Cationic tetrahydropyrazolopyridines, dye composition comprisin
such oxidation bases, implementation process therefor and use
thereof
The present invention relates to particular cationic
tetrahydropyrazolopyridine compounds and also to the use thereof
for dyeing keratin fibres, in particular human keratin fibres such as
the hair.
The invention also relates to a composition for dyeing
keratin fibres comprising such cationic tetrahydropyrazolopyridine
compounds in a suitable dyeing medium, and also to a dyeing
process and a multi-compartment device using the said composition.
The present invention relates to the field of dyeing keratin
fibres and more particularly to the field of hair dyeing.
It is known practice to dye keratin fibres, and in particular
human hair, with dye compositions containing oxidation dye
precursors, which are generally known as oxidation bases, such as
ortho- or para-phenylenediamines, ortho- or para-aminophenols and
heterocyclic compounds. These oxidation bases are colourless or
weakly coloured compounds, which, when combined with oxidizing
products, are able to produce coloured compounds by a process of
oxidative condensation.
It is also known that the shades obtained with oxidation
bases can be varied by combining them with couplers or coloration
modifiers, the latter being selected more particularly from aromatic
meta-diaminobenzenes, meta-aminophenols, meta-diphenols and
certain heterocyclic compounds such as indole compounds.
The variety of molecules used as oxidation bases and
couplers allows a wide range of colours to be obtained.
The "permanent" coloration obtained by means of these
oxidation dyes must moreover satisfy a certain number of
requirements. Thus, it must have no toxicological drawbacks, it
must allow shades to be obtained in the desired strength, and it must
show good fastness with respect to external agents such as light, bad
weather, washing, permanent-waving, perspiration and rubbing.
The dyes must also allow grey hair to be covered, and they
must be as unselective as possible, i.e. they must make it possible to
produce the smallest possible coloration differences along the same
lock of keratin fibre, which is generally differently sensitized (i.e.
damaged) between its end and its root.
It is also known practice to use oxidation bases of the paraphenylenediamine,
para-toluenediamine or para-aminophenol type
for dyeing keratin fibres, especially the hair.
However, these oxidation bases generally have the drawback
of giving colorations that are not sufficiently strong, chromatic or
fast with respect to external agents and/or that are too selective.
Furthermore, these oxidation bases have unfavourable harmlessness.
There is thus a real need for oxidation bases that have
improved dyeing properties, especially in terms of strength,
chromaticity, colour buildup, selectivity and/or resistance with
respect to external agents, and that are also capable of leading to a
wider range of colours, while at the same time improving the
harmlessness of the oxidation bases used in oxidation dyeing.
These aims are achieved with the present invention, one
subject of which is especially cationic tetrahydropyrazolopyridines
of formula (I), optical isomers and geometrical isomers thereof,
addition salts thereof and/or solvates thereof:
in which formula (I):
R2, R 3, 4 and R represent, independently of each other, a
hydrogen atom; a halogen atom; a linear or branched C1-C4 alkyl
radical; a linear or branched C1-C4 hydroxyalkyl radical;
R2 and R 3, R 3 and R4 or R4 and R may form, together with the
carbon atoms to which they are attached, a saturated,
unsaturated or aromatic 5- to 8-membered ring optionally
substituted with one or more radicals chosen from hydroxyl,
alkoxy, C1-C4 alkyl and C1-C4 hydroxyalkyl radicals;
Zi represents an oxygen atom or a group NR ;
R represents a hydrogen atom or a linear or branched C1-C4
alkyl radical;
Ri represents:
- a linear or branched Ci-C 2o alkyl radical, substituted and/or
interrupted with a cationic radical, the said alkyl radical
being optionally interrupted with one or more oxygen atoms
and/or with one or more groups NR6, optionally substituted
with one or more radicals chosen from hydroxyl and C1-C4
alkoxy or hydroxyalkyl radicals;
- a saturated, unsaturated or aromatic, 5- to 8-membered ring
or heterocycle substituted with a cationic radical and
optionally substituted with one or more radicals chosen
from hydroxyl and C1-C4 alkoxy or hydroxyalkyl radicals;
when Zi represents a group NR then:
■ Ri and R may form, together with the nitrogen atom to
which they are attached, a saturated, unsaturated, aromatic or
non-aromatic, 5- to 8-membered mono- or polycationic,
preferably monocationic, heterocycle, optionally substituted
with one or more radicals chosen from C1-C4 alkyl, hydroxyl,
C1-C4 alkoxyamino, (Ci-C 4)alkylamino, (Ci-C 4)dialkylamino,
thio SH, (Ci-C 4)alkylthio, carboxyl, C(0)OH or C(0)0 , M+
with M+, which may be present or absent depending on the
cationic charge number of the compound (I), representing an
alkali metal, alkaline-earth metal or ammonium; (CiC4)
alkylcarbonyl; sulfonyl -S(0)n-R, -S(0) p-0-R, -0-S(0) p-R
with R representing a hydrogen atom or a C1-C4 (hydroxy)alkyl
group, n = 0, 1 or 2, p = 1 or 2, amido -C(0)-NRR' or -N(R)-
C(0)-R\ -N(R)-C (0)-NRR* with R and R*, which may be
identical or different, representing a hydrogen atom or a C1-C4
(hydroxy)alkyl group, C1-C4 hydroxyalkyls, this heterocycle
possibly containing one or more heteroatoms chosen from N and
O, preferably N ,
■ R i and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated, 5- to 8-
membered noncationic heterocycle optionally substituted with
one or more radicals chosen from C1-C10 alkyl; hydroxyl OH;
C1-C4 alkoxy; amino; (Ci-C 4)alkylamino; (Ci-C 4)dialkylamino;
thio SH, (Ci-C 4)alkylthio, carboxyl, C(0)OH or C(0)0 , M+
with M+, which may be present or absent depending on the
cationic charge number of the compound (I), representing an
alkali metal, alkaline-earth metal or ammonium; (Ci-
C4)alkylcarbonyl; sulfonyl -S(0)n-R, -S(0) p-0-R, -0-S(0) p-R
with R representing a hydrogen atom or a C1-C4 (hydroxy)alkyl
group, n = 0, 1 or 2, p = 1 or 2, amido -C(0)-NRR* or -N(R)-
C(0)-R\ -N(R)-C (0)-NRR* with R and R*, which may be
identical or different, representing a hydrogen atom or a C1-C4
(hydroxy)alkyl group, C1-C4 hydroxyalkyls.
The invention also relates to the use of one or more cationic
tetrahydropyrazolopyridines of formula (I) as defined previously, as
oxidation bases for dyeing keratin fibres, in particular human
keratin fibres such as the hair.
The present invention also relates to a composition for
dyeing keratin fibres, in particular human keratin fibres such as the
hair, comprising, in a suitable dyeing medium, one or more cationic
tetrahydropyrazolopyridines of formula (I) as defined previously.
In particular, the invention also relates to the use of the said
composition for dyeing keratin fibres, in particular human keratin
fibres such as the hair.
The invention also relates to a process for dyeing keratin
fibres, in particular human keratin fibres such as the hair, in which
the said dye composition according to the invention is applied to the
said fibres in the presence of one or more oxidizing agents for a
time that is sufficient to obtain the desired coloration, after which
the resulting fibres are rinsed, optionally washed with shampoo,
rinsed again and dried or left to dry.
Another subject of the present invention concerns a mult i
compartment device or dyeing kit comprising a first compartment
containing a dye composition as described above and a second
compartment containing one or more oxidizing agents.
The multi-compartment device is thus suitable for
performing the dyeing process according to the invention.
The cationic tetrahydropyrazolopyridines according to the
invention thus make it possible to obtain improved dyeing of keratin
fibres, especially in terms of strength or chromaticity, and/or of
selectivity and/or of resistance to external agents such as shampoos,
sweat, light and permanent reshaping.
The cationic tetrahydropyrazolopyridines according to the
invention also make it possible to achieve a wide range of colours,
while at the same time improving the harmlessness of the oxidation
bases used in oxidation dyeing.
Furthermore, the cationic tetrahydropyrazolopyridine
compounds according to the invention show good solubility and
allow satisfactory colour buildup.
For the purposes of the present invention, the term "buildup"
of the colour of keratin fibres means the variation in coloration
between locks of undyed grey hair and locks of dyed hair.
Other characteristics, aspects, subjects and advantages of the
present invention will emerge even more clearly on reading the
description and the examples that follow.
. Cationic tetrahydropyrazolopyridine compounds
The cationic tetrahydropyrazolopyridine compounds o f
formula (I) as defined previously comprise a cationic charge by
virtue of the presence of a cationic radical in their structure.
In the context of the invention, the expression "cationic
radical present in the compound o f formula (I)" means any linear or
branched or heterocyclic radical comprising a quaternary
ammonium, this quaternary ammonium being of the type -N RaRbRc,
Ra , Rb and Rc, which may b e identical or different, representing a
Ci-C alkyl radical which may b e substituted with a hydroxyl. Ra
and Rb may together form a 5- to 8-membered heterocycle, the
radical Rc then being a Ci-C alkyl radical which may b e substituted
with a hydroxyl radical.
