新型抗肿瘤药物Zorifertinib的合成工艺研究  

Study on the synthesis process of a new antitumor drug zorifertinib

作　　者：蔡志强[1] 李举让 秦卫涛 韩晓 李春萌 张卫东 魏乐坤 李帅 CAI Zhi-qiang;LI Ju-rang;QIN Wei-tao;HAN Xiao;LI Chun-meng;ZHANG Wei-dong;WEI Le-kun;LI Shuai(Liaoning Province Professional and Technical Innovation Center for Fine Chemical Engineering of Aromatics Downstream,School of Petrochemical Engineering,Shenyang University of Technology,Shenyang 111003,China;Shandong Haiyou Freda Pharmaceutical Co.,Ltd.,Linyi 276000,China;Shandong Provincial Key Laboratory of Mucosa and Transdermal Drug Delivery Technology,Ji'nan 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]山东海佑福瑞达制药有限公司,山东临沂276000 [3]山东省黏膜与皮肤给药技术重点实验室,山东济南250101

出　　处：《中国药物化学杂志》2023年第11期829-835,共7页Chinese Journal of Medicinal Chemistry

基　　金：辽宁省自然科学基金项目(20180550016);辽宁省教育厅科学研究项目(LJGD2020015)。

摘　　要：目的改进新型抗肿瘤药物zorifertinib(AZD-3759)的合成工艺。方法以6-乙酰氧基-4-氧代-3,4-二氢-7-甲氧基喹唑啉(2)为起始原料,经氯代、胺化、还原、酰化、脱Boc、甲基化等反应得到zorifertinib(1),总收率为66.74%(以2计),纯度99.6%。结果与结论优化后的合成工艺反应条件温和,适合工业化生产。As a new antitumor drug,zorifertinib is popular among patients.In this paper,the final product zorifertinib was prepared with 6-acetoxy-4-ox0-3,4-dihydro-7-methoxyquinazoline as the starting material by seven steps.The total yield was 66.74%and the purity was 99.6%.Compared with the literature,the procedure was optimized and the optimal technological conditions were found.The structure of zorifertinib was confirmed by^(1)H-NMR and ESI-MS.The optimized synthesis process has mild reaction conditions,which is suitable for industrial production.

关 键 词：zorifertinib 抗肿瘤药物 工艺优化 合成 

分 类 号：R914[医药卫生—药物化学]