SB-590885的合成工艺研究  

Synthetic of SB-590885

作　　者：黄朋越 朱雄 赵永利 柴慧芳 赵春深[2,4,5] HUANG Peng-yue;ZHU Xiong;ZHAO Yong-li;CHAI Hui-fang;ZHAO Chun-shen(School of Chemistry and Chemical Engineering,Guizhou University,Guiyang 550025,China;School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China;School of Pharmaceutical Sciences,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Guizhou Engineering Laboratory for Synthetic Drugs,Guiyang 550025,China;Key Laboratory of Guizhou for Fermentation Engineering and Biopharmacy,Guiyang 550025,China)

机构地区：[1]贵州大学化学与化工学院,贵州贵阳550025 [2]贵州大学药学院,贵州贵阳55002 [3]贵州中医药大学药学院,贵州贵阳550025 [4]贵州省合成药物工程实验室,贵州贵阳550025 [5]贵州省发酵工程与生物制药重点实验室,贵州贵阳550025

出　　处：《化学研究与应用》2020年第6期1094-1099,共6页Chemical Research and Application

基　　金：贵州省2017年一流大学(一期)重点建设项目—药学实验教学中心平台建设项目(黔教高发[2017]158号)资助;贵州省国内一流建设学科项目(中药学)(GNYL[2017]号)资助。

摘　　要：SB-590885是一种新型的三芳基咪唑类B-Raf激酶抑制剂,已报道的合成方法收率较低且操作繁琐,不适合工业化生产。本文设计了一条新的合成路线,以4-溴吡啶盐酸盐为起始原料,经偶联、脱保护、加成、氧化、环合、水解等反应得到目标化合物,产物结构经1H NMR,13C NMR和MS确证,总收率为9.53%,该方法原料便宜易得、反应条件温和、操作简单且总收率较高,是一条适合工业化生产的合成路线。SB-590885 is a new type of triarylimidazole B-Raf kinase inhibitor.The reported synthesis method has low yield and complicated operation,which is not suitable for industrial production.In this paper,a new synthetic route was designed.4-Bromopyridine hydrochloride was used as the starting material,and the target compound was obtained through coupling,deprotection,addition,oxidation,cyclization,hydrolysis and other reactions.The structure of the product was confirmed by 1H NMR,13C NMR and MS,and the total yield was 9.53%.The method had the advantages of cheap and easily available raw materials,mild reaction conditions,simple operation and high overall yield.It was a synthetic route suitable for industrial production.

关 键 词：4-溴吡啶盐酸盐 SB-590885 B-Raf激酶抑制剂 合成 

分 类 号：O626.2[理学—有机化学]