Preferably, Ra , Rb and Rc, which may b e identical or
different, represent a Ci-C 2 alkyl radical, in particular methyl,
optionally substituted with a hydroxyl radical.
Preferably, when Ra and Rb together form a 5- t o 8-
membered heterocycle, the radical Rc then represents a Ci-C 2 alkyl
radical which may b e substituted with a hydroxyl radical.
Thus, the tetrahydropyrazolopyridines o f formula (I)
according to the invention bear a permanent cationic charge that i s
independent of the pH of the medium in which the compounds are
formulated.
Examples of cationic radicals that may be mentioned include
trimethylammonium, triethylammonium, dimethylethylammonium,
diethylmethylammonium, diisopropylmethylammonium,
diethylpropylammonium, hydroxyethyldiethylammonium, di- -
hydroxyethylmethylammonium and tri -P-hydroxyethylammonium
radicals.
The term "cationic heterocycle" means a 5- t o 8-membered
heterocycle in which at least one of the chain members i s a
quaternary ammonium as defined previously.
In particular, the cationic heterocycle is a 5- to 8-membered
heterocycle in which at least one of the chain members is a
quaternary ammonium as defined previously.
Examples of cationic heterocycles that may be mentioned
include imidazoliums, pyridiniums, piperaziniums, pyrrolidiniums,
morpholiniums, pyrimidiniums, thiazoliums, benzimidazoliums,
benzothiazoliums, oxazoliums, benzotriazoliums, pyrazoliums, for
example pyrrolidine, piperidine, morpholine and piperazine rings,
triazoliums and benzoxazoliums.
These cationic heterocycles are optionally substituted with
one or more identical or different radicals chosen from (Ci-C 4)alkyl
and (Ci-C 4)hydroxyalkyl radicals.
Preferably, the cationic radicals are chosen from
trimethylammonium, triethylammonium, dimethylethylammonium,
diethylmethylammonium, diisopropylmethylammonium,
hydroxyethyldiethylammonium, imidazoliums, pyridiniums,
piperaziniums, pyrrolidiniums, morpholiniums, pyrimidiniums,
thiazoliums and benzimidazoliums.
More preferentially, the cationic radicals are chosen from
trimethylammonium radicals and cationic heterocycles, especially
imidazolium, piperazinium, pyrrolidinium, piperidinium and
morpholinium.
Even more preferentially, the cationic radicals are chosen
from trimethylammonium and pyrrolidinium radicals, especially
trimethylammonium.
The term "saturated or unsaturated 5- to 8-membered noncationic
heterocycle" means a 5- to 8-membered ring in which at
least one of the ring members is a heteroatom chosen from O, N and
S, for instance imidazole or pyrimidine.
Preferably, when Ri represents a linear or branched C1-C20
alkyl radical, then the said radical is substituted with a cationic
radical.
According to one preferred embodiment, in formula (I), are
such that, taken together or separately:
• R2, R3, R 4 and R represent, independently of each other, a
hydrogen atom or a linear or branched C1-C4 alkyl radical,
preferably a hydrogen atom or a linear C1-C4 alkyl radical and even
more preferentially a hydrogen atom or a methyl radical,
• R2 and R3, R3 and R4 or R4 and R may form, together with
the carbon atoms that bear them, a saturated, unsaturated or
aromatic 5- to 8-membered and preferably 5- or 6-membered ring,
and preferably an unsubstituted 5- or 6-membered carbon-based
ring, and more preferentially R4 and R may form, together with the
carbon atoms that bear them, an unsubstituted 5- or 6-membered
carbon-based ring;
• Zi represents an oxygen atom or a group NR ;
• R represents a hydrogen atom or a linear or branched Ci-
C2 alkyl radical;
• Ri represents a linear or branched Ci-Cs alkyl radical,
substituted with a cationic radical, optionally substituted with one
or more radicals chosen from C1-C4 alkyl and C1-C4 alkoxy radicals,
or
• Ri represents a saturated, unsaturated or aromatic, 5- to 8-
membered non-cationic ring or heterocycle, substituted with a
cationic radical,
• when Zi represents NR then:
■ Ri and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated cationic
5- to 8-membered heterocycle optionally substituted with
one or more radicals chosen from C1-C10 alkyl, hydroxyl,
C1-C4 alkoxy, amino, (Ci-C 4)alkylamino, di(Ci-
C4)alkylamino, (Ci-C 4)alkylcarbonyl, amido and C1-C4
hydroxyalkyl radicals, it being possible for this heterocycle
to contain one or more heteroatoms chosen from N or O,
preferably N,
■ Ri and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated noncationic
5- to 8-membered heterocycle substituted with a
cationic radical and optionally substituted with one or more
radicals chosen from C1-C10 alkyl, hydroxyl, C1-C4 alkoxy,
amino, (C1-C4)alkylamino, di(C 1-C4)alkylamino, (C l -
C4)alkylcarbonyl, amido and C1-C4 hydroxyalkyl radicals.
Preferably, R2 and R3, on the one hand, represent a hydrogen
atom and R4 and R , on the other hand, represent a hydrogen atom
or a Ci-C4 alkyl radical, especially methyl.
More preferentially, R2, R3, R4 and R represent a hydrogen
atom.
Preferably, Z \ represents a group NR with R possibly being
a hydrogen atom.
According to a first preferred variant of the invention, R2,
R3, R4 and R represent a hydrogen atom, Z \ represents a group NH
and Ri represents a saturated linear C2-Cs alkyl radical, optionally
interrupted with a heteroatom such as oxygen or a group NH, Ri
being substituted with a cationic radical chosen from
trimethylammonium radicals and imidazolium, piperazinium,
pyrrolidinium, piperidinium or morpholinium cationic heterocycles.
In accordance with this first variant, Ri is substituted with a
trimethylammonium radical.
According to a second preferred variant of the invention, R2,
R3, R4 and R represent a hydrogen atom, Z \ represents a group NR
and R1 and R form, together with the nitrogen atom to which they
are attached, a saturated or unsaturated, 5- to 8-membered noncationic
heterocycle, substituted with a cationic radical preferably
chosen from trimethylammonium, diethylmethylammonium,
imidazolium, piperazinium, piperidinium, pyrrolidinium and
morpholinium radicals.
In accordance with this second variant and even more
preferentially, the non-cationic heterocycle is chosen from
pyrrolidine, piperidine and morpholine, this ring being substituted
with a cationic radical chosen from trimethylammonium and
diethylmethylammonium radicals.
In accordance with this variant and even more preferentially,
the non-cationic heterocycle is chosen from pyrrolidine, piperidine
and morpholine, this ring being substituted with a cationic radical
chosen from trimethylammonium and diethylmethylammonium
radicals.
According to a third preferred variant of the invention, R2,
R3, R4 and R represent a hydrogen atom, Z \ represents a group NR
and Ri and R form, together with the nitrogen atom to which they
are attached, a cationic heterocycle chosen from piperazinium,
imidazolium, pyrrolidinium, piperidinium and morpholinium
substituted with one or more identical or different radicals chosen
from Ci-C4 hydroxyalkyl and Ci-C4 alkyl, preferentially a
piperazinium radical substituted with one or more identical or
different radicals chosen from Ci-C4 hydroxyalkyl and Ci-C4 alkyl.
According to one embodiment, Z represents an oxygen atom.
According to another embodiment, Z represents a group NR ,
in which Ri and R form, together with the nitrogen atom to which
they are attached, a saturated or unsaturated, 5- to 8-membered
cationic heterocycle, optionally substituted with one or more
radicals chosen from Ci-C4 alkyl and Ci -C4 hydroxyalkyl radicals,
this heterocycle containing a nitrogen atom other than that
belonging to the group NR .
In the context of the invention, a derivative of formula (I) is
understood to encompass all mesomeric or isomeric forms.
The electrical neutrality of the compounds of formula (I) is
ensured by an organic or mineral, cosmetically acceptable anion or
mixture of anions, noted An .
An- denotes, for example, a halide such as chloride,
bromide, fluoride or iodide; a hydroxide; a sulfate; a hydrogen
sulfate; an alkyl sulfate in which the linear or branched alkyl part is
of Ci-C , such as the methyl sulfate or ethyl sulfate ion; a
carbonate; a hydrogen carbonate; a salt of a carboxylic acid, such as
formate, acetate, citrate, tartrate or oxalate; an alkylsulfonate for
which the linear or branched alkyl part is of Ci-C , such as the
methylsulfonate ion; an arylsulfonate for which the aryl part,
preferably phenyl, is optionally substituted with one or more C1-C4
alkyl radicals, for instance 4-tolylsulfonate; an alkylsulfonate such
as mesylate.
The compounds of general formula (I) may be in free form
or in the form of salts, such as addition salts with an inorganic acid
preferably chosen from hydrochloric acid, hydrobromic acid,
sulfuric acid and phosphoric acid or with an organic acid such as,
for example, citric acid, succinic acid, tartaric acid, lactic acid, 4-
toluylsulfonic acid, benzenesulfonic acid, acetic acid, paratoluenesulfonic
acid, formic acid and methanesulfonic acid.
