盐酸埃罗替尼的合成工艺改进  

Improved Synthesis of Erlotinib Hydrochloride

作　　者：赵臣康 蔡志强[1] 李帅 ZHAO Chen-kang;CAI Zhi-qiang;LI Shuai(Liaoning Province Professional and Technical Innovation Center for Fine Chemical Engineering of Aromatics Downstream, School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, China;Key Laboratory for Chemical Drug Research of Shandong Province, Instiitute of Phamaceutical Sciences of Shandong Province, Jinan 250101, China)

机构地区：[1]沈阳工业大学石油化工学院辽宁省芳烃下游精细化工专业技术创新中心,辽宁辽阳111003 [2]山东省药学科学院化学药物重点实验室,山东济南250101

出　　处：《合成化学》2021年第6期520-524,共5页Chinese Journal of Synthetic Chemistry

基　　金：辽宁省自然科学基金资助项目(20180550016);辽宁省教育厅科学研究项目(LJGD2020015);沈阳市科技计划项目(18-004-4-32)。

摘　　要：探索了一条全新的盐酸埃罗替尼的公斤级合成路线。以2-氨基-4,5-双(2-甲氧基乙氧基)苯甲酸乙酯为起始原料,经甲酰胺环合,POCl_(3)氯化,最后与间乙炔苯胺胺化后成盐制得盐酸埃罗替尼,总收率72.9%,纯度99.84%,其结构经^(1)H NMR、^(13)C NMR、IR和MS(ESI)确证,并探讨了中间体和目标化合物合成工艺的影响因素。A new synthetic route for preparation of Erlotinib hydrochloride was reported.Erlotinib hydrochloride was prepared from 2-amino-4,5-bis(2-methoxyethoxy)ethyl benzoate 1 as the starting material,by means of formamide cyclization,chlorination,and amination reaction.The total yield was 72.9%and the purity of the target product was over 99%.The structures were confirmed by ^(1)H NMR,^(13)C NMR,IR and MS(ESI).The synthetic route has the advantages of simple operation,high yield and high purity,which is suitable for industrial production.

关 键 词：靶向药物 埃罗替尼 工艺优化 抗肿瘤 喹唑啉 合成 

分 类 号：O626.3[理学—有机化学] R914.5[理学—化学]