抗疟药氯喹的合成工艺改进  

Improved synthetic process of antimalarial drug chloroquine

作　　者：张耀华 张兴海 刘焕珍 赵楚涵 余坤矫 赵建宏[2] ZHANG Yao-hua;ZHANG Xing-hai;LIU Huan-zhen;ZHAO Chu-han;YU Kun-jiao;ZHAO Jian-hong(Shanghai Pharmaceuticals Holding Co.,Ltd.,Shanghai 200020,China;School of Pharmcy,East China University of Science and Technology,Shanghai 200237,China;College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]上海医药集团股份有限公司,上海200020 [2]华东理工大学药学院,上海200237 [3]浙江工业大学药学院,浙江杭州310014

出　　处：《中国药物化学杂志》2023年第6期446-448,共3页Chinese Journal of Medicinal Chemistry

摘　　要：目的研究氯喹的合成新方法。方法以4,7-二氯喹啉为原料,与2,2,2-三氟乙醇经芳香亲核取代反应转化成7-氯-4-(2,2,2-三氟乙氧基)-喹啉,再与侧链2-氨基-5-二乙胺基戊烷经芳香亲核取代反应制得目标化合物。结果与结论在相对温和的条件下实现C-N键偶联制得氯喹,2步反应总收率为80.2%(以4,7-二氯喹啉计),产品纯度99.8%(HPLC归一化法)。改进后的路线具有条件较温和、杂质少、纯度高、操作简便和收率较高等优点。An improved synthetic method of chloroquine was developed in this study.With 4,7-dichloroquinoline(2)as the raw material,the target compound was prepared firstly by protection and activation with 2,2,2-trifluoroethanol,and then reacted with 2-amino-5-diethylaminopentane(4)through nucleophilic aromatic substitution reaction,with an overall yield of 80.2%(based on 2)and a purity of 99.8%(HPLC).The structures of 7-chloro-4-(2,2,2-trifluoroethoxy)-quinoline(3)and chloroquine(1)were confirmed by MS and^(1)H-NMR.This synthetic route has the advantages of lower reaction temperature,less impurities and high purity,higher safety,easy operation and higher yield.

关 键 词：N^(4)-(7-氯-4-喹啉基)-N^(1) N^(1)-二乙基-1 4-戊二胺 氯喹 工艺改进 

分 类 号：R914[医药卫生—药物化学]