METHOD OF OBTAINING APOPTOSIS STIMULATOR ABT-263 Russian patent published in 2014 - IPC C07D295/155 C07F7/18 C07C47/453 

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