For the purposes of the present invention, the cationic
charge originating from the acid salt of compound (I) is not
considered as a cationic radical borne by Z \ .
The compounds of general formula (I) may also be in the
form of solvates, for example in the form of a hydrate or of a
solvate of a linear or branched Ci-C alcohol such as ethanol or
isopropanol.
Preferably, the cationic tetrahydropyrazolopyridines of
formula (I) according to the invention are chosen from the
following compounds and mixtures thereof, and also the geometrical
or optical isomer forms thereof, the organic or mineral acid salts
thereof or the solvates thereof such as hydrates:
5

ompoun

5

NH2 4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4H-
1 / —N N cyclopenta[e]pyrazolo[ l ,5
\ -a]pyridin-2-yl)- l , l -
dimethylpiperazin- 1-ium,
An
Compound 29
4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4Hcyclopenta[
e]pyrazolo[ 1,5
-a]pyridin-2-yl)- l -(2-
hydroxyethyl)- 1-
methylpiperazin- 1-ium,
An
Compound 30
NH2 ^OH 4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4Hcyclopenta[
e]pyrazolo[ 1,5
-a]pyridin-2-yl)- l , l -
bis(2-
hydroxyethyl)piperazin- 1-
ium, An
Compound 31
l - {2-[(3-amino-4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-
yl)oxy] ethyl} -3-methyllH-
imidazol-3-ium, An
Compound 32
Preferably, the cationic tetrahydropyrazolopyridines
according to the invention are chosen from compounds 1, 2 and 3,
and also mixtures thereof.
An- has the same meaning as indicated previously.
. Synthetic process
The present invention also relates to a process for
synthesizing a cationic tetrahydropyrazolopyridine of general
formula (I) as defined above starting with compounds (A), (B), (C)
and (D) according to the following scheme:
in which Rl Zl R2, R3, R4 and R have the same meanings as those
indicated in formula (I), and in which:
- in a step (i), an N-aminopyridinium derivative of formula
(A) is reacted with at least two equivalents of 1,1-bis(methylthio)-
2-nitroethylene, preferably in a polar solvent, to obtain a 2-
methylsulfanyl-3-nitropyrazolo[ 1,5-a]pyridine derivative of formula
(B),
- in a step (ii), an oxidation reaction is performed on the
sulfur atom in position 2 of the compound of formula (B) to obtain
the sulfonyl derivative thereof of formula (C),
- in a step (iii), the compound of formula (C) is reacted with
a nucleophilic compound of formula R1Z1H or R1Z1- , M+ with M+
representing an alkali metal or an alkaline-earth metal such as Li,
Na or K, in order to replace the group -S(0) 2-CH3 with a group -
iRi in order to obtain the compound of formula (D), and
- in a step (iv), one or more reduction reactions are
performed in a polar solvent on the compound of formula (D) to
give a cationic tetrahydropyrazolopyridine of formula (I).
Step (i) for obtaining the compound of formula (B) from the
N-aminopyridinium derivative of formula (A) may be performed
under the conditions described in the publication entitled
Heterocycle, Vol. 6, No. 4, 1977.
Depending on the nature of the groups Rl in the compound
of formula (D), it is possible to perform one or more reduction
reactions. These reductions may be performed sequentially, i.e. by
first reducing the nitro function to an amino function, and then
reducing the pyridine ring.
The reduction of the nitro group of these compounds is
performed under standard conditions, for example by performing a
hydrogenation reaction under heterogeneous catalysis in the
presence of Pd/C, Pd(II)/C, Ni/Ra, etc., or alternatively by
performing a reduction reaction with a metal, for example with zinc,
iron, tin, etc. (see Advanced Organic Chemistry, 3rd Edition, J .
March, 1985, Wiley Interscience and Reduction in Organic
Chemistry, M. Hudlicky, 1983 , Ellis Horwood Series Chemical
Science).
According to one particular embodiment, the cationic
tetrahydropyrazolopyridine compounds of general formula (I), in
which Zi corresponds to an oxygen atom and Ri corresponds to a C2
alkyl radical substituted with a cationic trimethylammonium radical,
may be obtained according to the following reaction scheme:
in which Rl Zl R2, R 3, R4 and R have the same meanings as those
indicated in formula (I) and R'i represents a C2 alkyl radical
substituted with a group -NR7R8, R 7 and R , which may be identical
or different, representing a Ci-C alkyl radical which may be
substituted with a hydroxyl, and
in which:
- steps (i), (ii) and (iv) are identical to those described
previously, and
- in a step (iii) l , the compound of formula (C) is reacted
with a compound of formula R'iZiH or R'iZ , M+ with M+
representing an alkali metal or an alkaline-earth metal such as Li,
Na or K, in order to replace the group -S(0) 2-CH3 with a group -
ZlR' l such as R7R8N(CH 2)2OH or an alkoxide R7R N(CH2)20 M+
with M+ as defined previously, to obtain the compound of formula
(Dl), and then, in a step (iii)2, an alkylation step is performed on
the compound of formula (Dl ) to obtain a compound of formula
(D'l).
According to another embodiment, the cationic
tetrahydropyrazolopyridine compounds of general formula (I), in
which Zi corresponds to an oxygen atom and Ri corresponds to a C2
alkyl radical substituted with a cationic trimethylammonium radical,
may also be obtained according to the following reaction scheme:
in which Rl Zl R2, R 3, R4 and R have the same meanings as those
indicated in formula (I) and R"i represents a C2 alkyl radical
substituted with a hydroxyl group, and in which:
- steps (i), (ii) and (iv) are identical to those described
previously, and
- in a step (iii)' l , the compound of formula (C) is reacted
with a nucleophilic compound of formula R"iZiH or R iZ , M+
with M+ representing an alkali metal or an alkaline-earth metal such
as Li, Na or K, in order to replace the group -S(0) 2-CH 3 with a
group -ZiR"i such as 1,2-dihydroxyethane, in order to obtain the
compound of formula (D2), and then
- in a step (iii)'2, a substitution step is performed on the
hydroxyl group with a (C1-C6)alkylsulfonyl, arylsulfonyl or
benzylsulfonyl Ra-S(0)2-0-, especially with a halide compound
such as the mesyl or tosyl halide, to obtain the compound of
formula (D'2) comprising a nucleofugal leaving group Ra-S(0)2-0
with Ra representing a group (Ci-C )alkyl, aryl or benzyl;
- in a step (iii)'3, a substitution step is performed on the
group Ra-S(0) 2- with an amine group to obtain the compound of
formula (Dl), followed by performing a reaction directed towards
rendering the compound of formula (Dl ) cationic, or
"cationization", in order to obtain the compound of formula (D' l).
In particular, the substitution reaction (iii)" l is performed in
a dipolar solvent such as acetonitrile, tetrahydrofuran (THF) or in
dimethylformamide (DMF) or N-methylpyrrolidone (NMP), or in an
alcohol such as ethanol, in the presence of a base such as
triethylamine, ethyldiisopropylamine, sodium hydroxide or
potassium hydroxide, for example, and one or more equivalents of
R"iZiH for 1 to 24 hours at a temperature from 20°C to the reflux
temperature of the solvent.
The hydroxyl function thus introduced is then replaced with
a halide in order to introduce a leaving group (for example a mesyl
or tosyl halide) in a solvent such as acetonitrile, tetrahydrofuran
(THF) or in an alcohol such as ethanol, for example, in the presence
of a base such as triethylamine, ethyldiisopropylamine, sodium
hydroxide or potassium hydroxide, for example, for 1 to 24 hours at
a temperature from 20°C to the reflux temperature of the solvent.
The substitution of the leaving group introduced during the
preceding step is carried out by reaction with an amine or an
alcohol.
The cationization is performed by reaction with at least one
equivalent of an alkyl or aryl halide, methyl sulfate or an alkyl
carbonate in a solvent such as tetrahydrofuran (THF), acetonitrile,
dioxane or ethyl acetate for 15 minutes to 24 hours at a temperature
ranging from 15°C to the reflux temperature of the solvent, to give
the cationic nitro compounds.
Thus, step (iii) defined in the synthetic process may be
performed in several steps.
A subject of the present invention is also the compounds of
formula (D) as defined in the synthetic schemes mentioned above
and in which Rl Zl R2, R3, R4 and R have the same meanings as
those indicated in formula (I) of the cationic
tetrahydropyrazolopyridine compounds.
Preferably, the compounds of formula (D) are chosen from
the compounds that lead to the cationic tetrahydropyrazolopyridine
compounds 1 to 35 mentioned previously.
Preferentially, the compounds of formula (D) are chosen
from the compounds that lead to the cationic
tetrahydropyrazolopyridine compounds 1, 2 and 3.
