CA2677295A1 - Method for preparing fluorinated sulphanylamides and sulphinamidines and uses thereof - Google Patents

Abstract

The present invention relates to a process for preparing polyfluorinated sulfanylamides of the formula (I) and polyfluorinated sulfinamidines of the formula (II), wherein R1-R4 are defined as in the claims and their precursors.

Description

PROCESS FOR THE PREPARATION OF SULFANYLAMIDES AND SULFINAMIDINES
FLUORES AND THEIR USES

The present invention relates to a process for preparing sulfanylamides and fluorinated sulfinamidines.

The present invention relates to a method for preparing new polyfluorinated sulfanylamides and sulfinamidines and their precursors and use potential of these sulfanylamides as possible substitutes for groups hydrophobic or to carboxylic acids contained in certain molecules organic-or as a perfluoroalkylsulfanylation agent.

The chemistry of fluorine has experienced a spectacular development in recent decades because of the importance that fluoride molecules have of the fields as diverse as polymers, battery salts, surfactants, assets, dyes, liquid crystals, coolants, agrochemicals and pharmacy [(a) Topics in Applied Chemistry. Organofluorine Chemistry, Principles and Commercial Applications. RE Banks, BE Smart and JC Tatlow. Plenum Press, New York, 1994 (b) Chem. Organic. Chem., 2004, No. 5, Fluorine Special Issue in Life Sciences (c) Chemistry of Organic Fluorine Compounds. Compounds It. A Critical Review. Mr.
Hudlicky and AE Pavlath. ACS Washington, 1995 (d) Organofluorine Compounds. Chemistry and Applications. T. Hiyama. Springer, 2000].

In the field of pharmacy, the figures show that the number of molecules with at least one fluorine atom and in development clinical or has been multiplied by 2.5 in twenty years [Inventory of Industrial Fluoro-Biochemicals.
A. Becker. Eyrolles, Paris, 1996]. Therapeutic indications corresponding are from the central nervous system to the anti-cancer antibiotics, anti-diabetics, anti-inflammatories and antihypertensives [Chemistry Bioorganic and Medicinal Fluorine, JP Bégué, D. Bonnet-Delpon, CNRS Editions, 2005]. In Reason to its marked lipophilicity, its small size and the polarized nature of the CF link [(a) Fluorine-Containing Molecules. Structure, Reactivity, Synthesis and Applications. JF
Liebman, A. Greenberg, WR Dolbier. VCH, Weinheim, 1988 (b) Organofluorine Chemistry. K. Uneyama. Blackwell Publishing, Oxford, 2006 (c) Scholfield, H.
J. Fluorine Chem. 1999, 100, 7-11], the introduction of one or more fluorine atoms into a biologically active molecule often results in better properties pharmaco kinetics (thanks to increased resistance to metabolism and gastric absorption facilitated intestinal tract), as well as enzymatic or cellular activities improved (thanks to a permeation facilitated through the membranes, a recognition sometimes

2 improved with the target or irreversible inhibition thereof) [Biomedical Frontiers of Fluorine Chemistry. I. Ojima, JR McCarthy, JT Welch. ACS, Washington, 1996]. The The most commonly used polyfluorinated groups in agrochemicals and pharmaceuticals are CF3 groups, OCF3, SCF3, SO2CF3, OCHF2 and SCHF2 all characterized by one character hydrophobic marked.

The methods of introducing fluorine or polyfluorinated groups are numerous and apply both aliphatic and aromatic series [(a) Organofluorine Compounds. Chemistry and Applications. T. Hiyama. Springer, 2000 (b) Organofluorine Chemistry. K. Uneyama. Blackwell Publishing, Oxford, 2006 (c) Houben-Weyl Methods of Organic Chemistry. 4th Edition. Organo-Fluorine Compounds. Volume E10. B.
Baasner, H. Hagemann, JC Tatlow. George Thieme, Verlag, Stuttgart, 1999 (d) Langlois, BR;
Ratton, S .; Paris, JM Chemical News 2006, No. 301-302, 56-66]. We will mention, among most used reactions, the transformation of alcohols and functions carbonyls in corresponding fluorinated and difluorinated derivatives by trifluoride diethylaminosulfur (DAST) [(a) Middleton, WJJ Org. Chem. 1975, 40, 574-578 (b) Hudlicky, M.
Org.
React. 1988, 35, 513-637], the Halex reactions which convert a halogeno-or nitro-arenas in fluoroarenas [(a) Clark et al. Chem. Soc. Rev. 1999, 28, 225-231 (b) The Roots of Organic Development. P244-292. BR Langlois, L. Gilbert, G. Forat.
Elsevier Amsterdam, 1996], electrophilic fluorination of ketones by N-fluoro sulfonylimides or Selectfluor [(a) Banks, REJ Fluorine Chem. 1998, 87, 1-17 (b) Cahard et al.
Chem. Rev. 2004, 104, 6119-6146] or even the reactions of trifluoromethylation, those of carbonyl compounds by nucleophilic means, with the reagent of Ruppert (CF3TMS) [(a) Prakash et al. Chem. Rev. 1997, 97, 757-786 (b) Langlois and al.
Synthesis 2003, 185-194], and electrophilically with Umemoto's reagent [Umemoto, T. Chem. Rev. 1996, 96, 1757-1778], or those of halo-aromatics [Burton et al.
J. Am. Chem. Soc. 1986, 108, 832-834].

These fluoridation methods often have limitations so that the introduction of a fluorine or a polyfluorinated group on a given molecule to a position given, still remains today, in many cases, a delicate problem for the chemist. Given the importance of fluorinated molecules, all improvements known methods of fluoridation or any new discoveries methodologies or Fluoridation reagents would be of great use in many areas. In particular, the discovery of new methods for the direct introduction of a SCF3 group (aromatic trifluoromethylsulfanylation reactions, aliphatic or on a hetero atom) using non-toxic reagents under conditions sweet,

3 allow to overcome the limitations of the methods described today and so easier access to molecules of interest for their applications potential agrochemistry and pharmacy, areas where molecules containing a SCF3 group are Common [(a) Inventory of Industrial Fluoro-Biochemicals. A. Becker.
Eyrolles, Paris, 1996 (b) Fluorine Compounds as Agrochemicals. 2nd Edition. SB Walker. BARK
Information Services, Wokingham, UK, 1995]. The known methods of direct trifluoromethylsulfanylation rely on mechanisms of nature electrophilic (via a SCF3 + species), nucleophilic (via a SCF3 species) or radical (via a SCF3 species) and use reagents such as CF3SCI [Haas et al. :
(a) Chem.
Ber. 1976, 109, 2475-2484 (b) Helv. Chim. Acta 1979, 62, 1442-1450 (c) J.
Fluorite Chem. 1984, 24, 363-368], CF3SSCF3 [Peach, ME Can. J. Chem. 1967, 45, 429-432]
CF3SH [Harris et al. J. Am. Chem. Soc. 1961, 83, 840-845], Hg (SCF3) 2 [Brandt et al.
J. Chem. Soc. 1952, 2198-2205], AgSCF3 [Emelus et al. J. Chem. Soc. 1961 2599], CuSCF3 [Yagulpolskii et al. Synthesis 1975, 721-723] or MSCF3 (with M + = Cs +
or Me4N +) [Tyraa et al. J. Fluorine Chem. 2003, 119, 101-107] which are usually very toxic (or are prepared from very toxic compounds) and give place to reactions that are not transferable on an industrial scale (gaseous state, excessive cost and difficult handling due to toxicity).

Among the molecules carrying a SCF3 group, trifluoromethylsulfanylamides who are characterized by an N-SCF3 group are poorly documented because mainly obtained by reacting an amine (primary or secondary) or an amide with (toxic gas) [(a) Haas et al. J. Heterocycl. Chem. 1986, 23, 1079-1084 (b) Shreeve and al. Inorg. Chem. 1985, 24, 2126-2129 (c) Munavalli et al. Phosphorus Sulfur Silicon Relat. Elem. 2003, 178, 107-113], or CF3SSCF3 whose toxicity comparable to that of phosgene [Peach, ME Can. J. Chem. 1967, 45, 429-432]. Other methods use CF3SNH2 [Haas et al. Chem. Ber. 1982, 115, 523-532] or CF3SNCO [(a) Haas and al.
Chem. Ber. 1982, 115, 533-539 (b) Haas, A. Chem. Ber. 1966, 99, 3103-3107], reagents also toxic, for the preparation of cyclic sulphanylamides or derivatives thereof of carbamates and ureas. Although not easily accessible, trifluorométhylsulfanylamides may have various biological properties as illustrated by the molecules below [Patents Bayer AG (WO2002006277, 2002; DE2045441, 1972 ;
DE2103199, 1972); Boehringer-Mannheim patent (DE2727550, 1979); patents Merck (GB2266527, 1993, EP481671, 1992, EP199630, 1986)].

4 O
CF3 \ ~ i0 SCF3 CF3S.N ~ pp O SCF3 MeN / yNr ~ NO Me \ p Me N ~ H-SCF3 N OE
~ Ph t OF ~ p I i Me CN p Herbicide Anti-inflammatory anticancer agent In addition, trifluoromethylsulfinamidines constitute another class of molecules bearing a SCF3 group, the latter being integrated into a sequence of type N = S (CF3) -N. These compounds are hardly and exclusively prepared for from CF3SF3 [(a) Glemser et al. Z. Naturforsch., B 1978, 33, 1417-1421 (b) Mews et al.
Chem. Ber. 1991, 124, 2411-2416 (c) Yagupolskii et al. Zh. Org. Khim. 1980 16, 863-867]. This reagent is itself prepared from SF4, a compound with difficulty manipulable, which explains the limited number of trifluoromethylsulfinamidines known.
The subject of the present invention is a process for the preparation of the compound sulfanylamide of formula (I) and the sulfinamidine compound formula (II) R1 / N \ SR ~ N ,, S ~ N, R (~~) in which a) R, represents:
or an optionally substituted aryl group;
or an optionally substituted heteroaryl group;
or an optionally substituted alkyl group;
or an optionally substituted cycloalkyl group;
or an optionally substituted heterocycloalkyl group;
or an -SO 2 -aryl group in which the aryl is optionally substituted;
or a -SO 2 -heteroaryl group where the heteroaryl is optionally substituted;
or a -SO 2 -fluoroalkyl group;
or a -CO 2 -aryl group wherein the aryl is optionally substituted;
or a -CO 2 -heteroaryl group where the heteroaryl is optionally substituted;
or a -CO 2 -alkyl group in which the alkyl is optionally substituted;

b) R2 represents a perfluorofluoroalkyl or difluoromethylene group substituted with -S-aryl, -S-heteroaryl or benzoxazol-2-yl. The aryl, heteroaryl and benzoxazole groups are optionally substituted,

C) R3 and R4 represent independently of each other an alkyl group, alkoxyalkyl or cycloalkyl or R3 and R4 together with the atom of nitrogen to which they are attached, a saturated or unsaturated heterocycle of 3 to 7 optionally comprising another heteroatom (such as piperidinyl, pirrolidinyl or morpholinyl);
characterized in that the following steps are carried out:

a first step, in which the compound of formula (IV) is condensed to a compound of formula (V) in the presence of a tertiary amine (such as triethylamine N, N-diisopropylethylamine, pyridine, 2,6-lutidine) in an organic solvent, of preferably in a non-polar solvent such as dichloromethane, to give the compound of formula (III), wherein R 1, R 2, R 3 and R 4 are such that defined previously and R5, R6 and R7 independently of one another represent group selected from optionally substituted alkyl or aryl groups;

F_S, N, R3 (V) ~ Ra F, S ~ N, R (III) + F: I 3 R2 R6 (IV) a second step, in which the compound of formula (III) is itself condensate to a compound of formula R, NH 2, where R, is as defined above, in presence of a tertiary amine (such as triethylamine, N, N-diisopropylethylamine pyridine, 2,6-lutidine) in an organic solvent, to give a sulfanylamide formula (I) or a sulfinamidine compound of formula (II), wherein R ,, R2, R3 and R4 are as previously defined;

6 NOT
F, N, ~
FS R3 R1 ~ N ~~ SN, R3 Ri S
II

(III) (II) (I) optionally a third step, in which the sulfinamidine compound of formula (II) is converted into an organic solvent in the presence of an acid for give a sulfanylamide compound of formula (I), wherein R 1 and R 2, R 3 and R4 are as defined previously.

