkyl (C₁-VS₂) amino;</li><li>a phenyl radical.</li></ul>

0019Preferably, the radicals R₁ and R₂, identical or not, are chosen from a methyl, ethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, phenyl radical.

0020According to another embodiment, the radicals R₁ and R₂ together with the nitrogen atoms to which they are attached form a 5 or 6-membered ring, saturated or unsaturated, optionally substituted.

0021Preferably, the radicals R₁ and R₂ together with the nitrogen atoms to which they are attached, form a pyrazolidine, pyridazolidine ring, optionally substituted by a C 1 alkyl radical₁-VS₄, hydroxy, (C₁-VS₂) alkoxy, carboxy, carboxamido, amino, (di) alkyl (C₁-VS₂) amino.

0022Even more advantageously, the radicals R₁ and R₂ together with the nitrogen atoms to which they are attached, form a pyrazolidine, pyridazolidine ring.

0023Regarding R radicals₃ and R₄, the latter, identical or different, are more particularly chosen from a hydrogen atom; a C 1 alkyl radical₁-VS₄ linear or branched, optionally substituted by one or more hydroxy, (C₁-VS₂) alkoxy, amino, a (di) alkyl (C₁-VS₂) amino; a phenyl radical optionally substituted by a hydroxy, amino, (C₁-VS₂) alkoxy.

0024Preferably, the radicals R₃ and R₄, identical or not, are chosen from a hydrogen atom, methyl, ethyl, isopropyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 2-carboxyethyl. According to a particular embodiment, the radicals R₃ and R₄, represent a hydrogen atom.

0025According to another embodiment, the radicals R₃ and R₄ together with the nitrogen atom to which they are attached form a 5 or 7-membered ring chosen from the heterocycles pyrrolidine, piperidine, homopiperidine, piperazine, homopiperazine; said rings possibly being substituted by one or more hydroxy, amino, (di) alkyl (C) radicals₁-VS₂) amino, carboxy, carboxamido, C-alkyl₁-VS₄ optionally substituted by one or more hydroxy, amino, (di) alkylamino in C₁-VS₂.

0026More particularly, the radicals R₃ and R₄ together with the nitrogen atom to which they are attached form a 5 or 7-membered ring chosen from pyrrolidine, 2,5-dimethylpyrrolidine, pyrrolidine-2-carboxylic acid, 3-hydroxypyrrolidine-2- acid carboxylic acid, 4-hydroxypyrrolidine-2-carboxylic acid, 2,4-dicarboxypyrrolidine, 3-hydroxy-2-hydroxymethylpyrrolidine, 2-carboxamidopyrrolidine, 3-hydroxy-2-carboxamidopyrrolidine, 2- (diethylcarboxamido) pyrrolidine , 2-hydroxymethyl pyrrolidine, 3,4-dihydroxy-2-hydroxymethyl pyrrolidine, 3-hydroxypyrrolidine, 3,4-dihydroxy pyrrolidine, 3-amino pyrrolidine, 3-methylamino pyrrolidine, 3-dimethylamino-pyrrolidine, 4-amino-3 -hydroxy pyrrolidine, 3-hydroxy-4- (2-hydroxyethyl) amino-pyrrolidine, piperidine, 2,6-dimethylpiperidine, 2-carboxypiperidine, 2-carboxamidopiperidine, 2-hydroxymethylpiperidine, 3-hydroxy- 2-hydroxymethylpiperidine, 3-hydroxypiperidine, 4-hydroxypiperidine, 3-hydroxymethylpiperidine, homopiperidine, 2-carboxyhomopiperidine, 2-carboxamidohomopiperidine, homopiperazine, N-methyl-homopiperazine, N- (2-hydroxyethyl) -homopiperazine.

0027Preferably, the radicals R₃ and R₄ together with the nitrogen atom to which they are attached form a 5 or 7-membered ring chosen from pyrrolidine, 3-hydroxypyrrolidine, 3-aminopyrrolidine, 3-dimethylamino-pyrrolidine, pyrrolidine-2-carboxylic acid , 3-hydroxypyrrolidine-2-carboxylic acid, piperidine, hydroxypiperidine, homopiperidine, diazepane, N-methyl homopiperazine, N β-hydroxyethylhomopiperazine.

0028In accordance with an even more preferred embodiment of the invention, the radicals R₃ and R₄ together with the nitrogen atom to which they are attached form a 5-membered ring such as pyrrolidine, 3-hydroxypyrrolidine, 3-aminopyrrolidine, 3-dimethylamino-pyrrolidine.

0029The compounds of formula (I) can optionally be salified with strong mineral acids such as for example HCl, HBr, Hl, H₂SO₄, H₃PO₄, or organic acids such as, for example, acetic, lactic, tartaric, citric or succinic, benzenesulfonic, para-toluenesulfonic, formic, methanesulfonic.

0030They can also be in the form of solvates, for example a hydrate or a linear or branched alcohol solvate such as ethanol or isopropanol.

0031Mention may be made, as examples of derivatives of formula (I), of the compounds presented below or their addition salts.<ul id="ul0004" list-style="none" compact="compact"><li>4,5-diamino-1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5-methylamino-1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5-dimethylamino-1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (2-hydroxyethyl) amino-1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (pyrrolidin-1-yl) -1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (piperidin-1-yl) -1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li></ul><ul id="ul0005" list-style="none" compact="compact"><li>4,5-diamino-1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5-methylamino-1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5-dimethylamino-1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (2-hydroxyethyl) amino-1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (pyrrolidin-1-yl) -1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>4-amino-5- (piperidin-1-yl) -1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li></ul><ul id="ul0006" list-style="none" compact="compact"><li>4,5-diamino-1,2-diethyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1,2-phenyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1-ethyl-2-methyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-2-ethyl-1-methyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1-phenyl-2-methyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1- (2-hydroxyethyl) -2-methyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-2- (2-hydroxyethyl) -1-methyl-1,2-dihydro-pyrazol-3-one.</li></ul><ul id="ul0007" list-style="none" compact="compact"><li>2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-methylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-dimethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-ethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-isopropylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3- (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3- (2-hydroxypropyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-bis (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3- (3-hydroxy-pyrroiidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3- (piperidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li></ul><ul id="ul0008" list-style="none" compact="compact"><li>2,3-diamino-6-hydroxy-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2,3-diamino-6-methyl-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2,3-diamino-6-dimethyl-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li></ul><ul id="ul0009" list-style="none" compact="compact"><li>2,3-diamino-5,6,7,8-tetrahydro-1H, 6H-pyridazino [1,2-a] pyrazol-1-one</li><li>2,3-diamino-5,8-dihydro-1H, 6H-pyridazino [1,2-a] pyrazol-1-one</li></ul><ul id="ul0010" list-style="none" compact="compact"><li>4-Amino-5-dimethylamino-1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5-ethylamino-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5-isopropylamino-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5- (2-hydroxy-ethylamino) -1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5- (2-dimethylamino-ethylamino) -1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5- [bis- (2-hydroxy-ethyl) -amino] -1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5- (3-imidazol-1 -yl-propylamino) -1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5-dimethylamino-1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5-ethylamino-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5-isopropylamino-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5- (2-hydroxy-ethylamino) -1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5- (2-dimethylamino-ethylamino) -1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5- [bis- (2-hydroxy-ethyl) -amino] -1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5- (3-imidazol-1-yl-propylamino) -1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1.2-diethyl-5- (3-hydroxy-pyrrolidin-1-yl) -1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1.2-diethyl-5-pyrrolidin-1-yl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-5- (3-dimethylamino-pyrrolidin-1-yl) -1,2-diethyl-1,2-dihydro-pyrazol-3-one</li><li>4-Amino-1,2-diethyl-5- (4-methyl-piperazin-1-yl) -pyrazolidin-3-one</li><li>2,3-Diamino-6-hydroxy-6,7-dihydro-5H-pyrazolo [1,2-a] pyrazol-1-one</li></ul> some of which are shown below to illustrate names by chemical structures:<tables id="tabl0001" num="0001"><img file="EP1550656A1_D0002.tif" /></tables><tables id="tabl0002" num="0002"><img file="EP1550656A1_D0003.tif" /></tables><tables id="tabl0003" num="0003"><img file="EP1550656A1_D0004.tif" /></tables>

0032Among these compounds, the diamino-N, N-dihydropyrazolone derivatives of formula (I) or their addition salts, which are particularly preferred, are:<ul id="ul0011" list-style="none" compact="compact"><li>2,3-Diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-Amino-3-ethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-Amino-3-isopropylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-Amino-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>4,5-diamino-1,2-dimethyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1,2-diethyl-1,2-dihydro-pyrazol-3-one.</li><li>4,5-diamino-1,2-di- (2-hydroxyethyl) -1,2-dihydro-pyrazol-3-one.</li><li>2-amino-3- (2-hydroxyethyl) amino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2-amino-3-dimethylamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</li><li>2,3-diamino-5,6,7,8-tetrahydro-1H, 6H-pyridazino [1,2-a] pyrazol-1-one</li></ul>

0033The oxidation base or bases of the invention are generally present each in an amount between 0.001 to 10% by weight approximately of the total weight of the dye composition, preferably between 0.005 and 6%.

