马来酸桂哌齐特的合成  

Synthesis of cinepazide maleate

作　　者：王绍杰[1] 杨卓[1] 张廷剑[1] 王晓燕[1] 陈博[1] 赵勇[1] 薛明星[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2010年第4期278-281,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的改进马来酸桂哌齐特的合成方法。方法以四氢吡咯为原料,与氯乙酰氯酰化得到中间体N-(2-氯乙酰基)四氢吡咯(1);以(E)-3,4,5-三甲氧基肉桂酸为原料,与特戊酰氯成混合酸酐后再与无水哌嗪进行单酰化反应制得中间体(E)-1-(3,4,5-三甲氧基)肉桂酰基哌嗪(2);中间体1与中间体2发生烃化反应制备桂哌齐特游离碱(3),3与马来酸成盐得目标化合物。结果与结论以(E)-3,4,5-三甲氧基肉桂酸计,经3步反应合成了马来酸桂哌齐特,总收率为68.88%,其结构经1H-NMR、MS谱确证。Aim To improve the synthetic method of cinepazide maleate.Methods N-（2-Chloroacetyl） pyrrolidine（1） was synthesized from pyrrolidine via acylation with chloroacetyl chloride;Then（E）-3,4,5-trimethoxycinnamic acid was reacted with pivaloyl chloride to provide mixed anhydride followed by reaction with anhydrous piperazine to give（E）-1-（3,4,5-trimethoxycinnamoyl） piperazine（2）;Finally,1 was brought into alkylation with 2 to obtain cinepazide（3）,which was treated with maleic acid to give the target compound.Results and conclusion Cinepazide maleate was synthesized via a three-step procedure from（E）-3,4,5-trimethoxycinnamic acid in a total yield of 68.88% and its structure was confirmed by 1H-NMR and MS.

关 键 词：马来酸桂哌齐特 (E)-1-(3 4 5-三甲氧基)肉桂酰基哌嗪 单酰化 合成 

分 类 号：R914[医药卫生—药物化学]