The term "optionally substituted aryl" means an aryl group optionally substituted with one or more (for example from 1 to 3) groups, identical or different from each other, selected from the following atoms and groups :
= halogen, = optionally substituted alkyl, = alkoxy, = optionally substituted aryl, optionally substituted heteroaryl, = alkylene, = alkynyl, = fluoroalkyl, = fluoroalkoxy, = -O-aryl optionally substituted, = -O-heteroaryl optionally substituted, = -S-alkyl, = -S-fluoroalkyl, = -S-aryl optionally substituted, = -S-heteroaryl optionally substituted, = -CN, = -NO2, = heterocycloalkyl, = -N (Ra) (Rb), 0 -N (Ra) CO (Rb),

7 = -N (Ra) COO (Rc), = -N (Rc) CON (Ra) (Rb), = -N (Ra) SO2 (Rc), = -OSO2Rc, = -SOzN (Ra) (Rb), = -SO2 (Rc), = -CON (Ra) (Rb), = -CORb and = -COOR, where Ra and Rb are independently selected from hydrogen, a group (VS,-C4) optionally substituted alkyl, (C 1 -C 4) fluoroalkyl, cycloalkyl, aryl eventually substituted, optionally substituted heteroaryl, heterocycloalkyl and Rc takes values of R. except hydrogen, or Ra and Rb together with the nitrogen atom which they are attached, a saturated or unsaturated heterocycle of 3 to 7 members, comprising possibly another heteroatom.

The term "optionally substituted heteroaryl" means a group heteroaryl optionally substituted with one or more (eg 1 to 3) groups, identical or different from each other, chosen from among the atoms and groups following:
= halogen, = optionally substituted alkyl, = alkoxy, = optionally substituted aryl, optionally substituted heteroaryl, = alkylene, = alkynyl, = fluoroalkyl, = fluoroalkoxy, = -O-aryl optionally substituted, = -O-optionally substituted heteroaryl, = -S-alkyl, = -S-fluoroalkyl, = -S-aryl optionally substituted, O-S-heteroaryl optionally substituted, WO 2008/11069

8 PCT / FR2008 / 000136 = -CN, = -NO2, = heterocycloalkyl, = -N (Ra) (Rb), = -N (Ra) CO (Rb), = -N (Ra) COO (R), = -N (R.) CON (Ra) (Rb), = -N (Ra) SOz (Rc), = -OSO2R, ~, = -SO2N (Ra) (Rb), = -SO2 (R1), = -CON (Ra) (Rb), = -CORb and = -COORc, where Ra, Rb and Rc are as previously defined;

In particular, the term "optionally substituted alkyl" means an alkyl group optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, selected from the following atoms and groups:
= halogen, = optionally substituted aryl, optionally substituted heteroaryl, = heterocycloalkyl, = alkoxy, = fluoroalkyl, = fluoroalkoxy, = -O-aryl optionally substituted, = -O-optionally substituted heteroaryl, = -S-alkyl, = -S-fluoroalkyl, = -S-aryl optionally substituted, = -S-heteroaryl optionally substituted, = -CN, = -NO2, 0 -SO2N (Ra) (Rb),

9 = -SO2 (Rc), = -CORb, = -COORc, = -CON (Ra) (Rb), = -N (Ra) (Rb), = -N (Ra) CO (Rb), = -N (Ra) COO (Rc), = -N (Rc) CON (Ra) (Rb), and = -N (Ra) SO2 (Rc), where Ra, Rb and Rc are as previously defined;

In the context of the present invention, and unless otherwise stated in the text, we means by:
a halogen atom: a fluorine, a chlorine, a bromine or an iodine.
an alkyl group: a saturated aliphatic group comprising from 1 to 12 atoms carbon (advantageously from 1 to 6 carbon atoms) and being linear or branched.
By way of examples, mention may be made of methyl, ethyl and propyl groups.
isopropyl, butyl, isobutyl, tertbutyl, pentyl, hexyl, etc.
an alkoxy group: an -O-alkyl radical where the alkyl group is such that defined previously.
an alkoxyalkyl group: a radical of formula alkyl-O-alkyl, where the groups alkyl, identical or different from each other, are as defined previously.
a fluoroalkyl group: an alkyl group as defined above and comprising between 1 and 13 fluorine atoms, preferably from 1 to 5.
examples, we can mention the groups -CH2F, -CHF2, -CF3, -CH2CF3 and -CF2CF3. The group is told perfluoroalkyl when each hydrogen atom of the alkyl group is replaced by a fluorine atom as in -CF2CF3.
a fluoroalkoxy group: an alkoxy group as defined above and comprising between 1 and 9 fluorine atoms. As examples, mention may be made of groups -O-CH2F, -O-CHF2, -O-CF3, -O-CH2CF3 and -OCF2CF3, -OCH (CF3) 2. The group is told perfluoroalkoxy when each hydrogen atom of the alkyl group is replaced by a fluorine atom as in -OCF2CF3.
an alkylene group: a linear or branched hydrocarbon group having one or several unsaturations and having from 2 to 12 carbon atoms, preferentially between 2 and 6 carbon atoms. The substituents ethylenyl, 1-methylethylenyl, prop-1-enyl, prop-2-enyl, Z-1-methylprop-1-enyl, E-1-methylprop-1-enyl, Z-1,2-dimethyl-prop-1-enyl, E-1,2-dimethylprop-1-enyl, but-1,3-dienyl, 1-methylidenyl-prop-2-enyl, Z-2-methylbut-1,3-dienyl, E-2-methylbut-1,3-dienyl, 2-methyl-1-methylidenylpropyl 2-enyl, undec-1-enyl and undec-10-enyl are examples of alkylene substituents.
an alkynyl group: a linear or branched hydrocarbon substituent having at At least two unsaturations carried by a pair of vicinal carbon atoms, having 2 at 12 carbon atoms, preferably between 2 and 6 carbon atoms. The ethynyl, prop-1-ynyl, prop-2-ynyl, and but-1-ynyl substituents are examples of alkynyl substituent.
a cycloalkyl group: a saturated mono or polycyclic hydrocarbon group or

Partially unsaturated, having from 3 to 12 carbon atoms, preferably between 3 and 6 carbon atoms. Cyclopropyl, cyclobutyl and cyclopentyl substituents cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, cycloheptyl, bicyclo [2.2. 1] heptyl, cyclooctyl, bicyclo [2.2.2] octyl, adamantyl and perhydronaphthyl are examples of cycloalkyl substituents.
a heterocycloalkyl group: a cyclic carbon group comprising between 4 and 8-membered and between 1 and 4 heteroatoms selected from nitrogen, oxygen and sulfur.
This heterocycloalkyl group may be substituted, at any position, understood on nitrogen atoms of the ring, by one or more groups, identical or different from each other, selected from fluorine and atkyl groups optionally substituted, alkoxy, alkoxyalkyl, oxo, -CF3, -OCF3, -COOalkyl, -CO-NRR ', NRCOR' and -NRR ', where R
and R 'represent a hydrogen atom or a - (C 1 -C 4) alkyl group. As For example, there may be mentioned morpholine, pyrrolidine, piperidine, piperazine, 2-pyrrolidinone 2-piperidinone, imidazoline, and imidazolidine 2,4-dione.
an aryl group: a mono- or polycyclic aromatic substituent having 6 at 14 carbon atoms. The substituents phenyl, naphth-1-yl, naphth-2-yl, anthracene-9-yl, 1,2,3,4-tetrahydronaphth-5-yl and 1,2,3,4-tetrahydronaphth-6-yl are examples of aryl substituent.
a heteroaryl group: a mono- or heteroaromatic substituent polycyclic having 1 to 13 carbon atoms and 1 to 4 heteroatoms. The substituents pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, 1,2,4-triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, 1,3,5-triazinyl, indolyl, benzo [b] furyl, benzo [b] thienyl, indazolyl, benzimidazolyl, azaindolyl, quinolyl, isoquinolyl, carbazolyl and acridyl are examples of substituents heteroaryl.
a heteroatom: at least one divalent atom, different from carbon. N, O
and S are examples of heteroatoms.

11 There may be mentioned a preparation method according to the present invention as that defined previously for which Ri represents':
or an aryl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, chosen from atoms and groups:
= halogen, = optionally substituted alkyl, = alkoxy, = optionally substituted aryl, optionally substituted heteroaryl, = alkylene, = alkynyl, = fluoroalkyl, = fluoroalkoxy, = -S-fluoroalkyl, = -CN, = -NO2, = heterocycloalkyl, = -N (Ra) (Rb), = -N (Ra) CO (Rb), = -N (Ra) COO (R), = -OSO2Rc, = -CON (Ra) (Rb), = -CORb and = -COOR, where Ra and Rb are independently selected from hydrogen, optionally substituted (C 1 -C 4) alkyl group, (C 1 -C 4) fluoroxyalkyl, cycloalkyl, optionally substituted aryl, heteroaryl optionally substituted, heterocycloalkyl and R, takes the values of Ra except hydrogen, or Ra and Rb together with the nitrogen atom to which they are attached, a saturated or unsaturated heterocycle of 3 to 7 links optionally comprising another heteroatom;
or a heteroaryl optionally substituted with one or more example 1 to 3) groups, identical or different from each other, selected from the following atoms and groups:

12 = halogen, = optionally substituted alkyl, = alkoxy, = fluoroalkyl, = fluoroalkoxy, = -CN, = -N (Ra) (Rb), = -CORb and = -COOR, where Ra, Rb and R are as previously defined;
or an alkyl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, chosen from atoms and groups:
= halogen, = optionally substituted aryl, optionally substituted heteroaryl, = heterocycloalkyl, = alkoxy, = -S-alkyl, = fluoroalkyl, = fluoroalkoxy, = -CN, = -NO2 = -COOR, = -CON (Ra) (Rb), = -N (Ra) (Rb), = -N (Ra) CO (Rb), = -N (Ra) COO (R, -), = -N (Rc) CON (Ra) (Rb), and = -N (Ra) SO2 (Rc), where Ra, Rb and Rc are as previously defined;
or a group -SO 2 -aryl where aryl is optionally substituted with one or several (for example 1 to 3) groups, identical or different from each other others, selected from the following atoms and groups:
0 halogen,

13 = alkyl, = alkoxy, = fluoroalkyl, = fluoroalkoxy, = -CN, = -NO2, = -N (Ra) (Rn), = -CORb and = -COOR ,, where Ra, Rb and Rc are as previously defined;
or a -SO 2 -heteroaryl group where the heteroaryl is optionally substituted by one or more (for example 1 to 3) groups, identical or different from each other, selected from atoms and groups following:
= halogen, = alkyl, = alkoxy, = fluoroalkyl, = fluoroalkoxy, = -CN, = -N (Ra) (Rb), = -CORb and = -COOR ,, where Ra, Rb and Rc are as previously defined;
or a -SO 2 -fluoroalkyl group;
or a -CO 2 -alkyl group where the alkyl is optionally substituted by a or several (for example 1 to 3) groups, identical or different others, chosen from the following atoms and groups:
= fluorine, = optionally substituted aryl, optionally substituted heteroaryl, = heterocycloalkyl, = alkoxy, = -S-alkyl, Fluoroalkyl,

14 = fluoroalkoxy, = -CN, = -NO2 = -COOR ,, = -CON (Ra) (Rb), = -N (Ra) (Rb), = - V (Ra) CO (Rb), = -N (Ra) COO (Rc), = -N (Rc) CON (Ra) (Rb), and = -N (Ra) SO2 (Rc), where Ra, Rb and R are as defined above.

