马来酸桂哌齐特合成工艺的改进

目的改进马来酸桂哌齐特的合成工艺,为工业化生产奠定基础。方法以四氢吡咯为原料,先与氯乙酰氯成酰胺,再与哌嗪发生取代反应制得中间体[(1-四氢吡咯基)甲基]哌嗪(2);化合物2与氯乙酰氯和三苯基膦反应,经异丙醇重结晶得到稳定的有机鏻盐(3);化合物3与3,4,5-三甲氧基苯甲醛发生Wittig反应,再与马来酸成盐得目标化合物马来酸桂哌齐特(1)。结果与结论经5步反应合成了马来酸桂哌齐特,其结构经1H-NMR和M S确证,总收率为52.3%;用乙醇-丁酮重结晶,再用丁酮重结晶可得到马来酸桂哌齐特的稳定晶型。

Improved synthesis of cinepazide maleate

Abstract: Objective To improve the synthetic process of cinepazide maleate (1). Methods 2-(piperazin-1-yl)-1-(pyrrolidin-1-yl)ethanone (2) was synthesized from pyrrolidine via amidation and substitution, followed by treating with chloroacetyl chloride and triphenylphosphine in a ‘‘one pot’’ manner to give the corresponding phosphonium chloride 3 in a stable and pure form after crystallization from isopropanol. Eventually, 3 was brought into Wittig reaction with 3,4,5-trimethoxybenzaldehyde and successively treated with maleic acid to give the target 1. Results and Conclusion 1 was prepared in a total yield of 52.3 % via a 5-step sequence. The crude product was first crystallized in a mixture of ethanol and butanone, and then in butanone to give the stable crystal.