0034The dye composition of the invention may contain one or more couplers conventionally used for dyeing keratin fibers. Among these couplers, mention may in particular be made of meta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthalene couplers, heterocyclic couplers and their addition salts.

0035By way of example, mention may be made of 2-methyl 5-aminophenol, 5-N- (β-hydroxyethyl) amino 2-methyl phenol, 6-chloro-2-methyl-5-aminophenol, 3-amino phenol, 1,3-dihydroxy benzene, 1,3-dihydroxy 2-methyl benzene, 4-chloro 1,3-dihydroxy benzene, 2,4-diamino 1- (β-hydroxyethyloxy) benzene, 2- amino 4- (β-hydroxyethylamino) 1-methoxybenzene, 1,3-diamino benzene, 1,3-bis- (2,4-diaminophenoxy) propane, 3-ureido aniline, 3-ureido 1-dimethylamino benzene , sesamol, 1-ß-hydroxyethylamino-3,4-methylenedioxybenzene, α-naphthol, 2 methyl-1-naphthol, 6-hydroxy indole, 4-hydroxy indole, 4-hydroxy N-methyl indole, 2 -amino-3-hydroxy pyridine, 6-hydroxy benzomorpholine 3,5-diamino-2,6-dimethoxypyridine, 1-N- (β-hydroxyethyl) amino-3,4-methylene dioxybenzene, 2,6- bis- (β-hydroxyethylamino) toluene and their addition salts with an acid.

0036In the composition of the present invention, the coupler or couplers are each generally present in an amount of between 0.001 and 10% by weight approximately of the total weight of the dye composition, preferably between 0.005 and 6%.

0037The composition of the present invention may also comprise one or more additional oxidation bases conventionally used in oxidation dyeing other than those described above. By way of example, these additional oxidation bases are chosen from para-phenylenediamines, bis-phenylalkylenediamines, para-aminophenols, bis-para-aminophenols, ortho-aminophenols, ortho-phenylenediamines, heterocyclic bases different from the derivatives of formula (I) as defined above and their addition salts.

0038Among the para-phenylenediamines, there may be mentioned by way of example, para-phenylenediamine, para-toluylenediamine, 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-amino N, N-diethyl 3-methyl aniline, N, N-bis- (β-hydroxyethyl) para-phenylenediamine, 4-N, N-bis- (β-hydroxyethyl) amino 2-methyl aniline, 4-N, N-bis- (β-hydroxyethyl) amino 2-chloro aniline, 2-β-hydroxyethyl para-phenylenediamine, 2-fluoro para-phenylenediamine, 2-isopropyl para-phenylenediamine, N- (β-hydroxypropyl) para-phenylenediamine, 2-hydroxymethyl para- phenylenediamine, N, N-dimethyl 3-methyl para-phenylenediamine, N, N- (ethyl, β-hydroxyethyl) para-phenylenediamine, N- (β, γ-dihydroxypropyl) para-phenylenediamine, N- (4'-aminophenyl) para-phenylenediamine, N-phenyl para-phenylenediamine, 2-β-hydroxyethyloxy para-phenylenediamine, 2-β- acetylaminoethyloxy para-phenylenediamine, N- (β-methoxyethyl) para-phenylenediamine, 4-aminophenylpyrrolidine, 2-thienyl para-phenylenediamine, 2-β hydroxyethylamino 5-amino toluene, 3-hydroxy 1- (4'- aminophenyl) pyrrolidine and their acid addition salts.

0039Among the para-phenylenediamines mentioned above, para-phenylenediamine, para-toluylenediamine, 2-isopropyl para-phenylenediamine, 2-β-hydroxyethyl para-phenylenediamine, 2-β-hydroxyethyloxy para-phenylenediamine, 2 , 6-dimethyl para-phenylenediamine, 2,6-diethyl para-phenylenediamine, 2,3-dimethyl para-phenylenediamine, N, N-bis- (β-hydroxyethyl) para-phenylenediamine, 2-chloro para- phenylenediamine, 2-β-acetylaminoethyloxy para-phenylenediamine, and their addition salts with an acid are particularly preferred.

0040Among the bis-phenylalkylenediamines, there may be mentioned by way of example, N, N'-bis- (β-hydroxyethyl) N, N'-bis- (4'-aminophenyl) 1,3-diamino propanol, N , N'-bis- (β-hydroxyethyl) N, N'-bis- (4'-aminophenyl) ethylenediamine, N, N'-bis- (4-aminophenyl) tetramethylenediamine, N, N'-bis- ( β-hydroxyethyl) N, N'-bis- (4-aminophenyl) tetramethylenediamine, N, N'-bis- (4-methyl-aminophenyl) tetramethylenediamine, N, N'-bis- (ethyl) N, N ' -bis- (4'-amino, 3'-methylphenyl) ethylenediamine, 1,8-bis- (2,5-diamino phenoxy) -3,6-dioxaoctane, and their addition salts with an acid.

0041Among the para-aminophenols, there may be mentioned by way of example, para-aminophenol, 4-amino 3-methyl phenol, 4-amino 3-fluoro phenol, 4-amino 3-hydroxymethyl phenol, 4- amino 2-methyl phenol, 4-amino 2-hydroxymethyl phenol, 4-amino 2-methoxymethyl phenol, 4-amino 2-aminomethyl phenol, 4-amino 2- (β-hydroxyethyl aminomethyl) phenol, 4- amino 2-fluoro phenol, and their addition salts with an acid.

0042Among the ortho-aminophenols, there may be mentioned by way of example, 2-amino phenol, 2-amino 5-methyl phenol, 2-amino 6-methyl phenol, 5-acetamido 2-amino phenol, and their addition salts with an acid.

0043Mention may be made, among heterocyclic bases, by way of example, of pyridine derivatives, pyrimidine derivatives and pyrazole derivatives.

0044Among the pyridine derivatives, mention may be made of the compounds described for example in patents GB 1 026 978 and GB 1 153 196, such as 2,5-diamino pyridine, 2- (4-methoxyphenyl) amino 3-amino pyridine, 2,3-diamino 6-methoxy pyridine, 2- (β-methoxyethyl) amino 3-amino 6-methoxy pyridine, 3,4-diamino pyridine, and their addition salts with an acid.

0045Other pyridine oxidation bases useful in the present invention are the 3-amino pyrazolo- [1,5-a] -pyridine oxidation bases or their addition salts described for example in patent application FR 2 801 308. By way of example, mention may be made of pyrazolo [1,5-a] pyridin-3-ylamine; 2-acetylamino pyrazolo- [1,5-a] pyridin-3-ylamine; 2-morpholin-4-yl-pyrazolo [1,5-a] pyridin-3-ylamine; 3-amino-pyrazolo [1,5-a] pyridin-2-carboxylic acid; 2-methoxy-pyrazolo [1,5-a] pyridine-3-ylamino; (3-amino-pyrazolo [1,5-a] pyridine-7-yl) -methanol; 2- (3-amino-pyrazolo [1,5-a] pyridine-5-yl) -ethanol; 2- (3-amino-pyrazolo [1,5-a] pyridine-7-yl) -ethanol; (3-amino-pyrazolo [1,5-a] pyridine-2-yl) -methanol; 3,6-diamino-pyrazolo [1,5-a] pyridine; 3,4-diamino-pyrazolo [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] pyridine-5-ol; 3-amino-pyrazolo [1,5-a] pyridine-4-ol; 3-amino-pyrazolo [1,5-a] pyridine-6-ol; 3-amino-pyrazolo [1,5-a] pyridine-7-ol; as well as their addition with an acid or with a base.