In addition, there may be mentioned a preparation method according to the present invention as previously defined for which R, represents:
or an aryl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, selected from a halogen atom (such as CI and F), a - (C 1 -C 4) alkyl group, - (C, -C4) alkoxy, - (C1-C4) perfluoroalkyl, - (C1-C4) perfluoroalkoxy, -NO2i - (C3-C6) optionally substituted heterocycene, -N (Ra) (Rb), -N (Ra) CO (Rb), -OSO2R, -CORb and -COOR, where Ra and Rb are independently selected from a hydrogen atom, a - (C 1 -C 4) alkyl group optionally substituted or (C, -C4) perfluoroalkyl and Rc takes the values of Ra except hydrogen;
or a group -SO 2 -aryl where aryl is optionally substituted with one or several (for example 1 to 3) groups, identical or different from each other other, selected from a halogen atom, a - (C 1 -C 4) alkyl group, - (C, -C4) alkoxy, - (C1-C4) perfluoroalkyl, - (C1-C4) perfluoroalkoxy;
or a -SO 2 -heteroaryl group where the heteroaryl is optionally substituted by one or more (for example 1 to 3) groups, identical or different from each other, chosen from a halogen atom, a group - (C 1 -C 4) alkyl, - (C 1 -C 4) alkoxy, - (C 1 -C 4) perfluoroalkyl, - (C, -C4) perfluoroalkoxy;
or a -SO 2 - (C 1 -C 4) perfluoroalkyl group;
- a -CO2- (C, -C3) alkyl group where the alkyl is optionally substituted by one or more (for example 1 to 3) groups, identical or different each other, selected from a fluorine atom, a group - (C, -C4) perfluoroalkyl, - (C1-C4) perfluoroalkoxy, optionally substituted aryl, NO2, -N (Ra) (Rb), -CORb, -COOR, where Ra, Rb and R, are as defined previously;
Or a heteroaryl optionally substituted with one or more example 1 to 3) groups, identical or different from each other, chosen from a halogen atom, a - (C 1 -C 4) alkyl group, - (C 1 -C4) perfluoroalkyl, - (C 1 -C 4) perfluoroalkoxy, - (C 1 -C 4) alkoxy, -CN, -CORb, -COOR, where Rb and R, are as previously defined;
Or - - (C 1 -C 6) alkyl optionally substituted with one or more (by example 1 to 3) groups, identical or different from each other, chosen from a fluorine atom, a - (C 1 -C 4) perfluoroalkyl group, -NO 2, -CN, optionally substituted aryl, optionally substituted heteroaryl or -NRdRe, where Rd and Re are H or - (C 1 -C 4) alkyl.
There may also be mentioned a preparation method according to the present invention such as previously defined for which R, represents:

or an aryl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, chosen from a halogen atom (such as CI and F), a - (C 1 -C 4) alkyl group, - (C, -C4) alkoxy, -CF3, -NO2, -NHCORd (with Rd, as defined above), CO (C, -C4) alkyl, - (C3-C6) heterocycloalkyl optionally substituted with a or several groups, identical or different from each other, chosen from an oxo and (C 1 -C 2) alkyl group optionally substituted with a heteroaryl;
or an -SO 2 -aryl group in which the aryl is optionally substituted with one or several (for example 1 to 3) groups, identical or different from each other other, selected from a halogen atom, a - (C 1 -C 4) alkyl group, -C4) alkoxy, - (C1-C4) perfluoroalkyl, - (C1-C4) perfluoroalkoxy;
or a -SO 2 -heteroaryl group where the heteroaryl is optionally substituted by one or more (for example 1 to 3) groups, identical or different from each other, chosen from a halogen atom, a group - (C 1 -C 4) alkyl, - (C 1 -C 4) alkoxy, - (C 1 -C 4) perfluoroalkyl, - (C, -C4) perfluoroalkoxy;
or a -SO 2 - (C 1 -C 4) perfluoroalkyl group;

- a -CO2- (C, -C3) alkyl group where the alkyl is optionally substituted by one or more (for example 1 to 3) groups, identical or different each other, selected from a fluorine atom, a group - (C, -C4) perfluoroalkyl, - (C1-C4) perfluoroalkoxy, optionally substituted aryl, NO2, -N (Ra) (Rb), -CORb, -COOR, where Ra, Rb and R are as defined previously;
or a heteroaryl optionally substituted with one or more example 1 to 3) groups, identical or different from each other, chosen from a halogen atom, a - (C 1 -C 4) alkyl, - (Cl-C4) perfluoroalkyl, - (C 1 -C 4) perfluoroalkoxy, - (C 1 -C 4) alkoxy, -CN, -CORb, -COOR, ~, where Rb and R, are as previously defined;
or an alkyl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, chosen from a fluorine atom, - (C 1 -C 4) perfluoroalkyl group (such as -CF 3, -CF 2 CF 3), NO2, -CN, optionally substituted aryl, optionally heteroaryl substituted or -NRdRe, where Rd and Re are H or - (C, -C4) alkyl.

Preferably, the subject of the present invention is a preparation process such as defined previously for which R2 represents a group - (C, -C2) perfluoroalkyl.
The present invention also preferably relates to a method of preparation as defined above for which R3 and R4 represent independently of one another an alkyl or alkoxyalkyl group or else R3 and R4 form together, with the nitrogen atom to which they are attached, a group morpholinyl.
Preferably, the subject of the present invention is a preparation process such than previously defined for which R5, R6 and R7 represent a group methyl.

According to the present invention, the compound of formula (III) is obtained by reaction of compounds of formula (IV), and (V), preferably in a ratio (IV) / (V) between 1 and 2 equivalent, at a temperature between -40 C and 40 C, in the presence of preference from one to two equivalents, a tertiary amine (such as triethylamine, N, N-diisopropylethylamine, pyridine, 2,6-lutidine), in an organic solvent, preference a non-polar solvent such as dichloromethane.

F = SN \ Rs (V) R
F ~
+ - ~ F ~ S-NR3 (III) FI

R2 Si ~ R6 (IV) According to the present invention, sulfanylamides of formula (I) and sulphinamidines formula (II) are obtained by adding to the preceding reaction mixture containing the compound of formula (III), a compound of formula R, NH 2, preferably a equivalent to a temperature between -40 C and 40 C.

Ra Ra i Ri-NH2H
F_SN.R3 R ~ / N ~ S, N, R3 and / or R1 / N ~ S ~ RZ

(III) (II) (I) or spontaneously When the sulfinamidine intermediate of formula (II) is isolable and stable, he can be converted to the sulfanylamide compound of formula (I) by reaction in a solvent organic compound, such as dichloromethane, in the presence of an organic acid or mineral, by trifluoroacetic acid, at a temperature between 0.degree.
boiling temperature of the solvent.
The present invention also relates to the process for the preparation of a compound of formula (Ib; s) in which Ro is an alkyl, alkylene, alkynyl group, eventually substituted, obtained by alkylation of the compounds of formula (I), wherein R 1 and R 2 are such as previously defined. Thus, according to the present invention, the compounds of formula (I) are reacted with an alkylating agent of formula RoX or RoOSOzR, where X
is a halogen atom and R is an optionally substituted alkyl or aryl group, in presence of an organic or inorganic base such as sodium hydride NaH, in a aprotic polar solvent such as dimethylformamide, at a temperature range especially between -20 C and 60 C.

H
IV RoX I ~
~
R ~ / SR ~~ ~ S

(I) (Ibis) The present invention also relates to intermediate compounds formula (I), (II) and (III):

HRR

N ~ / N ~~ N`1 F, ,, N, RS Ri S R3 FS R3 (I) (II) (III) in which R 1, R 2, R 3 and R 4 are as defined above.
The preparation of intermediates of formula (I), (II) and (III) The sulfanylamides (I), (Ibis) and sulfinamidines (II) according to the invention can find applications in the field of agrochemistry and pharmacy, as substitutes to molecules containing fluoroalkyl, fluoroalkoxy hydrophobic groups, fluoroalkylsulfanyl or fluoroalkylsulfonyl, such as CF3, OCF3, SCF3 and SO2CF3 in replacing said hydrophobic groups with NROSR2 and N = S (R2) NR3R4 groups as described in the present invention and with Ro, R2, R3 and R4 defined as previously.

By way of non-limiting example, the molecules below are inhibitors tyrosine IGF1-R kinase [Baserga, R. Exp. Cell. Res., 1999, 253, 1-6 for a review on this kinase]:

R

ON ~ O
NOT
NOT

The table below shows that the molecule where R NHSCF3, prepared according to the The present invention is comparable in terms of biochemical activities and cellular phones molecules described in patent FR2850652 with R = OCF3, SCF3 or SO2CF3.

R IC50 IGF1-R '(nM) IC50 ELISA2 (nM) IC50 MEF3 (nM) OCF3 162,337,274 1: HTRF format. 2: Inhibition of autophosphorylation of IGF1-R in cellulo.
3: Inhibition of IGF1-induced proliferation of a MEF line.

Sulfanylamides (I) wherein R 1 is -SO 2 -aryl, -SO 2 -heteroaryl, -SO 2 fluorooalkyle, -CO2-alkyl, -CO2-aryl or -CO2-heteroaryl, where the aryl, heteroaryl groups and alkyl can be optionally substituted, can find applications in the domain of pharmacy, as substitutes for molecules containing a function acid carboxylic acid by replacing said carboxylic acid with a group -SO 2 -NH-S-R2 or -OCO-NH-S-R2 as described in the present invention and with R2 defined as previously. This replacement is possible in these cases because of the character acid compounds R, -NH-S-R2. By way of non-limiting example, the compound p S02-NH-SCF3 has a measured pKa of 5.4 (titration with D-Pas in MeOH / KCl 0.15M at C), while the pKa of benzoic acid is 4.2.
Sulfanylamides (I) or (Ib; s) where R, is an aryl group (advantageously phenyl), R2 is a trifluoromethyl group and for the compound of formula (Ibis) Ro is a methyl group can be used as agent of perfluoroalkylsulfanylation -preferentially trifluoromethyl- and pentafluoroethyl-sulfanylation of compounds aromatic, heteroaromatic, alkenyl and alkynyl, according to the three equations below.

Thus, the subject of the present invention is also the use of the compounds of Formula (I) and (IBI) as a perfluoroalkylsulfanylation agent of aryl compounds, heteroaryl, alkenyl and alkynyl as defined below. according to the invention, the substrate unsaturated compound and the compound (I), in equimolar amount, are reacted in presence either of an excess of sulphonic acid (preferentially para-toluenesulfonic or camphor sulphonic acid) or hydrochloric acid in ether, excess of a salt Sulfonic acid (preferentially the sodium salt of the para-toluene) and a Lewis acid (such as ethyl trifluoroborate) in a solvent nonpolar as dichloromethane and at a temperature between 0 and 40 C, for give compounds having an SR2 function.

, / SRz / SR2 RSO3H
R1-N \ or R1-N \ + AH A-SRZ

(Leq.) (I) (Ibis) (VI) where A = aryl group (eg A-SCF3)

15 or heteroaryl , SR2 / SR2 Ria Rib CHZCIZ RZS Rid R1-N ~ or R1-N ~ + Rb H Ra Ric Rid RS03H or HCI / EtzO RiC OSO2R or CI
(Ibis) (léq.) Or BF3 Et20, RSO2ONa (VII) (I) (for example SR2 = SCF3 or SCF2CF3) / SRZ CHZCIZ R g OTs R1-N + R ~ e = Rf 2-, ~ (for example SR2 = SCF3) Ro RS03H Rie Rif (léq.) or BF3 Et20, (Ibis) RSO2ONa (VIII) a single Z or E stereoisomer of undetermined nature The resulting polyfluorinated compounds are potential compounds interesting for various applications, especially agrochemistry and the pharmacy, for example as building blocks for building biological molecules active more complex.

The starting compounds and the reagents, when their method of preparation is not not described below, are commercially available or described in the literature or may be prepared by methods described therein or which are known of the Man of the art.
The invention is also described by the following examples given as illustration of the invention.

Example 1: 5,5-Dimethyl-1-quinolin-4-ylmethyl-3- (4-trifluoromethyl) sulfanylamino-phenyl) imidazolidine-2,4-dione, trifluoroacetate (Compound 1) 1.1: 3- (4-nitro-phenyl) -5,5-dimethyl-1-quinolin-4-ylmethylimidazolidine-2,4-dione To a solution of 1.000 g of methyl ester of 2-methyl-2-[(Quinolin-4-ylmethyl) -amino] propionic acid (prepared according to the process described in the application patent FR2850652), in 40 ml of tetrahydrofuran, at a temperature in the region of 20 C, is added 1,600 g of 4-nitrophenyl isocyanate. The mixture obtained is stirred at this same temperature for 18 hours. 20 ml of methanol are then added and the mixture is stirred for 15 minutes at room temperature. The resulting solution is concentrated under reduced pressure to give a yellow powder which is taken up in 150 ml of methanol. The suspension obtained is filtered on sintered glass to give 1,400 g of 3- (4-nitro-phenyl) -5,5-dimethyl-1-quinolin-4-ylmethyl-imidazolidine-2,4-dione, under made of bright yellow powder (MS: M = 391 g / mol).

1.2: 3- (4-aminophenyl) -5,5-dimethyl-1-quinolin-4-ylmethylimidazolidin-2,4-dione To a mixture of 1,350 g of 3- (4-nitro-phenyl) -5,5-dimethyl-1-quinolin-4-ylmethyl-imidazolidine-2,4-dione and 0.130 g of 5% palladium on carbon in 70 ml ethanol, at a temperature in the region of 55 ° C., are added dropwise ml of hydrazine hydrate. The resulting reaction mixture is then stirred at this same temperature for 3h30 then cooled and filtered on celite. The filtrate obtained is concentrated under reduced pressure to give 1,180 g of 3- (4-amino-phenyl) -5,5-dimethyl-1-quinolin-4-ylmethylimidazolidine-2,4-dione as a white powder grayish (MS:
M + = 360 g / mol).

