Tivozanib的合成  

Synthesis of Tivozanib

作　　者：王京[1,2] 王亚楼[1] 覃语燕[1] 

机构地区：[1]中国药科大学药学院,江苏南京210009 [2]遵义医学院药学院,贵州遵义563003

出　　处：《中国医药工业杂志》2013年第6期541-544,共4页Chinese Journal of Pharmaceuticals

基　　金：江苏省高等学校大学生实践创新训练计划资助项目(2012JSSPITP0249)

摘　　要：3,4-二甲氧基苯胺(2)与乙氧基亚甲基丙二酸二乙酯经取代、环合、水解、脱羧及氯代反应制得4-氯-6,7-二甲氧基喹啉(6);或以2、米氏酸和原甲酸三甲酯为原料,经取代、环合、氯代反应制得6。6与4-氨基-3-氯苯酚盐酸盐(7)进行醚化反应后,再与3-氨基-5-甲基异噁唑进行成脲反应制得抗肿瘤药tivozanib,总收率约35%～37%(以2计)。4-Chloro-6,7-dimethoxyquinoline（6） was synthesized from 3,4-dimethoxyaniline（2） and ethoxymethylenemalonic acid diethyl ester by substitution, cyclization, hydrolysis, decarboxylation and chlorination. In another route, 6 was synthesized from 2, Meldrum＇s acid and trimethyl orthoformate by substitution, cyclization and chlorination. Then 6 was etherizied with 4-amino-3-chlorophenol hydrochloride （7） and coupled with 3-amino-5- methylisoxazole by ureapoiesis to yield the antitumor drug tivozanib with an overall yield of 35 %-37% （based on compound 2）.

关 键 词：tivozanib VEGFR抑制剂 抗肿瘤药 合成 

分 类 号：R979.19[医药卫生—药品]