Method of obtaining apoptosis stimulator abt-263

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide or its pharmaceutically acceptable salt, which includes: (a) interaction of 4,4-dimethylcyclohexanone, alkylformiate, selected from group, including methylformiate, ethylformiate, n-propylformiate, tertbutylformiate and their any combination, and first base, selected from group, including sodium hydrate, sodium tert-butoxide, potassium tert-butoxide and their any combination, with obtaining (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with separation or without separation of (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; (b) interaction of (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base, selected from group, including triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and their any combination, and first reagent silyl ether protecting group, selected from group, including trimethylchlorosilane, tert-butylchlorodimethylsilane, triisopropylchlorosilane, tert-butylchlorodiphenylsilane and their any combination, with obtaining first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with separation or without separation of first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; (c) interaction of first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorophenylmagnesium bromide with obtaining first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol; with separation or without separation of first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol; (d) interaction of first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol and first acid, selected from group, including tetra-n-butylammoniumfluoride, trifluoroacetic acid, hydrochloric acid, sulfuric acid and any their combination, with obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, with separation or without separation of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde; (e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazin-1-ylbenzoate and first reducing agent, selected from group, including sodium triacetoxyborohydrode, sodium cyanoborohydride and their combinations, with separation or without separation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoate; (f) ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoate interaction of and aqueous solution of third base, selected from group, including sodium hydroxide, potassium hydroxide and their combinations, with separation or without separation of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoic acid; and (g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoic acid, 4-(((1R)-3-morpholin-4yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide and first binding reagent, selected from group, including 1-ethyl-3(3-(dimethylamino)propyl)-carbodiimidhydrochloride, dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidasole and their any combination, with or without fourth base, selected from group, including 1,8-diazabicyclo(5.4.0)undec-7-ene, potassium tret-butoxide and their combinations, and with or without first auxiliary binding reagent, selected from group, including 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-aza-benzotriazole and any their combination, with separation or without separation of N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide.

EFFECT: new method of obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide, which can be applied in medicine as stimulator of apoptosis.

10 cl, 17 ex

 

The AREA BELONGS TO the PRESENT INVENTION

The present invention relates, inter alia, to new compounds and synthesis methods, including the methods used to obtain the N-arylsulfonamides stimulators of apoptosis.

BACKGROUND of INVENTION

New N-arylsulfonamides stimulators of apoptosis are described, for example, in patent publication US 2005/0159427A1, the patent publication U.S. 7390799 B2 (hereinafter indicated as “'799 Patent”) and other documents. Methods of synthesis for the preparation of N-arylsulfonamides stimulators of apoptosis described in the '799 Patent, and K. Ding, et al. (Synthesis, 2008, 15, 2398-2404).

BRIEF description of the INVENTION

The present invention provides, among other things, safe, effective and cost efficient ways to obtain the N-arylsulfonamides stimulators of apoptosis.

One aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) vzaimode the op perate (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, the second substrate and the first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-the l)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dim is titiklekapan;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(m) the interaction of 2-forbindelsesfaneblad and the first fluoride source to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) wsimages the Viy 2-forbindelseshandtering, reagent of Ruppert (CH3SiCF3and second fluoride source, to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide first and NH3source to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, first svyazivalsa what about the reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; with the highlight is the group or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(r) the interaction of the first triftoratsetofenona metal, the first source of halftoned and a first catalyst to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((triptime the l)sulfonyl)benzosulfimide and the first source NH 3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, in the with:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-DIMET cyclohexanol; with the selection or no selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)what antinoi acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and

4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimetil2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-d is methylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium obtaining 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and aquatic plants is ora ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide to the lia to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the selection or no selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-44-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(r) the interaction of the sodium triftoratsetata, bis-(2-forfinal)iodonitrotetrazolium and copper oxide(I) to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)with Lionel)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-cardionephrology and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first binding reagent, with or without the fourth reason, and with or without auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or it is pharmaceutically acceptable salts, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another aspect of the present invention relates to the compound or its pharmaceutically acceptable salt selected from (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone and (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)stands is)-4,4-dimethylcyclohexanone.

Another aspect of the present invention relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt.

DETAILED DESCRIPTION of the PRESENT INVENTION

The fragments, which variables are represented by identifiers (capital letters with numeric and/or alphabetic index) and can be specifically embodied in this application.

The term "alkyl", as used in this application means C1-alkyl, C2-alkyl, C3-alkyl, C4-alkyl, C5-alkyl and C6-alkyl.

The term "C1-alkyl", as used in this application, means methyl.

The term "C2-alkyl", as used in this application means ethyl.

The term "C3-alkyl", as used in this application means prop-1-yl and prop-2-yl (isopropyl).

The term "C4-alkyl", as used in this application means a buta-1-yl, but-2-yl, 2-methylprop-1-yl and 2-methylprop-2-yl (tert-butyl).

The term "C5-alkyl", as used in this application means 2,2-dimethylpropyl-1-yl (neo-pentyl), 2-methylbut-1-yl, 2-methylbut-2-yl, 3-methylbut-1-yl, 3-methylbut-2-yl, Penta-1-yl, Penta-2-yl and Penta-3-yl.

The term "C6-alkyl", as used in this application means 2,2-dimethylbutan-1-yl, 2,3-dimethylbutan-1-yl, 2,3-dimethylbutan-2-yl, 3,3-dimethylbutan-1-yl, 3,3-dimethylbutan-2-yl, 2-Etherboot-1-yl, Gex-1-yl, the CEN-2-yl, Gex-3-yl, 2-methylpent-1-yl, 2-methylpent-2-yl, 2-methylpent-3-yl, 3-methylpent-1-yl, 3-methylpent-2-yl, 3-methylpent-3-yl, 4-methylpent-1-yl and 4-methylpent-2-yl.

The term "alcohol"as used in this application means methanol, ethanol, isopropanol, tert-butanol and the like, or their mixture.

The term "bis-(2-forfinal)iodone alkyl-sulfonate"as used in this application means bis-(2-forfinal)iodone methylsulfonate, bis-(2-forfinal)iodone hexanesulfonate, bis-(2-forfinal)iodonitrotetrazolium, bis-(2-forfinal)iodonitrotetrazolium, bis-(2-forfinal)ideiasnet, bis-(2-forfinal)iodone poly(vinyl)sulfonate and the like.

The term "bis-(2-forfinal)idaniel-sulfonate"as used in this application means bis-(2-forfinal)etonianswhen, bis-(2-forfinal)iodone para-toluensulfonate, bis-(2-forfinal)hedonistically, bis-(2-forfinal)iodinedeficient and the like.

The term "bis-(2-forfinal)iodone cycloalkyl-sulfonate"as used in this application means bis-(2-forfinal)idenitification, bis-(2-forfinal)iodonicotinate and the like.

The term "bis-(2-forfinal)stonyhearted-sulfonate"as used in this application means bis-(2-forfinal)idenitification, bis-(2-forfinal)iodone-2-pyridylsulfonyl, bis-(2-forfe the Il)iodone-3-pyridylsulfonyl, bis-(2-forfinal)iodomethyl-5-sulfonate, bis-(2-forfinal)jordaniangovernment and the like.

Compounds of the present invention may contain one or more asymmetrically substituted carbon atoms in the R configuration or s Compounds containing an asymmetrically substituted carbon atoms, enriched in one configuration versus another, is assigned to the configuration, which is present in larger quantities, preferably from 85% to 95% concentration, more preferably from 95% to 99% enrichment, and even more preferably more than 99% enrichment. Accordingly, the compounds of the present invention can exist as enantiomers, mixtures of enantiomers, diastereomers with relative stereochemistry, diastereomers with absolute stereochemistry, diastereomers containing at least one asymmetrically substituted carbon atom, which is enriched in one configuration, and at least one asymmetrically substituted carbon atom, which is not enriched, and mixtures of the above compounds.

Compounds of the present invention can also contain one or more than one double bond carbon-carbon bonds or double bonds, the carbon-nitrogen. Accordingly, the compounds of the present invention may exist as geometric isomers or Z or E configuration is or as a mixture of geometric isomers.

The terms "R", "S", "Z" and "E" correspond, as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-10.

Compounds of the present invention can exist in the form of an acid additive salts or basic additive salts and can be obtained in the process of their selection or after purification. Acid additive salts of the compounds obtained by reaction with acid. For example, it is assumed that the invention includes such salts of the compounds of the present invention, as the acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, bansilalpet, bisulfate, butyrate, comfort, camphorsulfonate, citrate, digluconate, formate, fumarate, glycerol, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonic, methanesulfonate, naphthalenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, triptorelin pair-toluensulfonate, undecanoate. Basically additive salts of the compounds of the present invention can be obtained by communicating with a base, such as hydroxide, carbonate, bicarbonate, phosphate, hydrogen phosphate or dihydrophosphate cations such as the cations of calcium, iron, lithium, potassium, sodium or magnesium.

The term "selection", and is used in this application, means separation of compounds from the solvent, antibacterial or a mixture of solvent and antibacterial with receiving solid, semi-solid substances or syrup. Typically, this is done using tools such as centrifugation, filtration using a vacuum or without vacuum, filtration under positive pressure, distillation, evaporation or a combination thereof. The selection can include or not include cleaning, in which process chemicals, chiral, or chemical and chiral purity of the isolate grows. Cleaning is usually carried out through methods such as crystallization, distillation, extraction, filtration through an acidic, neutral or basic alumina, filtration through an acidic, neutral or basic carbon, column chromatography on a column with a chiral stationary phase, filtration through porous paper, plastic or glass barrier, column chromatography on silica gel, ion exchange chromatography, recrystallization, high-performance liquid chromatography normal phase high-performance liquid chromatography with reversed phase, grinding into powder, etc.

The phrase "selection or no selection"used in this application means that the implementation of the present invention is not required widelooking connection after each stage to the next stage. This decision on the basis of stability, purity, dissolution of the next stage and so on can easily make an ordinary specialist in the field.

Illustrative compounds and intermediate compounds were named using ACD/ChemSketch Version 5.06 (05 June 2001, Advanced Chemistry Development Inc., Toronto, Ontario) or ChemDraw® Version 9.0.5 (CambridgeSoft, Cambridge, MA). N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide named as in the '799 Patent.

Methods of synthesis for the preparation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, intermediates in the synthesis stimulators of apoptosis described in the '799 Patent, and K. Ding, et al. (Synthesis. 2008, 15, 2398-2404, which is then specified as a reference document Ding). '799 Patent describes the synthesis using triptoreline, gas toxicity problem. In addition, at a later stage oxidation using RuCl3and NaIO4to obtain a strong exothermic reaction. Reference document Ding describes many chemical stages to obtain 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid with low overall yield. In addition, a very high temperature is s reactions are not readily achievable or ideal on a large scale. Finally, in the synthesis described in the reference document Ding, use relatively expensive starting material.

The authors of the present invention in previous studies of the synthesis described in the reference document Ding, et al., revealed a number of problems. First of all chemicals used and the techniques are potentially genotoxic because of brominated products obtained by the joint use of Hydrobromic and triperoxonane acids. Also, when using these or other acids, such as methanesulfonate acid, receive various impurities that are inefficiently removed by typical cleaning methods, such as crystallization. The yield, purity, and processing time were violated. Finally, poor physical properties of selected intermediates did filtering slow and inefficient. The present invention avoids these disadvantages.

The METHODS of EMBODIMENTS of the PRESENT INVENTION

One alternative embodiment of the present invention, thus, relates to a method for obtaining protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxym is tilen)-4,4-dimethylcyclohexanone; and

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone and (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or pharmaceutically acceptable salts of such compounds, obtained as described in the previous variant embodiments.

Another variant embodiment relates to the compound (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((triisopropyl the Lil)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt for use in obtaining the compounds such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, which is incorporated into the present application by reference.