1.3: 5,5-Dimethyl-1-quinolin-4-ylmethyl-3- (4-trifluoromethylsulfanylamino) phenyl) imidazolidine-2,4-dione, trifluoroacetate To a solution of 0.260 g of N, N-diisopropylethylamine in 15 ml of dichloromethane under an inert atmosphere of argon and at a similar temperature from -20 C, 0.135 ml of diethylaminosulfur trifluoride is added dropwise (DAST). The mixture obtained is stirred at this same temperature for 10 minutes then cooled to -20 C before adding 0.150 ml of (trifluoromethyl) trimethylsilane and stirring at -20 C
during 1 hour. To the resulting mixture, a suspension of 0.360 g of 3- (4-aminophenyl) -5,5-dimethyl-1-quinolin-4-ylmethyl-imidazolidine-2,4-dione in 5 ml of ethyl acetate and 5 ml of dichloromethane. The mixture is then stirred during 3 hours at 0 C then 48 hours at room temperature, before adding a solution saturated of sodium hydrogencarbonate. The organic phase is separated, dried over sulfate magnesium, filtered and concentrated under reduced pressure. The residue obtained is put in solution in 50 ml of dichloromethane. 0.500 ml is added dropwise acid trifluoroacetic acid at room temperature and the resulting mixture is allowed to even temperature for 18 hours. The solution is then concentrated under pressure reduced and the residue obtained is purified by preparative LC / MS (water / acetonitrile gradient at 0.07%
trifluoroacetic acid). 0.010 g of 5,5-dimethyl-1 are thus obtained.
quinolin-4-ylmethyl-3- (4-trifluorométhylsulfanylamino-phenyl) imidazolidine-2,4-dione, trifluoroacetate under light beige powder form (Yield 2%, MS M '= 461 g / mol).
1 H-NMR (300MHz, DMSO d6): δ ppm 8.90 (bd, 1H); 8.50 (s, 1H); 8.29 (d broad, 1H); 8.10 (broad d, 1H); 7.85 (broad t, 1H); 7.72 (broad t, 1H) ; 7.64 (d, 1H);
7.36 (bd, 2H); 7.20 (broad d, 2H); 5.15 (brs, 2H); 1.42 (s large, 6H).

Example 2: 4-methyl-N - [(trifluoromethyl) thio] benzenesulfonamide (Compound 21) 2.1: N- [difluoro (trifluoromethyl) -A4-sulfanyl] -N, N-diethylamine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature neighbor of -20 ° C., 0.135 ml of DAST is added dropwise. The reaction medium is agitated to this same temperature for 10 minutes before the addition of 0.150 ml of (Trifluoromethyl) trimethylsilane. After 1 hour, with stirring at -20 ° C., performs a 19 F NMR assay of the reaction medium. N-compound [difluoro (trifluoromethyl) -A 4-sulfanyl] -N, N-diethylamine, not isolated, was quantitatively produced.
19 F-NMR (282 MHz, CFCl3): δ ppm + 2.31 (q, 2 F), -64.81 (t, 3 F).

2.2 N - [(diethylamino) (trifluoromethyl) -14-sulfanylidene] -4-methylbenzenesulfonamide (Compound 37) To the reaction mixture of step 2.1, 0.17 g of 4-methylbenzenesulfonamide dissolved in 2 ml of anhydrous ethyl acetate. The middle The reaction mixture is then stirred at room temperature for 18 hours. The gross The reaction is subsequently washed with an aqueous solution (6%) of NaHCO 3 before being dried over Na2SO4. The organic phase is concentrated and purified by chromatography on silica in the presence of 0.5% triethylamine (pentane / acetone: 8/1). We gets 0.325 g of the expected product in the form of a yellow oil (Yield 95%, LC / MS M + =

g / mol).

2.3: 4-methyl-N - [(trifluoromethyl) thio] benzenesulfonamide (Compound 21) To a solution of 0.342 g of N - [(diethylamino) (trifluoromethyl) - ~, 4-sulfanylidène] -4-methylbenzenesulfonamide in 2 ml of dichloromethane, 0.260 ml is added acid trifluoroacetic at room temperature. The reaction medium is by the following agitated to 50 C for 24 hours. Finally, the crude reaction product is washed with water and then dried sure Na2SO4. After evaporation under reduced pressure, 0.260 g of 4-methyl-N-[(trifluoromethyl) thio] benzenesulfonamide in the form of a white powder (Yield 96%
LC / MS M + = 271 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.81 (d, 2H); 7.35 (d, 2H); 6.75 (s wide, 1H);
2.45 (s, 3H).

Example 3: 1- (4 - {[(trifluoromethyl) thio] amino} phenyl) ethanone (Compound 18) 3.1: 4- [difluoro (trifluoromethyl) -14-sulfanyl] morpholine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature neighbor of -20 C is added dropwise 0.137 ml of trifluoride morpholinosoufre. The the reaction medium is stirred at this same temperature for 10 minutes before adding 0.150 ml of trifluoromethyltrimethylsilane. After 1 hour, with stirring 20 C, we performs a 19F NMR assay of the reaction medium. The compound 4-[difluoro (trifluoromethyl) -4-sulfanyl] morpholine, not isolated, was produced quantitatively.
19 F-NMR (282 MHz, CFCl 3): 8 ppm + 2.66 (q, 2F); -63.72 (t, 3F).

3.2: 1- (4 - {[morpholin-4-yl (trifluoromethyl) -X4-sulfanylidène] amino} phenyl) ethanone (Compound 36) To the reaction mixture of step 3.1, 0.125 g of 1- (4-aminophenyl) ethanone dissolved in 2 ml of anhydrous dichloromethane. The middle The reaction mixture is then stirred at ambient temperature for 4 hours. The gross reaction is subsequently washed with an aqueous solution (6%) of NaHCO 3 before being dried on Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of the crude reaction product (Pentane / acetone: 4/1), 0.224 g of (4 - {[morpholin 4-yl (trifluoromethyl) -X4-sulfanylidene] amino} phenyl) ethanone as a powder white (yield 70%, LC / MS M + = 320 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.81 (d, 2H); 7.35 (d, 2H); 6.75 (s wide, 1H);
2.45 (s, 3H).
3.3: 1- (4 - {[(trifluoromethyl) thio] amino} phenyl) ethanone (Compound 18) At a temperature of 0 ° C., 0.090 ml of acid are added dropwise.
trifluoroacetic acid to a solution of 0.320 g of compound obtained in step 3.2 in 2 ml of dichloromethane. The reaction medium is subsequently stirred at room temperature ambient for 12 hours. Finally, the crude reaction product is washed with water and then dried on Na2SO4.
After evaporation under reduced pressure, the residue is purified by chromatography on silica (Pentane / acetone: 60/1) to give 0.207 g 1- (4-{[(trifluoromethyl) thio] amino} phenyl) ethanone in the form of a powder of beige (Yield 88%, LC / MS M + = 235 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.91 (d, 2H); 7.16 (d, 2H); 6.11 (s large, 1H);
2.56 (s, 3H).

Example 4: 1- (4 - {[(trifluoromethyl) thio] amino} phenyl) ethanone (Compound 18) Alternatively to Example 3, 1- (4-{[(trifluoromethyl) thio] amino} phenyl) ethanone can be prepared according to the following procedure: to the reaction mixture of the step 2.1, we 0.135 g of 1- (4-aminophenyl) ethanone dissolved in 2 ml of anhydrous dichloromethane. The reaction medium is then stirred at room temperature ambient for 4 hours before being washed with an aqueous solution (6%) of NaHCO 3 and to be dried over Na2SO4. After filtration and evaporation under reduced pressure, the gross The reaction mixture is solubilized in 2 ml of anhydrous dichloromethane and then cooled.
to one at a temperature of 0 ° C. 0.070 ml of acid is then added dropwise.
trifluoroacetic and the reaction medium is stirred at room temperature for 1 h. Finally, gross The reaction mixture is washed with water and then dried over Na 2 SO 4. After evaporation under pressure When reduced and washed with pentane, 0.164 g of 1- (4-{[(trifluoromethyl) thio] amino} phenyl) ethanone in the form of a powder of beige (Yield 70%, LC / MS M + = 235 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.91 (d, 2H); 7.16 (d, 2H); 6.11 (s large, 1 H);
2.56 (s, 3H).
Example 5 Benzyl [(trifluoromethyl) thio] carbamate (Compound 22) 5.1: Benzyl [diethylamino (trifluoromethyl) -X4-sulfanylidene] carbamate (Compound 42) To the reaction mixture of step 2.1, 0.151 g of benzyloxycarbamate dissolved in 2 ml of anhydrous dichloromethane. The environment The reaction mixture is then stirred at room temperature for 48 hours. The gross The reaction is subsequently washed with an aqueous solution (6%) of NaHCO 3 before being dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of the crude reaction product (Pentane / acetone: 15/1), gets 0.222 benzyl [(1Z) - (diethylamino) (trifluoromethyl) -; 4-sulfanylidene] carbamate form a yellow oil (Yield 69%, LC / MS M + = 322 g / mol).

5.2 Benzyl [(trifluoromethyl) thio] carbamate (Compound 22) To a solution of 0.322 g of benzyl [diethylamino (trifluoromethyl) - ~, 4-sulfanylidene] carbamate dissolved in 2 ml of dichloromethane is added 0.260 ml trifluoroacetic acid at room temperature. The reaction medium is thereafter stirred at 50 ° C. for 24 hours. Finally, the crude reaction product is washed with water then dried on Na2SO4. After evaporation under reduced pressure and washing with ether diethyl 0.201 g of benzyl [(trifluoromethyl) thio] carbamate is obtained in the form of powder orange color (yield 80%, LC / MS M + = 251 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.43-7.39 (solid, 5H); 6.15 (s large, 1H) 5.42 (s, 2H).
Example 6: 4-Nitro-N - [(trifluoromethyl) thio] aniline (Compound 17) 6.1: N, N-diethyl-1,1,1-trifluoro-N = (4-nitrophenyl) methane sulfinimidamide (Compound 33) To the reaction mixture of step 2.1, 0.175 ml of N, N-diisopropylethylamine, then 5 minutes later against the current of N2, 0.140 g of 4-nitroaniline. The reaction medium is subsequently stirred at 0 ° C. for 3 hours.
hours. Finally, The crude reaction product is washed with an aqueous solution (6%) of NaHCO 3 and then dried.
sure Na2SO4. After evaporation under reduced pressure and purification by chromatography on reaction crude in the presence of 0.5% triethylamine (Pentane /
Acetone:
30/1), 0.247 g of N, N-diethyl-1,1,1-trifluoro-N '(4-nitrophenyl) methane sulfinimidamide in the form of a brown oil (yield 80%, LC / MS M + =

g / me).

6.2: 4-nitro-N - [(trifluoromethyl) thio] aniline (Compound 17) At a temperature of 0 ° C., 0.090 ml of acid are added dropwise.
trifluoroacetic acid to a solution of 0.309 g of compound obtained in step 6.1 in 2 ml of dichloromethane. The reaction medium is subsequently stirred at room temperature ambient for 1 hour. Finally, the crude reaction product is washed with water and then dried on Na2SO4. After evaporation under reduced pressure, 0.238 g of 4-nitro-N-[(trifluoromethyl) thio] aniline as a brown powder. The yield is quantitative (LC / MS M + = 238 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 8.22 (m, 2H); 7.20 (m, 2H); 5.64 (s large, 1H).
Example 7 N - {[1,3-benzoxazol-2-yl (difluoro) methyl] thio} -1-phenylmethanamine (Compound 8) 7.1: N - {[1,3-benzoxazol-2-yl (difluoro) methyl] (difluoro) -4-sulfanyl} -N, N-diethylamine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature of -0.15 ml of trifluoride are added dropwise.
diethylaminosulfur. The the reaction medium is stirred at this same temperature for 10 minutes before adding 0.241 g of 2- [difluoro (trimethylsilyl) methyl] -1,3-benzoxazole. After 1 hour under stirring at room temperature, an assay is carried out in 19 F NMR of the medium reaction. The compound N - {[1,3-benzoxazol-2-yl (difluoro) methyl] (difluoro) -A4-sulfanyl} -N, N-diethylamine, not isolated, was quantitatively produced.

