苹果酸阿莫曲坦的合成  

Synthesis of Almotriptan Malate

作　　者：于圆圆[1] 金华[1] 李建其[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海200437

出　　处：《中国医药工业杂志》2011年第6期401-403,共3页Chinese Journal of Pharmaceuticals

基　　金：国家"重大新药创制"科技重大专项(2009ZX09301-007)

摘　　要：对硝基氯苄经亚硫酸钠磺化、五氯化磷氯代、四氢吡咯取代、催化氢化、重氮化和还原制得4-(吡咯烷-1-基磺酰甲基)苯肼盐酸盐(7),与4-氯-1-羟基丁烷磺酸钠反应后,再经成腙、环合和甲基化"一锅法"制得阿莫曲坦粗品,经成富马酸盐纯化,再与苹果酸成盐制得苹果酸阿莫曲坦,总收率约6%(以对硝基氯苄计)。4-(Pyrrolidine-1-sulfonylmethyl)phenylhydrazine hydrochloride(7) was synthesized from 4-nitrobenzyl chloride(2) by sulfonation with sodium sulfite,chlorination with phosphorus pentachloride,replacement with pyrrolidine,catalytic hydrogenation,followed by diazotization and reduction.Compound 7 was allowed to react with sodium 4-chloro-1-hydroxybutane-1-sulfonate,and then by hydrazone formation,cyclization and methylation to give almotriptan,which was purified by formation of its fumarate and reacted with malic acid to provide almotriptan malate.The overall yield was about 6% based on compound 2.

关 键 词：苹果酸阿莫曲坦 5-HT1B/1D受体激动剂 抗偏头痛药 合成 

分 类 号：R9[医药卫生—药学]