0046Among the pyrimidine derivatives, mention may be made of the compounds described for example in patents DE 23 59 399; JP 88-169571; JP 05-63124; EP 0 770 375 or patent application WO 96/15765 such as 2,4,5,6-tetra-aminopyrimidine, 4-hydroxy 2,5,6-triaminopyrimidine, 2-hydroxy 4,5,6-triaminopyrimidine, 2,4-dihydroxy 5,6-diaminopyrimidine, 2,5,6-triaminopyrimidine, and pyrazolo-pyrimidine derivatives such as those mentioned in patent application FR-A-2 750 048 and among which may be mentioned pyrazolo - [1,5-a] -pyrimidine-3,7-diamine; 2,5-dimethyl pyrazol o- [1,5-a] -pyrimidine-3,7-diamine; pyrazolo- [1,5-a] -pyrimidine-3,5-diamine; 2,7-dimethyl pyrazolo- [1,5-a] -pyrimidine-3,5-diamine; 3-amino pyrazolo- [1,5-a] -pyrimidin-7-ol; 3-amino pyrazolo- [1,5-a] -pyrimidin-5-ol; 2- (3-amino pyrazolo- [1,5-a] -pyrimidin-7-ylamino) -ethanol, 2- (7-amino pyrazolo- [1,5-a] -pyrimidin-3-ylamino) - ethanol, 2 - [(3-amino-pyrazolo [1,5-a] pyrimidin-7-yl) - (2-hydroxy-ethyl) -amino] -ethanol, 2 - [(7-amino-pyrazolo (1,5- a] pyrimidin-3-yl) - (2-hydroxy-ethyl) -amino] -ethanol, 5,6-dimethyl pyrazolo- [1,5-a] -pyrimidine-3,7-diamine, 2,6-dimethyl pyrazolo- [1,5-a] -pyrimidine-3,7-diamine, 2, 5, N 7, N 7-tetramethyl pyrazolo- [1,5-a] -pyrimidine-3, 7-diamine, 3-amino-5-methyl-7-imidazolylpropylamino pyrazolo- [1,5-a] -pyrimidine and their acid addition salts and their tautomeric forms, when there is a tautomeric equilibrium.

0047Among the pyrazole derivatives, mention may be made of 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 as 4,5-diamino 1-methyl pyrazole, 4,5-diamino 1- (β-hydroxyethyl) pyrazole, 3,4-diamino pyrazole, 4,5-diamino 1- (4'-chlorobenzyl) pyrazole, 4,5-diamino 1,3-dimethyl pyrazole, 4,5-diamino 3-methyl 1-phenyl pyrazole, 4,5-diamino 1-methyl 3-phenyl pyrazole, 4-amino 1,3-dimethyl 5-hydrazino pyrazole, 1-benzyl 4,5-diamino 3-methyl pyrazole, 4,5-diamino 3-tert-butyl 1-methyl pyrazole, 4,5-diamino 1-tert-butyl 3-methyl pyrazole, 4,5-diamino 1- (β-hydroxyethyl) 3-methyl pyrazole, 4,5-diamino 1-ethyl 3-methyl pyrazole, 4,5-diamino 1- ethyl 3- (4'-methoxyphenyl) pyrazole, 4,5-diamino 1-ethyl 3-hydroxymethyl pyrazole, 4,5-diamino 3-hydroxymethyl 1-methyl pyrazole, 4,5-diamino 3-hydroxymethyl 1- isopropyl pyrazole, 4,5-diamino 3-methyl 1-isopropyl pyrazole, 4-amino 5- (2'-aminoethyl) amino 1,3-dimethyl pyrazole, 3,4,5-triamino pyrazole, 1-methyl 3, 4,5-triamino pyrazole, 3,5-diamino 1-methyl 4-methylamino pyrazole, 3,5-diamino 4- (β-hydroxyethyl) amino 1-methyl pyrazole, and their addition salts with an acid.

0048The oxidation base (s) present in the composition of the invention are generally present each in an amount between 0.001 to 10% by weight approximately of the total weight of the dye composition, preferably between 0.005 and 6%.

0049In general, the addition salts of the oxidation bases and of the couplers which can be used in the context of the invention are in particular chosen from addition salts with an acid such as hydrochlorides, hydrobromides, sulfates, citrates, succinates, tartrates, lactates, tosylates, benzenesulfonates, phosphates and acetates and addition salts with a base such as soda, potash, ammonia, amines or alkanolamines.

0050The dye composition in accordance with the invention may also contain one or more direct dyes which can in particular be chosen from nitro dyes of the benzene series, azo direct dyes, methine direct dyes. These direct dyes can be of nonionic, anionic or cationic nature.

0051The medium suitable for dyeing, also called dye support, is a cosmetic medium generally consisting of water or of a mixture of water and at least one organic solvent to dissolve the compounds which would not be sufficiently soluble in it. water. As organic solvent, mention may, for example, be made of lower C alkanols.₁-VS₄, such as ethanol and isopropanol; polyols and polyol ethers such as 2-butoxyethanol, propylene glycol, propylene glycol monomethyl ether, monoethyl ether and diethylene glycol monomethyl ether, as well as aromatic alcohols such as benzyl alcohol or phenoxyethanol, and mixtures thereof.

0052The solvents are preferably present in proportions preferably of between 1 and 40% by weight approximately relative to the total weight of the dye composition, and even more preferably between 5 and 30% by weight approximately.

0053The dye composition in accordance with the invention may also contain various adjuvants conventionally used in compositions for dyeing the hair, such as anionic, cationic, nonionic, amphoteric, zwitterionic surfactants or their mixtures, anionic polymers, cationic, non-ionic, amphoteric, zwitterionic or their mixtures, mineral or organic thickening agents, and in particular associative thickeners, anionic, cationic, nonionic and amphoteric polymers, antioxidants, penetration agents, sequestering agents, perfumes, buffers, dispersing agents, conditioning agents such as for example volatile silicones or non-volatile, modified or unmodified, film-forming agents, ceramides, preserving agents, opacifying agents.

0054The above adjuvants are generally present in an amount for each of them of between 0.01 and 20% by weight relative to the weight of the dye composition.

0055Of course, those skilled in the art will take care to choose this or these optional complementary compounds in such a way that the advantageous properties intrinsically attached to the oxidation dye composition according to the invention are not, or not substantially, altered. by the addition (s) envisaged.

0056The pH of the dye composition in accordance with the invention is generally between 3 and 12 approximately, and preferably between 5 and 11 approximately. It can be adjusted to the desired value by means of acidifying or basifying agents usually used in dyeing keratin fibers or even using conventional buffer systems.

0057Among the acidifying agents, there may be mentioned, by way of example, mineral 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.

0058Among the basifying agents, there may be mentioned, by way of example, ammonia, alkali carbonates, alkanolamines such as mono-, di- and triethanolamines as well as their derivatives, sodium or potassium hydroxides and compounds of formula (II) below:<chemistry id="chem0002" num="0002"><img file="EP1550656A1_D0005.tif" /></chemistry> in which W is a propylene residue optionally substituted by a hydroxyl group or a C 1 alkyl radical₁-VS₄ ; R_at, R_b, R_vs and R_d, identical or different, represent a hydrogen atom, a C 1 alkyl radical₁-VS₄ or C hydroxyalkyl₁-VS₄.

0059The dye composition according to the invention can be in various forms, such as in the form of liquids, creams, gels, or in any other form suitable for dyeing keratin fibers, and in particular human hair.

0060The process of the present invention is a process in which the composition according to the present invention as defined above is applied to the fibers, and the color is revealed using an oxidizing agent. The color can be revealed at acidic, neutral or alkaline pH and the oxidizing agent can be added to the composition of the invention just at the time of use or it can be used from an oxidizing composition containing it , applied simultaneously or sequentially to the composition of the invention.

0061According to a particular embodiment, the composition according to the present invention is mixed, preferably at the time of use, with a composition containing, in a medium suitable for dyeing, at least one oxidizing agent, this oxidizing agent being present in enough to develop color. The mixture obtained is then applied to the keratin fibers. After an exposure time of 3 to 50 minutes approximately, preferably 5 to 30 minutes approximately, the keratin fibers are rinsed, washed with shampoo, rinsed again and then dried.

0062The oxidizing agents conventionally used for the oxidation dyeing of keratin fibers are for example hydrogen peroxide, urea peroxide, alkali metal bromates, persalts such as perborates and persulfates, peracids and oxidase enzymes among which there may be mentioned peroxidases, 2-electron oxidoreductases such as uricases and 4-electron oxygenases such as laccases. Hydrogen peroxide is particularly preferred.

0063The oxidizing composition may also contain various adjuvants conventionally used in compositions for dyeing the hair and as defined above.

0064The pH of the oxidizing composition containing the oxidizing agent is such that after mixing with the dye composition, the pH of the resulting composition applied to the keratin fibers preferably varies between 3 and 12 approximately, and even more preferably between 5 and 11 It can be adjusted to the desired value by means of acidifying or basifying agents usually used in dyeing keratin fibers and as defined above.

0065The ready-to-use composition which is finally applied to the keratin fibers can be in various forms, such as in the form of liquids, creams, gels or in any other form suitable for dyeing keratin fibers, and especially human hair.