1 H NMR (282 MHz, CFCl 3): δ ppm -0.92 (m, 2 F), -91.06 (m, 3 F).

7.2: N - {[1,3-Benzoxazol-2-yl (difluoro) methyl] thio} -1-phenylmethanamine (Compound 8) At room temperature, 0.110 ml of benzylamine is added dropwise at room temperature.
reaction mixture of step 7.1. The reaction medium is thereafter agitated to room temperature for 24 hours. Finally, the crude reaction product is washed with solution aqueous (6%) NaHCO3 and then dried over Na2SO4. After evaporation under pressure reduced and purification by chromatography on silica of the crude reaction (Pentane /
ethyl acetate: 40/1), 0.107 g of N - {[1,3-benzoxazol-2-yl (difluoro) methyl] thio} -1-phenylmethanamine in the form of a white powder (Yield 35%
LC / MS M + = 306 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.86 (m, 1H); 7.64 (m, 1H); 7.53 to 7.44 (Solid, 2H); 7.40-7.26 (solid, 5H); 4.28 (d, 2H); 3.27 (brs, 1H).
Example 8: N '- {3-cyano-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -1H-pyrazol 5-yl} -N, N-diethyl-1,1,2,2,2-pentafluoroethane suifinimidamide (Compound 25) 8.1: N '[difluoro (pentafluoroethyl) -A4-sulfanyl] -N, N-diethylamine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature neighbor of -20 C is added dropwise 0.135 ml of trifluoride diethylaminosulfur (DAST). The reaction medium is stirred at this same temperature for 10 minutes.
minutes before the addition of 0.180 ml of (pentafluoroethyl) trimethylsilane. After 1 hour, under stirring at -20 ° C, a 19F NMR assay of the reaction medium is carried out. The compound N '[difluoro (pentafluoroethyl) -A4-sulfanyl] -N, N-diethylamine, not isolated, was product quantitatively.
19 F-NMR (282 MHz, CFCl 3): δ ppm + 3.32 (m, 2 F); -78.52 (t, 3F); -106.18 (m, 2 F).
8.2: N '- {3-cyano-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -1H-pyrazol-5-yl} -N, N-diethyl 1,1,2,2,2-pentafluoroethane sulfinimidamide (Compound 25) At a temperature of -20.degree. C., 0.322 g of (2,6 dichloro-4-trifluoromethylphenyl) -3-cyano-5-aminopyrazole in solid form at mixed reaction of step 8.1. The reaction medium is then stirred at ambient temperature during 48h. Finally, the crude reaction product is washed with an aqueous solution (6%) of NaHCO3 then dried over Na2SO4. After evaporation under reduced pressure and wash at pentane, 0.054 g of N '- {3-cyano-1- [2,6-dichloro-4- are obtained.
(Trifluoromethyl) phenyl] -1H
pyrazol-5-yl} -N, N-diethyl-1,1,2,2,2-pentafluoroethane sulfinimidamide under form of a brown powder (Yield 10%, LC / MS M + = 542g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.69 (m, 2H); 5.90 (s, 1H); 3.40 (m, 4H);
1.23 (t, 6H).

Example 9 N, N-diethyl-N '- [(pentafluoroethyl) thio] pentane-1,4-diamine (Compound 7) At a temperature of -20 ° C., 0.200 ml of N, N- is added dropwise.
diethylpentane-1,4-diamine to the reaction mixture of step 8.1. The environment reaction is then stirred at room temperature for 4 hours. Finally, the crude reaction is washed with an aqueous solution (6%) of NaHCO3 and then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on crude silica (Pentane / acetone: 1/1), 0.062 g of N, N-diethyl-N 'is obtained.
[(Pentafluoroethyl) thio] pentane-1,4-diamine as a colorless oil (Yield 20%
LC / MS M + = 308 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 3.34 (brs, 1H); 3.05 (m, 1H); 2.60 (q, 4H);
2.49 (t, 2H); 1.55-1.44 (solid, 4H); 1.16 (d, 3H); 1.07 (t, 6H).

Example 10 N - [(trifluoromethyl) thio] aniline (Compound 9) At a temperature of -20 ° C., 0.091 ml of aniline is added dropwise.
reaction mixture of step 2.1. The reaction medium is thereafter agitated to room temperature for 12 hours. Finally, the crude reaction is washed by one aqueous solution (6%) of NaHCO3 and then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of crude reaction (Pentane / acetone: 60/1), 0.156 g of N-[(trifluoromethyl) thio] aniline under form of a yellow oil (Yield 81%, LC / MS M + = 193 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.35 (m, 2H); 7.15 (m, 2H); 7.06 (m, 1H) 5.09 (bs, 1H).

Example 11: 4-chloro-N - [(trifluoromethyl) thio] aniline (Compound 11) At a temperature of -20.degree. C., 0.127 g of 4-chloroaniline to the reaction mixture of step 2.1. The reaction medium is thereafter stirred at room temperature for 12 hours. Finally, the raw reaction is washed by an aqueous solution (6%) of NaHCO3 and then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of crude reaction (Pentane / ethyl acetate: 50/1), 0.150 g of 4-chloro-N-[(trifluoromethyl) thio] aniline as a yellow oil (Yield 66%; LC / MS
M + = 227 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.26 (d, 2H); 7.04 (d, 2H); 5.14 (s large, 1H).
Example 12 Benzyl (4 - {[(trifluoromethyl) thio] amino} phenyl) carbamate (Compound 19) To the reaction mixture of step 2.1, 0.175 ml of N, N-diisopropylethylamine, then 5 minutes later against the current of N2, 0.242 g of benzyl (4-aminophenyl) carbamate. The reaction medium is subsequently stirred at for 3 hours before being washed with an aqueous solution (6%) of NaHCO 3 and to be dried over Na2SO4. After filtration and evaporation under reduced pressure, the gross The reaction mixture is solubilized in 2 ml of anhydrous dichloromethane and then cooled.
to one temperature of 0 ° C. 0.030 ml of acid is then added dropwise.
trifluoroacetic.
After 1 hour, with stirring at ambient temperature, the reaction medium is washed to the water then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of the crude reaction product (Pentane / Acetone: 8/1), gets 0.150 benzyl (4 - {[(trifluoromethyl) thio] amino} phenyl) carbamate in the form of a powder brown color (Yield 44%, LC / MS M + = 342 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.41-7.26 (solid, 7H); 7.01 (m, 2H); 6.68 (s broad, 1H); 5.19 (s, 2H); 5.14 (bs, 1H).

Example 13: N '- {3-cyano-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -1H-pyrazol-5-yl} -1,1,1-trifluoro-N, N-bis (2-methoxyethyl) methane sulfinimidamide (Compound 27) 13.1: N- [difluoro (trifluoromethyl) -A4-sulfanyl] -bis (2-methoxyethyl) amine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature neighbor of -20 ° C., 0.468 ml of a commercial solution is added dropwise.
50% molar of bis (methoxyethyl) aminosulfur trifluoride (Deoxofluor) in the tetrahydrofuran.
The reaction medium is stirred at this same temperature for 10 minutes.
before the addition of 0.150 ml of (trifluoromethyl) trimethylsilane. After 1 hour, under agitation to-20 C, a 19 F NMR assay of the reaction medium is carried out. N-compound 5 [difluoro (trifluoromethyl) -A4-sulfanyl] -bis (2-methoxyethyl) amine, not isolated, was produced quantitatively.
19 F-NMR (282 MHz, CFCl 3): δ ppm + 2.04 (q, 2 F), -65.53 (t, 3 F).

13.2: N '{3-cyano-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -1H-pyrazol-5-yl} -1,1,1 Trifluoro-N, N-bis (2-methoxyethyl) methane sulfinimidamide (Compound 27) At a temperature of -20.degree. C., 0.322 g of (2,6 dichloro-4-trifluoromethylphenyl) -3-cyano-5-aminopyrazole in solid form at mixed reaction of step 13.1. The reaction medium is then stirred at ambient temperature For 18 hours. Finally, the crude reaction product is washed with an aqueous solution (6%) NaHCO3 then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of the crude reaction product (pentane / acetone: 10/1), we obtain 0.429 g of M {3-cyano-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -1H-pyrazol-5-yl} -1,1,1 trifluoro-N, N-bis (2-methoxyethyl) methane sulfinimidamide in the form of a oil Viscous yellow color (Yield 78%, LC / MS M + = 552 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.69 (s, 2H); 6.15 (s, 1H); 3.58 to 3.42 (Solid, 8H); 3.33 (s, 6H).

Example 14: N - {[difluoro (phenylthio) methyl] thio} aniline (Compound 14) 14.1: N '{[difluoro (phenylthio) methyl] (difluoro) -A4-sulphanyl} -N, N-diethylamine To a solution of 0.130 g of N, N-diisopropylethylamine in 2 ml of anhydrous dichloromethane, under an inert atmosphere of nitrogen and at a temperature neighbor of -20 C is added dropwise 0.135 ml of trifluoride diethylaminosulfur (DAST). The reaction medium is stirred at this same temperature for 10 minutes.
minutes before the addition of 0.232 g of [difluoro (phenylthio) methyl] trimethylsilane. After 1 hour, with stirring at -20 ° C., a 19 F NMR assay of the reaction medium is carried out.
The N '{[difluoro (phenylthio) methyl] (difluoro) -A4-sulphanyl} -N, N-diethylamine, no isolated, was produced quantitatively.
19 F-NMR (282 MHz, CFCl 3): δ ppm -0.44 (m, 2 F), -63.02 (m, 2 F).

14.2: N - {[difluoro (phenylthio) methyl] thio} aniline (Compound 14) At a temperature of -20 ° C., 0.091 ml of aniline is added dropwise.
reaction mixture of step 14.1. The reaction medium is thereafter agitated to room temperature for 48 hours. Finally, the crude reaction is washed by one aqueous solution (6%) of NaHCO3 and then dried over Na2SO4. After evaporation under reduced pressure and purification by chromatography on silica of crude reaction (Pentane / acetone: 60/1), 0.158 g of N-{[difluoro (phenylthio) methyl] thio} aniline as a colorless oil (Yield) 56%; LC / MS
M + = 283 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.69 (m, 2H); 7.55-7.42 (solid, 3H); 7.24 (M, 2H); 7.00-6.92 (solid, 3H); 5.23 (bs, 1H).

Example 15: N-methyl-N - [(trifluoromethyl) thio] aniline (Compound 43) To a solution, cooled to -10 ° C., 0.193 g of N-[(Trifluoromethyl) thio] aniline (Compound 9, Example 10) in 2 ml of anhydrous dimethylformamide, is added 0.048 g NaH with vigorous stirring. The resulting mixture is maintained for 10 minutes.
minutes to -10 C before the introduction of 0.075 ml of iodomethane, dropwise. We leash then the reaction medium with stirring at ambient temperature for 4 hours.
hours. The The mixture obtained is then taken up in a Pentane / H 2 O mixture. The sentence organic is separated, dried over Na 2 SO 4 and then concentrated under vacuum to give a residue which is purified by chromatography on silica (Pentane). 0.172 g of N-methyl-N-[(trifluoromethyl) thio] aniline as a colorless oil (Yield 83%;
LC / MS M + = 207 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.34-7.22 (solid, 4H); 6.97 (m, 1H); 3.50 (S, 3H).

Example 16: N - [(trifluoromethyl) thio] -N-undecylaniline (Compound 46) To a solution, cooled to -10 ° C., 0.193 g of N-[(Trifluoromethyl) thio] aniline (Compound 9, Example 10) in 2 ml of anhydrous dimethylformamide, is added 0.048 g NaH with vigorous stirring. The resulting mixture is maintained for 10 minutes.
minutes to -10 C before the introduction of 0.278 ml of 1-iodoundecane dropwise. We leash then the reaction medium with stirring at ambient temperature for 4 hours.
hours. The The mixture obtained is taken up in a Pentane / H 2 O mixture. The organic phase is separated, dried over Na 2 SO 4 and then concentrated under vacuum to give a residue which is purified by chromatography on silica (Pentane). 0.264 g of N-[(trifluoromethyl) thio] -N-undecylaniline in the form of a colorless oil (Yield 76%; LC / MS
M + = 347 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.33-7.22 (solid, 4H); 6.97 (m, 1H); 3.73 (m broad, 2H); 1.72 (m, 2H); 1.33-1.28 (massive, 16H); 0.9 (t, 3H).
The use of the compounds obtained according to the present invention as a perfluoroalkylsulfanylation of aromatic, heteroaromatic compounds, alkenyls and alkynyls is also described by the following examples:
Example 17: (1 R *, 2R *) - 2 - [(trifluoromethyl) thio] cyclohexyl-4-methylbenzene sulfonate (Compound 68) To a solution of 0.193 g of N - [(trifluoromethyl) thio] aniline (Compound 9, Example 10) in 2 ml of dichloromethane, 0.102 ml of cyclohexene is added, followed by minutes later, 0.475 g of para-toluenesulphonic acid monohydrate is added under solid form. The reaction medium is then heated for 18 hours at 50 ° C.
gross The reaction mixture is finally washed with water and then dried over Na 2 SO 4. After evaporation under reduced pressure, the residue is purified by silica chromatography (Pentane / Acetone:
80/1). 0.276 g of (1RR, 2R-) - 2 - [(trifluoromethyl) thio] cyclohexyl-4-methylbenzenesulfonate in the form of a yellow powder (Yield 78%;
LC / MS
M + = 354 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.80 (d, 2H); 7.35 (d, 2H); 4.49 (ddd, 1H);
3.29 (ddd, 1H); 2.44 (s, 3H); 2.22 (m, 1H); 2.03 (m, 1H); 1.69 to 1.65 (massive, 3H); 1,48-1.44 (massive, 3H).

