洛美曲索的合成  

Synthesis of Lometrexol

作　　者：徐赟[1] 吴晗[1] 刘增路[1] 杨世琼[1] 毛振民[1] 

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2009年第3期165-167,共3页Chinese Journal of Pharmaceuticals

基　　金：上海市科学技术委员会科研项目(024319231)

摘　　要：1,1,3,3-四甲氧基丙烷经水解、溴化后与2,4-二氨基-6-羟基嘧啶反应生成吡啶并[2,3-d]嘧啶环衍生物,经氨基保护、Heck反应、脱硅后与N-(4-碘代苯甲酰基)-L-谷氨酸二乙酯再经Heck反应、氢化和水解制得抗肿瘤药洛美曲索,总收率约15%。Lometrexol was synthesized, from 1,1,3,3-tetramethoxypropane by hydrolysis, bromination, reaction with 2,4-diamino-6-hydroxypyrimidine to give pyrido [2,3-d] pyrimidine derivative, which was subjected to protection of amino group, Heck reaction, desilication, Heck reaction with diethyl N- （4-iodobenzoyl） -L-glutamate, followed by hydrogenation and hydrolysis with an overall yield of about 15 %.

关 键 词：洛美曲索 抗肿瘤药 合成 

分 类 号：R979.1[医药卫生—药品]