马来酸桂哌齐特合成工艺的优化

以四氢吡咯为原料,与氯乙酰氯反应生成N-(2-氯乙酰基)四氢吡咯;以(E)-3,4,5-三甲氧基肉桂酸为原料,与1,1-羰基二咪唑反应生成活性酯后再与N-叔丁氧羰基哌嗪反应,生成物经过脱保护得到关键中间体1-(3,4,5-三甲氧基肉桂酰基)哌嗪盐酸盐;再经烃化反应制备桂哌奇特游离碱,与马来酸成盐得到目标化合物。产品结构经1H NMR确认,总收率为46%。该合成工艺简便、合理、可行,适合工业化生产。

Optimization on the Synthesis Process of Cinepazide Maleate

N-(2-Chloroacetyl)pyrrolidine(5) was synthesized from pyrrolidine by its reaction with chloroacetyl chloride.(E)-3,4,5-Trimethoxycinnamic acid was reacted with 1,1’-carbonyldiimidazole to provide an ester followed by reaction with N-tert-butyloxycarbonylpiperazine and then deprotection to give the key intermediate 1-(3,4,5-trimethoxycinnamoyl)piperazine hydrochloride(3).Cinepazide was obtained by reaction of 3 and 5 and further transformed into cinepazide maleate(1).The structure of 1 was confirmed by 1H NMR.