Another variant embodiment relates to the compound (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Another variant embodiment relates to the compound (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-2-(((tert-butyl(di is ethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Compounds described in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203 include 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-(((1R)-3-(dimethylamino)-1-((phenylthio)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((5-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylthio)methyl)propyl)amino)-4-nitration-2-yl)sulfonyl)benzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-phenoxybenzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(23-b)pyridine-5-yloxy)benzamide and the like.

One alternative embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Examples of alkylphosphates used to implement the present invention are methylformate, ethyl formate, n-paperformat, tert-bodyformat and the like.

The first examples of the bases used for practical implementation is tvline of the present invention, are sodium hydride, tert-piperonyl sodium tert-piperonyl potassium and the like.

The second examples of the bases used for the practical implementation of the present invention are triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and the like.

Examples of the first reagent silylating protective groups used for the practical implementation of the present invention include trimethylchlorosilane, tert-BUTYLCARBAMATE, triisopropylchlorosilane, tert-butylchloroformate and the like.

Examples of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone used for the practical implementation of the present invention include (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and the like.

Examples of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone used for the practical implementation of the present invention include (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorp the Nile)-4,4-dimethylcyclohexane and the like.

The first examples of acids used for the practical implementation of the present invention are Tetra-n-butylammonium, triperoxonane acid, hydrochloric acid, triftormetilfullerenov acid, sulfuric acid and the like.

Stage (a) is usually carried out for from about 6 to about 18 hours in a solvent such as tetrahydrofuran, N,N-dimethylformamide (DMF), mixtures thereof and the like.

Stage (b) is usually carried out for from about 4 to about 16 hours in solvents such as tetrahydrofuran, DMF, toluene, 2-methyltetrahydrofuran, ethyl acetate, mixtures thereof and the like.

Stage (c) is generally carried out from about 2 to about 4 hours in a solvent comprising toluene, diethyl ether, tetrahydrofuran, N,N-dimethylformamide and the like or mixtures thereof.

Stage (d) is generally carried out from about 1 to about 4 hours in solvents such as toluene, diethyl ether, tetrahydrofuran, N,N-dimethylformamide, water, methanol and the like or mixtures thereof.

Another variant embodiment relates to a method for ethyl 4-(4-((2-(4-chlorophenyl)-5,5-(dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-di is ethylcyclohexyl-1-EN-1-yl)methyl)piperazine-1-yl)benzoate.

The first examples of the reducing agents used for the practical implementation of the present invention include triacetoxyborohydride sodium and cyanoborohydride sodium.

Stage (e) is generally carried out from about 10 to about 16 hours in solvents such as dichloromethane, acetonitrile, toluene, diethyl ether, tetrahydrofuran, N,N-dimethylformamide, methyl tert-butyl ether, mixtures thereof and the like.

Another variant of the embodiment refers to ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate obtained as described in the previous variant embodiments.

Another variant of the embodiment refers to ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant of the embodiment refers to ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent which claims the US 61/145611, 61/120275, 61/181180 and 61/181203.

Another variant embodiment relates to a method for producing 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, including:

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and third base, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid.

Examples of third bases used for the practical implementation of the present invention are sodium hydroxide, potassium hydroxide and the like.

Stage (f) is generally carried out from about 10 hours to about 20 hours in solvents such as ethanol, tetrahydrofuran, heptane, 2-methyltetrahydrofuran, water, mixtures thereof and the like.

Another variant embodiment pertains to 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment pertains to 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid or its pharmaceutically acceptable salt, for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)IU who yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant embodiment pertains to 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethy is-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone.

Another variant of the embodiment refers to (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone and (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)CEC is hexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; and

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate.

Another variant of the embodiment refers to ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for producing 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, including:

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid.

Another variant embodiment pertains to 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex--EN-1-yl)methyl)piperazine-1-yl)benzoic acid or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, at a temperature of from about -10°C to about 0°C, with a selection or no selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane at a temperature of from about -10°C to about 0°C to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone.

Another option vopl the post belongs to (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone and (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone or pharmaceutically acceptable salts of such compounds, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium at a temperature of from about -10°C to about 0°C to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane at a temperature of from about -10°C to about 0°C to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) the interaction of (E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -10°C to about 5°C to obtain ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone, and

(d) interaction ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid at a temperature of from about 5°C to about 20°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde Il is its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate.

Another variant of the embodiment refers to ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for producing 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, including:

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid.

Another variant embodiment pertains to 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid or her farm is citiesi acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first binding reagent, with or without the fourth reason, and with or without auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant embodiment relates to a method for obtaining a stimulator of apoptosis or its pharmaceutically acceptable salts, such as those described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first available benzosulfimide and the first binding reagent, with or without the fourth reason, and with or without auxiliary linking reagent, selection or no selection stimulator of apoptosis.

Examples of the first binding reagents are 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidazole and the like.

Examples of the first auxiliary binding reagents include 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-Aza-benzotriazole and the like.

The fourth examples of the bases include 1,8-diazabicyclo(5.4.0)undec-7-ene, tert-piperonyl potassium and the like.

Examples of stimulators of apoptosis include 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-(((1R)-3-(dimethylamino)-1-((phenylthio)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide, 4-(4-((2-(4-shall lorgeril)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((5-(((1R)-3-(isopropyl(methyl)amino)-1-((phenylthio)methyl)propyl)amino)-4-nitration-2-yl)sulfonyl)benzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((4-((3-morpholine-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-phenoxybenzamide, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)-N-((3-nitro-4-((tetrahydro-2H-Piran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridine-5-yloxy)benzamide and the like.

The first examples of suitable benzosulfimide include 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, (R)-4-(4-(dimethylamino)-1-(phenylthio)butane-2-ylamino)-3-nitrobenzenesulfonamide and the like.

Stage (g) is generally carried out from about 36 to about 50 hours in solvents such as dichloromethane, acetonitrile, dioxane, tetrahydrofuran, mixtures thereof and the like.

Another variant embodiment relates to a method for obtaining a stimulator of apoptosis or its pharmaceutically acceptable salts, compounds, such as those described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first available benzosulfimide and the first binding reagent, with or without the fourth reason, and with or without auxiliary linking reagent, selection or no selection stimulator of apoptosis.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, comprising:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methylpiperazin-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first binding reagent, with or without the fourth reason, and with or without auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, emitting the do without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant embodiment relates to a method for obtaining a stimulator of apoptosis or its pharmaceutically acceptable salts, such as those described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first of a suitable amine, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, allocation or no allocation stimulator of apoptosis.

Another variant embodiment relates to a method for obtaining a stimulator of apoptosis or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventout is and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first of a suitable amine, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, allocation or no allocation stimulator of apoptosis.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, comprising:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and water solution is hydroxide sodium, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant embodiment relates to a method for obtaining a stimulator of apoptosis or its pharmaceutically acceptable salts, as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first of a suitable amine, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, with allocation or no allocation stimulator of apoptosis.

Another variant of the embodiment refers to the way the receiving stimulator of apoptosis or its pharmaceutically acceptable salt, so, which are described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, the first of a suitable amine, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, with allocation or no allocation stimulator of apoptosis.

Another variant embodiment relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or pharmaceutical is acceptable salt, including:

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides, and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)- 1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((Tr is permitil)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohex is canola and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)b is zolsulphonate or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohe is sanona or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)hydroxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-harfe who yl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides, and 4 dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium at a temperature of from about -10°C to about 0°C, to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the allocation of the or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane at a temperature of from about -10°C to about 0°C, to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)the methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -10°C to about 5°C, obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorphen the l)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid at a temperature from about 5°C to about 20°C, to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carb is dimethylformamide and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

One alternative embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and fifth base to obtain (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4-dimethylcyclohexanone;

(i) the interaction of 2-(diethoxylate)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone; and

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and second acid to obtain 2-(4-chlorophenyl)-5,5-immiscibles-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

The fifth examples of the bases used for the practical implementation of the present invention include N,N-diisopropylethylamine, 1,8-diazabicyclo(5.4.0)undec-7-ene and the like.

The second examples of the acid used for the practical implementation of the present invention include an aqueous solution of floristware the Noah acid, sulfuric acid and the like.

Stage (h) is usually carried out for from about 1 to about 3 hours in a solvent such as dichloromethane and the like.

Stage (i) is usually carried out for from about 1 to about 3 hours in a solvent such as tetrahydrofuran, diethyl ether, mixtures thereof and the like.

Stage (j) is usually carried out for from about 15 to about 20 hours in a solvent such as tetrahydrofuran, diethyl ether, mixtures thereof and the like.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and N,N-diisopropylethylamine obtaining (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4-dimethylcyclohexanone;

(i) the interaction of 2-(diethoxylate)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone; and

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and an aqueous solution of hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting what if no selection 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and N,N-diisopropylethylamine at a temperature of from about -60°to about -90°C to obtain (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4 - dimethylcyclohexanone;

(i) the interaction of 2-(diethoxylate)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -60°C to about -10°C to obtain 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone; and

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and an aqueous solution of hydrochloric acid at a temperature from about 50°C to about 80°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and fifth base to obtain (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4-dimethylcyclohexanone;

(i) the interaction of 2-(diethoxylate)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone;

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and second acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)PR who drank)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and N,N-diisopropylethylamine obtaining (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4-dimethylcyclohexanone;

(i) the interaction of 2-(diethoxylate)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone;

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and an aqueous solution of hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(h) interaction 4,4-dimethylcyclohexanone, detoxicationwith and N,N-diisopropylethylamine at a temperature of from about -60°to about -90°C to obtain (2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 2-(diethoxylate)-4,4-dimethylcyclohexanone;

(i) the interaction of 2-(detox is methyl)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -60°C to about -10°C to obtain 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone, emitting or without isolating the 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone;

(j) the interaction of 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone and an aqueous solution of hydrochloric acid at a temperature from about 50°C to about 80°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C is about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

One alternative embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded; and

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, the first phase of the catalyst, the fifth substrate and the first palladium catalyst to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-d is methylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Examples of the first interphase catalysts used for the practical implementation of the present invention include tetrabutylammonium, tetrapropylammonium, tributylammonium, tetraethylammonium, tetraoctylammonium, tetrabutylammonium, benzyltrimethylammonium, benzyltriethylammonium, tetrabutylammonium, tetrabutylammonium and the like.

The fifth examples of the bases used for the practical implementation of the present invention include carbonate to the lia, potassium phosphate, potassium fluoride, tert-piperonyl potassium and the like.

The first examples of palladium catalysts used for the practical implementation of the present invention include palladium(II)acetate, Tris(dibenzylideneacetone)dipalladium(0), tetrakis(triphenylphosphine)palladium(0), (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium(II) and the like.

Phase (k) is usually carried out for from about 15 to about 20 hours in a solvent such as dichloromethane, N,N-dimethylformamide, mixtures thereof and the like.

Stage (l) is usually carried out for from about 5 to about 10 hours in a solvent such as water or a mixture of water and one or more organic solvents, such as toluene, methylene chloride, DMF and the like.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded; and

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, tetrabutylammonium, potassium carbonate and palladium(II) acetate to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-carbamide is Yes, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention, thus, relates to a method for obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride at a temperature of from about 20°C to 45° C to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded; and

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, tetrabutylammonium, potassium carbonate and palladium (II) acetate at a temperature from about 20°C to 45°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde.

Another variant embodiment relates to 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to an str is trained to obtain N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded;

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, the first phase of the catalyst, the fifth substrate and the first palladium catalyst to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the, I can pay tithing auxiliary binding reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded;

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, tetrabutylammonium, potassium carbonate and palladium (II) acetate to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethy cyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described the previous is eat variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(k) the interaction of 4,4-dimethylcyclohexanone and phosphorus oxychloride at a temperature of from about 20°C to 45°C to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada, emitting or without isolating the 2-chloro-5,5-dimethylcyclohex-1-interbanded;

(l) the reaction of 2-chloro-5,5-dimethylcyclohex-1-encebollada, 4-Chlorfenvinphos acid, tetrabutylammonium, potassium carbonate and palladium (II) acetate at a temperature from about 20°C to 45°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide at temperature is from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)- 1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

One alternative embodiment of the present invention, thus, relates to a method for producing 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and the first fluoride source to obtain 2-forbindelsen is lforida, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3and second fluoride source to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)is sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its salts.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

Examples of the first fluoride sources used for the practical implementation of the present invention include Tetra-n-butylammonium and potassium fluoride and mixtures thereof.