Example 18: (1 R ", 2R *) - 1-propyl-2 - [(trifluoromethyl) thio] pentyl-4-methylbenzene sulfonate (Compound 61) To a solution of 2 ml of dichloromethane containing 0.207 g of N-methyl-N-[(trifluoromethyl) thio] aniline (Compound 43, Example 15), 0.112 g of (Z) -oct-4-ene and 0.291 g of sodium salt of para-toluenesulfonic acid is added, dropwise by drop and under vigorous stirring, 0.635 ml of a 48% commercial solution of BF3-Et20. The mixed resulting is then stirred for 4 hours at room temperature and then is diluted by Et20 / H2O mixture. The organic phase is separated, washed twice using a 2N HCl solution, dried over Na 2 SO 4 and then concentrated in vacuo. The residue is purified by chromatography on silica (Pentane / acetone: 100/1) to give 0.246 g of (1 R *, 2R`) -1-propyl-2 - [(trifluoromethyl) thio] pentyl-4-methylbenzenesulfonate, form a colorless oil (Yield 64%, LC / MS M + = 384 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.81 (m, 2H); 7.37 (m, 2H); 4.68 (dt, 1H) 3.30 (dt, 1H); 2.45 (s, 3H); 1.80-1.48 (solid, 4H); 1.38-1.24 (massive, 3H); 1.12 (m, 1 H) ; 0.86 (t, 3H); 0.81 (t, 3H).
Example 19: (1R ", 2R *) - 2-chlorocyclohexyltrifluoromethyl sulfide (Compound 74) In a solution of 1 ml of dichloromethane containing 0.193 g of N-[(trifluoromethyl) thio] aniline (Compound 9, Example 10), 0.101 ml of cyclohexene. After 5 minutes, 1 ml of a solution is added dropwise.
acid 2N hydrochloric acid in diethyl ether. The reaction medium is then agitated to room temperature for 2 hours. The crude reaction is finally extracted by a Et20 / H2O mixture. The organic phase is separated, dried over Na 2 SO 4 then concentrated in vacuo to give 0.205 g of (1 R-, 2R -) - 2-chlorocyclohexyltrifluoromethylsulfide (Yield 94%, LC / MS M + = 218 g / mol).

1 H NMR (300 MHz, CDCl 3): δ ppm 4.10 (m, 1H); 3.45 (m, 1H); 2.39 (m, 1H) 2.22 (m, 1H); 1.86-1.67 (solid, 3H); 1.62-1.38 (massive, 3H).

Example 20: 1 - {[(trifluoromethyl) thio] methylene} heptyl-4-methyl-benzenesulfonate (Compound 79) To a solution of 2 ml of dichloromethane containing 0.207 g of N-methyl-N-[(trifluoromethyl) thio] aniline (Compound 43, Example 15), 0.152 ml of oct-1-yne and 0.291g of sodium tosylate in 2 ml of dichloromethane are added dropwise and under vigorous stirring, 0.635 ml of a 48% commercial solution of BF3-Et2O. The middle The reaction mixture is then stirred for 48 hours at room temperature. The gross The reaction mixture is then taken up in an Et 2 O / H 2 O mixture before being washed twice.
times to using a 2N HCI solution. The organic phase is dried over Na 2 SO 4 and gets 0.170 g of 1 - {[(trifluoromethyl) thio] methylene} heptyl-4-methyl-Benzenesulfonate after purification by chromatography on silica (Pentane / acetone: 100/1) of the crude reaction (Yield 41%, LC / MS M + = 414 g / mol).
1 H NMR (300 MHz, CDCl 3): 8 ppm 7.80 (m, 2H); 7.37 (m, 2H); 5.87 (s, 1H);
2.47 (s, 3H); 2.38 (t, 2H); 1.42 (m, 2H); 1.32-1.17 (massive, 6H); 0.86 (t, 3H).
Example 21: 3 - [(trifluoromethyl) thio] indole (Compound 80) In a solution of 2 ml of dichloromethane containing 0.193 g of N-[(trifluoromethyl) thio] aniline (Compound 9, Example 10), 0.117 g is added indole. After minutes, 0.485 g of para-toluenesulphonic acid monohydrate is added and the mixed The reaction mixture is then heated for 18 hours at 50 ° C.
is finally extracted with an Et 2 O / H 2 O mixture. The organic phase is separated, dried over Na2SO4 then concentrated under vacuum. The residue is purified by chromatography on Silica (Pentane /
Acetone: 20/1) to give 0.156 g of 3 - [(trifluoromethyl) thio] indole (Yield) 72%; LC / MS
M + = 217 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 8.56 (brs, 1H); 7.80 (m, 1H); 7.53 (d, 1H);
7.42 (m, 1H); 7.32-7.24 (massive, 2H).

Example 22: 2,4-Dimethoxy - [(trifluoromethyl) thio] benzene (Compound 88) In a solution of 2 ml of dichloromethane containing 0.193 g of N-[(trifluoromethyl) thio] aniline (Compound 9, Example 10), 0.134 g of 1,3 (Dimethoxy) benzene. After 5 minutes, 0.485 g of paraben toluenesulfonic monohydrate and the reaction mixture is then heated for 18 hours to 50 C. The The crude reaction product is finally extracted with an Et 2 O / H 2 O mixture. The sentence organic is separated, dried over Na 2 SO 4 and then concentrated under vacuum. The residue is purified by chromatography on silica (Pentane / acetone: 200/1) to give 0.214 g of 2,4 dimethoxy - [(trifluoromethyl) thio] benzene (yield 90%, LC / MS M + = 238 g / mol).
1 H NMR (300 MHz, CDCl 3): δ ppm 7.53 (m, 1H); 6.54-6.50 (massive, 2H); 3.88 (S, 3H); 3.83 (s, 3H).
Example 23: 2 - [(trifluoromethyl) thio] -1,2,3,4-tetrahydronaphthalene (Compound 77) In a solution of 2 ml of dichloromethane containing 0.193 g of N-[(trifluoromethyl) thio] aniline (Compound 9, Example 10), 0.150 ml of Phenylbut-1-ene. After 5 minutes, 0.180 ml of triflic acid, drop by drop.
The reaction medium is then stirred at ambient temperature for 24 hours. The gross The reaction mixture is finally extracted with an Et 2 O / H 2 O mixture. The organic phase is separated, dried over Na 2 SO 4 and then concentrated under vacuum. The residue is purified by chromatography on silica (Pentane / acetone: 80/1) to give 0.165 g of 2-[(Trifluoromethyl) thio] -1, 2,3,4-tetrahydronaphthalene (Yield 71%, LC / MS M + = 232 g / mol).

1 H NMR (300 MHz, CDCl 3): δ ppm 7.16-7.05 (solid, 4H); 3.69 (m, 1H); 3.27 (M, 1H); 3.04-2.86 (solid, 3H); 2.30 (m, 1H); 1.98 (m, 1H).

The following tables illustrate the chemical structures and properties Of some compounds of formula (I), formula (II) and formula (Ibis) according to the invention.

In these paintings:

In the column PF (melting point), represents an oil at temperature ambient, and Me and Et respectively represent methyl and ethyl groups.

VS
N d = E ô ô ô
E
N Ç
X ~
NOT

O
Q G1 O G> O
NL ~ G ~ G ~ G ~ G> G ~
vs.
O QC. EE
OC
! O x ~, Up ~ ~ 0 = d O
it Q- ON Ov ~ i not ~
a ~ -Xm QQC
7 cy E mrr Ç O www V
(D
EU
~ oh vi a to Z ~
= ~ .-:
_ EQ
~ (, U-_ N fn (D 2) _ fp O
ZE f ~ D.
U ~

OO - 2) 2) (~ 21 VO = 1n mm C = O ~ ~ d) = ~
0 00 a _ Co U) NM: O p1 ln ~ mm L.
CD
_ M = 2 CO ~ f4 EE
`t6 CM
N - CD N,.
Q to U 10 N ~ N
_ D CO ~ CO Cfl tn U ~ -a M 4) Ci M -a ~ j Z ~ .-. 2) r- ~ QcC ~ N = ~ ûc0 NN

~ p ap Op = ~ i V
Q ~
M
.U. ~
CC /) LL
UQ U- U
z ~ UU LL
o ~. U
NOT
A
-at VN
BORN
= f9 V) a OO
D ~

of Cr lp N ~ ZN

d ô ô ô ô ô ô ô
~ ~ NM 00 d 0 O CIO 0 CF) r 0. + ~~ ..
rr N
Gi `Gi LQ` Lt ~ O
~
Q. 0 .y G1 0 O r Ox Ox O ~ OE OO O ~
~ COCOCC Cx C = CO
okay 0 0 ~ d ~ W ~ O ~ W
OH Ov Z i Oy 0 ON O

rrrrrr = ON CV N CO>. NOT
O 0 0 0 0 G ~ 0 IZ Q. Q QC Q Q.
E ~ rrrmr UWWWWWW
VI`

LL p , .., .-. ..., _ _ _ -~.
NOT
MN 2 _ N = ~ _ 2 2 E cd m MW) ~, v .. EN 'nm E ~
O `- O` ~ ~ "cA ~ t Cp ~ tn 2 O ppp lc ~
~ O 00 ~ v) `- 'c ~) M tn M tA Cp <n tA ~
o ~ M c'a E ~ ^ N ~~ ^ NE ~ ~ EE N_ I- O
v = _ cn MM
NAME .-. 'q * MMN = N =
E ~ r -p ~
MMM ~ U7 OMO
"E
N Ln MN u ~! ~ P ~ r (fl ~ L) ..
ZM r ~ .. Cfl 00 ~ ~ 00 M
N ~ NMN f ~ I ~ O
MM ~
LL
C4 li ti U o, z LL
UUU ~ U
U

zz o d Z ~ 11) ~ D f ~ CO Q1 d ~ o ~ ô
~ tp t ~ 0 ~ t ~~ f! MMO ~ 0 d gt d O 0 0 O d 0 0 V t VV r VNNN
G ~ d 4 ~ r G ~ G ~ G1 G ~ d CC tD oo ea Q e ~ Q eC
0 C. C y C d C Q., ~ a ~. ~, ~. ~, ox oE ox oK oE
~ ~ c = x ~ c = c = X ccc arow 0 0 w O tf! OO tn O fn p N aJ f ~ rrrrrrrr Oo NNN CV NNN

QCQQC QQQ C.
E ev mm ea the 0 R
UWWWWWWWW

LJ. 00 co _ = - = 2 = - 2 N 2 -fQ
C ~) N 2) NN ~ 2 ~ NN
NE n -6 _ -6 m .6 _ E
r O ~ O ~ ~ N 00 M ~ i. "~ N ~ NN 4) ~ I ~ m CO = CO = Lq NN ~ fa ~ N p- m .. .-. . = -. N ~. ==. f ~ L6 fn ~ (A
E v. ~ _ ... _. ~
MNN
b N = NN p ~ N p ~ m ~ ~ 0 ~ fa NNM ~ O Cr) CO
.. '~ v O ~ lC) E ln ~ E r-, ~
O cn NOT
CO C0 .- cn CD N cl ~
cl ~ M 2 f0 ~ NO ~

LLLL

V li ~ i li I ~ u ~ LL lL
UUUOOOO
- ~ ~ 0 - LL LL o O r N Ci le tn Co 1-Zrrrrrrrr 4.0 oh d EO ô ô ô ô
ti N 000 N
= O
G ~ O
ti 0 O Cq NOT
O ~ LQNN Q.
G. COQ C. QOQ ~
LL
~ LL - LL LL LL F. d OHI fi d 'oh Foa y N NNN) N
Q. ~ M QG ~ QQ
O
OWOWWW ww U

o ~ CO ~ M
~ rn rn ti rn ~ rn U-rn ~ ~ rn ti rn =
M Ci ^ N .- = d) EEON v = v N _ ~
~
_ ~ ~ (Q Ln f0 to E 2 L [) t ~ "~ I ~ CO - MN ~ ~ M
O .. t0 00 (a .- .- N (0 .-. O.
' O
2 ~ cfl ~ E ^ ^ ~
Ln ~ 2 2Ln ~
~ ~ .-. ..
II NNN. ~ ~ M .. N = NNM ~ N _ ~ N
m = ~ (O
ON m NU) of fA fD ~ (o N
.. .. o0 ~ f ~ LO NO
I ~ I ~ CO

N LL LL LL LL LL LL
~ UUUUUU
(0 at O
yo == = oo ~

o = (Z = o = (Z2 ô
M_ O \ / \ OO
_ Z
Z ~ NNNN

d Q

VS
U
_NOT
CL
ENN Co N 0 aD CO
N QE ~ E M.
vs, p = ~ ,, KW 0 W
~ n WWNWM
NOT
Q
cu = r, ~

MM a) â O) NU

_, _. _, _. =.
.-. .-. _ O
QN Cr ^ N 2 UO ~) ~ ~ NO ~ M

(0 O
LZZ ._ "= ^ ~ .., C ...
~ + G ~ i1 T
r> Ç 0 N 1d N ~ N
CY pv - EE
11 .. O
Q- 10 ~ M ~ t E

Z ~ ~ ~ ~ ~ M
U
\ _ O
W w it Q.

