抗肿瘤药物奥莫替尼的合成  

Synthesis of Antitumor Drug Olmutinib

作　　者：肖珍 周玲佳 王秋秋 朱五福 XIAO Zhen;ZHOU Ling-jia;WANG Qiu-qiu;ZHU Wu-fu(School of Pharmacy,Jiangxi Science and Technology Normal University,Nanchang 330013,China)

机构地区：[1]江西科技师范大学药学院

出　　处：《合成化学》2020年第1期53-57,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21662014)

摘　　要：对抗肿瘤药奥莫替尼(1)的合成工艺进行了优化。以3-氨基噻吩-2-羧酸甲酯和尿素为起始原料,经环合制得噻吩并嘧啶母核,再经氯代、亲核取代、还原等反应合成1,其结构经1 H NMR和IR确证。与专利报道的以3-氨基噻吩-2-羧酸甲酯为起始原料的工艺路线相比,优化后的工艺路线具有后处理操作简单,总收率较高(25.7%)等优点。The synthesis process of Olmutinib(1)was improved by analyzing existing patents and literatures.Starting with the methyl 3-aminothiophene-2-carboxylate and urea,the thiophene pyrimidine mother nucleus was synthesized by cyclizing reaction.Then after chlorination,nucleophilic substitution,nitro reduction,1 was obtained.The structure was confirmed by 1 H NMR and IR.Compared with the patented process routes which started with 3-aminothiophene-2-carboxylate,the optimized process exhibited advantages of simple post-treatment operation and high total yield(25.7%).

关 键 词：奥莫替尼 EGFR抑制剂 噻吩 工艺优化 药物合成 

分 类 号：R914.5[医药卫生—药物化学] O626[医药卫生—药学]