Examples of the second fluoride sources used for the practical implementation of the present invention include Tris(dimethylamino)sulfonethylmethane, Tetra-n-butylammonium, cesium fluoride, tetraethylorthosilicate and tetraethylorthosilicate./p>

Examples of the first sources of NH3used for the practical implementation of the present invention include an aqueous solution of ammonium hydroxide, a solution of ammonia in methanol, ammoniabased, a solution of ammonia in isopropyl alcohol, hexamethyldisilazane.

The sixth examples of the bases used for the practical implementation of the present invention include triethylamine and the like.

Stage (m) is usually carried out for from about 30 minutes to about 2 hours in a solvent such as tetrahydrofuran, acetonitrile, water, mixtures thereof and the like.

Stage (n) is usually carried out for from about 30 minutes to about 2 hours in a solvent such as dichloromethane, tetrahydrofuran, toluene, dimethoxyethane, N-methyl-2-pyrrolidone and mixtures thereof such.

Phase (o) is usually carried out for from about 15 to about 25 hours.

Phase (p) is usually carried out for from about 30 minutes to about 24 hours in a solvent such as acetonitrile, tetrahydrofuran, ethyl acetate, isopropyl alcohol, isopropyl acetate, dimethoxyethane, dichloromethane, toluene, mixtures thereof and the like.

Stage (q) is usually carried out for from about 12 to about 24 hours in a solvent such as ethyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, mixtures thereof and the like.

Another variant of the embodiment of the present invention relates to a method floor the treatment of 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium obtaining 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)PR who drank)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for producing 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium at a temperature of from about -10°to about 10°C to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine at approximately room temperature to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at a temperature of from about 110°C to about 130°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((triptime the l)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide at a temperature of from about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, allocation or no allocation 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and the first fluoride source to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3and W is cerned fluoride source to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3pick 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorp the Nile)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium obtaining 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide the reed;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)met the l)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium at a temperature of from about 0°to about 10°C to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine at approximately room temperature to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at a temperature of from about 110°C to about 130°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide at a temperature of about is about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, allocation or no allocation 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable Sol is, obtained as described in the previous variant embodiments.

One alternative embodiment of the present invention, thus, relates to a method for producing 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(r) the interaction of the first triftoratsetofenona metal, the first halftoned and a first catalyst to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-Yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide for use in obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt for use in the formation of compounds, such as described, for example, in Patent publication U.S. US2005/0159427A1, '799 Patent and Provisional patent applications U.S. 61/145611, 61/120275, 61/181180 and 61/181203.

The first examples of catalysts used for the practical implementation of the present invention include CuI, Cu2O, CuCl triftormetilfosfinov complex of copper (I), triplet copper, CuSCN, copper acetate and palladium(II) acetate alone or in combination with ligands, such as, tetramethylethylenediamine, 4,4'-di is pet-butyl-2,2'-dipyridyl, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2-acetylcyclohexanone, N,N-diethylaniline, triphenylphosphine, tri-tert-butylphosphine, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 1,1'-bis(diphenylphosphino)ferrocene, 2-(di-tert-butylphosphino)biphenyl, triphenylphosphite, triphenylphosphine, dimethylmethylphosphonate, 1,3-bis(2,4,6-trimetilfenil)-1,3-dihydro-2H-imidazol-2-ilidene, 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ilidene, 1,3-bis(1-substituted)imidazole-2-ilidene, 1,3-di-tert-butylimidazole-2-ilidene and the like.

Examples of the first triptoreline metals used for the practical implementation of the present invention include triptoreline potassium, triptoreline lithium, triptoreline rubidium, triptoreline cesium and the like.

Examples of the first sources of halftoned used for the practical implementation of the present invention include mesityl-2-torpedinidae, bis-(2-forfinal)jodonnell-sulfonates, bis-(2-forfinal)idaniel-sulfonates, bis-(2-forfinal)hedonically-sulfonates, bis-(2-forfinal)stonyhearted-sulfonates, bis-(2-forfinal)iodomethylphosphonate, bis-(2-forfinal)stonyhearted and the like.

Stage (r) is usually carried out for from about 10 hours to about 20 hours to dissolve the barely, such as N,N-dimethylformamide, dimethylsulfoxide, dimethylacetamide, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone, diglyme, tert-butyl methyl ether, methylenechloride, chloroform, carbon tetrachloride, acetone, ethyl acetate, isopropylacetate, acetonitrile, benzonitrile, toluene, benzene, mesitylene, xylene, anisole, chlorobenzene, torbenson, hexane, heptane, pentane, methanol, ethanol, propanol, butanol, tert-butanol, hexanol, octanol, pyridine, tri-butylamine, mixtures thereof and the like.

Another variant of the embodiment of the present invention relates to a method for producing 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(r) the interaction of nutrititional, bis-(2-forfinal)iodonitrotetrazolium and copper oxide (I) to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifter ethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for producing 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(r) the interaction of nutrititional, bis-(2-forfinal)iodonitrotetrazolium and copper oxide (I) at a temperature of from about 0°C to about 110°C to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at a temperature of from about 110°C to 130°C with floor is rising 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide at a temperature of from about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, allocation or no allocation 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzo is sulfonamida, including:

(r) the interaction of nutrititional, bis-(2-forfinal)iodonitrotetrazolium and a first catalyst to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((three is tormentil)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(r) the interaction of nutrititional, bis-(2-forfinal)iodonitrotetrazolium and copper oxide (I) to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzazolyl orida, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-C is logex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(r) the interaction of nutrititional, bis-(2-forfinal)iodonitrotetrazolium and copper oxide(I) at a temperature of from about 0°C to about 110°C to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at a temperature from about 40°C to about 50°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide at a temperature of from about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-(phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethy is cyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)shall ethyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(m) the interaction of 2-forbindelsesfaneblad and the first fluoride source to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3and second fluoride source to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)IU who yl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, atilf is Miata and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the selection or no selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-44-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; and

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium obtaining 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine to obtain 1-fluoro-2-((Tr is permitil)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-DIMET the l-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium at a temperature of from about -10°C to about 0°C to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane at a temperature of from about -10°C to about 0°C to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without the adelene (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -10°C to about 5°C to obtain ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and

(d) interaction ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid at a temperature of from about 5°C to about 20°C to obtain 2-(4-chlorophenyl)-5,5-dim testicles-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium at a temperature of from about 0°to about 10°C to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;

(n) the interaction of 2-forbindelseshandtering, reagent Rupert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine at approximately room temperature to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at the temperature from about 110°C to about 130°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide at a temperature of from about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, allocation or no allocation 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate and the first base to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base and first reagent silylating protective group from the receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-x is arvanil)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; with the release or no release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and

(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and the first reductant, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third substrate, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(r) the interaction of sodium triftoratsetofenona, bis-(2-forfinal)iodonitrotetrazolium and a first catalyst to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting Ilias selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds of obtaining 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent and, optionally, the first auxiliary linking reagent, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((panels JPanel)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous variant embodiments.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohe is sanona or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)hydroxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; and

(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorp the Nile)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(r) the interaction of sodium triftoratsetofenona, bis-(2-forfinal)iodonitrotetrazolium and copper oxide (I) to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)self the Nile)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, obtained as described in the previous version of the incarnation.

Another variant of the embodiment of the present invention relates to a method for obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, including:

(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium at a temperature of from about -10°C to about 0°C to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;

(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or is diisopropylaniline at a temperature of from about -10°C to about 0°C to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;

(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine at a temperature of from about -10°C to about 5°C to obtain ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and

(d) interaction ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trim Telcell)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid at a temperature from about 5°to about 20°C to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;

(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium at a temperature of from about 15°C to 30°C, with allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;

(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide at a temperature of from about 55°C to about 75°C, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;

(r) the interaction of sodium triftoratsetofenona, bis-(2-forfinal)iodonitrotetrazolium and copper oxide (I) at a temperature of from about 0°C to about 110°C to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;

(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid at a temperature of from about 110°C to about 130°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(p) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzolsulfonat the chloride and an aqueous solution of ammonium hydroxide at a temperature of from about -5°C. to about -60°C to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, with the selection or no selection 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;

(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine at a temperature from about 40°C to about 50°C to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, allocation or no allocation 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and

(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine at a temperature of from about 25°C to about 35°C, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

Another variant embodiment pertains to N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salt, is received, as described in the previous variant embodiments.

The following schemes and examples are intended for what is considered the most useful and understandable procedures and conceptual aspects of the present invention.

SCHEMA

Scheme 1

Scheme 1 presents three ways of synthesis used to obtain the aldehyde intermediate (2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde) (4) of (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone (IA). Aldehyde intermediate compound (4) can then be subjected to interaction with ethyl 4-(piperazine-1-yl)benzoate (4A) to obtain ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate, which is hydrolized to obtain 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid (6).

One such way involves reacting 4,4-dimethylcyclohexanone (IA) and alkylphosphate, such as, but not limited to, ethyl formate, in the presence of a base such as, but not limited to, tert-piperonyl potassium, to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone (1). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, tetrahydrofuran, then warmed to room temperature the tours and stirred over night. (2E)-2-(Hydroxymethylene)-4,4-dimethylcyclohexanone (1) is then subjected to interaction with the bottom, such as, but not limited to, triethylamine, and a reagent silylating protective group such as, but not limited to, triisopropylsilane, obtaining protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone (2). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, 2-methyltetrahydrofuran. (4-Chlorophenyl)magnesium bromide is then added to a solution of protected alcohol (2) to obtain the protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone (3). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, tetrahydrofuran, toluene or mixtures thereof. Protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone (3) can be treated with acid, such as, but not limited to, HCl, to obtain the aldehyde intermediate (2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde) (4).

The other path includes the interaction of dimethylcyclohexanone (IA) with the obtained solution detoxicationwith obtaining 2-(diethoxylate)-4,4-dimethylcyclohexanone (8). The reaction is usually carried out at a temperature below room temperature in RAS is varicela, such as, but not limited to, methylene chloride. Chlorpheniramine then added to a solution of 2-(diethoxylate)-4,4-dimethylcyclohexanone (8) to obtain 1-(4-chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexanone (9). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, tetrahydrofuran. 1-(4-Chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexane (9) can be treated with acid, such as, but not limited to, HCl, to obtain the aldehyde intermediate (2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde) (4).

Another way involves the interaction of dimethylcyclohexanone (IA) with POCl3to obtain 2-chloro-5,5-dimethylcyclohex-1-encebollada (10). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, methylene chloride, N,N-dimethylformamide or mixtures thereof. Aldehyde intermediate compound (2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde) (4) can be obtained from 2-chloro-5,5-dimethylcyclohex-1-encebollada (10) by reacting the latter with 4-Chlorfenvinphos acid, interfacial catalyst, such as, but not limited to, tetrabutylammonium, palladium catalyst, such as, but not limited to, palladium (II) acetate in n outstay Foundation, such as, but not limited to, K2CO3. The reaction is usually carried out at a temperature above room temperature, in a solvent such as, but not limited to, water.