The invention also relates to the use of one or more cationic
tetrahydropyrazolopyridine compounds of formula (I) as defined
previously, in the presence of one or more oxidizing agents, for
dyeing keratin fibres, in particular human keratin fibres such as the
hair.
III. Dye composition
The present invention also relates to a composition for
dyeing keratin fibres, in particular human keratin fibres such as the
hair, comprising, in a suitable dyeing medium, one or more cationic
tetrahydropyrazolopyridine compounds of formula (I) as defined
above.
Preferably, the dye composition comprises one or more
cationic tetrahydropyrazolopyridine compounds of formula (I)
chosen from compounds 1 to 35, and mixtures thereof.
More preferentially, the dye composition comprises one or
more cationic tetrahydropyrazolopyridine compounds of formula (I)
chosen from compounds 1, 2 and 3, and mixtures thereof.
The cationic tetrahydropyrazolopyridines as defined
previously may be present in the composition according to the
invention in a content ranging from 1% to 20% by weight and
preferably in a content ranging from 1% to 5% by weight relative to
the total weight of the dye composition.
The dye composition according to the invention may contain
and preferably contains one or more couplers that are
conventionally used for dyeing keratin fibres. Among these
couplers, mention may be made especially o f metaphenylenediamines,
meta-aminophenols, meta-diphenols,
naphthalene couplers and heterocyclic couplers, and the addition
salts thereof.
Examples of couplers that may be mentioned include 2-
methy 1-5 -amino phenol, 5-N -(P-hydroxyethyl)amino-2-methylphenol,
6-chloro-2-methyl-5-aminophenol, 3-aminophenol, 2,4-dichloro-3-
aminophenol, 5-amino-4-chloro-o-cresol, 1,3-dihydroxybenzene,
1.3- dihydroxy-2-methylbenzene, 4-chloro- 1,3-dihydroxybenzene,
2.4- diamino- 1-(P-hydroxyethyloxy)benzene, 2-amino -4- (-
hydroxyethylamino)- 1-methoxybenzene, 1,3-diaminobenzene, 1,3-
bis(2,4-diaminophenoxy)propane, 3-ureidoaniline, 3-ureido- l -
dimethylaminobenzene, sesamol, 1-P-hydroxyethylamino-3,4-
methylenedioxybenzene, cc-naphthol, 2-methyl- 1-naphthol, 1,5-
dihydroxynaphthalene, 2,7-naphthalenediol, l -acetoxy-2-
methylnaphthalene, 6-hydroxyindole, 4-hydroxyindole, 4-hydroxy-
N-methylindole, 2-amino-3-hydroxypyridine, 6-
hydroxybenzomorpholine, 3,5-diamino-2,6-dimethoxypyridine, 2,6-
dihydroxy-3-4-dimethylpyridine, 3-amino-2-methylamino-6-
methoxypyridine, 1-N- ( -hydroxy ethyl)amino- 3,4-
methylenedioxybenzene, 2,6-bis (P-hydroxyethylamino)toluene and
3-methyl- 1-phenyl-5-pyrazolone and the addition salts thereof with
an acid.
In the dye composition o f the present invention, the
coupler(s), i f they are present, generally represent an amount o f
between 0.00 1% and 10% by weight approximately relative to the
total weight of the composition, and preferably between 0.005% and
6% by weight relative to the total weight of the composition.
The dye composition o f the invention may optionally
comprise one or more additional oxidation bases conventionally
used for the dyeing o f keratin fibres, other than the compounds o f
formula (I).
By way o f example, these additional oxidation bases are
chosen from para-phenylenediamines other than the bases of
formula (I), bis(phenyl)alkylenediamines, para-aminophenols, bispara-
aminophenols, ortho-aminophenols and heterocyclic bases, and
the addition salts thereof.
Among the para-phenylenediamines, examples that may b e
mentioned include para-phenylenediamine, para-toluenediamine, 2-
chloro-para-phenylenediamine, 2,3-dimethyl-par aphenylenediamine,
2,6-dimethyl-para-phenylenediamine, 2,6-
diethyl-para-phenylenediamine, 2,5-dimethyl-par aphenylenediamine,
,-dimethyl-para-phenylenediamine, N,Ndiethyl-
para-phenylenediamine, N,N-dipropyl-paraphenylenediamine,
4-amino-N,N-diethyl-3-methylaniline, N,Nbis
(P-hydroxyethyl)-para-phenylenediamine, 4-N,N-bis ( -
hydroxy ethyl) amino -2-met hylaniline, 4-N,N-bis ( -
hydroxyethyl)amino - -chloro aniline, 2-P-hydroxyethyl-paraphenylenediamine,
2-fluoro-para-phenylenediamine, 2-isopropylpara-
phenylenediamine, N-( -hydroxypropyl) -paraphenylenediamine,
2-hydroxymethyl-para-phenylenediamine, N,Ndimethyl-
3-methyl-para-phenylene diamine, N-ethyl-N-(Phydroxyethyl)-
para-phenylenediamine, N-(P,y-dihydroxypropyl)-
para-phenylenediamine, N-(4 '-amino phenyl) -par aphenylenediamine,
N-phenyl-para-phenylenediamine, 2--
hydroxyethyloxy-para-phenylenediamine, 2-P-acetylaminoethyloxypara-
phenylenediamine, N-( -methoxyethyl) -par aphenylenediamine,
4-aminophenylpyrrolidine, 2-thienyl-paraphenylenediamine,
2-P-hydroxyethylamino-5-aminotoluene and 3-
hydroxy- l -(4'-aminophenyl)pyrrolidine, and the addition salts
thereof with an acid.
Among the para-phenylenediamines mentioned above, paraphenylenediamine,
para-toluenediamine, 2-isopropyl-paraphenylenediamine,
2-P-hydroxyethyl-para-phenylenediamine, 2--
hydroxyethyloxy-para-phenylenediamine, 2,6-dimethyl-par aphenylenediamine,
2,6-diethyl-para-phenylenediamine, 2,3-
dimethyl-para-phenylene diamine, N,N-bis(P-hy droxyethyl) -paraphenylenediamine,
2-chloro-para-phenylenediamine and 2--
acetylaminoethyloxy-para-phenylenediamine, and the addition salts
thereof with an acid, are particularly preferred.
Among the bis(phenyl)alkylenediamines, examples that may
be mentioned include N,N'-bis(P-hydroxyethyl)-N,N'-bis(4'-
aminophenyl)- l ,3-diaminopropanol, N,N'-bis(P-hy droxyethy1)-
N,N'-bis(4'-aminophenyl)ethylenediamine, N,N'-bis(4-
aminophenyl)tetramethylenediamine, N,N'-bis(P- hydro xyethyl) -
N,N'-bis(4-aminophenyl)tetramethylenedi amine, N,N'-bis(4-
methylaminophenyl)tetramethylenediamine, N,N'-bis(ethyl)-N,N'-
bis(4'-amino-3 '-methylphenyl)ethylenediamine and l ,8-bis(2,5-
diaminophenoxy)-3,6-dioxaoctane, and the addition salts thereof
with an acid.
Among the para-aminophenols, examples that may be
mentioned include 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-
(P-hydroxyethylaminomethyl)phenol, 4-amino-2-fluorophenol, 1-
hydroxy-4-methylaminobenzene and 2,2'-methylenebis(4-
aminophenol), and the addition salts thereof with an acid.
Among the ortho-aminophenols, examples that may be
mentioned include 2-aminophenol, 2-amino-5-methylphenol, 2-
amino-6-methylphenol and 5-acetamido-2-aminophenol, and the
addition salts thereof with an acid.
Mention may be made, among heterocyclic bases, by way o f
example, of pyridine derivatives, pyrimidine derivatives and
pyrazole derivatives.
Among the pyridine derivatives, mention may be made o f the
compounds described, for example, in patents GB 1 026 978 and GB
1 153 196, for instance 2,5-diaminopyridine, 2-(4-
methoxyphenyl)amino-3-aminopyridine, 2,3-diamino-6-
methoxypyridine, 2-(P-methoxyethyl)amino-3-amino-6-
methoxypyridine and 3,4-diaminopyridine, and the addition salts
thereof with an acid.
Among the pyrimidine derivatives, mention may be made o f
the compounds described, for example, in patents DE 2 359 399; JP
88- 169 57 1; JP 05-63 124; EP 0 770 375 or patent application WO
96/1 5765, for instance 2,4,5,6-tetraaminopyrimidine, 4-hydroxy-
2,5,6-triamino pyrimidine, 2-hydroxy-4,5,6-triaminopyrimidine, 2,4-
dihydroxy-5,6-diaminopyrimidine and 2,5,6-triaminopyrimidine,
and pyrazolopyrimidine derivatives such as those mentioned in
patent application FR-A-2 750 048, and among which mention may
be made of pyrazolo[ l ,5-a]pyrimidine-3,7-diamine, 2,5-
dimethylpyrazolo[ 1,5-a]pyrimidine-3,7-diamine, pyrazolo[ 1,5-
a]pyrimidine-3,5-diamine, 2,7-dimethylpyrazolo[ 1,5-a]pyrimidine-
3,5-diamine, 3-aminopyrazolo[ 1,5-a]pyrimidin-7-ol, 3-
aminopyrazolo[ 1,5-a]pyrimidin-5-ol, 2-(3-aminopyrazolo[ 1,5-
a]pyrimidin-7-ylamino)ethanol, 2-(7-aminopyrazolo[ 1,5-
a]pyrimidin-3-ylamino)ethanol, 2-[(3-aminopyrazolo[ 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[ 1,5-a]pyrimidine-
3,7-diamine, 2,5,N7,N7-tetramethylpyrazolo[ 1,5-a]pyrimidine-3,7-
diamine and 3-amino-5-methyl-7-
imidazolylpropylaminopyrazolo[ 1,5-a]pyrimidine, and the addition
salts thereof with an acid, and the tautomeric forms thereof, when a
tautomeric equilibrium exists.
