西达本胺的工艺优化  

Process Optimization of Chidamide

作　　者：赵建宏[1] 户晖 关禹[1] 廖凡[1] 虞心红[1] 

机构地区：[1]华东理工大学药学院绿色制药工艺与技术实验室,上海200237

出　　处：《中国医药工业杂志》2017年第7期994-996,共3页Chinese Journal of Pharmaceuticals

摘　　要：(E)-3-(3-吡啶)丙烯酸经羰基二咪唑活化生成活泼中间体(E)-3-(3-毗啶)丙烯酰咪唑(3)后,与4-氨甲基苯甲酸的钠盐在水和二氯甲烷的混合溶剂中经相转移催化反应得4-[N-[(E)-3-(3-吡啶)丙烯酰基]氨甲基]苯甲酸(5),避免了3遇水分解,将收率从62%提高至80%。5与3,4-二氨基氟苯在N,N'-二环己基碳二亚胺和催化量的1-羟基苯并三唑作用下缩合得西达本胺,将间位杂质降至5%以内,粗品经乙醇重结晶后纯度达99.5%,总收率61.5%。4-[N-[（E）-3-（3-Pyridin）acroloyl]amidomethyl]benzoic acid（5） was synthesized via a phase transfer catalysis reaction of 4-amidomethyl benzoate sodium and （E）-3-（3-pyridin）acroloyl imidazole（3） which was prepared from （E）-3-（3-pyridin）acrylic acid in a mixed solvent of dichloromethane and water, the decomposition of 3 could be avoided and the yield was increased from 62% to 80% . Then 5 reacted with 3,4-diaminofluorobenzene in the presence of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole followed by recrystallization from ethanol to afford chidamide with an overall yield of 61.5% and a purity of 99.5% .

关 键 词：西达本胺 组蛋白脱乙酰酶抑制剂 相转移催化反应 工艺优化 

分 类 号：R979.1[医药卫生—药品]