0066The invention also relates to a device with several compartments or "kit" for dyeing in which a first compartment contains the dye composition of the present invention defined above and a second compartment contains an oxidizing composition. This device can be equipped with a means enabling the desired mixture to be delivered to the hair, such as the devices described in patent FR-2,586,913 in the name of the applicant.

0067From this device, it is possible to dye the keratin fibers using a process which comprises mixing a dye composition comprising at least one oxidation base of formula (I) with an oxidizing agent, and the application of the mixture obtained on the keratin fibers for a time sufficient to develop the desired coloration.

0068A subject of the present invention is also the use for the oxidation dyeing of keratin fibers, and in particular human keratin fibers such as the hair, of a diamino-N, N-dihydropyrazolone derivative of formula (I) or one of its addition salts as defined above.

0069Another object of the present invention also constitutes the amino-N, N-dihydro-pyrazolone derivatives of formula (I ') below, and their addition salts:<chemistry id="chem0003" num="0003"><img file="EP1550656A1_D0006.tif" /></chemistry> formula in which:<ul id="ul0012" list-style="none" compact="compact"><li>R '₁, R '₂, R '₃ and R '₄ respectively have the same meanings as R₁, R₂, R₃ and R₄, provided that<ul id="ul0013" list-style="bullet" compact="compact"><li>R '₁ and R '₂ do not simultaneously represent a methyl radical when R '₃ and R '₄ represent a hydrogen atom and</li><li>R '₁₃ does not represent a group Ar-N = N- when R '₃ and R '₄ simultaneously represent a hydrogen atom.</li></ul></li><li>R '₁₃ represents a nitro, nitroso or arylazo group Ar-N = N-, the aryl radical Ar being optionally substituted by a C alkyl radical₁-VS₄, amino, (di) alkyl (C₁-VS₄) amino, C alkoxy₁-VS₂, sulfonic, carboxy, halogen.</li></ul>

0070All that has been said previously about the preferred definitions of the radicals 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.

0071Another object of the present invention also consists of the diamino-N, N-dihydro-pyrazolone derivatives of formula (I ") below, and their addition salts:<chemistry id="chem0004" num="0004"><img file="EP1550656A1_D0007.tif" /></chemistry>    formula in which R ''₁, R ''₂, R ''₃ and R ''₄ have the same meanings as those indicated previously in the text for R '₁, R '₂, R '₃, R '₄.

0072Here again, all that has been indicated previously concerning the preferred definitions of the radicals R '₁, R '₂, R '₃ and R '₄, is valid for R ''₁, R ''₂, R ''₃ and R ''₄ and will not be repeated in this part of the text.

0073The amino-N, N-dihydropyrazolone and diamino-N, N-dihydropyrazolone derivatives in accordance with the invention and in which the radicals R ′₃ and R '₄ on the one hand and R ''₃ and R ''₄ on the other hand represent a hydrogen atom can be obtained from intermediates and synthetic routes described in the literature and in particular 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 US4128425 and US 2841584 and the references cited.

0074According to these references, the compounds of formula (I) having the radicals R₃ and R₄ equal to hydrogen atoms can be obtained from the synthetic route shown in scheme A below:<chemistry id="chem0005" num="0005"><img file="EP1550656A1_D0008.tif" /></chemistry>

0075The compounds according to the invention and in which the radicals R₁ and R₂ simultaneously represent a methyl group and the radicals R₃ and R₄ hydrogen atoms can be obtained by taking inspiration from the method described in Justus Lieb.Ann.Chem., 686, 134 (1965) (diagram B):<chemistry id="chem0006" num="0006"><img file="EP1550656A1_D0009.tif" /></chemistry>

0076The compounds according to the invention and whose radical R₁ represents a methyl group, R₂ a phenyl radical, and the radicals R₃ and R₄ hydrogen atoms can be obtained by taking inspiration from the method described in, J. Org.Chem., 23, 2029 (1958), J.Am.Chem.Soc., 73, 3240 (1951) (diagram C ):<chemistry id="chem0007" num="0007"><img file="EP1550656A1_D0010.tif" /></chemistry>

0077The compounds according to the invention and in which the radicals R₁ and R₂ together form a 5-membered ring with radicals R₃ and R₄ represent hydrogen atoms can be obtained by taking inspiration from the method described in J. Het. Chem., 2001, 38 (3), 613-616 (diagram D):<chemistry id="chem0008" num="0008"><img file="EP1550656A1_D0011.tif" /></chemistry>

0078According to a new process, the compounds of formula (I) can be obtained according to the synthesis illustrated in scheme E:<chemistry id="chem0009" num="0009"><img file="EP1550656A1_D0012.tif" /></chemistry>

0079According to this new method, the following steps are implemented:<ul id="ul0014" list-style="none" compact="compact"><li>a) step 1: reacting a compound <b><u>at</u></b><maths id="math0001" num=""><math display="block"><mrow><msub><mrow><mtext mathvariant="bold">R</mtext></mrow><mrow><mtext mathvariant="bold">1</mtext></mrow></msub><msub><mrow><mtext mathvariant="bold">HN-NHR</mtext></mrow><mrow><mtext mathvariant="bold">2</mtext></mrow></msub><mspace linebreak="newline" /><munder accentunder="true"><mrow><mtext mathvariant="bold">at</mtext></mrow><mo>̲</mo></munder></mrow></math><img file="EP1550656A1_D0013.tif" /></maths>with a compound <b><u>b</u></b> : <chemistry id="chem0010" num="0010"><img file="EP1550656A1_D0014.tif" /></chemistry> to obtain a 5-amino-1,2-dihydro-pyrazol-3-one compound <b><u>vs</u></b> : <chemistry id="chem0011" num="0011"><img file="EP1550656A1_D0015.tif" /></chemistry></li><li>b) step 2: the derivative is reacted <b><u>vs</u></b> thus obtained an aryldiazonium salt (Ar-NH₂, NaNO₂, H⁺) to obtain an azo compound <b><u>f</u></b> : <chemistry id="chem0012" num="0012"><img file="EP1550656A1_D0016.tif" /></chemistry></li><li>c) step 3: optionally a step of functionalization of the primary amine group of the resulting azo compound is carried out <b><u>f</u></b> to get a compound <b><u>g</u></b> following :<chemistry id="chem0013" num="0013"><img file="EP1550656A1_D0017.tif" /></chemistry></li><li>d) step 4: a reduction reaction of the azo compound is carried out <b><u>f</u></b> or <b>g</b> to obtain, respectively, a compound <b><u>e</u></b> or <b><u>h</u></b> amine:<chemistry id="chem0014" num="0014"><img file="EP1550656A1_D0018.tif" /></chemistry></li></ul>

0080The possible stage of functionalization of the primary amine group in position 5 into secondary and tertiary amine NR₃R₄, to get the compounds <b><u>g,</u></b> is carried out according to conventional organic synthesis methods (alkyl halide, alkyl O-sulfonate, alkyl trialkylammonium, reductive amination, etc ... see for example <i>Advanced Organic Chemistry, 3</i>^<i>th</i><i> editing,</i> 1985 , <i>J. March, Willey Interscience).</i>

0081The reduction of the azo group leads to the compounds <b><u>e</u></b> and <b><u>h</u></b> according to the invention. The reduction step is carried out in a conventional manner, for example by carrying out a hydrogenation reaction by heterogeneous catalysis in the presence of Pd / C, Pd (II) / C, Ni / Ra, etc. <u>or</u> again by carrying out a reduction reaction with a metal, for example with zinc, iron, tin, etc. (see Advanced Organic Chemistry, 3^th edition, J. March, 1985, Willey Interscience and Reduction in organic Chemistry, M. Hudlicky, 1983, Ellis Horwood Chemical Science Series).