Among the pyrazole derivatives that may be mentioned are
the compounds described in the patents DE 3843892, DE 4 133957
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-(P-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-benzyl-4,5-diamino-3-methylpyrazole, 4,5-
diamino-3 - t r t -butyl- 1-methylpyrazole, 4,5-diamino - 1-t r t -butyl-3 -
methylpyrazole, 4,5-diamino - 1-(P-hydroxyethyl)-3 -methylpyrazole,
4,5-diamino - 1-ethy 1-3 -methylpyrazole, 4,5-diamino - 1-ethy 1-3 -(4 '-
methoxyphenyl)pyrazole, 4,5-diamino- 1-ethyl-S
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 '-
amino ethyl) amino - 1,3-dimethylpyrazole, 3,4,5-triaminopyrazole, 1-
methyl-3,4,5-triaminopyrazole, 3,5-diamino- l -methyl-4-
methylaminopyrazole, 3,5-diamino-4 -(P-hydroxyethyl)amino- 1-
methylpyrazole, and the addition salts thereof with an acid.
In general, the addition salts of the additional oxidation
bases and o f the couplers that can be used in the context of the
invention are especially chosen from addition salts with an acid,
such as hydrochlorides, hydrobromides, sulfates, citrates,
succinates, tartrates, lactates, tosylates, benzenesulfonates,
phosphates and acetates, and the addition salts with a base such as
sodium hydroxide, potassium hydroxide, aqueous ammonia, amines
or alkanolamines.
The dye composition in accordance with the invention may
also contain one or more direct dyes that may in particular be
chosen from nitrobenzene dyes, azo direct dyes and methine direct
dyes. These direct dyes may be of nonionic, anionic or cationic
nature.
The medium that is suitable for dyeing, also known as the
dye support, generally comprises water or a mixture of water and of
one or more organic solvents, for example C1-C4 lower alkanols
such as ethanol and isopropanol, polyols, for instance propylene
glycol, dipropylene glycol or glycerol, and polyols, for instance
dipropylene glycol monomethyl ether.
The solvent(s) are generally present in proportions that may
be between 1% and 40% by weight approximately and more
preferably between 3% and 30% by weight approximately relative to
the total weight of the dye composition.
The dye composition in accordance with the invention may
also contain various adjuvants conventionally used in hair dye
compositions, such as anionic, cationic, nonionic, amphoteric or
zwitterionic surfactants or mixtures thereof, anionic, cationic,
nonionic, amphoteric or zwitterionic polymers or mixtures thereof,
inorganic or organic thickeners, and in particular anionic, cationic,
nonionic and amphoteric polymeric associative thickeners,
antioxidants, penetrants, sequestrants, fragrances, buffers,
dispersants, conditioning agents, for instance volatile or non
volatile, modified or unmodified silicones, film-forming agents,
ceramides, preserving agents and opacifiers.
The above adjuvants are generally present in an amount, for
each of them, of between 0.0 1% and 20% by weight relative to the
weight of the composition.
Needless to say, a person skilled in the art will take care to
select this or these optional additional compound(s) such that the
advantageous properties intrinsically associated with the oxidation
dye composition in accordance with the invention are not, or are not
substantially, adversely affected by the envisaged addition(s).
The 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 may be adjusted to
the desired value by means of acidifying or basifying agents usually
used in the dyeing of keratin fibres, or alternatively using standard
buffer systems.
Among the acidifying agents, mention may be made, by way
of example, of inorganic or organic acids, for instance hydrochloric
acid, orthophosphoric acid, sulfuric acid, carboxylic acids, for
instance acetic acid, tartaric acid, citric acid and lactic acid, and
sulfonic acids.
Among the basifying agents that may be mentioned, for
example, are aqueous ammonia, alkaline carbonates, alkanolamines
such as monoethanolamine, diethanolamine and triethanolamine and
derivatives thereof, sodium hydroxide, potassium hydroxide and the
compounds of formula (II) below:
N W N
R Rd (II)
in which W is a propylene residue optionally substituted
with a hydroxyl group or a C1-C4 alkyl radical; and Ra, Rb, Rc and
Rd, which may be identical or different, represent a hydrogen atom
or a C1-C4 alkyl or C1-C4 hydroxyalkyl radical.
The composition according to the invention may comprise
one or more oxidizing agents.
The oxidizing agents are those conventionally used for the
oxidation dyeing of keratin fibres, for example hydrogen peroxide,
urea peroxide, alkali metal bromates, persalts such as perborates
and persulfates, peracids and oxidase enzymes, among which
mention may be made of peroxidases, 2-electron oxidoreductases
such as uricases, and 4-electron oxygenases, for instance laccases.
Hydrogen peroxide is particularly preferred.
The dye composition with or without oxidizing agent
according to the invention may be in various forms, such as in the
form of liquids, creams or gels, or in any other form that is suitable
for dyeing keratin fibres, and especially human hair.
It may result from the mixing, at the time of use, of several
compositions.
In particular, it results from the mixing of at least two
compositions, one comprising one or more oxidation bases chosen
from the compounds of formula (I) or addition salts thereof with an
acid, optionally one or more additional oxidation bases other than
the compounds of formula (I) or salts thereof, and optionally one or
more couplers, and a second composition comprising one or more
oxidizing agents as described previously.
In particular, the invention also relates to the use of a dye
composition as defined previously for dyeing keratin fibres, in
particular human keratin fibres such as the hair.
The present invention also relates to a process for dyeing
keratin fibres, in particular human keratin fibres such as the hair, in
which the said dye composition according to the invention is
applied to the said fibres in the presence of one or more oxidizing
agents for a time that is sufficient to obtain the desired coloration,
after which the resulting fibres are rinsed, optionally washed with
shampoo, rinsed again and dried or left to dry.
The colour may be revealed at acidic, neutral or alkaline pH
and the oxidizing agent may be added to the composition of the
invention just at the time of use, or it may be used starting with an
oxidizing composition containing it, applied simultaneously or
sequentially to the composition of the invention.
In one particular embodiment, the composition devoid of
oxidizing agent according to the present invention is mixed,
preferably at the time of use, with a composition containing, in a
medium appropriate for dyeing, one or more oxidizing agents, these
oxidizing agents being present in an amount sufficient to develop a
colouring. The mixture obtained is then applied to the keratin
fibres.
In accordance with this particular embodiment, a ready-touse
composition is obtained, which is a mixture of a composition
according to the invention with one or more oxidizing agents.
After a leave-on time of from 3 to 50 minutes approximately
and preferably 5 to 30 minutes approximately, the keratin fibres are
rinsed, washed with shampoo, rinsed again and then dried.
The oxidizing agents are those indicated above.
The oxidizing composition may also contain various
adjuvants conventionally used in compositions for dyeing the hair
and as defined above.
The 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 fibres
preferably varies between 3 and 12 approximately and more
preferably still between 5 and 11. It may be adjusted to the desired
value by means of acidifying or basifying agents usually used in the
dyeing of keratin fibres and as defined above.
The ready-to-use composition which is ultimately applied to
the keratin fibres may be in a variety of forms, such as in the form
of liquids, creams or gels or any other form appropriate for carrying
out dyeing of keratin fibres, and in particular of human hair.
Another subject of the invention is a dyeing "kit" or mult i
compartment device in which a first compartment contains the dye
composition devoid of oxidizing agent of the present invention
defined above, comprising one or more oxidation bases chosen from
the compound of formula (I) or the addition salts thereof with an
acid, and a second compartment contains one or more oxidizing
agents.
These devices may be equipped with a means for dispensing
the desired mixture on the hair, such as the devices described in
patent FR-2 586 913 in the name of the Applicant.
The examples that follow serve to illustrate the invention
without, however, being limiting in nature.
EXAMPLES
Synthesis examples:
Example 1_: Synthesis of l -(3-amino-4, 5,6,7-
tetrahydropyrazolo[ 1,5-a]pyridin-2-yl)-N,N,N-trimethylpyrrolidin-
3-aminium chloride hydrochloride
Step 1: Synthesis of 2-methylsulfanyl-3-nitropyrazolo[ 1,5-
alpyridine
2-Methy su If anyl- 3-n itropyrazolo[1,5-a]pyrid ine
A solution of 111 g of 1-N-aminopyridinium (0.5 mol) in
DMF (500 ml) is prepared in a 2-litre three-necked flask equipped
with a mechanical stirrer and an internal temperature probe, and
placed under a stream of nitrogen.