Scheme 2

Scheme 2 represents the two ways used to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (17). One way involves reacting commercially available 2-forbindelsesfaneblad (11) with TBAF (Tetra-n-butylammonium) to obtain 2-forbindelseshandtering (12). The reaction is usually carried out at a temperature below room temperature in a solvent such as, but not limited to, tetrahydrofuran. 2-Forbindelseshandtering (12) can be converted to 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene (13) by reacting with a reagent of Ruppert (CH3SiCF3), using as catalyst(((CH3)2N)3S)+(F2Si(CH3)3)-, also known as the TASF. The reaction is usually carried out at approximately room temperature in a solvent such as, but not limited to, tetrahydrofuran, dichloromethane, toluene, dimethoxyethane or mixtures thereof. 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene (13) can be subjected to interaction with chlorosulfonic acid with the floor is the group of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide (14). The reaction is usually carried out at elevated temperature prior to cooling to add SO2Cl2used for damping chlorosulfonic acid. 4-Fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide (15) can be obtained from 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide (14) by reacting the latter with an aqueous solution of ammonium hydroxide. The reaction is usually carried out in a solvent such as acetonitrile, tetrahydrofuran, ethyl acetate, isopropyl alcohol, isopropyl acetate, dimethoxyethane, dichloromethane, toluene or mixtures thereof. (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine (16), obtained as described in U.S. Patent No. 7390799 B2, can be subjected to interaction with 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide (15) in the presence of a base such as, but not limited to, triethylamine, to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (17). The reaction is usually carried out at elevated temperatures in a solvent such as, but not limited to, ethyl acetate.

The other path includes a first interaction of the reagent, such as bis-(2-forfinal)iodonitrotetrazolium (J. Org. Chem. 2008, 73, 4602), and reagent such as triptoreline sodium, in the presence of Cu(I)/Cu(III) or Pd(II)/Pd(IV) catalyst to obtain 1-fluoro-2-((trifter ethyl)sulfonyl)benzene (13). The reaction is usually carried out at elevated temperatures in a solvent such as, but not limited to, N,N-dimethylformamide, dimethylsulfoxide, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone, diglyme and CH2Cl2. The catalysts include, but are not limited to, CuI, Cu2O, CuCl complex triftoratsetata copper (I) benzene, CuSCN Cu(OAc), Pd(OAc)2alone or in combination with ligands, such as tetramethylethylenediamine, 4,4'-decret-butyl-2,2'-dipyridyl, phenanthroline, 2-acetylcyclohexanone, N5N-diethylaniline, phosphines and the like. Other metals, such as Nickel, cadmium, cobalt, tin, iron, rhodium, iridium and platinum, or combinations thereof, as in the metallic form or in the form of salts or complexes, can also be effective in this chemical process.

Scheme 3

As shown in Scheme 3, 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid (6) can be subjected to interaction with 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (17) to obtain compounds such as N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (), using methods known in the prior art is widely known from the literature and such, which are described in the “Examples” section below.

EXPERIMENTAL PART

Compounds of the present invention can be obtained using methods of chemical synthesis, examples of which are presented below. It should be clear that the order of stages in these ways you can change, you can use other reagents, solvents and reaction conditions than those specifically listed below, and vulnerable groups can be protected, and they can be removed protection, if necessary, using NH, C(O)OH, OH, SH protective groups.

The following abbreviations have the indicated value. ADDP means 1,1'-(azodicarbon)dipiperidino; AD-mix-β means a mixture of (DHQD)2PHAL, K3Fe(CN)6, K2CO3and K2SO4; 9-BBN means 9-borabicyclo(3.3.1)nonan; Boc means tert-butoxycarbonyl; (DHQD)2PHAL means hydrogenizing 1,4-phthalazinedione ether; DBU means of 1,8-diazabicyclo(5.4.0)undec-7-ene; DIBAL means diisobutylaluminium; DIEA means diisopropylethylamine; DMAP means N,N-dimethylaminopyridine; DMF means N,N-dimethylformamide; dmpe means 1,2-bis(dimethylphosphino)ethane; DMSO means dimethylsulfoxide; dppb means 1,4-bis(diphenylphosphino)-butane; dppe means l,2-bis(diphenylphosphino)ethane; dppf means l'-bis(diphenylphosphino)ferrocene; dppm means l,l-bis(diphenylphosphino)methane; EDAC•ΗC1 means of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide; Fmoc means fluorenylmethoxycarbonyl; HATU means Gex-atorvastat O-(7-asobancaria-1-yl)-N,N ' N ' N'-tetramethylurea; HMPA means of hexamethylphosphoramide; IPA means isopropyl alcohol; MP-BH3means macroporous trimetilammoniietilakrilata; TEA means triethylamine; TFA means triperoxonane acid; THF means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; NMP means N-methylpyrrolidine; PPh3means triphenylphosphine.

EXAMPLE 1

(2E)-2-(Hydroxymethylene)-4,4-dimethylcyclohexanone

4,4-Dimethylcyclohexanone (20 g), ethyl formate (15,8 g of 1.35 EQ.) and tetrahydrofuran (100 ml) was loaded in a 250 ml flask and the mixture was cooled to 0-5ºC. Tert-piperonyl potassium (1M in tetrahydrofuran 191 ml, 1.2 EQ.) was slowly added while maintaining the temperature below 0ºC. The reaction mixture was stirred at a temperature of from -5 to +5ºC and completion of reaction was monitored by means of GC analysis. After stirring over night not watched any of the original substance. Was slowly added water (140 ml) and the resulting mixture was extracted with heptane (150 ml). the pH of the aqueous layer was made using 6 M HCl to pH 1-2 (~40 g of HCl and was extracted with toluene (80 ml). The organic layer was washed with 20% aqueous Rast is the EOS of NaCl (2×140 ml). A solution of the product in toluene was used directly in the next stage within 12 hours (storage at 0ºC).

EXAMPLE 2

(2E)-4,4-Dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone

EXAMPLE 1 (21 g in the form of an 18% solution in toluene) was loaded into a 1-l flask followed by the addition of 2-methyltetrahydrofuran (300 ml). The reaction mixture was cooled to a temperature in the range of 0-5ºC and downloaded triethylamine (20,67 g, 1.5 EQ.), maintaining the reaction temperature between 0-5ºC. Slowly downloaded triisopropylsilane (TIPSCl) (28,9 g, 1.1 equiv.) maintaining the reaction temperature between 0-5ºC. The reaction mixture was stirred at a temperature in the range of 0-5ºC and tracked the completion of the reaction by GC method. Added heptane (430 ml) and the temperature brought up to 10ºC. Was added water (300 ml), maintaining the internal temperature below 15ºC. The reaction mixture is thoroughly stirred and the layers were separated. The organic layer was washed with water (2×200 ml), 20% aqueous NaCl solution (200 ml) and 20% aqueous NaCl solution (360 ml). The organic layer was subjected to distillation to about 100 ml and was replaced by toluene (280 ml). Specified in the title compound was stored in the form of a solution in toluene in the refrigerator.1H NMR (400 MHz, CDCl3) δ of 1.03 (s, 6H) of 1.07 (d, J=5,76 Hz, 14H) 1,10 (s, 10H) (overlapping resonances with residual solvent) of 1.23 (DD, J=14,55, 6,59 Hz, 3H) 1,26-of 1.29 (m, 2H) (the residual is the solvent) of 1.64 (t, J=7,00 Hz, 2H) to 2.06 (s, 1H), 2.26 and-of 2.28 (m, 2H) of 2.38 (t, J=7,00 Hz, 2H) of 7.55 (t, J=I,92 Hz, 1H) ppm Mass spectrum: DCI/NH3M+1 = 311 atomic units of mass; M + NH3= 328 atomic units of mass.

EXAMPLE 2A

(2E)-4,4-Dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone

EXAMPLE 1 (0.5 g, 1 EQ.), of 0.47 ml of triethylamine (of 1.05 equiv.) and 5 ml of anhydrous tetrahydrofuran were mixed together in a round bottom flask in an atmosphere of N2. Trimethylsilane (0,43 ml of 1.05 equiv.) was added dropwise at ambient temperature and the mixture was stirred at ambient temperature for 18 hours. The reaction was suppressed by using 10 ml of 1 n HCl solution and 10 ml of ethyl acetate. The organic layer was isolated and concentrated and the residue was purified column chromatography using 5% heptane in ethyl acetate.

EXAMPLE 3

(2E)-1-(4-Chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol

For EXAMPLE 2 (26 g, in the form of a solution in toluene) was added anhydrous tetrahydrofuran (65 ml). The resulting mixture was cooled to a temperature of from -5 to 0ºC. In a separate flask was loaded anhydrous tetrahydrofuran (65 ml) and 1 M solution of (4-chlorophenyl)minibrain (172 ml, 2.05 EQ.). The mixture of the reactants were cooled to a temperature of from -5 to 0ºC. The mixture of EXAMPLE 2 in toluene was slowly added to the Grignard reagent, maintaining the reaction temperature below 5ºC. The reaction was monitored using HPLC and determined that she end is on, after about one hour. The reaction mixture is slowly extinguished methanol (91 ml), maintaining the internal temperature below 5ºC.

EXAMPLE 4

2-(4-Chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde

The solution from EXAMPLE 3 was slowly treated with 2 N. a solution of HCl (240 ml), maintaining the internal temperature below 20ºC. The content was stirred at -20 ░ C for 10-12 hours and the mixture was monitored by the method of GC analysis. Isopropylacetate (130 ml) were loaded into the reaction mixture and the layers were mixed and separated. The organic layer was washed with water (45 ml), 1% aqueous solution of NaHCO3(45 ml) and 20% aqueous NaCl (2×45 ml). The product mixture was subjected to azeotropic drying by replacing the solvent with toluene (125 g) with a 32% solution specified in the connection header.1H NMR (400 MHz, DMSO-d6) of 0.95 δ (s, 6H) of 1.48 (t, J=6,45 Hz, 2H) 2,03 (t, J=1,92 Hz, 2H) 2,53-to 2.57 (m, J=6,38, 6,38, 2,20, to 2.06 Hz, 2H) of 7.36 (DDD, J=8,75, 2,54, 2.30 Hz, 2H) 7,47 (DDD, J=8,78, 2,54, and 2.26 Hz, 2H) 9,37 (s, 1H) ppm Mass spectrum: DCI/ NH3M+1 = 248 atomic units of mass; M+NH3= 266 atomic units of mass.

EXAMPLE 4

2-(4-Chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde

EXAMPLE 9 was dissolved in 50 ml of tetrahydrofuran was added 40 ml of 6 N. aqueous HCl. The mixture was heated to 65°C for 17 hours. The reaction mixture was cooled, neutralized to pH~7 with the help of 18% Na2CO3, were extracted by a simple ether and washed with water what astora NaCl. The organic layers were concentrated to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) of 0.95 δ (s, 6H) of 1.48 (t, J=6,45 Hz, 2H) 2,03 (t, J=1,92 Hz, 2H) 2,53-to 2.57 (m, J=6,38, 6,38, 2,20, to 2.06 Hz, 2H) of 7.36 (DDD, J=8,75, 2,54, 2.30 Hz, 2H) 7,47 (DDD, J=8,78, 2,54, and 2.26 Hz, 2H) 9,37 (s, 1H) ppm Mass spectrum: DCI/ NH3M+1 = 248 atomic units of mass; M+NH3= 266 atomic units of mass.

EXAMPLE 4

2-(4-Chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde

EXAMPLE 10 (1.00 equiv.) 4-Chlorfenvinphos acid (1,11 equiv.) tetrabutylammonium (0.99 EQ.), the palladium (II) acetate (0,021 equiv.) K2CO3(2,45 EQ.) and H2O (10,0 about.) was added and was stirred. The mixture was degirolami using cycle high vacuum and purging with nitrogen, at least three times, and then was heated to 45ºC. The reaction mixture was stirred at 45ºC nitrogen purging for about 6 hours. The reaction mixture was cooled to room temperature and was diluted using H2O (15,0 about.). The diluted mixture was extracted using CH2Cl2(9,0 about. × 3). CH2Cl2the extracts were combined and washed using H2O (9,0 about. × 3) and then dried over Na2SO4. Solid Na2SO4was filtered and washed using CH2Cl2(5,0 about.). The filtrate and washing were combined and concentrated.1H NMR (400 MHz, DMSO-d6) of 0.95 δ (s, 6H) of 1.48 (t, J=6,45 Hz, 2H) 2,03 (t, J=1,92 Hz, 2H) 2,53-to 2.57 (m, J=6,3, 6,38, 2,20, to 2.06 Hz, 2H) of 7.36 (DDD, J=8,75, 2,54, 2.30 Hz, 2H) 7,47 (DDD, J=8,78, 2,54, and 2.26 Hz, 2H) 9,37 (s, 1H) ppm Mass spectrum: DCI/ NH3M+1 = 248 atomic units of mass; M+NH3= 266 atomic units of mass.

