Synthesis process, and crystalline form of 4-ä3-ÄCis-hexahydrocyclopentaÄCÜpyrrol-2(1H)-YLÜpropoxyübenzamide hydrochloride and pharmaceutical compositions containing it.
LECOUVE JEAN PIERRE,GAILLARD MARINA,ROBERT NICOLAS
申请号：
AP2012006280
公开号：
AP2012006280A0
申请日:
2012.05.28
申请国别(地区):
AP
年份:
2012
代理人:
摘要：
Synthesizing 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1H)-yl]propoxy}benzamide hydrochloride (I), comprises reacting 2-methoxy-1-[2-(2-methoxy-acetyl)-cyclopentyl]-ethanone (II) with an ammonia to form tetrahydro-cyclopenta[c]pyrrole-1,3-dione (III), reducing (III) to yield octahydro-cyclopenta[c]pyrrole (IV), which is subsequently subjected to: either a coupling reaction with a benzamide compound (V)； or a reductive amination with a benzamide compound (VI) to give free base of (I), which is soaked in hydrochloric acid to form (I) i.e isolated in the form of a solid. Synthesizing 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1H)-yl]propoxy}benzamide 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1H)-yl]propoxy}benzamide hydrochloride (I), comprises reacting 2-methoxy-1-[2-(2-methoxy-acetyl)-cyclopentyl]-ethanone (II) with an ammonia, where the reaction mixture is then subjected to pyrolysis, at a temperature of greater than 100[deg] C to form tetrahydro-cyclopenta[c]pyrrole-1,3-dione (III), reducing (III) to yield (3aR,6aS)-octahydro-cyclopenta[c]pyrrole (IV), which latter compound is subsequently subjected: either to a coupling reaction, under basic conditions in a polar medium, with a benzamide compound of formula (V)； or to a reductive amination with a benzamide compound of formula (VI) to give free base of (I), which is soaked in hydrochloric acid to form (I) i.e. isolated in the form of a solid. Y1 : -CH 2-Hal or -CH 2-OSO 2-R； Hal : halo； R : 1-6C alkyl or -C 6H 4-CH 3； either R1a, R2a : 1-6C alkyl； or R1aR2a : -(CH 2) n-； and n : 2-3, where one of R1a and R2a is H and the other is 1-6C alkyl. Independent claims are included for: (1) a crystalline form-I of (I) having an X-ray diffraction pattern on powder having diffraction lines as given in the specification； and (2) a composition comprising (I) in combination with one or more inert vehicles. [Image] ACTIVITY : Nootropic； Dermatological； Neuroprotective； Antiparkinsonian； Cerebroprotective； Antialcoholic； Vasotropic； T