0082According to a new process, the 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] -pyrazol-1-one and 2,3-diamino-5,6,7 derivatives, 8-tetrahydro-1H, 6H-pyridazino [1,2-a] -pyrazol-1-one in accordance with formula (I) are obtained according to the synthesis illustrated by scheme F:<chemistry id="chem0015" num="0015"><img file="EP1550656A1_D0019.tif" /></chemistry>

0083According to this method, the following steps are implemented:<ul id="ul0015" list-style="none"><li>a) step 1: reacting a compound <b><u>a1</u></b> following :<chemistry id="chem0016" num="0016"><img file="EP1550656A1_D0020.tif" /></chemistry> with a compound <b><u>a2</u></b> : <chemistry id="chem0017" num="0017"><img file="EP1550656A1_D0021.tif" /></chemistry> to get a compound <b><u>a3:</u></b><chemistry id="chem0018" num="0018"><img file="EP1550656A1_D0022.tif" /></chemistry> in which :<ul id="ul0016" list-style="none" compact="compact"><li>the radical R₁₀ represents a hydrogen atom, a carboxy; a carboxamido; a C 1 alkyl radical₁-VS₄ optionally substituted by one or more hydroxy, amino, (di) -alkylamino, alkoxy, carboxy, sulfonyl radicals;</li><li>the radicals R₁₁ and R₁₂ independently represent hydrogen atoms, halogen atoms; amino radicals; (di) alkyl (C₁-VS₄) amino; hydroxy; carboxy; carboxamido; (VS₁-VS₂) alkoxy; C 1 alkyl radical₁-VS₄ optionally substituted by one or more hydroxy, amino, (di) -alkylamino, alkoxy, carboxy, sulfonyl radicals;</li><li>X represents a halogen atom or an alkyl sulfonate.</li><li>r is an integer between 1 and 3;</li></ul></li><li>b) step 2: the compound is reacted <b><u>a3</u></b> with an amine of formula NHR₃R₄ to get a compound <b><u>a4</u> :</b><chemistry id="chem0019" num="0019"><img file="EP1550656A1_D0023.tif" /></chemistry></li><li>c) step 3: the compound is reacted <b><u>a4</u></b> with at least one alkylsulfonyl, arylsulfonyl or perfluoroalkylsulfonyl halide RO₂SX₁ (R represents an alkyl, an aryl or a perfluoroalkyl, X₁ represents a halogen), in a solvent with a boiling point between 60 ° C and 190 ° C to obtain a compound <b><u>at 5</u></b> : <chemistry id="chem0020" num="0020"><img file="EP1550656A1_D0024.tif" /></chemistry></li><li>d) step 4: the compound <b>at 5</b> resulting is then heated in a solvent with a boiling point between 60 ° C and 190 ° C to obtain a compound <b><u>a6</u> :</b><chemistry id="chem0021" num="0021"><img file="EP1550656A1_D0025.tif" /></chemistry></li><li>e) step 5: The compound <b><u>a6</u></b> obtained is reduced to obtain the compound <b><u>a7</u></b> of formula below (III):<chemistry id="chem0022" num="0022"><img file="EP1550656A1_D0026.tif" /></chemistry></li></ul>

0084More particularly, according to this process, 3,5-dibromo-4-nitropyrazole <b><u>a1,</u></b> obtained for example according to the method described in DE 4234885, reacts with the reagent <b>a2,</b> preferably in a solvent with a boiling point between 60 ° C and 190 ° C. By way of example, mention may be made of pentanol, dimethylformamide, N-methylpyrrolidine. 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 advantageously maintained between 60 ° C and 160 ° C, preferably between 80 ° C and 120 ° C.

00851-hydroxyalkyl-3,5-dibromo-4-nitropyrazole <b><u>a3</u></b> is preferably isolated by precipitation or crystallization after adding ice to the reaction medium.

0086In step 2, the derivative <b><u>a3</u></b> is reacted with an NHR amine₃R₄, preferably in a solvent with a boiling point 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 consumption of the reagents, the compound 5-amino-4-nitro-3-bromo-1-hydroxyalkylpyrazole<b><u>a4</u></b> is isolated by precipitation or crystallization using water.

0087In accordance with step 3, the derivative <b><u>at 5</u></b> is obtained by alcohol reaction <b><u>a4</u></b> and an alkylsulfonyl, arylsulfonyl or perfluoroalkylsulfonyl halide. The reaction preferably takes place in an aprotic solvent such as for example tetrahydrofuran, dioxane. The reaction advantageously takes place at a temperature between -20 ° C and 60 ° C, preferably between 0 ° C and 25 ° C. In addition, this step takes place in the presence of an organic or mineral base such as, for example, potassium carbonate, triethylamine, N-methylmorpholine. After disappearance of the reagents, the compound <b><u>at 5</u></b> is isolated by precipitation or crystallization from water.

0088Sulfonate <b><u>at 5</u></b> obtained at the end of stage 3 is put, in stage 4, in solution or in dispersion in a solvent of boiling point ranging between 60 ° C and 190 ° C, preferably between 90 ° C and 140 ° C. The temperature of the reaction medium is then brought between 90 ° C and 140 ° C, preferably between 105 ° C and 125 ° C until total consumption of the sulfonate<b><u>at 5</u>.</b> After returning to ambient temperature, the compound perhydro-pyrazolo [1,2-a] pyrazol-1-one (r = 1), perhydro-pyridazino [1,2-a] pyrazol-1-one (r = 2) or perhydro-diazepino [1,2-a] pyrazolone (r = 3) <b><u>a6</u></b> crystallizes and is isolated by conventional methods of organic synthesis.

0089The final compound <b><u>a7</u></b> according to the invention is obtained, in a step 5 by reduction of the nitro derivative <b><u>a6,</u></b> the reduction methods used being for example a hydrogenation by heterogeneous catalysis in the presence of Pd / C, Pd (II) / C, Ni / Ra, etc ... or also such a reduction reaction with a metal, for example with zinc, iron, tin, etc., (see Advanced Organic Chemistry, 3^th edition, J. March, 1985, Willey Interscience and Reduction in organic Chemistry, M. Hudlicky, 1983, Ellis Horwood Chemical Science Series).

0090The examples which follow serve to illustrate the invention without, however, being limiting in nature.

EXAMPLES

<u>EXAMPLE 1 Synthesis of 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 5 dihydrochloride</u>

0091<chemistry id="chem0023" num="0023"><img file="EP1550656A1_D0027.tif" /></chemistry>

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

<u>1</u>

00920.369 mole of sodium acetate is introduced into a solution of 0.184 mole of dibromonitropyrazole in 250 ml of N-methyl pyrrolidone in a 500 ml three-necked flask and the reaction medium is brought to 80 ° C.

0093At this temperature, 0.369 mole of 3-bromo propanol is added dropwise. This temperature is maintained for 5 hours. After cooling to room temperature, the medium is poured onto ice with stirring. 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol 1 precipitates. It is drained, dried and obtained with a yield of 75%.

0094The mass of the expected compound C₆H₇Br₂NOT₃O₃ is detected by mass spectrometry.

0095NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

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

<u>2</u>

00960.135 mole of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol is dispersed in a 500 ml three-necked flask containing 150 ml of ethanol <b>1</b>, heats to 60 ° C, then adds 0.825 mole of benzylamine in 30 minutes.

0097After 6 hours at 60 ° C, the reaction medium is cooled to room temperature. 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propan-1-ol <b>2</b> is precipitated by pouring the reaction medium onto 1 liter of ice with stirring. After spinning and drying under vacuum in the presence of P₂O₅, the compound <b>2</b> is isolated with a yield of 90%. NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure. <tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="6" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="26.25mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="26.25mm" /><colspec colnum="3" colname="col3" colwidth="26.25mm" /><colspec colnum="4" colname="col4" colwidth="26.25mm" /><colspec colnum="5" colname="col5" colwidth="26.25mm" /><colspec colnum="6" colname="col6" colwidth="26.25mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col6" align="left">Elementary analysis:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">theoretical</entry><entry namest="col2" nameend="col2" align="left">C43.96</entry><entry namest="col3" nameend="col3" align="left">H4.26</entry><entry namest="col4" nameend="col4" align="left">N15.77</entry><entry namest="col5" nameend="col5" align="left">O13.51</entry><entry namest="col6" nameend="col6" align="left">Br22.50</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">measured</entry><entry namest="col2" nameend="col2" align="left">C44.09</entry><entry namest="col3" nameend="col3" align="left">H4.22</entry><entry namest="col4" nameend="col4" align="left">N15.44</entry><entry namest="col5" nameend="col5" align="left">O14.37</entry><entry namest="col6" nameend="col6" align="left">Br21.50</entry></row></tbody></tgroup></table></tables>

-Step 3: synthesis of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propyl methanesulfonate <b>3</b>

00980.126 mol of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propan-1- are introduced into a 500 ml three-necked flask containing 200 ml of THF ol <b>2</b> and 15.82 ml of triethylamine. The mixture obtained is then cooled to 5 ° C. and 0.126 mole of mesyl chloride is poured in 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 <b>3</b> is precipitated by pouring the reaction medium onto 800 ml of ice.

0099After filtration, the solid is washed thoroughly with water and with diisopropyl ether. Drying is carried out under vacuum in the presence of P₂O₅. The yield of this stage is 94%

0100The mass of the expected compound C₁₄H₁₇BrN₄O₅S is detected by mass spectrometry.