EXAMPLE 4

2-(4-Chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde

EXAMPLE 1 (2.0 g, 1 EQ.), 2.2 ml of triethylamine (1.2 EQ.) and 30 ml of anhydrous tetrahydrofuran were mixed together in a round bottom flask in an atmosphere of N2. tert-BUTYLCARBAMATE (2.35 g, 1.2 EQ.) was added dropwise at ambient temperature and the mixture was stirred at ambient temperature for 1 hour. The mixture was cooled to 0ºC and slowly added to 28.6 ml solution of 1 M 4-chlorpheniramine in tetrahydrofuran. After complete addition, the reaction mixture was stirred at 0°C for 30 minutes. The reaction was suppressed by using 90 ml of 1 N. aqueous HCl solution and 90 ml of ethyl acetate. The organic layer was isolated and concentrated and the residue was purified column chromatography using 5% heptane in ethyl acetate.

EXAMPLE 5

Ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate

Ethyl 4-piperazine-1-eventout (14 g) was treated with triacetoxyborohydride sodium (23 g) and tetrahydrofuran (187 g), was stirred for 15 minutes, treated with a solution of EXAMPLE 4 in toluene (42,1 g, 32.5% of aldehyde) for 20-30 minutes and was stirred for 6 hours, with the separation of the receiving gaseous hydrogen. After 12 hours no starting material was not detected by HPLC. Was added methyl tert-butyl ether (70 g) and the reaction was suppressed 20% aqueous solution of ammonium chloride (170 g). Again with evolution of gaseous hydrogen. The two layers were stirred for 30 minutes and separated. The extract was washed with water (135 g), concentrated to about 115 ml, was diluted with tetrahydrofuran (125 g), concentrated to 115 ml, was loaded tetrahydrofuran (125 g), concentrated to 115 ml and loaded ethanol (220 g), causing the formation of solids. The suspension was concentrated to about 70 ml, was loaded ethanol (165 g) and was stirred for 2-3 hours (the concentration of the solution was 3,01 mg/ml) and was filtered. The solid was washed with ethanol (2×77 g) and dried in a vacuum oven at 40ºC for 10 hours. The mixture of solids and tetrahydrofuran (41 g) was heated at 50ºC for 30 minutes, treated with ethanol (146 g), was stirred for 1 hour, cooled to 20ºC (concentration of the solution was 5,12 mg/ml) and was filtered. The solid was washed with ethanol (73 g) and dried in a vacuum oven at 40ºC for 10 hours. The mixture of solids and tetrahydrofuran (37 g) was heated to 50ºC for 30 minutes, treated with ethanol (133 g), was stirred for 1 hour, cooled to 20ºC (solution concentration was 5.1 mg/ml) and was filtered. The solid is washed on the in once with ethanol (67 g) and dried in a vacuum oven at 40ºC for 10 hours.

EXAMPLE 6

4-(4-((2-(4-Chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid

2-Methyltetrahydrofuran (20 g) and heptane (63 g) was mixed to homogeneity for use in the washing quality product. NaCl (48 g) was dissolved in water (146 g) for use in the final processing. KH2PO4(40 g) and NaCl (51 g) was dissolved in water (291 g) for use in the final processing. NaOH solution (13 g) was dissolved in water (113 g), treated with EXAMPLE 5 and 2-methyltetrahydrofuran (125 g), was stirred for 30 minutes, brought to 25-30ºC, were treated with ethanol (81 g)was transferred into the flask, maintaining the internal temperature below 35ºC, brought to 65 ± 5ºC, stirred for at least 16 hours until completion of the reaction according to HPLC analysis (<1% of EXAMPLE 5), was cooled to -20 ░ C and allowed to settle for about 30 minutes. The bottom layer was removed after sampling to determine the loss of product. Part of the solution of monopotassium phosphate (219 g) was transferred into the reactor and the contents were stirred for 30 minutes and allowed to settle for 30 minutes. The bottom layer was removed after sampling to determine the loss of the product after determining pH. About half of the 25% of the mass. aqueous solution of NaCl (91 g) was loaded into the reactor and the contents were stirred for at least 15 minutes and allowed to stand for 15 minutes. Neither the tion layer was transferred into a drying drums after sampling the product losses and the remaining 25% of the mass. NaCl solution (about 97 g) was loaded into the reactor. The contents were stirred for at least 15 minutes and allowed to settle for at least 1 hour. The bottom layer was transferred into a drying drums after sampling the product loss. 2-Methyltetrahydrofuran (125 g) was loaded into the reactor and the contents were stirred for at least 10 minutes. The solution is transferred through a nylon filter, washed in the reactor using a 2-methyltetrahydrofuran for washing cans (4 g of 2-methyltetrahydrofuran on canister) and subjected to vacuum distillation at a temperature of a casing of about 40 to about 214 ml. of Maintaining a vacuum and a volume of approximately 214 ml, 2-methyltetrahydrofuran (375 g) was added in portions to a solution of the product, which azeotrope dried. Conducted sampling of the solution in the distillation process to determine the moisture content (goal <1% water). The solution was concentrated in vacuum to about 73 ml and the internal temperature was brought to about 45ºC (goal: 40). The content was stirred for 1 hour, and treated with heptane (172 g) for 30 minutes and stirred at about 45ºC (goal:40°C) within 2 hours and about 25ºC (goal: 20) for 2 hours. A suspension of the product was subjected to vacuum distillation to 140 ml and the internal temperature was brought to about 25ºC (goal: 20). The mixture was filtered under vacuum and fluid recircula the Wali once to rinse the flask. The filtrate was washed part of the solution of heptane/2-methyltetrahydrofuran (41 g), providing the possibility of precipitation leaching on the cake for at least 15 minutes before application of the vacuum. The washing was repeated using the rest of the quantities heptane/2-methyltetrahydrofuran (about 22 g), again allowing precipitation leaching on the cake for at least 15 minutes before application of the vacuum. Sampling of liquids and leaching was carried out separately on the definition of product losses. Filter tank blew at least for 2 hours with nitrogen and the product was transferred to a drying apparatus and dried under vacuum with a nitrogen purge at a temperature below or equal to 40ºC (goal: 35ºC) at least within 12 hours.

EXAMPLE 7

N-(4-(4-((2-(4-Chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide

A mixture of 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide (8,575 g) (EXAMPLE 17), EXAMPLE 6 (6.4 g), 4-dimethylaminopyridine (4.4 g), 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides (4.1 g) and dichloromethane (80 g) was heated at 30ºC, cooled to room temperature, extinguished using N,N-dimethylethylenediamine (1.1 g)was subjected distill the tion to 30 ml, treated water (5,4 g) and ethyl acetate (97 g)was subjected to distillation to 65 ml) was treated with water (5,4 g) and ethyl acetate (97 g)was subjected to distillation up to 80 ml and treated with 10% solution of acetic acid/0.75 percent of a saturated salt solution (182 g) and ethyl acetate (65 g). The layers were separated and the extract was washed using 10% aqueous solution of acetic acid/0.75 percent of a saturated salt solution (182 g), 25% aqueous solution of K2HPO4(180 g) and pH 7 buffer solution (163 g), concentrated to 35 ml and subjected to distillation with ethyl acetate (120 g, 120 g and 60 g) with concentration up to 35 ml after each addition. The extract was then treated with ethyl acetate (60 g) and the solution was diluted with ethanol (71 g) and filtered for final purification through 0.5 micron polypropylene filter to the reactor with an ethyl acetate (20 g) washing. In a separate reactor received a HCl solution (2.8 g) in ethanol (80 g) and filtered for final purification through a separate filter and introduced into the reactor. By filtration of the solution for the cleaning of the removed residual phosphate salt after the final extraction. The solution was concentrated to about 150 ml and maintained at this level, providing additional displacement ethanol (160 g), was heated at 45ºC, were processed using seed crystals (90 mg) in ethanol (1 g), was stirred for 12 hours, ohlazhdeniya 20ºC and stirred for another 4 hours. Analysis of the filtrate showed the completion of crystallization. The suspension was filtered and the solids washed with ethanol (2×57 g). Washing used in suspension without the use of vacuum (contact time 15-25 minutes for each), and then removed via vacuum filtration. Conducted sampling of wet cakes for determination of impurities and the need for recrystallization. The solids were dried in vacuum and nitrogen at 50ºC for 3 days. Analysis of sample from the drying apparatus (method GPAS for determining residual solvents) showed that drying is complete.1H NMR (400 MHz, methanol-d4) δ ppm 1,08 (s, 5H) of 1.57 (t, J=6,38 Hz, 2H) 2,11 (s, 2H) and 2.26-of 2.34 (m, 1H) 2,40 (t, J=5,69 Hz, 2H) 3,18-of 3.27 (m, 4H) 3,42 (DD, J=14, 48mm, to 4.87 Hz, 2H) 3,69 (s, 2H) a 3.87 (s, 2H) 4,14 (s, 1H) 6,99 (TD, J=6,07, of 2.54 Hz, 3H) 7,11-7,19 (m, 5H) 7,29-to 7.32 (m, 2H) 7,37-7,41 (m, 2H) 7,76 (d, J=9,06 Hz, 2H) 8,07 (DD, J=9,19, 2,33 Hz, 1H) 8,29 (d, J=2.20 Hz, 1H).

EXAMPLE 8

2-(Diethoxylate)-4,4-dimethylcyclohexanone

To 34 ml of HC(OCH2CH3)3(0.2 mol) at -38°C was added dropwise a solution of 31 ml BF3(OCH2CH3)2in 90 ml of CH2Cl2(0.24 mol) over 15 minutes at a temperature of around 30ºC. The mixture was heated to 0ºC and was stirred for 10 minutes with obtaining detoxicationwith. The mixture was cooled to -78°C and added to 12.6 g of dimethylcyclohexanone in 40 ml of CH2Cl2(0.1 mol), followed by adding dropwise 52 ml of N,N (0.3 mol) over 30 minutes. The mixture was stirred at -78°C for 1.5 hours. The cooled reaction mixture is extinguished in 1000 g of an aqueous solution of 6.5% NaHCO3. Added dichloromethane (250 ml) and the mixture was stirred intensively for 10 minutes. The organic layers were washed using 400 g of chilled aqueous solution of 1% H2SO4and then 400 g of chilled water. The organic layers were dried over MgSO4was filtered and the filtrate was concentrated to obtain specified in the connection header. GC-MS: 183(ms/z).

EXAMPLE 9

1-(4-Chlorophenyl)-2-(diethoxylate)-4,4-dimethylcyclohexane

EXAMPLE 8 was dissolved in 200 ml of tetrahydrofuran, cooled to -78°C and was added to 195 ml of 1M chlorpheniramine (0.2 mol) for 25 minutes. The mixture was stirred at a temperature of around 20ºC for 2 hours. The reaction mixture was extinguished using 200 g of 20% aqueous solution of NH4Cl at a temperature of about -7°C, were extracted using 400 ml of ethyl acetate, then washed with 20% aqueous solution of NH4Cl, 5% aqueous solution of NaHCO3and 25% aqueous NaCl solution. The organic layers were concentrated to obtain specified in the connection header.

