Buterizine

Buterizine,Shanghai Chemfrom Chemical Co., Ltd.

Vasodilator (peripheral).

ChEBI: Buterizine is a diarylmethane.

A mixture of 10.3 parts of 1-chloro-4-(chloromethyl)-2-nitrobenzene, 25.2 parts of 1-(diphenylmethyl)piperazine and 120 parts of ethanol is stirred and refluxed for 4 h. The reaction mixture is cooled and evaporated. The residue is taken up in about 100 parts of water and the product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using trichloromethane as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2,2'- oxybispropane and hexane (1:2 by volume). The product is filtered off, washed with hexane and dried, yielding 19.6 parts of 1-(4-chloro-3- nitrophenylmethyl)-4-(diphenylmethyl)piperazine; melting point 101.6°C.
During 20 h, gaseous ethanamine is bubbled through a stirred and hot (60- 70°C) mixture of 1-(4-chloro-3-nitrophenylmethyl)-4- (diphenylmethyl)piperazine and dimethylsulfoxide. The reaction mixture is cooled and poured onto ice-water. The precipitated product is filtered off, washed with water and taken up in methylbenzene. The latter is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol as eluent. The pure fractions are collected and the eluent is evaporated, yielding 4-[4- (diphenylmethyl)-1-piperazinylmethyl]-N-ethyl-2-nitrobenzenamine; melting point 128.2°C (crystallized from 2,2'-oxybispropane).
A solution of 4-[4-(diphenylmethyl)-1-piperazinylmethyl]-N-ethyl-2- nitrobenzenamine in methanol is hydrogenated at normal pressure and at room temperature with Raney-nickel catalyst. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated, yielding 4-[4-(diphenylmethyl)-1-piperazinylmethyl]-N1-ethyl-1,2- benzenediamine.
A mixture of 4-[4-(diphenylmethyl)-1-piperazinylmethyl]-N1-ethyl-1,2- benzenediamine and acetic acid is stirred at room temperature till all solid enters solution. Then there are added pentyl ethanimidate hydrochloride and stirring is continued first for 1 h at room temperature and further for 1 h at reflux. The reaction mixture is evaporated and the residue is stirred in water. The whole is alkalized with a sodium hydroxide solution and the product is extracted with dichloromethane. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol as eluent. The pure fractions are collected and the eluent is evaporated. The product is filtered off and dried, yielding 5-[4-(diphenylmethyl)-1-piperazinylmethyl]-1-ethyl-2-butyl-1Hbenzimidazole; melting point 124.8°C (crystallized from 4-methyl-2- pentanone).

Vasodilator