Potassium carbonate (207.3 g, 3 eq.) is then added in a
single portion, followed by 1,1-bis(methylthio)-2-nitroethylene
( 165 .2 g, 2 eq.), also in a single portion. The reaction medium sets
to a solid. 500 ml of DMF are added in order to make the reaction
medium more fluid.
After stirring for 48 hours at room temperature, the reaction
medium is poured onto 4 litres of ice-water. The precipitate formed
is filtered off and washed thoroughly with water (5 litres) and then
dried at 80°C under vacuum.
The solid thus obtained is freed of the excess l,l-bis(methylthio)-2-
nitroethylene (30 mol% determined by ^-NMR) by reslurrying in ethyl
acetate. After draining the product by suction and drying, 72 g of a
beige-yellow solid corresponding to the expected product are
obtained.
The NMR spectrum indicates that the product obtained
corresponds to the expected product.
Step 2 : Synthesis of 2-methanesulfonyl-3-nitropyrazolo[ 1,5-
2-Methanesulfonyl-3-nitropyrazolo[1 ,5-a]pyridine
880 g of Oxone (5 eq.), 2 litres of water and 60 g of 2-
methylsulfonyl-3-nitropyrazolo[ 1,5-a]pyridine (0.287 eq.) obtained
previously are successively placed in a 4-litre three-necked flask
equipped with a mechanical stirrer and an internal temperature
probe. The mixture is stirred at room temperature.
To complete the reaction, Oxone (120 g, 0.7 eq.) is added,
and, after stirring for 4 hours at room temperature, the reaction is
complete.
The solid formed is drained by suction and washed
thoroughly with water until a filtrate no longer containing any
peroxides is obtained. It is then placed under vacuum at 40°C over
P205 .
59 g of expected product are obtained in the form of a beigeyellow
powder.
The NMR spectrum indicates that the product obtained
corresponds to the expected product.
Step 3: Synthesis of N,N-dimethyl- l -(3-nitropyrazolo[ l ,5-
a |pyridin-2-yl)pyrrolidin-3-amine
5 ml of NMP (N-methylpyrrolidone), 3 g of 2-
(methylsulfonyl)-3-nitropyrazolo[ 1,5-a]pyridine and 3.77 ml of 3-
(dimethylamino)pyrrolidine are placed in a 100 ml three-necked
flask on which is mounted a bubble condenser, a thermometer and a
magnetic stirrer, and the mixture is heated at 80°C for 1 hour.
After cooling the reaction medium to room temperature, it is
poured into a mixture of 200 g of ice and water. The yellow
compound that crystallizes out is drained off by suction on a No. 3
sinter and washed with 2 100 ml of water and then with 3 100 ml
of isopropyl ether. After drying at 35°C under vacuum in the
presence of P205 for 12 hours, 3.26 g of a yellow solid
corresponding to the expected compound are recovered.
The NMR (1H 400 MHz and 13C 100.6 1 MHz DMSO-d6)
and mass spectrometry analyses are in accordance with the expected
structure.
The quasi-molecular ion (MH)+ of the expected molecule,
C13H17N502, is mainly detected.
Step 4 : Synthesis of N,N,N-trimethyl- l -(3-nitropyrazolo[ l ,5-
alpyridin-2-yl)pyrrolidin-3-aminium methyl sulfate
25 ml of THF, 3.26 g (0.0 1 mol) of ,-dimethyl- 1-(3-
nitropyrazolo[ 1,5-a]pyridin-2-yl)pyrrolidin-3-amine and, dropwise,
1.89 ml (0.02 mol) of dimethyl sulfate are added to a 100 ml threenecked
flask on which is mounted a bubble condenser, a
thermometer and a magnetic stirrer, at 50°C.
The reaction is monitored by TLC (eluent: 95/5
dichloromethane/methanol).
The medium is cooled to room temperature and the yellow
solid formed is drained by suction on a No. 3 sinter and washed
with 2x 100 ml of THF and then with 3 100 ml of isopropyl ether.
After drying at 35°C under vacuum in the presence of P205 for 12
hours, 3.2 g of a yellow solid corresponding to the expected
structure are recovered.
The NMR (1H 400 MHz and 13C 100.6 1 MHz DMSO-d6)
and mass spectrometry analyses are in accordance with the expected
structure.
Step 5: Synthesis of. 1-(3 -amino -4, 5,6,7-
tetrahydropyrazolo[ 1,5-alpyridin-2-yl)-N,N,N-trimethylpyrrolidin-
3-aminium chloride hydrochloride
100 ml of ethanol/water (9/1), 1 g (2.56 mmol) of ,,-
trimethyl- 1-(3-nitropyrazolo[ 1,5-a]pyridin-2-yl)pyrrolidin-3-
aminium methyl sulfate and 0.3 g of 50% aqueous 5% palladium are
placed in a 300 ml hydrogenator.
The system is purged three times with nitrogen and then
once with hydrogen, and the reduction reaction is then performed at
a hydrogen pressure of 8 bar, with stirring.
After reaction for 2 hours, the hydrogen consumption falls to
zero. After purging several times by flushing with nitrogen, the
catalyst is removed by filtration under nitrogen.
The filtrates are acidified with 6N hydrochloric isopropanol
and the solvents are evaporated off under vacuum. The residue is
taken up in a methanol/petroleum ether mixture, followed by
evaporation under vacuum until a brown powder corresponding to
the expected compound is obtained.
The NMR analyses (1H 400 MHz and 1 C 100.6 1 MHz
DMSO-d ) are in accordance with the expected structure.
The expected cation, C i4H2 6 +, is mainly detected.
Example 2
Synthesis of N,N-dimethyl-N'-(3-nitropyrazolo[ 1,5-
a]pyridin-2-yl) ethane- 1,2-diamine metho sulfate
N,N,N-trimethyl-2-[(3-nitropyrazolo [1 ,5-a]pyridin-2-yl )amino]
eth anamin ium methosulfate
35 g (0. 140) mol of N,N-dimethyl-N'-(3-nitropyrazolo[ 1,5-
a]pyridin-2-yl)ethane- 1,2-diamine are placed in a 500 ml threenecked
flask equipped with a bubble condenser, a thermometer and
a 50 ml dropping funnel, under magnetic stirring, and containing
200 ml of THF. The temperature is brought to 50°C using an oil
bath, and dimethyl sulfate ( 1.1 equivalents) is added dropwise; a
yellow precipitate forms. The reaction is monitored by TLC (eluent:
98/2 dichloromethane/methanol) until the starting material has
disappeared. The solid formed is drained by suction and then
washed several times with THF. After drying under vacuum in the
presence of P2O5, 50.8 g of yellow powder are recovered.
The NMR analyses (1H 400 MHz and 13C 100.6 1 MHz
DMSO-d6) are in accordance with the expected structure.
The expected cation, C12H 14N502+, is mainly detected at
m/z = 264 in ES+.
Synthesis of [2-(3-aminopyrazolo[ 1,5-a]pyridin-2-
ylamino)ethyl]trimethylammonium chloride dihydrochloride
150 ml of ethanol, 30 ml of water, 8 g (2 1.3 1 mmol) of N,Ndimethyl-
N'-(3-nitropyrazolo[ 1,5-a]pyridin-2-yl)ethane- 1,2-diamine
methosulfate and 0.8 g of 50% aqueous 5% palladium are placed in
a 300 ml hydrogenator.
The system is purged three times with nitrogen and then
once with hydrogen, and the reduction reaction is performed at a
hydrogen pressure of 8 bar, with stirring.
After reaction for 2 hours, the hydrogen consumption falls to
zero. After purging several times by flushing with nitrogen, the
catalyst is removed by filtration under nitrogen.
The filtrates are acidified with 6N hydrochloric isopropanol
and the solvents are evaporated off under vacuum. The residue is
taken up in a methanol/petroleum ether mixture, followed by
evaporation under vacuum until a grey powder corresponding to the
expected compound is obtained, in a mass of 6 g .
The NMR analyses (1H 400 MHz and 13C 100.6 1 MHz
DMSO-d6) are in accordance with the expected structure.
Analysis by mass spectrometry confirms the product: the
expected cation [C 12H24N5]+ is mainly detected at m/z ESP+ =
238.
EXAMPLE 3:
2-(4-Methylpiperazin- 1-yl)-3-nitropyrazolo[ 1,5-a]pyridine
5 ml of NMP, 3 g of 2-(methylsulfonyl)-3-nitropyrazolo[ 1,5-
ajpyridine and 3.3 ml of 1-methylpiperazine are placed in a 100 ml
three-necked flask on which is mounted a bubble condenser, a
thermometer and a magnetic stirrer, and the mixture is heated at
80°C for 3 hours.