0101NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure. <tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="7" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="22.50mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="22.50mm" /><colspec colnum="3" colname="col3" colwidth="22.50mm" /><colspec colnum="4" colname="col4" colwidth="22.50mm" /><colspec colnum="5" colname="col5" colwidth="22.50mm" /><colspec colnum="6" colname="col6" colwidth="22.50mm" /><colspec colnum="7" colname="col7" colwidth="22.50mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col7" align="left">Elementary analysis:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Theory</entry><entry namest="col2" nameend="col2" align="left">C38.81</entry><entry namest="col3" nameend="col3" align="left">H3.96</entry><entry namest="col4" nameend="col4" align="left">N12.93</entry><entry namest="col5" nameend="col5" align="left">018.46</entry><entry namest="col6" nameend="col6" align="left">S7.40</entry><entry namest="col7" nameend="col7" align="left">Br18.44</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Measured</entry><entry namest="col2" nameend="col2" align="left">C39.03</entry><entry namest="col3" nameend="col3" align="left">H3.91</entry><entry namest="col4" nameend="col4" align="left">N12.83</entry><entry namest="col5" nameend="col5" align="left">018.52</entry><entry namest="col6" nameend="col6" align="left">S7.29</entry><entry namest="col7" nameend="col7" align="left">Br18.26</entry></row></tbody></tgroup></table></tables>

-Step4: synthesis of 3- (benzylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

<u>4</u>

01020.1 mol of 3- [5- (benzylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propyl methanesulfonate is dispersed with stirring in a 500 ml three-necked flask containing 300 ml of pentanol <b>3</b> and brings the reaction medium to 130 ° C for 2 hours.

0103After cooling to room temperature, the solid formed is drained on a frit, washed with diisopropyl ether and dried under vacuum in the presence of P₂O₅, 3- (Benzylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1- one <b>4</b> is obtained with a yield of 86%. NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure. The mass of the expected compound C₆H₁₁NOT₄O is detected by mass spectrometry. <tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="5" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="31.50mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col5" align="left">Elementary analysis:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Theory</entry><entry namest="col2" nameend="col2" align="left">C56.72</entry><entry namest="col3" nameend="col3" align="left">H5.49</entry><entry namest="col4" nameend="col4" align="left">N20.36</entry><entry namest="col5" nameend="col5" align="left">O17.44</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Measured</entry><entry namest="col2" nameend="col2" align="left">C56.68</entry><entry namest="col3" nameend="col3" align="left">H5.13</entry><entry namest="col4" nameend="col4" align="left">N20.38</entry><entry namest="col5" nameend="col5" align="left">O17.69</entry></row></tbody></tgroup></table></tables>

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

<u>5</u>

010420 g of 3- (benzylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1- are introduced into a 1 liter autoclave containing 800 ml of ethanol one <b>4</b> and 4g of 5% palladium on charcoal. The reduction is then carried out under a hydrogen pressure of 8 bars and at a temperature between 50 ° C and 100 ° C (stirring between 1000 and 2500 rpm)

0105After 4 hours of reaction, it no longer consumes hydrogen and the medium is cooled to 20 ° C.

0106The catalyst is removed under nitrogen by filtration, then hydrochloric ethanol is added to the filtrate. The crystallized product is drained, washed with diisopropyl ether, then dried under vacuum in the presence of P₂O₅. 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride<b>5</b> is obtained with a yield of 89%. The mass of the expected compound is detected by mass spectrometry. NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure. <tables id="tabl0007" num="0007"><table frame="all"><tgroup cols="6" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="26.25mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="26.25mm" /><colspec colnum="3" colname="col3" colwidth="26.25mm" /><colspec colnum="4" colname="col4" colwidth="26.25mm" /><colspec colnum="5" colname="col5" colwidth="26.25mm" /><colspec colnum="6" colname="col6" colwidth="26.25mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col6" align="left">Elementary analysis:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Theoretical</entry><entry namest="col2" nameend="col2" align="left">C31.73</entry><entry namest="col3" nameend="col3" align="left">H5.33</entry><entry namest="col4" nameend="col4" align="left">N24.67</entry><entry namest="col5" nameend="col5" align="left">07.07</entry><entry namest="col6" nameend="col6" align="left">Cl31.22</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Measured</entry><entry namest="col2" nameend="col2" align="left">C31.45</entry><entry namest="col3" nameend="col3" align="left">H5.20</entry><entry namest="col4" nameend="col4" align="left">N24.62</entry><entry namest="col5" nameend="col5" align="left">07.24</entry><entry namest="col6" nameend="col6" align="left">Cl30.86</entry></row></tbody></tgroup></table></tables>

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

0107<chemistry id="chem0024" num="0024"><img file="EP1550656A1_D0028.tif" /></chemistry>

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

<u>6</u>

010815 mmol of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol in 30 ml of ethanol are introduced into a three-necked flask, with stirring. The homogeneous medium is heated to 75 ° C. then 93 mmol of ethylamine are added dropwise and the stirring is continued for four hours.

0109After cooling to room temperature, the medium is poured onto ice and 3- [3-bromo-5- (ethylamino) -4-nitro-1H-pyrazol-1-yl] propan-1-ol <b>6</b> precipitate.

0110The yellow solid is drained, then washed abundantly with water and with diisopropyl ether. Drying is carried out under vacuum in the presence of P₂O₅. The mass recovered is 3.6 g.

0111NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0112The 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] propyl methanesulfonate

<u>7</u>

011311.2 mmol of 3- [3-bromo-5- (ethylamino) -4-nitro-1H-pyrazol-1-yl] propan-1-ol are introduced into a 100 ml three-necked flask containing 30 ml of THF. <b>6</b> and 1.6 ml of triethylamine. The homogeneous orange mixture obtained is cooled to 0 ° C. and 1.44 ml of mesyl chloride are poured in 20 minutes.

0114The reaction medium is maintained at this temperature for 2 hours then 3- [5- (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate <b>7</b> is precipitated by pouring the reaction medium onto 500 ml of ice.

0115The yellow solid is drained, then washed abundantly with water and with diisopropyl ether; drying is carried out under vacuum in the presence of P₂O₅. The mass recovered is 3.1 g.

0116NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0117The mass of the expected compound C₉H₁₅BrN₄O₅S is detected by mass spectrometry.

-Step 4: synthesis of 3- (ethylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-alpyrazol-1-one

<u>8</u>

01188 mmol of 3- [5- (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propyl methanesulfonate are dispersed with stirring in a 50 ml three-necked flask containing 20 ml of pentanol <b>7</b>, and brings the reaction medium to 130 ° C for 2 hours. After cooling to room temperature, the solid formed is drained, then washed with diisopropyl ether.

0119After drying under vacuum 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 are obtained <b>8.</b>

0120NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0121The mass of the expected compound is detected by mass spectrometry.

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

<u>9</u>

01221.45 g of 3- (ethylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1- are introduced into a 300 ml autoclave containing 200 ml of ethanol. one <b>8</b> and 300 mg of 5% palladium on charcoal. The reduction is carried out under a hydrogen pressure of 8 bars at a temperature of 60 ° C (stirring at 1700 rpm). After 2 hours of reaction, there is no more consumption of hydrogen and the medium is cooled to 20 ° C.

0123The catalyst is removed by filtration under nitrogen and the filtrate is diluted with 100 ml of hydrochloric isopropyl ether.

0124The pale yellow solution is evaporated to dryness then the solid is taken up with an ethanol / isopropyl ether mixture. 2-amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride<b>9</b> precipitate; it is drained and after drying under vacuum in the presence of P₂O₅, 1.18 g of 2-amino-3- (ethylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride are recovered <b>9.</b>NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure. The mass of the expected compound C₈H₁₄NOT₄O is detected by mass spectrometry.

<u>Example 3: 2-amino-3- (isopropylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride 13</u>

0125<chemistry id="chem0025" num="0025"><img file="EP1550656A1_D0029.tif" /></chemistry>

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

<u>10</u>

012615 mmol of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol in 30 ml of ethanol are introduced into a three-necked flask, with stirring. The homogeneous medium is heated to 75 ° C., then 93 mmol of isopropylamine are added dropwise while stirring is continued for four hours.

0127After cooling to room temperature, the medium is poured onto ice, then neutralized with hydrochloric acid. Extract 3- [3-bromo-5- (isopropylamino) -4-nitro-1 H-pyrazol-1-yl] propan-1-ol<b>10</b> with dichloromethane.

0128After drying the organic phase over sodium sulphate and removing the solvent by evaporation under vacuum, 4.37 g of 3- [3-bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-yl] propan are obtained -1-ol <b>10.</b>

0129NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0130The mass of the expected compound C₉H₁₅BrN₄O₃ is detected by mass spectrometry.