EXAMPLE 10

2-Chloro-5,5-dimethylcyclohex-1-interbanded

A solution of N,N-dimethylformamide (1,37 EQ.) in CH2Cl2(1.5 on.) was cooled to 0ºC and then POCl3(1.25 EQ.) was slowly added to N,N-dimethylformamide solution at a temperature below 25 is C. The resulting solution was allowed to warm to room temperature. A solution of 4,4-dimethylcyclohexanone (1.00 equiv.) in CH2Cl2(1,4 about.) was slowly added to the above solution at a temperature below 30ºC and then the reaction mixture was stirred at 45ºC during the night. The reaction mixture was extinguished in chilled 10% solution of sodium acetate (30,0 about.) at temperatures below 15 ° C, with subsequent addition of CH2Cl2flush (4,6 about.). Hydrated mixture was stirred while allowing to warm to room temperature. The organic layer was separated and then the aqueous layer was extracted with the help of CH2Cl2(7,6 about. × 3). The organic layer and CH2Cl2the extracts were combined and concentrated to obtain a solution and this solution was used in the next stage without purification.1H NMR (400 MHz, CDCl3) δ a 10.1 (1H, s, CHO)1H NMR (400 MHz, CDCl3) δ a 10.1 (1H, s, CHO), 2,61-to 2.57 (2H, m), is 2.09 (2H, s), 1,54-is 1.51 (2H, m)of 0.95 (6H, s).

EXAMPLE 11

2-Forbindelsesfaneblad

Specified in the title compound was commercially purchased from Sigma-Aldrich.

EXAMPLE 12

2-Forbindelseshandtering

In a 100 l round bottom flask, equipped with top mixer input for nitrogen, a temperature sensor and an ice bath, was loaded 2-forbindelsesfaneblad (50 g) and tetrahydrofuran (220 g). The solution was cooled to-5ºC help when the ice baths. To the reactor was slowly added tetrabutylammonium (270 ml of 1M solution in tetrahydrofuran). The internal temperature was maintained below 8ºC. After complete addition, the HPLC analysis showed complete reaction. The reaction was suppressed by the slow addition of 250 g of water. Then to the reaction mixture were added 430 g of toluene. The layers were separated. The organic layer was washed using 250 g of water twice. The organic layer was subjected to vacuum distillation at a bath temperature of 48ºC.1H NMR (400 MHz, CDCl3) δ 8,01-of 7.96 (m, 1H), 7,76-7,83 (m, 1H), 7,32-7,44 (m, 2H).

EXAMPLE 13

1-fluoro-2-((trifluoromethyl)sulfonyl)benzene

A solution of EXAMPLE 12 (44,3 g) in a solution of 450 ml was added into a round bottom flask, equipped with top mixer input for nitrogen, the cooling bath and the temperature sensor. The mixture was cooled to 12ºC. (((CH3)2N)3S)+(F2Si(CH3)3)-also known as TASF (6,1 g)was added in one portion. To the reaction mixture was slowly added to the reagent of Ruppert (370 g, CH3SiCF3), while maintaining the internal temperature below 23ºC. The reaction was completed after adding. Was added water (220 g) quenching the reaction, the layers were separated and the organic layer was washed twice using 220 g of water. The organic solution was subjected to vacuum distillation at a bath temperature of 50ºC. To the residue were added and C is an (500 g) and the mixture was subjected to distillation to remove solvent. 1H NMR (400 MHz, CDCl3) δ 8,01-with 8.05 (m, 1H), 7,84-7,87 (m, 1H), 7,44-of 7.48 (m, 1H), was 7.36-7,39 (m, 1H).

EXAMPLE 13

1-fluoro-2-((trifluoromethyl)sulfonyl)benzene

In a 1-l three-neck round bottom flask equipped with a magnetic stir bar and J-Chem thermocouple, downloaded triptoreline sodium (9,29 g, 59.5 mmol), bis-(2-forfinal)iodonitrotetrazolium (18.5 g, with 45.8 mmol) (J. Org. Chem. 2008, 73, 4602) and copper oxide(I) (0,131 g to 0.92 mmol). The flask was purged with nitrogen for 30 minutes. Degassed N,N-dimethylformamide (225 ml) was added to the flask and the reaction mixture was stirred at 50ºC for 16 hours in a positive nitrogen atmosphere. The reaction mixture was cooled to room temperature, diluted using 500 ml of isopropylacetate and was transferred into a 2 l separating funnel. The organic layer was washed using 500 ml of 5% aqueous solution of K2CO3. The organic layer was washed with water (500 ml × 2) followed by rinsing by using 250 ml of saturated salt solution. The organic layer was dried over magnesium sulfate, filtered through diatomaceous earth and concentrated in vacuum to obtain specified in the connection header. The product was further purified by distillation.1H NMR (500 MHz, CDCl3) δ 8,03 (t, J=7,3, 1H), a 7.85 (DD, J=7,5, 13,2, 1H), 7,45 (t, J=7,7, 1H), was 7.36 (t, J=9,1, 1H),19F NMR (470 MHz, CDCl3) δ 77,4 (d, J=9,4, 3F), d 102,7 (m, 1F). HPLC: Bond SB-C18 of 4.6×150 mm, 3.5 µm, way: 90% of 0.1% H3PO4and 1% CH 3CN gradual change to 90% CH3CN within 7 minutes, hold for 3 minutes, gradually changing to 10% CH3CN for 1 min; peak at 6,58 minutes

EXAMPLE 13

1-fluoro-2-((trifluoromethyl)sulfonyl)benzene

Mesityl-2-torpedinidae (Sanford M et al. JACS, 2005, 127, 7330 and Widdowson, D. et al. Tepahedron Letters 2000, 41, 5393.) (0.1 g, 0,204 mmol), triptoreline sodium (0.035 g, 0,224 mmol) and copper oxide(I) (2,92 mg, at 0.020 mmol) were weighed into a reactor equipped with a magnetic rod stirrer. Was added N,N-dimethylformamide (1 ml), the reactor was closed and heated at 25°C for 24 hours. HPLC analysis of the crude reaction mixture showed the formation specified in the connection header.

EXAMPLE 14

4-Fluoro-3-((trifluoromethyl)sulfonyl)benzosulphochloride

EXAMPLE 13 (80 g) were loaded into a reactor equipped with top mixer input for nitrogen, a refrigerator, a scrubber, a temperature sensor and a heating bath. Was slowly added chlorosulfonic acid (307 g) via addition funnel. The mixture was then heated to 120ºC and maintained for 22 hours at 120ºC. The mixture was cooled to room temperature. Thionyl chloride (118 g) was added to the reaction mixture in one portion at ambient temperature. The mixture was stirred at 25 ºC for 24 hours. Took the test, and analysis HPLC showed that the reaction was completed and remained 1,1% with Lanovoy acid. Isopropylacetate (775 g) was cooled to-50ºC. To isopropylacetate the solution was added water (600 g). The reaction mixture was transferred slowly to a mixture of isopropylacetate/ice through an addition funnel. The internal temperature was increased to 0,8ºC in the process of adding. The cooled reaction mixture was heated to 15 ° C and the layers were separated. The organic layer used in the next stage (EXAMPLE 15) without highlighting.

EXAMPLE 15

4-Fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide

The solution from EXAMPLE 14 were loaded into a flask, equipped with top mixer input for nitrogen, a temperature sensor and a cooling bath. The solution was cooled to-50ºC using baths acetone/dry ice. The ammonium hydroxide solution (238 g) was slowly added to the reaction mixture via an addition funnel. The internal temperature was maintained at about 40ºC. HPLC analysis showed complete reaction. The solution was cooled to-60ºC. To the reaction mixture was slowly added 6N HCl (600 g) to maintain the temperature below 35ºC. The mixture was heated to room temperature. The layers were separated and the organic layer was washed two times with the help of 375 g of 4 n HCl solution. The organic layer was subjected to vacuum distillation at a bath temperature of from 40 to 50ºC. To the residue was added toluene (700 g) and the mixture was stirred at room temperature for one hour. The mixture shown is ovale and washed with toluene to obtain specified in the connection header.

EXAMPLE 16

(1R)-3-Morpholine-4-yl-1-((phenylthio)methyl)Propylamine

Specified in the title compound can be obtained, as described in U.S. Patent No. 7390799 B2.

EXAMPLE 17

4-(((1R)-3-Morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide

Specified in the title compound can be obtained, as described in U.S. Patent No. 7390799 B2.

The above description is intended to illustrate the present invention and not for limitation. It is assumed that the volume of an invention covered by obvious variations and modifications, as defined in the claims.

1. The method of obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide or its pharmaceutically acceptable salts, including:
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and a first reducing agent selected from the group comprising triacetoxyborohydride sodium, cyanoborohydride sodium and combinations thereof, with the allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and water plants is ora third base, selected from the group comprising sodium hydroxide, potassium hydroxide and combinations thereof, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first binding reagent selected from the group comprising 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidazole and any combination of them, with or without the fourth base selected from the group comprising 1,8-diazabicyclo(5.4.0)undec-7-ene, tert-piperonyl potassium and combinations thereof, and with or without the first auxiliary linking reagent selected from the group comprising 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-Aza-benzotriazol and any combination of them, with the allocation or no allocation N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

2. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate selected from the group comprising methylformate, atilf RMIT, n-paperformat, tert-bodyformat and any combination of them, and the first base selected from the group including sodium hydride, tert-piperonyl sodium tert-piperonyl potassium and any combination of them, to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base selected from the group comprising triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and any combination of them, and the first reagent silylating protective group selected from the group including trimethylchlorosilane, tert-BUTYLCARBAMATE, triisopropylchlorosilane, tert-butylchloroformate and any combination of them, with receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and
(d) interaction per the CSO protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid, selected from the group comprising Tetra-n-butylammonium, triperoxonane acid, hydrochloric acid, triftormetilfullerenov acid, sulfuric acid and any combination of them, to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and a first reducing agent selected from the group comprising triacetoxyborohydride sodium, cyanoborohydride sodium and combinations thereof, with the allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third base selected from the group comprising sodium hydroxide, potassium hydroxide and combinations thereof, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent selected from the group comprising 1-ethyl-3-(3-(dimetilan the but)propyl)-carbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidazole and any combination of them, and, optionally, the first auxiliary linking reagent selected from the group comprising 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-Aza-benzotriazol and any combination of them, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

3. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate selected from the group comprising methylformate, ethyl formate, n-paperformat, tert-bodyformat and any combination of them, and the first base selected from the group including sodium hydride, tert-piperonyl sodium tert-piperonyl potassium and any combination of them, to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base selected from the group comprising triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and any combination of them, and the first reagent silylating protective group selected from the group, Lucaya trimethylchlorosilane, tert-BUTYLCARBAMATE, triisopropylchlorosilane, tert-butylchloroformate and any combination of them, with receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and
(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid selected from the group comprising Tetra-n-butylammonium, triperoxonane acid, hydrochloric acid, triftormetilfullerenov acid, sulfuric acid and any combination of them, to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and a first reducing agent selected from the group comprising triacetoxyborohydride sodium, cyanoborohydride sodium and combinations thereof, in the division or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of the third base selected from the group comprising sodium hydroxide, potassium hydroxide and combinations thereof, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;
(m) the interaction of 2-forbindelsesfaneblad and the first fluoride source is selected from the group comprising Tetra-n-butylammonium, potassium fluoride, and a combination thereof, to obtain 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;
(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3and second fluoride source is selected from the group comprising Tris(dimethylamino)sulfonethylmethane, Tetra-n-butylammonium, cesium fluoride, tetraethylorthosilicate, and tetraethylorthosilicate and any combination of them, to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;
(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((triptime the l)sulfonyl)benzosulfimide;
(R) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3selected from the group comprising an aqueous solution of ammonium hydroxide, a solution of ammonia in methanol, ammoniabased, a solution of ammonia in isopropyl alcohol. hexamethyldisilazane and any combination of them, to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth grounds, including triethylamine, to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent selected from the group comprising 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidazole and any combination of them, and, optionally, n is pout auxiliary binding reagent, selected from the group comprising 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-Aza-benzotriazol and any combination of them, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

4. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, alkylphosphate selected from the group comprising methylformate, ethyl formate, n-paperformat, tert-bodyformat and any combination of them, and the first base selected from the group including sodium hydride, tert-piperonyl sodium tert-piperonyl potassium and any combination of them, to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base selected from the group comprising triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and any combination of them, and the first reagent silylating protective group selected from the group including trimethylchlorosilane, tert-BUTYLCARBAMATE, triisopropylchlorosilane, tert-butylchloroformate and any combination of them, with receipt of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with the release or no release of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(c) the interaction of the first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine with receipt of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; emitting or without release of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; and
(d) the interaction of the first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and the first acid selected from the group comprising Tetra-n-butylammonium, triperoxonane acid, hydrochloric acid, triftormetilfullerenov acid, sulfuric acid and any combination of them, to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and a first reducing agent selected from the group comprising triacetoxyborohydride sodium, cyanoborohydride sodium and combinations thereof, with the allocation or no allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)is piperazin-1-yl)benzoate and an aqueous solution of the third substrate, selected from the group comprising sodium hydroxide, potassium hydroxide and sichenia, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;
(r) the interaction of the first triftoratsetofenona metal, the first source of halftoned selected from the group comprising mesityl-2-torpedinidae, bis-(2-forfinal)jodonnell-sulfonates, bis-(2-forfinal)idaniel-sulfonates, bis-(2-forfinal)hedonically-sulfonates, bis-(2-forfinal)stonyhearted-sulfonates, bis-(2-forfinal)iodomethylphosphonate, bis-(2-forfinal)stonyhearted and combinations thereof, and the first catalyst selected from the group comprising CuI, Cu2O, CuCl triftormetilfosfinov complex of copper (I), triplet copper, CuSCN, copper acetate and palladium(II) acetate alone or in combination with ligands, such as tetramethylethylenediamine, 4,4'-decret-butyl-2,2'-dipyridyl, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2-acetylcyclohexanone, N,N-diethylaniline, triphenylphosphine, tri-tert-butylphosphine, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 1,1'-bis(diphenylphosphino)ferrocene, 2-(di-tert-butylphosphino)biphenyl, triphenylphosphite, triphenylphosphine, dimethylmethylphosphonate, 1,3-bis(2,4,6-trimetilfenil)-1,3-dihydro-2H-imidazol-2-yl) - Rev. den, 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ilidene, 1,3-bis(1-substituted)imidazole-2-ilidene, 1,3-di-tert-butylimidazole-2-ilidene and any combination of them, to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;
(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(R) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and the first source NH3selected from the group comprising an aqueous solution of ammonium hydroxide, a solution of ammonia in methanol, ammoniabased, a solution of ammonia in isopropyl alcohol, hexamethyldisilazane and any combination of them, to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and sixth bases include triethylamine, to obtain 4-(((1R)-3-morpholine-4-yl-1 -((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)PR who drank)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, the first binding reagent selected from the group comprising 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidazole and any combination of them, and, optionally, the first auxiliary linking reagent selected from the group comprising 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-Aza-benzotriazol and any combination of them, emitting or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

5. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)on the si)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;
(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl (dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;
(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexane is a or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

6. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxym is tilen)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2ND)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;
(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; emitting or without selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-BU is Il(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;
(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;
(m) the interaction of 2-forbindelsesfaneblad and Tetra-n-butylammonium obtaining 2-forbindelseshandtering, emitting or without isolating the 2-forbindelseshandtering;
(n) the interaction of 2-forbindelseshandtering, the reagent of Ruppert (CH3SiCF3) and Tris(dimethylamino)sulfonamidophenylhydrazine to obtain 1-fluoro-2-((triptime the Il)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;
(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(R) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-C is logex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

7. The method according to claim 1, including:
(a) interaction 4,4-dimethylcyclohexanone, ethylformate and tert-butoxide potassium to obtain (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, emitting or without selection (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone;
(b) interaction (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, triethylamine and trimethylchlorosilane, tert-butylcholinesterase or triisopropylchlorosilane to obtain (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone, emitting or without selection (2ND)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone;
(c) interaction (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohexanone and 4-chlorpheniramine obtaining ((2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)is XI)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone; with the selection or no selection (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone;
(d) interaction (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanol, (2E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanol, or (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-1-(4-chlorophenyl)-4,4-dimethylcyclohexanone and hydrochloric acid to obtain 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, emitting or without isolating the 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde;
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid;
(r) the interaction of sodium triftoratsetofenona, bis-(2-forfinal)idenitifcation the a and copper oxide(I) to obtain 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene, with the selection or no selection 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;
(o) the interaction of 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and chlorosulfonic acid to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(R) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide and an aqueous solution of ammonium hydroxide to obtain 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without allocation of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide;
(q) the interaction of 4-fluoro-3-((trifluoromethyl)sulfonyl)benzosulfimide, (1R)-3-morpholine-4-yl-1-((phenylthio)methyl)Propylamine and triethylamine to obtain 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, emitting or without isolating the 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)- 3-((trifluoromethyl)sulfonyl)benzosulfimide; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimides and 4-dimethylaminopyridine allocating or without isolating the N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-C is logex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

8. The method according to claim 1, including:
(e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazine-1-eventuate and triacetoxyborohydride sodium, emitting or without allocation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate;
(f) the interaction of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoate and an aqueous solution of sodium hydroxide, emitting or without isolating the 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid; and
(g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoic acid, 4-(((1R)-3-morpholine-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimides and 4-dimethylaminopyridine, emitting or without isolating the N-(4-(4-((2 -(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-EN-1-yl)methyl)piperazine-1-yl)benzoyl)-4-(((1R)-3-(morpholine-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzosulfimide.

9. The compound or its pharmaceutically acceptable salt selected from the group comprising (2E)-4,4-dimethyl-2-(((triisopropylsilyl)oxy)methylene)cyclohexanone, (2E)-4,4-dimethyl-2-(((trimethylsilyl)oxy)methylene)cyclohexanone and (2E)-2-(((tert-butyl(dimethyl)silyl)oxy)methylene)-4,4-dimethylcyclohex Canon.

10. The compound 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: disclosed are trialkoxysilanes of general formula I , where R1 -Si(OAlk)3 or R1=-CH=N-CH2CH2CH2Si(OAlk)3, R2=R3=-OCH2CH2O-, as silicon-containing additives for forming a monolayer on the surface of a tantalum anode made of pressed tantalum powder, as well as use of triethoxy-2-thienylsilane for the same purpose. Also disclosed is a method of making a cathode plate from a polymer electrolyte using the disclosed trialkoxysilanes and an oxide capacitor with a solid electrolyte, having a slug section of valve metals with a surface layer made of the disclosed trialkoxysilanes.

EFFECT: capacitors with improved technical and exploitational characteristics.

4 cl, 1 dwg, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), where Y is selected from -CRay=CRby- and -CHRay-CRby=CRcy-; each Ray, Rby and Rcy is independently selected from a hydrogen atom and unsubstituted C1-C12 alkyl; each R1, R2, R3, R4 and R5 is independently selected from a hydrogen atom and unsubstituted C1-C12 alkyl; R6 is selected from NR8R9 and OR10; W is selected from NR7; R7 is a hydrogen atom; R8 is a hydrogen atom; R10 is an unsubstuted C2-C12 alkenyl; R9 is a substituted C2-C12 alkenyl which is substituted in one or more positions by a halogen , OR', OCONHR' and OH, protected by a silyl ether, where R' is hydrogen; each of R11, R12, R13, R14 and R15 is independently selected from a hydrogen atom, ORa, OSiRaRbRc; and each Ra, Rb and Rc is independently selected from a hydrogen atom and unsubstituted C1-C12 alkyl. The invention also relates to a pharmaceutical composition having cytotoxic activity, which contains said compounds, use of compounds of formula (I) to prepare a medicinal agent for treating cancer and methods of producing compounds of formula (I).

EFFECT: compounds having cytotoxic activity.

23 cl, 10 dwg, 2 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to application of ester compounds of benzoic acid, taken from group, which includes 1-phenylvinyl 4-methoxybenzoate; 1-(4-methoxyphenyl)-vinyl 4-tert-butyl benzoate, 1-(4-tert-butylphenyl)-vinyl 4-methoxybenzoate, 1-phenylvinyl 4-tert-butyl benzoate, 4-benzoyloxy-2-methoxybenzolsulphonic acid, 3-diethylaminophenyl benzoate and 3-(1-pyrrolidinyl) phenyl benzoate and 3-methoxy salicylate, as component for preparing composition for protection of human organism or animal or material from ultraviolet radiation, containing effective quantity at least one of claimed compounds, as component for preparing composition, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, as component for preparing composition for individual hygiene, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, as component for preparing industrial composition, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, and as component for preparing composition, which at photo-regrouping shows quantity of obtained UV-B radiation.

EFFECT: invention also relates to composition for protecting human or animal organism or protection of material from ultraviolet radiation, contains effective quantity of at least one above mentioned ester compound of benzoic acid.

40 cl, 6 dwg, 33 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing glycidyloxyalkyl alkoxysilanes by hydrosilylation of olefin-glycide ether in the presence of a catalyst. Disclosed is a method of producing glycidyloxyalkyl alkoxysilanes of general formula (R")O-CnH2nSi(OR)3, wherein groups R independently denote a linear or branched alkyl with 1-4 carbon atoms, n is a number equal to 1, 2, 3, 4, 5, 6, 7 or 8, R'' denotes a group H2C(O)CH- or H2C(O)CHCH2-, by reacting (i) a functionalised alkene of general formula (R")OCnH2n-1 wherein R" denotes a group H2C(O)CH- or H2C(O)CHCH2-, and n is a number equal to 1, 2, 3, 4, 5, 6, 7 or 8, (ii) with at least one hydrogen alkoxysilane of general formula HSi(OR)3, wherein groups R independently denote a linear or branched alkyl with 1-4 carbon atoms, in the presence of (iii) at least one homogeneous catalyst selected from a group comprising Spayer catalysts and Karstedt catalysts, (iv) at least one solvent and/or at least one diluent and (v)at least one acid promoter from a group of mono- and dicarboxylic acids, wherein: components (i) alkene and (ii) hydrogen alkoxysilane, used in molar ratio of 1.8-1.0:1.0; catalyst (iii) is used in molar ratio to alkene (i) ranging from 1:1000000 to 1:25000; catalyst (iii) and promoter (v) are used in molar ratio from 1:250 to 1:25000 and the catalyst (iii) and promoter (v) are used together in a solvent and/or diluent in diluted form.

EFFECT: disclosed method enables to achieve high output of the end product compared with existing methods.

12 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to tyre and rubber industry, particularly heat stabilisers which protect rubber mixtures based on general-purpose rubber from heat ageing. The method of producing heat stabiliser involves reacting phenyl trichlorosilane with aldehyde alcohol in nitrogen medium in molar ratio 1:3.

EFFECT: method enables to obtain heat stabilisers from readily available material with improved thermomechanical properties; simple method of producing heat stabilisers due to realisation thereof in a single step and use of low temperatures.

1 dwg, 3 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing silicon-furan-containing monomers which are stable over time, can be combined with epoxy resins and can modify physical-mechanical and thermomechanical properties of cured epoxide compositions. The method involves reaction of tetrachlorosilane with furfuryl alcohol in a medium of pure acetone while cooling to 0-5°C in the presence of triethylamine. Molar ratio of tetrachlorosilane:furfuryl alcohol:triethylamine is equal to 1:4:4.

EFFECT: obtaining silicon-furan-containing monomers which are stable over time, can be combined with epoxy resins and can modify physical-mechanical and thermomechanical properties of cured epoxide compositions.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to materials for preventing or inhibiting scaling on equipment, used in industrial methods having alkaline process streams, and methods of preventing or inhibiting scaling using such materials. disclosed is a composition for reducing aluminosilicate scaling, which contains a polymer which is a product of reaction of a polyalkylene oxide polymer which is epoxide-blocked at the end and an organic compound containing amino functionality and -Si(OR")3 functionality, where R'' is selected from H, a substituted or unsubstituted C1-C20 alkyl, alkenyl, aryl or aralkyl group. Disclosed also is a method of reducing aluminosilicate scaling on equipment using the disclosed composition. The technical result is that when added to an alkaline process stream, the disclosed composition reduces or even completely prevents aluminosilicate scaling on surfaces of equipment such as walls of an evaporating apparatus and heating surfaces.