The medium is poured into a mixture of 200 g of ice and
water. The yellow compound that crystallizes out is drained off by
suction on a No. 3 sinter and washed with 2x100 ml of water and
then with 3 100 ml of isopropyl ether. After drying at 35°C under
vacuum in the presence of P205 for 12 hours, 2.35 g of a yellow
solid corresponding to the expected compound are recovered.
The NMR (1H 400 MHz and 1 C 100.6 1 MHz DMSO-d6) and
mass spectrometry analyses are in accordance with the expected
structure.
The quasi-molecular ions [M+H] +, [M+H+CH3CN]+,
[2M+H]+ and the ion of the expected molecule C12H1 5N502 are
mainly detected.
Synthesis of 1,1-dimethyl-4-(3-nitropyrazolo[ 1,5-a]pyridin-
2-yl)piperazin- 1-ium methyl sulfate
25 ml of THF, 2.35 g (0.0 1 mol) of 2-(4-methylpiperazin- 1-
yl)-3-nitropyrazolo[ 1,5-a]pyridine and, dropwise, 1.85 ml (0.02
mol) of dimethyl sulfate are added to a 100 ml three-necked flask
on which is mounted a bubble condenser, a thermometer and a
magnetic stirrer, at 50°C.
The reaction is monitored by TLC (eluent: 95/5
dichloromethane/methanol).
The medium is cooled to room temperature and the yellow
solid formed is drained by suction on a No. 3 sinter and washed
with 2x 100 ml of THF and then with 3 100 ml of isopropyl ether.
After drying at 35°C under vacuum in the presence of P205 for 12
hours, 3.2 g of a yellow solid corresponding to the expected
structure are recovered.
The NMR (1H 400 MHz and 13C 100.6 1 MHz DMSO-d6)
and mass spectrometry analyses are in accordance.
Synthesis of 4-(3-amino-4,5,6,7-tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl)- 1,1-dimethylpiperazin- 1-ium chloride hydrochloride
The compound is obtained according to a procedure identical
to that of Example 1, starting with 3 g of 1,1-dimethyl-4-(3-
nitropyrazolo[ 1,5-a]pyridin-2-yl)piperazin- 1-ium methyl sulfate.
The filtrates are acidified with 6N hydrochloric isopropanol
and the solvents are evaporated off under vacuum. The residue is
taken up in a methanol/petroleum ether mixture, followed by
evaporation under vacuum to give the expected compound in the
form of a beige-coloured powder (mass obtained = 1.7 g).
Analysis by mass spectrometry confirms the expected cation
[C 13H24N5]+.
The NMR analyses (1H 400 MHz and 13C 100.6 1 MHz
DMSO-d6) are in accordance with the expected structure.
Examples of dyeing
The following dye compositions (A) to (F) are prepared from
the ingredients below:
Compositions A B
1-(3 -amino -4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl)-N,N,N- 10 3 mol 10 3 mol
trimethy lpyrro lidin-3 -aminium
chloride hydrochloride
10 3 5-amino-2-methylphenol mol -
2-(2,4-diaminophenoxy)ethanol - 10 3 mol hydrochloride
Dye support (1) (*) (*)
Demineralized water qs 100 g 100 g
golden grey Shade observed brown
Compositions C D
[2-(3-aminopyrazolo[ l ,5-
a]pyridin-2-
ylamino) ethyl] trimethylammoni 10 3 mol 10 3 mol
um chloride dihydrochloride
5-amino-2-methylphenol 10 3 mol -
2-(2,4-diaminophenoxy)ethanol - 10 3 mol hydrochloride
Dye support (1) (*) (*)
Demineralized water qs 100 g 100 g
iridescent neutral Shade observed mahogany violet-grey red
Compositions E F
4-(3 -amino -4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl)- l , l - 10 3 mol 10 3 mol
dimethylpiperazin- 1-ium
chloride hydrochloride
10 3 5-amino-2-methylphenol mol -
2-(2,4-diaminophenoxy)ethanol - 10 3 mol hydrochloride
Dye support (1) (*) (*)
Demineralized water qs 100 g 100 g
Shade observed brick red bluish grey
9.5 dye support (1)
At the time of use, each composition is mixed with an equal
weight of 20-volumes aqueous hydrogen peroxide solution (6%> by
weight). A final pH of 9.5 is obtained.
Each mixture obtained is applied to locks of grey hair
containing 90% white hairs. After leaving the mixture on for 30
minutes, the locks are rinsed, washed with a standard shampoo,
rinsed again and then dried to give the various shades.
CLAIMS
1. Cationic tetrahydropyrazolopyridine of formula (I),
optical and geometrical isomers thereof, addition salts thereof
and/or solvates thereof:
in which formula (I):
• R2, R 3, R 4 and R represent, independently of each other, a
hydrogen atom; a halogen atom; a linear or branched C1-C4 alkyl
radical; a linear or branched C1-C4 hydroxyalkyl radical;
• R2 and R3, R3 and R4 or R4 and R may form, together with the
carbon atoms to which they are attached, a saturated,
unsaturated or aromatic 5- to 8-membered ring optionally
substituted with one or more radicals chosen from hydroxyl,
alkoxy, C1-C4 alkyl and C1-C4 hydroxyalkyl radicals;
• Zi represents an oxygen atom or a group NR ;
• R represents a hydrogen atom or a linear or branched C1-C4
alkyl radical;
• Ri represents:
- a linear or branched Ci-C 2o alkyl radical, substituted and/or
interrupted with a cationic radical, the said alkyl radical
being optionally interrupted with one or more oxygen atoms
and/or with one or more groups NR6, optionally substituted
with one or more radicals chosen from hydroxyl and C1-C4
alkoxy or hydroxyalkyl radicals;
- a saturated, unsaturated or aromatic, 5- to 8-membered ring
or heterocycle substituted with a cationic radical and
optionally substituted with one or more radicals chosen
from hydroxyl and C1-C4 alkoxy or hydroxyalkyl radicals;
when Zi represents a group NR then:
■ Ri and R may form, together with the nitrogen atom to
which they are attached, a saturated, unsaturated, aromatic or
non-aromatic, 5- to 8-membered mono- or polycationic,
preferably monocationic, heterocycle, optionally substituted
with one or more radicals chosen from C1-C4 alkyl, hydroxyl,
C1-C4 alkoxyamino, (Ci- C4)alkylamino, (Ci- C4)dialkylamino,
thio SH, (Ci-C4)alkylthio, carboxyl, C(0)OH or C(0)0-, M+
with M+, which may be present or absent depending on the
cationic charge number of the compound (I), representing an
alkali metal, alkaline-earth metal or ammonium; (Ci-
C4)alkylcarbonyl; sulfonyl -S(0) -R, -S(0) p-0-R, -0-S(0) p-R
with R representing a hydrogen atom or a C1-C4 (hydroxy)alkyl
group, n = 0, 1 or 2, p = 1 or 2, amido -C(0)-NRR' or -N(R)-
C(0)-R\ -N(R)-C(0)-NRR with R and R , which may be
identical or different, representing a hydrogen atom or a C1-C4
(hydroxy)alkyl group, C1-C4 hydroxyalkyls, this heterocycle
possibly containing one or more heteroatoms chosen from N and
O, preferably N,
■ Ri and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated, 5- to 8-
membered noncationic heterocycle optionally substituted with
one or more radicals chosen from C1-C10 alkyl; hydroxyl; C1-C4
alkoxy; amino; (Ci- C4)alkylamino; (Ci- C4)dialkylamino; thio
SH, (Ci-C4)alkylthio, carboxyl, C(0)OH or C(0)0-, M+ with
M+, which may be present or absent depending on the cationic
charge number of the compound (I), representing an alkali
metal, alkaline-earth metal or ammonium; (Ci- C4)alkylcarbonyl;
sulfonyl -S(0) -R, -S(0) p-0-R, -0-S(0) p-R with R representing
a hydrogen atom or a C1-C4 (hydroxy)alkyl group, n = 0, 1 or 2,
p = 1 or 2, amido -C(0)-NRR or -N(R)-C(0)-R\ -N(R)-C(0)-
NRR' with R and R', which may be identical or different,
representing a hydrogen atom or a C1-C4 (hydroxy)alkyl group,
C1-C4 hydroxyalkyls.
2 . Cationic tetrahydropyrazolopyridine of formula (I) according
to Claim 1, characterized in that the cationic radical is a linear or
branched or heterocyclic radical comprising a quaternary ammonium,
this quaternary ammonium being of the type -N+RaRbRc, with Ra, Rb
and Rc, which may be identical or different, representing a Ci-C alkyl
radical which may be substituted with a hydroxyl; Ra and Rb may
together form a 5- to 8-membered heterocycle, the radical Rc then
being a Ci-C alkyl radical that may be substituted with a hydroxyl.
