抗肿瘤药物阿法替尼的合成及工艺优化  

Synthesis and Optimization of Antitumor Agent Afatinib

作　　者：涂远彪 王敏[1] 孙超[1] 郑鹏武[1] 朱五福[1] 

机构地区：[1]江西科技师范大学药学院,江西南昌330013

出　　处：《化学试剂》2016年第8期795-799,共5页Chemical Reagents

基　　金：江西省教育厅科技项目(GJJ150796);江西省自然科学基金资助项目(20142BAB215020);大学生科研立项项目(20150904040)

摘　　要：以4-氟-2-氨基苯甲酸和醋酸甲脒为起始原料,经合环、硝化、氯代、缩合、硝基还原,再经缩合、Wittig-hornor反应制得阿法替尼,并进行合成工艺优化。阿法替尼的总收率达44.5%,优化多步反应条件,如用三氯化铁、活性炭和水合肼体系进行硝基氢化还原。优化后的反应处理更简单、产物收率较高、产品纯度好,适合工业化生产。To synthesize and optimize the synthetic process of afatinib. Using the 2-amino-4-fluorobenzoic acid and formamidine acetate as starting materials,afatinib was synthesized by cyclization and nitrification,followed by chlorization,condensation then hydrogenation,further condensation and through Wittig-horner reaction. The total yield was 44. 5% and most of the reactions conditions were optimized,such as nitro hydrogenation by hydrazine hydrate,ferric chloride and activated carbon. After optimization,with high yield and the reaction process is simple. The purity of the product was 99. 1%. It is suitable for industrial production.

关 键 词：阿法替尼 抗肿瘤药 合成工艺 

分 类 号：R914.5[医药卫生—药物化学]