抗肿瘤药物dacomitinib的合成工艺  

Synthetic process of antitumor drug dacomitinib

作　　者：程海博[1] 徐斌[1] 张惠斌[1] 周金培[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2014年第2期165-169,共5页Journal of China Pharmaceutical University

摘　　要：对抗肿瘤药物dacomitinib合成工艺进行改进。以4-氟-2-氨基苯甲酸为原料，经环合、硝化、卤代、偶联以及还原等反应，得到dacomitinib。目标化合物经质谱、核磁共振氢谱确证化学结构。以11步反应总收率36．1％，单步收率75％。90％合成目标化合物，无需特殊试剂和复杂分离纯化过程，降低了成本，优化了反应条件，操作更加简单实用。This paper describes a practical process for the preparation of antitumor drug dacomitinib. It was synthesized by eleven steps from 2-amino-4-fluorobenzoic acid by cyclization, nitration, halogenation, coupling and reduction reactions with the total yield of 36.1% and one-step yield of 75%-90 %. The intermediates and target compound were characterized by NMR and MS. This practical synthetic process of dacomitinib highlights comparable yield, low-cost, optimized condition and easier purification.

关 键 词：dacomitinib 酪氨酸激酶抑制剂 合成工艺 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]