3. Cationic tetrahydropyrazolopyridine of formula (I) according
to Claim 1 or 2, characterized in that, taken together or separately:
• R2, R3, R4 and R represent, independently of each other, a
hydrogen atom or a linear or branched Ci -C4 alkyl radical, preferably
a hydrogen atom or a linear Ci-C4 alkyl radical and even more
preferentially a hydrogen atom or a methyl radical,
• R2 and R3, R3 and R4 or R4 and R may form, together with
the carbon atoms that bear them, a saturated, unsaturated or aromatic
5- to 8-membered and preferably 5- or 6-membered ring, and
preferably an unsubstituted 5- or 6-membered carbon-based ring, and
more preferentially R4 and R may form, together with the carbon
atoms that bear them, an unsubstituted 5- or 6-membered carbon-based
ring;
• Zi represents an oxygen atom or a group NR ;
• R represents a hydrogen atom or a linear or branched Ci-C2
alkyl radical;
• Ri represents a linear or branched Ci-Cs alkyl radical,
substituted with a cationic radical, optionally substituted with one or
more radicals chosen from Ci-C4 alkyl and Ci-C4 alkoxy radicals,
or
• Ri represents a saturated, unsaturated or aromatic, 5- to 8-
membered non-cationic ring or heterocycle, substituted with a cationic
radical,
• when Z i represents N R then:
■ R i and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated cationic 5-
to 8-membered heterocycle optionally substituted with one or
more radicals chosen from Ci-Cio alkyl, hydroxyl, C 1-C4
alkoxy, amino, (Ci-C 4)alkylamino, di(Ci -C4)alkylamino, (Ci-
C4)alkylcarbonyl, amido and C 1-C4 hydroxyalkyl radicals, it
being possible for this heterocycle to contain one or more
heteroatoms chosen from N or O, preferably N,
or
■ R i and R may form, together with the nitrogen atom to
which they are attached, a saturated or unsaturated noncationic
5- to 8-membered heterocycle substituted with a
cationic radical and optionally substituted with one or more
radicals chosen from C 1-C 10 alkyl, hydroxyl, C 1-C4 alkoxy,
amino, (Ci-C 4)alkylamino, di(Ci-C 4)alkylamino, (Ci-
C4)alkylcarbonyl, amido and C 1-C4 hydroxyalkyl radicals.
4 . Cationic tetrahydropyrazolopyridine of formula (I) according
to any one of Claims 1 to 3, characterized in that the cationic radical
is chosen from trimethylammonium, triethylammonium,
dimethylethylammonium, diethylmethylammonium,
diisopropylmethyl ammonium, diethylpropylammonium,
hydro xyethyldiethylammonium, di-P-hydroxyethylmethylammonium
and tri -P-hydroxyethylammonium radicals.
5. Cationic tetrahydropyrazolopyridine of formula (I) according
to any one of Claims 1 to 3, characterized in that the cationic
heterocycle is chosen from imidazoliums, pyridiniums, piperaziniums,
pyrrolidiniums, morpholiniums, pyrimidiniums, thiazoliums,
benzimidazoliums, benzothiazoliums, oxazoliums, benzotriazoliums,
pyrazoliums, for example pyrrolidine, piperidine, morpholine and
piperazine rings, triazoliums and benzoxazoliums.
6 . Cationic tetrahydropyrazolopyridine of formula (I) according
to Claim 1 or 2, characterized in that R2 , R 3, R 4 and R represent a
hydrogen atom, Z \ represents a group NH and Ri represents a saturated
linear C2-C alkyl radical, optionally interrupted with a heteroatom
such as oxygen or a group NH, Ri being substituted with a cationic
radical chosen from trimethylammonium radicals and imidazolium,
piperazinium, pyrrolidinium, piperidinium or morpholinium cationic
heterocycles.
7 . Cationic tetrahydropyrazolopyridine of formula (I) according
to Claim 1 or 2, characterized in that R2, R3, R4 and R represent a
hydrogen atom, Z \ represents a group NR and Ri and R form,
together with the nitrogen atom to which they are attached, a saturated
or unsaturated, 5- to 8-membered non-cationic heterocycle, substituted
with a cationic radical preferably chosen from trimethylammonium,
diethylmethylammonium, imidazolium, piperazinium, piperidinium,
pyrrolidinium and morpholinium radicals.
8. Cationic tetrahydropyrazolopyridine of formula (I) according
to Claim 1 or 2, characterized in that R2, R3, R4 and R represent a
hydrogen atom, Z \ represents a group NR6 and Ri and R form,
together with the nitrogen atom to which they are attached, a cationic
heterocycle chosen from piperazinium, imidazolium, pyrrolidinium,
piperidinium and morpholinium substituted with one or more identical
or different radicals chosen from Ci-C4 hydroxyalkyl and Ci-C4 alkyl,
preferentially a piperazinium radical substituted with one or more
identical or different radicals chosen from Ci-C4 hydroxyalkyl and -
C4 alkyl.
9 . Cationic tetrahydropyrazolopyridine of formula (I) according
to any one of the preceding claims, characterized in that it is chosen
from the following compounds and the geometrical or optical isomer
forms thereof, the organic or mineral acid salts thereof or the solvates
thereof such as hydrates:

N H2 1-(3-amino-6,7-dimethyl-
4,5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl)-N-(2-
An- hydroxyethyl)-N,Ndimethylpyrrolidin-
3-
O H aminium, An-
Compound 21
1- {2- [(3 -amino -6, 7-
dimethyl-4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-
yl)oxy]ethyl} -N,N,Ntrimethylpyrrolidin-
3-
A - aminium, An-
Compound 22
3-[(3-amino-6,7-
dimethyl-4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl) amino ]-
,,-trimethylpropan-
1-aminium, An-
Compound 23
3-[(3-amino-6,7-
dimethyl-4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-yl)oxy]-
,,-trimethylpropan-
1-aminium, An-
Compound 24

NH2 4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4H-
1 / —N N cyclopenta[e]pyrazolo[ 1,5
\ -a]pyridin-2-yl)- l , l -
dimethylpiperazin- 1-ium,
An-
Compound 29
4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4Hcyclopenta[
e]pyrazolo[ 1,5
-a]pyridin-2-yl)- l -(2-
hydroxyethyl)- 1-
methylpiperazin- 1-ium,
An-
Compound 30
NH2 ^OH 4-(3 -amino -5, 5a,6,7,8,8 ahexahydro-
4Hcyclopenta[
e]pyrazolo[ 1,5
-a]pyridin-2-yl)- l , l -
bis(2-
hydroxyethyl)piperazin- 1-
ium, An-
Compound 31
NH2 l - {2-[(3-amino-4, 5,6,7-
tetrahydropyrazolo[ 1,5-
a]pyridin-2-
yl)oxy] ethyl} -3-methyllH-
imidazol-3-ium, An-
Compound 32
Process for synthesizing a cationic
tetrahydropyrazolopyridine of general formula (I) as defined above
starting with compounds (A), (B), (C) and (D) according to the
following scheme:
in which Rl Zl R2, R 3, R4 and R have the same meanings as those
indicated in formula (I), and
in which:
- in a step (i), an N-aminopyridinium derivative of formula (A)
is reacted with at least two equivalents of 1,1-bis(methylthio)-2-
nitroethylene, preferably in a polar solvent, to obtain a 2-
methylsulfanyl-3-nitropyrazolo[ 1,5-a]pyridine derivative of formula
(B),
- in a step (ii), an oxidation reaction is performed on the
compound of formula (B) to obtain an ,-dimethyl- 1-(3-
nitropyrazolo[ 1,5-a]pyridin-2-yl)pyrrolidin-3-amine derivative of
formula (C),
- in a step (iii), the compound of formula (C) is reacted with a
compound of formula R1Z1H or RiZT, M+ with M+ representing an
alkali metal or an alkaline-earth metal such as Li, Na or K, in order to
replace the group -S(0) 2-CH3 with a group -Z1R1 in order to obtain the
compound of formula (D), and
- in a step (iv), one or more reduction reactions are performed,
preferably in a polar solvent on the compound of formula (D) to give a
cationic tetrahydropyrazolopyridine of formula (I).
11. Compounds of formula (D) as defined in Claim 10 and in
which Ri , Zi , R2, R3, R4 and R are as defined according to any one of
Claims 1 to 8.
12. Composition for dyeing keratin fibres, in particular human
keratin fibres such as the hair, comprising, in a suitable dyeing
medium, one or more cationic tetrahydropyrazolopyridines of formula
(I) as defined in any one of Claims 1 to 9 .
13. Process for dyeing keratin fibres, in particular human
keratin fibres such as the hair, in which the dye composition as
defined according to Claim 12 is applied to the said fibres in the
presence of one or more oxidizing agents, and optionally one or more
couplers, for a time that is sufficient to obtain the desired coloration,
after which the resulting fibres are rinsed, optionally washed with
shampoo, rinsed again and dried or left to dry.
14. Use of one or more cationic tetrahydropyrazolopyridines of
formula (I) as defined according to any one of Claims 1 to 9, in the
presence of one or more oxidizing agents, for dyeing keratin fibres.
15. Multi-compartment device or dyeing kit, characterized in
that it comprises a first compartment containing a dye composition as
defined according to Claim 12 and a second compartment containing
one or more oxidizing agents.