阿西替尼的合成工艺研究  

Study on the synthesis of axitinib

作　　者：徐辰[1] 李鹏程[1] 孙超[1] 周国霖 沙洲[1] 张晓菁[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2014年第9期677-680,共4页Journal of Shenyang Pharmaceutical University

摘　　要：目的研究阿西替尼的合成工艺。方法以2-甲基-5-硝基苯胺为起始原料,经环合、碘代,钯催化Heck反应、还原、Sandmeyer反应、Ullmann偶联反应得到中间体,最后脱保护基得到阿西替尼。结果与结论目标化合物及部分中间体的化学结构经1H-NMR、13C-NMR和MS确证,总收率为30.3%(以2-甲基-5-硝基苯胺计),高于文献收率(25.0%)。Objective To study the synthetic process of axitinib. Methods Using 2-methyl-5-nitroaniline as starting material, axitinib was synthesized via 8 steps, including cyclization, iodination, reduction, Heck reaction, diazotization, reduction, Ullmann coupling reaction catalyzed by palladium, Sandmeyer reaction and deprotection. Result and Conclusion The total yield was 30. 3% which is higher than that of literature （25 % ）. The structures of the intermediates and axitinib were confirmed by 1H-NMR, 13 C-NMR and MS.

关 键 词：阿西替尼 抗肿瘤 血管内皮生长因子受体 合成工艺 

分 类 号：R914[医药卫生—药物化学]