琥珀酸普卡必利的合成

Synthesis of Prucalopride Monosuccinate

对氨基水杨酸经甲酯化、乙酰化、氯代、溴代、溴乙基化、在锌粉作用下环合及水解反应得到4-氨基-5-氯-2,3-二氢苯并呋喃-7-羧酸(10)。另用4-哌啶酮盐酸盐经甲氧丙基化及氨基化得到1-(3-甲氧基丙基)-4-哌啶胺(11)。10与11在羰基二咪唑作用下经缩合、成盐得到便秘治疗药琥珀酸普卡必利,总收率约10%(以对氨基水杨酸计)。

4-Amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid （10） was synthesized from 4-amino- 2-hydroxybenzoic acid by esterification, acetylation, chlorination, bromination, bromoethylation, cyclization catalysed by zinc and hydrolysis. Meanwhile 1-（3-methoxypropyl）-4-piperidine amine （11） was synthesized from 4-piperidone hydrochloride by reaction with 3-bromopropyl methyl ether and reductive amination with ammonia in the presence of H2/Pd-C. The condensation of compounds 10 and 11 followed by salification with succinic acid to give prucalopride monosuccinate with an overall yeild of about 10 % （based on 4-amino-2-hydroxybenzoic acid）.