-Step 3: synthesis of 3- [5- (isopropylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propyl methanesulfonate

<u>11</u>

013113.7 mmol of 3- [3-bromo-5- (isopropylamino) -4-nitro-1H-pyrazol-1-yl] propan-1- are introduced into a 50 ml three-necked flask containing 20 ml of THF ol <b>10</b> and 1.94 ml of triethylamine. The homogeneous orange mixture thus obtained is cooled to 0 ° C. and 1.76 ml of mesyl chloride are poured in 20 minutes.

0132The reaction medium is maintained at this temperature for 2 hours, then 3- [5- (ethylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate <b>11</b> is precipitated by pouring the reaction medium onto 500 ml of ice.

0133The yellow solid is drained, then washed abundantly with water and petroleum ether, drying is carried out under vacuum in the presence of P₂O₅. The mass recovered is 4.2 g.

0134NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0135The 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-a] pyrazol-1-one

<u>12</u>

0136In a 50 ml three-necked flask, 10 mmol of 3- [5- (isopropylamino) -3-bromo-4-nitro-1H-pyrazol-1-yl] propylmethanesulfonate are dispersed with stirring <b>11</b> in 20 ml of pentanol and heated to 130 ° C for 2 hours.

0137After cooling to room temperature, the solid obtained is drained on a frit, and washed with diisopropyl ether.

0138After drying under vacuum in the presence of P₂O₅, 1.71 g of 3- (isopropylamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1one <b>12</b> are obtained

0139NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0140The mass of the expected compound C₉H₁₄NOT₄O₃ is detected by mass spectrometry.

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

<u>13</u>

01411.70 g of 3- (isopropylaminoamino) -2-nitro-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1- are introduced into a 300 ml autoclave containing 200 ml of ethanol one <b>12</b> and 300 mg of 5% palladium on charcoal. The reduction is carried out at a temperature of 60 ° C. and under a hydrogen pressure of 6 bars (stirring at 2000 rpm).

0142After 2 hours of reaction, it no longer consumes hydrogen and the medium is cooled to 20 ° C. The catalyst is removed by filtration under nitrogen after cooling to room temperature and hydrochloric isopropyl ether is added.

0143The pale yellow solution is evaporated to dryness, then the solid is taken up in 50 ml of diisopropyl ether saturated with hydrochloric acid, the precipitate is recovered by draining. After drying under vacuum in the presence of P₂O₅, 1.5 g 2-amino-3- (isopropylamino) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dihydrochloride <b>13</b> are isolated.

0144NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0145The mass of the expected compound C₉H₁₆NOT₄O is detected by mass spectrometry.

<u>Example 4: 2-amino-3- dihydrochloride (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 17</u>

0146<chemistry id="chem0026" num="0026"><img file="EP1550656A1_D0030.tif" /></chemistry>

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

<u>14</u>

0147In a three-necked flask, with stirring, 15 mmol of 3- (3,5-dibromo-4-nitro-1H-pyrazol-1-yl) propan-1-ol are introduced into 20 ml of isopropanol. The homogeneous medium is heated to 75 ° C. then 90 mmol of pyrrolidine are poured dropwise and the stirring is continued for two hours.

0148After cooling to room temperature, the medium is poured onto ice and neutralized with hydrochloric acid. Extract 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propan-1-ol<b>14</b> with dichloromethane.

0149After drying the organic phase over sodium sulfate and distilling off the solvent by evaporation under vacuum, 4.8 g of 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1 are obtained. -yl) propan-1-ol <b>14.</b>

0150NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0151The mass of the expected compound C₁₀H₁₇BrN₄O is detected by mass spectrometry.

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

<u>15</u>

015230 mmol 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propan is introduced into a 100 ml three-necked flask containing 50 ml of THF -1-ol <b>14</b> and 4.25 ml of triethylamine. The homogeneous orange mixture obtained is cooled to 0 ° C. and 2.32 ml of mesyl chloride are poured in 20 minutes.

0153The 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 <b>15</b> is precipitated by pouring the reaction medium onto ice. The solid is drained, then dried under vacuum in the presence of P₂O₅. The mass recovered is 9.3 g.

0154NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0155The mass of the expected compound C₁₁H₁₉BrN₄O₃S is detected by mass spectrometry.

-Step 4: synthesis 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one

<u>16</u>

015622.5 mmol of 3- (3-bromo-4-nitro-5- (pyrrolidin-1-yl) -1H-pyrazol-1-yl) propylmethanesulfonate are introduced into a 250 ml three-necked flask <b>15</b> in 100 ml of pentanol. The medium thus obtained is brought to 130 ° C for 2 hours.

0157After cooling to room temperature, 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one <b>16</b> is extracted with dichloromethane.

0158After drying the organic phase over sodium sulfate and distilling off the solvent under vacuum, 1.2 g of 2-nitro-3-pyrrolidin-1-yl-6,7-dihydro-1H, 5H-pyrazolo are obtained. a] pyrazol-1-one <b>16</b>

0159NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0160The mass of the expected compound C₁₀H₁₄NOT₄O₃ is detected by mass spectrometry.

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

<u>17</u>

01611.1 g of 2-nitro-3- (pyrrolidin-1-yl) -6,7-dihydro-1H, 5H-pyrazolo [1,2-a] are introduced into a 300 ml autoclave containing 200 ml of ethanol pyrazol-1-one <b>16</b> and 300 mg of 5% palladium on charcoal. The reduction is carried out with stirring at 2000 rpm, at a temperature of 60 ° C. and under a hydrogen pressure of 6 bars.

0162After 2 hours of reaction, it no longer consumes hydrogen and the medium is cooled to 20 ° C.

0163The catalyst is removed by filtration under nitrogen after cooling to room temperature and hydrochloric isopropyl ether is added.

0164The pale yellow solution is evaporated to dryness, then the solid is taken up in 50 ml of diisopropyl ether saturated with hydrochloric acid, the precipitate is recovered by draining. After drying under vacuum 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-1-one 5 dihydrochloride are obtained <b>17.</b>

0165NMR analyzes (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) conform to the expected structure.

0166The mass of the expected compound C₁₀H₁₆NOT₄O is detected by mass spectrometry.

<u>Example 5. Synthesis of 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dimethanesulfonate</u>

0167<chemistry id="chem0027" num="0027"><img file="EP1550656A1_D0031.tif" /></chemistry>

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

016843g (0.245 mol) of 3-amino-6,7-dihydro-1H hydrochloride, 5H-pyrazolo [1,2-a] pyrazol-1 are dissolved in a 500 ml three-necked flask, with stirring, at room temperature -one in a mixture of 180 ml of water and 35 ml of 35% hydrochloric acid.

0169The mixture is cooled to 0 ° C. and a solution of 17.3 g of sodium nitrite (0.25 mole) in 20 ml of water is added dropwise over 30 minutes. The temperature of the reaction medium is maintained between 0 and + 5 ° C. throughout the duration of the addition and for one hour after the end of the addition.

0170The reaction medium is brought to pH 8 by addition of sodium hydroxide, with stirring, while maintaining the temperature between 0 and 5 ° C. 3-amino-2-nitroso-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one 2 precipitates in the form of a red orange solid which is filtered through sintered glass n ° 4, pasted in a minimum of 2-propanol, washed with diisopropyl ether and dried under vacuum in the presence of phosphorus pentaoxide. 35 g of orange-red product are thus obtained (yield: 85%).

0171The NMR (1 H 400 MHz and 13C 100.61 MHz DMSO d6) and mass spectra conform to the expected structure 2.

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

017233.6 g (0.2 mol) of 3-amino-2-nitroso-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one are introduced into a 1 liter autoclave <b><u>2</u>,</b> 500 ml of ethanol and 6 g of 5% palladium on carbon containing 50% water.

0173The medium is purged 3 times with nitrogen then 3 times with hydrogen and the temperature of the mixture is brought to 40 ° C.

0174The reduction is carried out in two hours under a pressure of 8 bars. This reduction is exothermic and the temperature reaches 70 ° C by itself.

0175The temperature is allowed to drop to 50 ° C. then the catalyst is filtered on a filter press under a stream of nitrogen.

0176The filtrate is poured into a mixture of 50 ml of ethanol and 40 ml of methane sulfonic acid, cooling to 0 ° C. 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one dimethanesulfonate<b><u>3</u></b> crystallizes in the form of a pale yellow solid which is drained on sintered glass No. 4, washed with diisopropyl ether then with petroleum ether and finally dried under vacuum in the presence of phosphorus pentoxide. 43g of pale yellow solid is thus obtained (yield: 65%).