The Q- oc ww . (D
The Q
. ~
- (D

O
~ LL
~ U ~ U
U
U) ~

MM U / UU / UU / U
N ~ I ~ I ~ I
U) zz '~ E3 Z z ~ O
Q
E zzz O
of AU) qe tn Co JZNNN

~
E
CD O O O O O O
CD MNMN t ~ !!
VS
d ~. .- .-.
N tC N tp N tC
O_d HHNN
cd cr! cr!
d Q GQ + - 'Q + r C. + r Q. ~
QE CD CD Co G1 Co 41 rd ~
fC W ~ WW ~ W C4 W ~ c% i WW w NN ô NN ô N ô
..r ..v U U ') we 1L. v at ~ _ ~ ~ ~ ~ ~ = ( N cfl = Co = (o 00 - -6 v E
= U lf) N 2 tn j ~ NNM 00 NNN e N
~ v) CO U) 'ev) mmmv) N
Co EEE .. `i` ii = _ C CD = NN CD N
cr) CD N the 00_ CD_ d) _ CO
~ MM CO CO CY CO 07 f- CF
11 ~ oO d ~ .. ~. ~. ~ NE
0 ~ - M
m MMM to Cp It M Cfl M CO MM ~ MM
NOT

¾ = ô WWWWW
U

NOT

~ V OWWWW

U

N L IL 1.L 1.L U.
~ UUUUUU
U

Z

LL ~ O
U
Z
ZNNNMMM

d ~ ô ô ô ô ô ô ô
00 tn ~ 1- OD ~
d N ~ r MMNN
O d N t ~ NG ~
C CV N
Q d Q d 0 E ~ d N
~ am ~ E c. Q.
WWWW ~ N dx WW
W

() NOT

LL ~

^ ^ .-. ., _ ^ ^ _ ^ _ ^ _ N Co N ^ _ .. NNNNNN
EE -00- -, ay M ~ Cfl 2 .m ^ ~ u ') ~ p ~ a ~
f ~ O tn Cfl M ~ y 0 NN p) _ = ~ NNN, d. (0 CO NMF NM
. ~ ~ E Nt .-. _. ~ _ ~ p C7 N ^ ^ ^. t! 7 _ -p 2 ONN tf) M = p! ~ NN = - = m NNMN
ly C? CC? E ~ N ~ E
f - M 00 M n M tf) M
p M p M ~ M f ~ N m NM
I-QO f ~ M I, M

NOT

_V o WW

V o WW
U

N ~ ~ LL LL LL. LL.
~ UUUUUU
0- ~ = 0 LL
zz ~ \ I LL
NN

~
VS
O
E ô ô ô ô
~ MO ~ 0 C ~ C
O

7 fA NNN
O 0 N Hf N fA! VN
cL O = N CL Q- G ~
OW ~ WWW
r K ~
WW ch N
V tn o U. ~ v 2 = 2 ~ _ M
C% 1 - ~ ^ - N = M = t0 00 Ln CO N
. ~. ~ _ .. `. 4-Z to, z tN MNM - ~ p NNNM t%) ~
1 ,: N
_ 2 v ^ ._ = ._ ^
'.. ~.
^ ^ m NN
0 NN -a MN CO N

l17 MN Ln NM

Cfl I- N
MMM ld M
I, M f ~

NOT

= O
~ U

NOT
M + IQ) _ ~ LLJ = O LI ~
U
LL-t LL

IL LL LL
~ UUU
o- 4 = oo = cn-o o == ~
_4_ o LL
G) G) MN

m a ~
this LL
at 2 = M 2 ^ 2 = _ - ~ MN
NOT
E
(0 M ~ ~ p ~ N ~
.. U p N cn p `- 'p N p BORN
MM = M ~ ~ _ 0 2 = N - -Ç-- 2 co M ~ ~ ~
(/) - û ~ v 4- p N ~ ~ ~ t ~ NN _ F
II ~ ~ NU) NOT
~ - Z ~ p 10 f M f C 0 N m ~ QN f ~

EEE f ~ C `- 'EE
NNNN ~ cli N N N
ti N ~ ~ ~ N
MMMN
MM
4) X
N r ~ r ~
~ UU
co Sd) S4) C ~ ô ô
LGCNN
U) II
~ UU
Co N IT U IL IL
UUU
or co 4 .m o - -= o n 2 E
d U o J2 v ~ Z d and d J

vs d O O O O O
~
N OMO ti CD CD t0 0 ~ 0 d .i ~

HE
at NOT
=
NN
NOT
M ~ +.-T = - `~ = ~ .. tn ~ ~

CD ~~~~~~~~~~~~~
a ~ o N = ~ 2 ~
= E ^ ^ COp N L6 N -0 - NN
MN ^ p NOT
OM uj ~ ~ p = ~ y ~ ~ rn O
_ m f0 (p f6 'e EO) fC
vf ~ `~ v-: p - ^ N p II vv ~ i ~ ~ ~ ~ ~ 2 ~ n ~ cn ~ ~ cfl <n EN
10 N N_Cu ~ ^ m ~ m ~ N pt ~ CN ~ f ~ C f ~ m E ~ ME ~
1 ^
ZEN ~ N CO NN (j IN tn (~ NI`
~ y (~ N 1 to 1 I 1 ~ 1 MM pc) N p ME
M
2 ~
U

o U \ \ \ / \ / \ / _ LL LL LL LL LL LL LL
UUUUUUU
o = -0 0- -o M ~ n ~ i ~ ~ ~ ~

a ~
~ ô ô ô ô ô ô ô
~

d (~ N
~
LL

=

= ~ _ ~ ^ N 2 M
Ci N d) MN CM `MMN
d) O ~ CO O the MM
M 00 N `2 2 ~
O rorn N Ln M CO ~ .-. v N w ^ N
~ _ mrv ~ v ~ tn N 2 t ~
II N
- ^ N Co û f N (~ pf ~ 0 ~ m N 2) _ ^ NEEEEE ~ m M
NEN ~ NN ~ j - N 0 ~ 0 ~
Ln f, ln f ~ ~ t ~ i ~ M ~ M
~ I ~ (M fM O Cr) ~ m m - - ~

N Li Li li li u li UUUUUU

o = o ~ ~
m O
NOT
= G1 1 ~ 1 ~ 00 1 ~
~ T rr! C d ~ _N d G ~
~ QCCQ
EEEE
KKKK
NG ~ E G1 G ~ G>
w OWOOO
Ç dddd O
V

O O O
N CD ~ p this L, L
at 0 = - I = _ 2 2 M
M ^ _ .-. NN
Co MU) = Ç _ N ~ = l1 ~ N
f9 in EE
C 0 Cp = "OO Cp OO. ~ O
M
NU ~ NN 6 - -0 CO O
= `N ^ ~ ~ .. ^ ^, ~ ~ f ~ ~. ~ N
Q. 2 U-) 00 = 2 = tA ~ I ~ O the O) N gt MMNM m MNN I- 0 _ o E (n Ea?
O 0 ~ 0 M
NM = ^ 2 G> = ~ O cMi cM = N LO lo 2 Cfl M
0 b.-R = - N-_ .-;
= p CL t /) O 'to OO
~ m '- CD CO - m E m M

.. N m MO '1;ce); m 7 C `OMN ~
NO 00 i 1 the I ~
~ + N a0 00 N
YU) BARE
O
0 QNN ~
Q

- G ~ OR ~ -0 O
NOO
Q ~ E 0 = cn = O 0 = cn = O o M + N
o OO -` ~ -O 0 Lj, .., Q f /) V) ~
> p ti ii QC ~ U
E
O
of ls NZ tG CO Co ~ J

d Ji! Rrr T

E ~ EEE
d O dd H ddddd O = CCCG
: 2 OOOOO
VS
~ U) NU) NN
O
V
~ ,, o 0 0 \ 0 .at \ \ \ \
t0 M t0 ~ I ~
this ~ 1 I 1 1 LL
at ^
^
_ LO
M cq .-.
CO N "0 _ _ _ BORN
.z ~ NN 1-- E _ E
U ') U CO N tn ppp ~ (7 N pp lf) pp M
p QO p MO LA
E r ,:

O NP ~ MMNNO = M = M f6 O ~ -p 1 MMN ~ ~ _ - ~ NNE
N ~ `~ Co l to MM - NNN ~ NN lf) r,, -: r- ~ .-. Nm MN
pp = NEEM
~ ^ r = N f ~ d NO ^ ~ N
N ~~ _ ap N = 2 p Co) CV N
00 p E
m CO Cfl EOE Cfl ~ tt. ~ M -m c'i MN ~
f ~ M ~ NNM
~

y-, ~ OI / ~ / (\

Q 0 = c ~ = O 0 = U) = 0 to 0) 0 = U) = 0 O p V + N - ~ 0 = ~ = 0 CI) O ~. ~~~.
OOV

LL
- - U
Z ~ mc ~ o Co OO
~ OTO el ~ -, p 1y T a 'O' ~
d VV ~ yv 3 d x C ~ G ~ G ~ w`O d CG ~
= d LO
v O ~ C = CCO O9 H lp OO

CNN yvy U `. ~ 4 O O O O
~ I, 00 1 ~ CD

Co LL LO V

_ _ ._ _ _ = - _ _ _ _ E
~ ~ L- Ln (0 ~
OO
v). C -: ~ = - = _ = p MN fC NCV f0 MMM = M CO N f0 E
~
have F ~ L-Ui ti = MC ~ O _ (7 CO (n 00 ~ 2 MN
m (p ~ ~
pm ~ NN

. .
CO 00 d7 `- 'EM
NOT
II ~ NM ~ c ~ p MM
MN ._ MMMMN
NOT
NOT
Lq M Ob M ~ ~ ^ N
Z = ~ ~ _ ~ NNNN ti 00 = 2 ON ~ E
...
MM
a CD
NMN
M
M f ~ MM ti M
4) N

O
, OI \ I ** ~ \
0 0 = U) = 0 O = U) = E
0 = cn = 0 0 = ~ = 0 ~
EO ~ 1 U O '== ~ ~% O', =
ea m there M U- U. NM
U- UU U-U U-U
tgoo ~ ~ i d dd d dd ddd NE ~ E a ~ EEE
ddma ~ mm axi mm E axi ax H i OOOWOOO
vs NNNN ~
O
vs.) ~ ô_ ô ô ô ô ô ô
~
tG 01 o lf) ~ O

co 2 = ^ .. _ = - = ~.
= - p N ~ = vi CO cY) =
U "rn cn ' Cf ~ ~ N ~ t%) m C7 di = cq N d) ^ OO
_ N ^ EE ao N `n MN
M
2 = M p δ = MNN 2 = v ~ ..
ON ~ M _ CD N f '= NNEE r- m M
(fl - - = _, FE
MM 00 ap _ N
MN _ N t ~ CV N - M a) M tl) ~ tA
a ^ = fu-4 = M ~ ti ^ EEE
_ - = p E = n =
CD% U ^ = pp ~ t1) NOT
Z ~ ~ ~ ~ N ~ N
.. v I ~
m (0 p NE LL) (M

