S1P3受体拮抗剂TY-52156的合成工艺优化  

Optimization of synthesis process of S1P3 receptor antagonist TY-52156

作　　者：樊玲玲 刘永淑 罗忠福 汤磊 李永 FAN Ling-ling;LIU Yong-shu;LUO Zhong-fu;TANG Lei;LI Yong(School of Pharmacy,Guizhou Medical University,Guiyang 550025,China;Guizhou Province Engineering Technology Research Center for Chemical Drug R&D,Guiyang 550004,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550025 [2]贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550004

出　　处：《化学研究与应用》2021年第4期772-776,共5页Chemical Research and Application

基　　金：贵州省化学合成药物研发利用工程技术研究中心项目(黔科合[2016]平台人才5402)资助;贵州省普通高等学校药物化学工程研究中心项目(黔教合KY字[2014]219号)资助;贵州省科技支撑计划项目(黔科合支撑[2017]2835号)资助;贵州省科技计划项目(黔科合基础[2019]1269和[2020]1Y111号)资助;国家自然科学基金项目(32060627)资助。

摘　　要：以3,3-二甲基-2-丁酮、乙酸乙酯和对氯苯胺为起始原料,经Claisen缩合、氯代、重氮化、亲核取代等五步反应生成目标产物TY-52156,总收率为42.4%。目标化合物结构经1H-NMR、13 C-NMR和HRMS确证。通过优化Claisen缩合(t-BuOK/MTBE)及亲核取代(AcONa/EtOH)两步的反应条件,使其总收率比原有路线提高了1.36倍,更适合较大规模制备TY-52156。Target product TY-52156 was obtained by classical Claisen condensation,chlorination,diazotization and nucleophilic substitution from starting materials 3,3-dimethyl-2-butanone,ethyl acetate and p-chloroaniline,and gave total yield in 42.4%.The structure of the target compound was confirmed by 1H-NMR,^(13)C-NMR and HRMS.By optimizing the reaction conditions of Claisen condensation(t-BuOK/MTBE)and nucleophilic substitution(AcONa/EtOH),the total yield was increased 1.36 folds compared with the traditional process,which was more suitable for large-scale preparation of TY-52156.

关 键 词：TY-52156 合成 工艺优化 

分 类 号：O625.65[理学—有机化学]