热休克蛋白90抑制剂SNX-2112的合成与优化  

Synthesis and optimization of heat shock protein 90 inhibitor SNX-2112

作　　者：罗文洁 张珩[1] 钟武 LUO We -jie;ZHANG Heng;ZHONG Wu(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430073,China;Natioual Engineering Research Center for the Strategic Drug,Institute of Pharmacology＆Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]武汉工程大学化工与制药学院,武汉430073 [2]国家应急防控药物工程技术研究中心军事科学院军事医学研究院毒物药物研究所,北京100850

出　　处：《国际药学研究杂志》2018年第3期226-229,共4页Journal of International Pharmaceutical Research

基　　金：国家"重大新药创制"科技重大专项资助项目(2018ZX09711003)

摘　　要：目的对热休克蛋白90(HSP90)抑制剂SNX-2112合成方法的探索及优化。方法以2-氟-4-溴苄腈作为起始原料,通过N-烃化、环化、脱保护、乌尔曼偶联、水解等反应得到目标产物。中间体及目标化合物的结构经MS和1H NMR确认。同时,采用微波法对关键中间体D的合成方法进行了优化。结果与结论微波法使中间体D合成方法操作简便可控,虽产率略低于文献报道值,但大大缩短反应时间,提高起始物料反应的原子经济性,更适合产业化。Objective To explore and optimize the synthesis of heat shock protein 90（HSP90）inhibitor SNX-2112. Methods Starting from 2-fluoro-4-bromobenzonitrile,the target product was obtained by the reaction of N-alkylation,cyclization,deprotection,Ullmann coupling and hydrolysis. The structures of intermediates and target compound were confirmed by MS and1 H NMR.Meanwhile,synthesis of the key intermediate D was optimized through microwave system. Results and Conclusion Although the yield of intermediate D is slightly lower than the literature value,the use of microwave synthesis could greatly reduce the reaction time and improve the atomic economy of the starting material reaction,which might be easier to control and be more suitable for industrialization.

关 键 词：热休克蛋白90(HSP90)抑制剂 乌尔曼偶联 工艺优化 

分 类 号：R916.42[医药卫生—药学]