~
~ N
NOT

4) N
LL
U
NOT
I ~ I ~ ~ LL
O
0 = cn = 0 0 = cn = 0 0 0 ~ ,.
IU
U.
U -MM
LL LL
UU

ti ti ti ~
o ~ N

NNN
E dd E x EE
~ W 0 WW
CN
O
U
oh O O
this LL
at ._ ~. ~.
^ _ = o = _ ^
NOT
= ~ MN
E
OO N Cfl = = - =
NOT
EENON
oE
.-. aO rn N .-. M ~ N 2 2 ~ N
0 2 N ~ N = N ~ ON Cp U) - m M ~ e ô ^ E ~
N ^ EN = ^ E
II M = ~ tn N ~? = I- 00 y 00 tM MMMM ~ p Qj = N
EEN - vf ~ N ~ 2) MM
Ln ~ MM = M ~ ~ M f ~
ONM ~
ti N I- (0. ~. ~ CO
00 vLO v N ln I`m Co N f ~ N
M cn cn there GU = ~

V L I \ I LL
~
OV

: -E 0 = ci ~ = 0 0 = O
~ = ~ = ~
V + ~ O ~
- I /% * II /
cunt U "
V

Z ~ ~ ti aoo d G rrrrr NNNNN
~ ~ dddd AT
EEEEE
d ~ d ~
H ddddx OOOOO
= U) NV) U) V) O
V

O O O O
~
00 N 00 OD tD
oh M ~ ~ M
d) U. Ln Ln rn ^ ._ V Ln GN 2 `~
EU Cfl EN
M Co I ~ M f-CO tt CO _ m ~
~ M

M - ~ 2 M = ~ ~ N ~ 2 vv 2 .-. NOT
II r ~
bO p ~ ca M rn rn i.rî rn00 fa f ~ (0. _ ~ `.
Z ~ 2 ~ ~ c ~ r 00 CM7 CMO r O f ~
-at M 00 'e M r - 'r p- ~ N ~
~ C6 C6 ~ ~
V ~
LL ~
, Z2 ~ Z = ~ P Z2 U) Z

v / \
~ 0o ô

~ ô N ~ ô ô

d NOT
= d NN
= OON
> Q Q N
EE
O d O
H dx E
C - - G ~
x OOW
= NN
O
~.) O O
QD CD OD
.-.
O
o L () U- o _ _ - = rn =

v ~ i =
NE tn Co v ~~ N v M
oc O "2 N = - 2 = (p" M
O = N
_ .-.
N _ 11 ~ NN ~ rn cn Cfl M
pl Mr pl f0 m - ui = - EEE
pp N v .. = 00 d) N v U) O 00 ZnMn 00 CD cF ~ M ~ n I`II ~ MI ~

LL
C ~ = LL
O 9) NU v ~ Z cn ~ ~
0 ô
O
EZ = Z = I ~
OQ
o =
- - ~ ô

Z
Z a ~ oa ~ oo ~ o ~

Claims (11)

A process for preparing the sulfanylamide compound of formula (I) and sulfinamidine compound of formula (II) in which a) R1 represents:
or an optionally substituted aryl;
or an optionally substituted heteroaryl;
or an optionally substituted alkyl;
or an optionally substituted cycloalkyl;
or an optionally substituted heterocycloalkyl;
or an -SO 2 -aryl group in which the aryl is optionally substituted;
or a -SO2-heteroaryl group where the heteroaryl is optionally substituted;
- a -SO2-fluoroalkyl group;
or a -CO2-aryl group where the aryl is optionally substituted;
or a -CO2-heteroaryl group where the heteroaryl is optionally substituted;
- a -CO2-alkyl group where the alkyl is optionally substituted;

b) R2 represents a perfluoroalkyl or substituted difluoromethylene group by a -S-aryl, -S-heteroaryl or optionally benzoxazol-2-yl group substituted c) R3 and R4 represent independently of each other an alkyl group, alkoxyalkyl or cycloalkyl or R3 and R4 together with the atom of nitrogen to which they are attached, a saturated or unsaturated heterocycle of 3 to 7 optionally comprising another heteroatom (such as piperidinyl, pirrolidinyl or morpholinyl);

characterized in that the following steps are carried out:

a first step, in which the compound of formula (IV) is condensed at a compound of formula (V) in the presence of a tertiary amine in a solvent organic, to give the compound of formula (III), wherein R1, R2, R3 and R4 are as previously defined and R5, R6 and R7 represent independently of one another a group selected from alkyl groups or optionally substituted aryl;

a second step, in which the compound of formula (III) is itself condensate to a compound of formula R1NH2, where R1 is as defined above, in presence of a tertiary amine in an organic solvent, to give a sulfanylamide of formula (I) and / or a sulfinamidine compound of formula (II), in which R1, R2, R3 and R4 are as defined above;

optionally a third step, in which the sulfinamidine compound of formula (II) or the sulfanylamide mixture of formula (I) and sulfinamidine formula (II) is converted into an organic solvent in the presence of an acid for give a sulfanylamide compound of formula (I), wherein R1 and R2, R3 and R4 are as defined previously. 2. Method according to claim 1, characterized in that the group aryl when it is said substituted, is an aryl group substituted by one or more groups, identical or different from each other, chosen from among the atoms and groups following:
.cndot. halogen, .cndot. optionally substituted alkyl, .cndot. alkoxy, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. alkylene, .cndot. alkynyl, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. -O-aryl optionally substituted, .cndot. -O-heteroaryl optionally substituted, .cndot. -S-alkyl, .cndot. -S-fluoroalkyl, .cndot. -S-aryl optionally substituted, .cndot. -S-heteroaryl optionally substituted, .cndot. CN, .cndot. -NO 2, .cndot. heterocycloalkyl, .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -N (R c) CON (R a) (R b), .cndot. -N (R a) SO2 (R c), .cndot. -OSO2R c, .cndot. -SO 2 N (R a) (R b), .cndot. -SO2 (R c), .cndot. -CON (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a and R b are independently selected from hydrogen, group (C1-C4) optionally substituted alkyl, (C1-C4) fluoroalkyl, cycloalkyl, aryl eventually substituted, optionally substituted heteroaryl, heterocycloalkyl and R c, take the values of R a except hydrogen, or R a and R b together with the atom of nitrogen to which they are attached, a saturated or unsaturated heterocycle of 3 to 7 members, comprising possibly another heteroatom. 3. Method according to any one of claims 1 to 2, characterized by the fact that the heteroaryl group when it is said substituted, is a group heteroaryl substituted by one or more groups, identical or different, of others, chosen among the following atoms and groups:
.cndot. halogen, .cndot. optionally substituted alkyl, .cndot. alkoxy, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. alkylene, .cndot. alkynyl, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. -O-aryl optionally substituted, .cndot. -O-heteroaryl optionally substituted, .cndot. -S-alkyl, .cndot. -S-fluoroalkyl, .cndot. -S-aryl optionally substituted, .cndot. -S-heteroaryl optionally substituted, .cndot. CN, .cndot. -NO 2, .cndot. heterocycloalkyl, .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -N (R c) CON (R a) (R b), .cndot. -N (R a) SO2 (R c), .cndot. -OSO2R c, .cndot. -SO 2 N (R a) (R b), .cndot. -SO2 (R c), .cndot. -CON (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a, R b and R c are as defined in claim 2. 4. Method according to any one of claims 1 to 3, characterized by made that the alkyl group, when it is said to be substituted, is an alkyl group substituted by one or several groups, identical or different from each other, chosen from the atoms and groups:
.cndot. halogen, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. heterocycloalkyl, .cndot. alkoxy, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. -O-aryl optionally substituted, .cndot. -O-heteroaryl optionally substituted, .cndot. -S-alkyl, .cndot. -S-fluoroalkyl, .cndot. -S-aryl optionally substituted, .cndot. -S-heteroaryl optionally substituted, .cndot. CN, .cndot. -NO 2, .cndot. -SO 2 N (R a) (R b), .cndot. -SO2 (R c), .cndot. -COR b, .cndot. -COOR c, .cndot. -CON (R a) (R b), .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -N (R c) CON (R a) (R b), and .cndot. -N (R a) SO2 (R c), where R a, R b and R c are as defined in claim 2. 5. Method according to claim 1, characterized in that R1 represents:
a) an aryl optionally substituted with one or more (for example 1 to 3) groups, identical or different from each other, selected from among the atoms and following groups:
.cndot. halogen, .cndot. optionally substituted alkyl, .cndot. alkoxy, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. alkylene, .cndot. alkynyl, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. -S-fluoroalkyl, .cndot. CN, .cndot. -NO 2, .cndot. heterocycloalkyl, .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -OSO2R c, .cndot. -CON (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a and R b are independently selected from hydrogen, optionally substituted (C1-C4) alkyl group, (C1-C4) fluoroxyalkyl, cycloalkyl, optionally substituted aryl, heteroaryl optionally substituted, heterocycloalkyl and R c takes the values of R a except hydrogen, or R a and R b together with the nitrogen atom to which they are attached, a saturated or unsaturated heterocycle of 3 to 7 links optionally comprising another heteroatom;
(b) a heteroaryl optionally substituted with one or more example 1 to 3) groups, identical or different from each other, chosen from carbon and groups:
.cndot. halogen, .cndot. optionally substituted alkyl, .cndot. alkoxy, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. CN, .cndot. -N (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a, R b and R c are as defined above;
c) an alkyl optionally substituted with one or more (for example 1 at 3) groups, identical or different from each other, selected from among the atoms and following groups:
.cndot. halogen, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. heterocycloalkyl, .cndot. alkoxy, .cndot. -S-alkyl, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. CN, .cndot. -NO 2 .cndot. -COOR c, .cndot. -CON (R a) (R b), .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -N (R c) CON (R a) (R b), and .cndot. -N (R a) SO2 (R c), where R a, R b and R c are as defined above;
d) an -SO2-aryl group where aryl is optionally substituted with one or several (for example 1 to 3) groups, identical or different from each other others, selected from the following atoms and groups:
.cndot. halogen, .cndot. alkyl, .cndot. alkoxy, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. CN, .cndot. -NO 2, .cndot. -N (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a, R b and R c are as defined above;
e) a -SO2-heteroaryl group where the heteroaryl is optionally substituted by one or more (for example 1 to 3) groups, identical or different ones of the others, selected from the following atoms and groups:
.cndot. halogen, .cndot. alkyl, .cndot. alkoxy, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. CN, .cndot. -N (R a) (R b), .cndot. -COR b and .cndot. -COOR c, where R a, R b and R c are as defined above;
f) a -SO2-fluoroalkyl group;
g) a -CO2-alkyl group where the alkyl is optionally substituted by a or several (for example 1 to 3) groups, identical or different from each other others, selected from the following atoms and groups:
.cndot. fluorine, .cndot. optionally substituted aryl, .cndot. optionally substituted heteroaryl, .cndot. heterocycloalkyl, .cndot. alkoxy, .cndot. -S-alkyl, .cndot. fluoroalkyl .cndot. fluoroalkoxy, .cndot. CN, .cndot. -NO 2 .cndot. -COOR c, .cndot. -CON (R a) (R b), .cndot. -N (R a) (R b), .cndot. -N (R a) CO (R b), .cndot. -N (R a) COO (R c), .cndot. -N (R c) CON (R a) (R b), and .cndot. -N (R a) SO2 (R c), where R a, R b and R c are as defined above. 6. Process according to any one of claims 1 to 5, characterized in that that R2 represents a (C1-C2) perfluoroalkyl group. 7. Method according to any one of claims 1 to 6, characterized in that that R3 and R4 independently of one another represent an alkyl group or alkoxyalkyl or R3 and R4 together with the nitrogen atom to which they are attached, a morpholinyl group. 8. Process according to any one of Claims 1 to 7, characterized in that that R5, R6 and R7 represent a methyl group. 9. Method according to any one of claims 1, 6, 7 or 8, characterized in that the compound of formula (III) is obtained by reaction of the compounds of formula (IV) and (V) at a temperature of from -40 ° C to 40 ° C. 10. Process according to claim 1, characterized in that the tertiary amine is selected from triethylamine, N, N diisopropylethylamine, pyridine or 2, 6-lutidine. 11. Process according to claim 1, characterized in that the solvent organic is a non-polar solvent which is preferably dichloromethane.