EFFECT: disclosed composition is effective at treatment concentrations which makes it cost effective.

5 cl, 11 tbl, 39 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel biologically active chemical compounds - silicon-titanium-containing polyol derivatives (glycerine, polyethylene glycol), as well as hydrogels based thereon. Disclosed are silicon-titanium-containing polyol derivatives, having transcutaneous, wound healing and regenerating activity, the composition of which in excess of polyol has the formula k(CH3)4-nSi(O-R-OH)n·Ti(O-R-OH)4·xHO-R-OH, where R=R1=CH2-CH(OH)-CH2: k=1 or 2, n=2 or 3, x=11 or 12; or R=R2=(CH2-CH2-O-)7,7CH2-CH2: k=1 or 2, n=2-4, x=2 or 3, with dynamic viscosity 1.5-90.0 Pa·s (25±0.5°C), obtained by reacting (methyl)ethoxysilane and tetrabutoxytitanium with polyol in molar ratio (1-2):1:(18-22) for R1 or (1-2):1:(8-15) for R2, respectively, while heating the reaction mass to temperature 90-140°C and holding at that temperature for not less than 6 hours with intense stirring, followed by removal of the formed alcohols. The invention also discloses hydrogels based on said polyol derivatives, containing water and a gelling additive, with the following ratio of components (wt %): silicon-titanium-containing polyol derivatives in excess of polyol - 70.730-94.970; gelling additive 0.002-0.060; water - the balance.

EFFECT: silicon-titanium-containing polyol derivatives and hydrogels based thereon are physiologically active compounds, exhibit transcutaneous and wound healing action, have significant effect on the morphofunctional condition of the skin and can be recommended for use as independent agents, as well as ointment bases of different pharmaceutical compositions with transcutaneous, wound healing and regenerating action.

2 cl, 2 dwg, 8 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel organosilicon compounds and a method of producing them. Disclosed are alkoxysilanes with hydrophilic N-(1,2-dihydroxypropyl)aminoalkyl-containing and N-trialkoxysilyl alkylurethane-containing groups and production method thereof via condensation of alkoxysilanes with N-(1,2-dihydroxypropyl)aminoalkyl groups with isocyanatoalkyl trialkoxysilane in a nitrogen current at temperature 75°C in the medium of dimethyl formamide.

EFFECT: disclosed compounds are chemically active, have high solubility in water and can be used for chemical modification of fibre materials in order to endow them with hydrophilic properties.

2 cl, 1 dwg, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to fine purification of alkylsiloxanes and alkylsilazanes which are used in making light-sensitive resistors and in microelectronics. Disclosed is a purification method comprising three basic steps: fractionation, filtration in liquid and vapour phases on porous polymer filters with pore size 0.1-0.2 mcm and evaporation, followed by condensation in bubble-free conditions at evaporation rate of 0.01-0.2 cm3/h·cm2.

EFFECT: disclosed method enables to obtain highly pure alkylsiloxanes and alkylsilazanes with basic substance content of about 99,99 wt % and content of heterogeneous trace elements less than 10 particles per cm3.

1 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to tranquilising compounds, contributing to reduction of anxiety, increase of cognitive and motor activity, namely to 4-(1-hydroxy-1-methyl-2-morpholinoethyl)benzoic acid (1) and 4-(1-hydroxy-2-morpholinocyclohexyl)benzoic acid (2), their pharmaceutically acceptable salts and esters. In addition, object of invention is also presented by method of obtaining and compounds.

EFFECT: compounds, possessing anxiolytic activity, which do not manifest considerable sedative action, hypotension and excitatory action on central nervous system.

2 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (XVIII): which can be used for monitoring and studying the metabolism in clinical and preclinical examinations. The invention also concerns a method for preparing the specified compound.

EFFECT: development of the effective method for preparing the compound.

2 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a tosylate salt of trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)-phenyl]-cyclobutane carboxamide of formula The invention also relates to a pharmaceutical composition, as well as a treatment method.

EFFECT: obtaining a novel biologically active salt of a compound, having activity on histamine receptor type 3.

11 cl, 1 ex, 1 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: there are described compound of formula, its pharmaceutically acceptable salt or their mixture, enentiomerically pure 4-{(R)-(3-aminophenyl)[4-(4-fluorobenzyl)pyperazin-1-yl]-N,N-diethylbenzamide or its pharmaceutically acceptable salt. Also described are method of anxiety therapy, method of pain therapy and method of depression therapy in animal.

EFFECT: compounds are of use in therapy, in particular for elimination of pain, depression and anxiety.

5 cl, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention refers to benzamide 4-(phenyl-piperazin-methyl) derivatives of the general formula I in which R1 - aryl, heteroaryl, selected from the group which includes difuryl, pyridyl and thienyl; R2 - hydrogen or C1-12 alkyl. The methods of preparation of the compounds, pharmaceutical composition on their basis and application while preparing medicines are described.

EFFECT: compounds can be applied to treatment of pain and functional gastroenteric upset.

8 cl, 1 ex

Casr antagonist // 2315036

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel compound represented by the following formula (1) , its pharmaceutically acceptable salts or optically active isomers wherein each symbol is given in the invention description. Proposed compound possesses antagonistic effect with respect to calcium-sensitive receptor (CASR). Also, invention relates to a therapeutically medicinal agent used in treatment of osteoporosis based on this compound, to a method for treatment of osteoporosis, calcium receptor antagonist and to agent promoting secretion of parathyroid hormone (PTH).

EFFECT: valuable medicinal properties of antagonist.

33 cl, 66 tbl, 5 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to R-2-aminoarylpropionic acid amides and pharmaceutical composition comprising thereof that can be used for prophylaxis and inhibition of recruiting and activation of leukocytes, and in treatment of pathologies directly dependent on indicated activation. Invention proposes compound of the general formula (1): wherein A, q, Ph and R have corresponding values, or its pharmaceutically acceptable salt. Also, invention describes a method for preparing amide of the formula (1) and pharmaceutical composition used in prophylaxis of leukocytes activation. Invention provides the development of pharmaceutical composition that can be used for prophylaxis and treatment of damaged tissues caused by enhancing activation of neutrophile granulocytes (polymorphonuclear leukocytes) in inflammation foci. Also, the invention relates to R-enantiomers 2-(aminoaryl)-propionylamides of the formula (1) that can be used for suppression of neutrophyles hemotaxis caused by IL-8. Also, compounds of this invention can be sued in treatment of psoriasis, ulcerous colitis, glomerulonephritis, acute respiratory insufficiency and rheumatic arthritis.

EFFECT: valuable medicinal properties of compounds.

8 cl, 16 ex

The invention relates to pharmaceutically acceptable salts of the compounds of formula (I) or solvate specified salts in which the compound of formula (I) is in the form of (R)-enantiomer, (S)-enantiomer or the racemate

The invention relates to derivatives of N-(4-carbamimidoyl) glycinamide formula (I), where E denotes hydrogen or HE, Q denotes hydrogen or alkyl, R is aryl, cycloalkyl or alkyl substituted radicals R1, R2, R3, R1denotes hydrogen, COOH, COO-alkyl or aryl, R2denotes hydrogen, aryl, cycloalkyl or heteroaryl, R3denotes hydrogen, aryl or HE (in any position other thanposition relative to the nitrogen atom is attached to an alkyl group R) or optional substituted by an amino group, three of the radicals X1-X4denote the group of C(Ra), C(Rb) or C(Rc), and the fourth represents C(Rd), Ra-Rddenote H, HE, NO2dialkylamino, halogen, alkyl, alkoxy, aryloxy, aralkylated, heteroarylboronic, geterotsiklicheskikh, COOH, COO-alkyl, NH-SO2-alkyl, NH-SO2-aryl, two adjacent groups Ra-Rbdenote alkylenedioxy, G1and G2denote hydrogen, HE, the invention relates to intermediate compounds of the formula (IV), (V), (VI) used in the methods of making compounds of formula (I), and are in взаимодействCN, the nitrile of formula (IV) is transformed into amidinopropane C(N-G1)NH-G2

The invention relates to new compounds of the formula (I), where R1is hydrogen or a fragment of ester, E is hydrogen or hydroxy, three of X1-X4denote the group of C(Ra), C(Rb) or C(Rc), and the fourth represents C(Rdor N, where Ra-Rdis hydrogen, alkenyl, quinil, alkenylacyl, alkoxy, alkylamino, alkoxyalkyl, alkoxyalkanols, alkoxycarbonylmethyl, alkoxycarbonylmethyl, alkoxycarbonylmethyl, alkyl, alkoxycarbonylmethyl, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl, allylurea, allylthiourea, alkylsulfonamides, alkylsulfonyl, aminoethoxy, arylalkyl, Allakaket, arylalkyl, arylalkylamine, arylcarboxylic, arylcarboxamide, aryloxy, aryloxyalkyl, arylsulfonyl, arylsulfonamides, carboxy, carboxylic, substituted alkyl, substituted amino, halogen, substituted halogen, cycloalkyl, substituted cycloalkyl, hydroxy, substituted hydroxy, heterocycle, substituted heterocycle, or two adjacent groups of Ra-Rdtogether form the fragment condensed di - or monooxygenase ring or aryl ring

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide or its pharmaceutically acceptable salt, which includes: (a) interaction of 4,4-dimethylcyclohexanone, alkylformiate, selected from group, including methylformiate, ethylformiate, n-propylformiate, tertbutylformiate and their any combination, and first base, selected from group, including sodium hydrate, sodium tert-butoxide, potassium tert-butoxide and their any combination, with obtaining (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with separation or without separation of (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; (b) interaction of (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, second base, selected from group, including triethylamine, 2,6-lutidine, pyridine, imidazole, diisopropylethylamine, N-methylmorpholine, dimethylaniline and their any combination, and first reagent silyl ether protecting group, selected from group, including trimethylchlorosilane, tert-butylchlorodimethylsilane, triisopropylchlorosilane, tert-butylchlorodiphenylsilane and their any combination, with obtaining first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone, with separation or without separation of first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone; (c) interaction of first protected (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone and 4-chlorophenylmagnesium bromide with obtaining first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol; with separation or without separation of first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol; (d) interaction of first protected (2E)-1-(4-chlorophenyl)-2-(hydroxymethylene)-4,4-dimethylcyclohexanol and first acid, selected from group, including tetra-n-butylammoniumfluoride, trifluoroacetic acid, hydrochloric acid, sulfuric acid and any their combination, with obtaining 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, with separation or without separation of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde; (e) interaction of 2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-carbaldehyde, ethyl 4-piperazin-1-ylbenzoate and first reducing agent, selected from group, including sodium triacetoxyborohydrode, sodium cyanoborohydride and their combinations, with separation or without separation of ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoate; (f) ethyl 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoate interaction of and aqueous solution of third base, selected from group, including sodium hydroxide, potassium hydroxide and their combinations, with separation or without separation of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoic acid; and (g) interaction of 4-(4-((2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-ene-1-yl)methyl)piperazin-1-yl)benzoic acid, 4-(((1R)-3-morpholin-4yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide and first binding reagent, selected from group, including 1-ethyl-3(3-(dimethylamino)propyl)-carbodiimidhydrochloride, dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1,1'-carbonyldiimidasole and their any combination, with or without fourth base, selected from group, including 1,8-diazabicyclo(5.4.0)undec-7-ene, potassium tret-butoxide and their combinations, and with or without first auxiliary binding reagent, selected from group, including 4-dimethylaminopyridine, hydroxybenzotriazole, 1-hydroxy-7-aza-benzotriazole and any their combination, with separation or without separation of N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide.

EFFECT: new method of obtaining N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperasin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzolsulfonamide, which can be applied in medicine as stimulator of apoptosis.

10 cl, 17 ex

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