LGK974的合成工艺研究  

Study on the Synthesis Process of LGK974

作　　者：骆荣双 黄朋越 刘春江 赵庆平 周志旭[1,2] 黄筑艳[1,2] LUO Rong-shuang;HUANG Peng-yue;LIU Chun-jiang;ZHAO Qing-ping;ZHOU Zhi-xu;HUANG Zhu-yan(School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China;Guizhou Engineering Laboratory for Synthetic Drugs,Guizhou University,Guiyang 550025,China;School of Chemistry and Chemical Engineering,Guizhou University,Guiyang 550025,China)

机构地区：[1]贵州大学药学院,贵州贵阳550025 [2]贵州大学贵州省合成药物工程实验室,贵州贵阳550025 [3]贵州大学化学与化工学院,贵州贵阳550025

出　　处：《合成化学》2020年第5期446-450,共5页Chinese Journal of Synthetic Chemistry

基　　金：贵州省科技计划项目(黔科合LH字[2016]7442号,黔科合平台人才[2018]5781号)。

摘　　要：LGK974是一种高度特异性和有效的Porcupine抑制剂。设计了一条新的合成路线,以2-氨基-5-溴吡啶、2-氯-3-甲基吡啶、2-氨基吡嗪和2-甲基-6-氯吡啶为起始原料,采用汇聚法,经取代、Suzuki、酰胺化等10步反应合成了LGK974,总收率11.5%,其结构经^1H NMR、^13C NMR和MS(ESI-TOF)确证。LGK974 is a highly specific and effective Porcupine inhibitor.In this work,a new synthetic route was designed,using 2-amino-5-bromopyridine,2-chloro-3-methylpyridine,2-aminopyrazine and 2-methyl-6-chloropyridine as materials by means of substitution,Suzuki reaction,amidation and so on.The structure was confirmed by ^1H NMR,^13C NMR and MS(ESI-TOF).The total yield was 11.5%.Compared with the reported route,the method has the advantages of simple operation,low cost,safety and environmental protection.

关 键 词：LGK974 Porcupine抑制剂 合成 工艺优化 SUZUKI反应 酰胺化 

分 类 号：O626.3[理学—有机化学] R914.5[理学—化学]