0177NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and mass conform to the expected structure <b><u>3</u></b>. <tables id="tabl0008" num="0008"><table frame="all"><tgroup cols="6" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="26.25mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="26.25mm" /><colspec colnum="3" colname="col3" colwidth="26.25mm" /><colspec colnum="4" colname="col4" colwidth="26.25mm" /><colspec colnum="5" colname="col5" colwidth="26.25mm" /><colspec colnum="6" colname="col6" colwidth="26.25mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col6" align="left">Elementary analysis:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Theory</entry><entry namest="col2" nameend="col2" align="left">C27.74</entry><entry namest="col3" nameend="col3" align="left">H5.23</entry><entry namest="col4" nameend="col4" align="left">N16.17</entry><entry namest="col5" nameend="col5" align="left">032.33</entry><entry namest="col6" nameend="col6" align="left">S18.51</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Measured</entry><entry namest="col2" nameend="col2" align="left">C27.16</entry><entry namest="col3" nameend="col3" align="left">H5.22</entry><entry namest="col4" nameend="col4" align="left">N15.63</entry><entry namest="col5" nameend="col5" align="left">032.81</entry><entry namest="col6" nameend="col6" align="left">S18.64</entry></row></tbody></tgroup></table></tables>

<u>Example 6: synthesis of 2,3-diamino-5,6,7,8-tetrahydro-9H-pyrazolo [1,2-a] pyridazin-1-one hydrochloride.</u>

0178<chemistry id="chem0028" num="0028"><img file="EP1550656A1_D0032.tif" /></chemistry>

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

017950 ml of toluene, 5 g (21.5 mmol) of N, N'-di-tert- are introduced into a 250 ml three-necked flask equipped with a condenser, a thermometer and a dropping funnel butoxycarbonylhydrazide, 680 mg of tetraethylammonium bromide and 25 ml of 50% sodium hydroxide.

0180The heterogeneous medium is heated to 100 ° C. and then 1,4-dibromobutane is added dropwise over 15 minutes.

0181The reaction medium is heated at 100 ° C for 3 days. After cooling, 100 ml of ethyl acetate are added and the mixture is transferred to a separatory funnel. The organic phase is washed with 4 times 70 ml of saturated aqueous sodium carbonate solution, then with 4 x 70 ml of water and finally with 4 x 70 ml of salt water. The organic phase is dried over sodium sulfate and the solvent is evaporated in vacuo. A colorless oil is thus obtained which crystallizes into a white solid.

0182A mass of 6.1 g is recovered (yield: 99%).

0183NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and mass conform to the expected structure <b><u>AT</u></b><u>.</u>

Synthesis of hexahydropyridazine dihydrochloride: B

01845.9 g of the compound are introduced into a 100 ml three-necked flask equipped with a condenser and a thermometer <b><u>AT</u></b> in 50 ml of 3/1 mixture of dioxane and 35% hydrochloric acid.

0185The colorless solution obtained is stirred at room temperature for 3 hours then the reaction medium is diluted with diisopropyl ether. The solvents are evaporated in vacuo. The pasty residue obtained is taken up in an ether / ethanol mixture. After filtration of the solid and drying under vacuum, 1.39 g of white solid are obtained.

0186NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and mass conform to the expected structure <b><u>B.</u></b>

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

01877.5 ml of ethanol, 1.5 ml of triethylamine and 0.73 ml of 3-amino-3-ethoxyacrylic acid are introduced into a 25 ml three-necked flask equipped with a condenser and a thermometer. 500 mg of hexahydropyridazine dihydrochloride (compound<b><u>B</u></b>) and stirred for 3 hours at room temperature.

0188The insoluble material is filtered and the solvent is distilled under vacuum. The solid is taken up in the minimum amount of water, filtered and dried under vacuum. 0.9 g of slightly yellow powder is thus obtained.

0189NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and mass conform to the expected structure <b><u>VS</u></b>.

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

019020 ml of 35% hydrochloric acid and 1 g of 3-amino-5,6,7,8-tetrahydro-1H- are introduced into a 50 ml three-necked flask equipped with a condenser and a thermometer. pyrazolo [1,2-a] pyridazin-1-one (compound <b><u>VS</u></b>).

0191Cool to 0 ° C and pour a solution of 675 mg sodium nitrite in 5 ml of water while maintaining this temperature. The color of the reaction mixture turns yellow to orange and a precipitate begins to form.

0192In 30 minutes, the reaction is complete and the orange solid is filtered through a No. 4 sintered glass, washed with water and then dried under vacuum. The yield is 78.3%.

0193NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) mass conform to the expected structure <b><u>D.</u></b>

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

01941.3 g of 3-amino-2-nitroso-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a] pyridazin-1- are introduced into a 300 ml autoclave containing 250 ml of ethanol. one (compound <b><u>D</u></b>) and 250 mg of 5% palladium on carbon. The reduction is carried out with stirring at 2000 rpm, at a temperature of 60 ° C. and under a hydrogen pressure of 6 bars.

0195After 2 hours of reaction, there is no more hydrogen consumption and the medium is cooled to 20 ° C.

0196The catalyst is removed by filtration under nitrogen after cooling to room temperature and the solution is poured onto 75 ml of hydrochloric dioxane.

0197The solution thus obtained is evaporated until a slightly yellow powder is obtained which is taken up in diisopropyl ether.

0198The solid is recovered by filtration. After drying under vacuum in the presence of phosphorus pentoxide, 1.1 g of 2,3-diamino-5,6,7,8-tetrahydro-1H-pyrazolo [1,2-a] pyridazin-1-one are obtained.

0199NMR spectra (¹H 400 MHz and ¹³C 100.61 MHz DMSO d₆) and mass conform to the expected structure <b><u>E.</u></b>

EXAMPLES OF DYEING

<u>Examples 1 to 3: Dyeing in an acid medium from 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</u>

0200The following dye compositions are prepared:<tables id="tabl0009" num="0009"><img file="EP1550656A1_D0033.tif" /></tables><tables id="tabl0010" num="0010"><img file="EP1550656A1_D0034.tif" /></tables>

0201At the time of use, each composition is mixed with an equal weight of hydrogen peroxide at 20 volumes (6% by weight). A final pH of 7 is obtained.

0202Each mixture obtained is applied to locks of gray hair containing 90% white hairs. After 30 minutes of laying, the locks are rinsed, washed with a standard shampoo, rinsed again and then dried.

0203The nuances obtained are shown in the table below: <tables id="tabl0011" num="0011"><table frame="all"><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left"><b>Example</b></entry><entry namest="col2" nameend="col2" align="center"><b>1</b></entry><entry namest="col3" nameend="col3" align="center"><b>2</b></entry><entry namest="col4" nameend="col4" align="center"><b>3</b></entry></row></thead><tbody valign="top"><row rowsep="1"><entry namest="col1" nameend="col1" align="left"><b>Nuance observed</b></entry><entry namest="col2" nameend="col2" align="center">chromatic orange</entry><entry namest="col3" nameend="col3" align="center">intense chromatic red</entry><entry namest="col4" nameend="col4" align="center">chromatic orange</entry></row></tbody></tgroup></table></tables>

<u>Examples 4 to 6: Dyeing in an alkaline medium from 2,3-diamino-6,7-dihydro-1H, 5H-pyrazolo [1,2-a] pyrazol-1-one</u>

0204The following dye compositions are prepared:<tables id="tabl0012" num="0012"><img file="EP1550656A1_D0035.tif" /></tables><tables id="tabl0013" num="0013"><img file="EP1550656A1_D0036.tif" /></tables>

0205At the time of use, each composition is mixed with an equal weight of hydrogen peroxide at 20 volumes (6% by weight). A final pH of 9.5 is obtained.

0206Each mixture obtained is applied to locks of gray hair containing 90% white hairs. After 30 minutes of laying, the locks are rinsed, washed with a standard shampoo, rinsed again and then dried.

0207The nuances obtained are shown in the table below: <tables id="tabl0014" num="0014"><table frame="all"><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="center"><b>Example</b></entry><entry namest="col2" nameend="col2" align="center"><b>4</b></entry><entry namest="col3" nameend="col3" align="center"><b>5</b></entry><entry namest="col4" nameend="col4" align="center"><b>6</b></entry></row></thead><tbody valign="top"><row rowsep="1"><entry namest="col1" nameend="col1" align="center"><b>Nuance observed</b></entry><entry namest="col2" nameend="col2" align="center">chromatic orange</entry><entry namest="col3" nameend="col3" align="center">chromatic red</entry><entry namest="col4" nameend="col4" align="center">chromatic orange</entry></row></tbody></tgroup></table></tables>