FXIa抑制剂关键母核1-取代的嘧啶酮的合成研究  

Study on Synthesis of 1-substituted Pyrimidinone Scaffold in FXIa Inhibitors

作　　者：蒙柳卫 李清[1] MENG Liu-wei;LI Qing(School of Pharmacy,Guangxi Medical University,Guangxi Nanning 532001,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《广州化工》2022年第10期58-60,105,共4页GuangZhou Chemical Industry

基　　金：国家自然科学基金项目(21762009)。

摘　　要：1-取代的嘧啶酮是FXIa抑制剂的关键骨架,探究其合成工艺对FXIa抑制剂合成具有重要意义。通过亲核取代反应难以合成具有手性的1-取代的嘧啶酮。本文采用嘧啶酮与氨基酸酯直接进行缩合反应的方法,得到具有手性中心的1-取代的嘧啶酮。通过对影响产率的主要因素进行考察,确定最佳的实验条件为:乙腈作为溶剂,反应温度为25℃,n(HATU):n(氨基酸酯)=1.5:1。在该反应条件下,目标化合物产率为36%。1-substituted pyrimidinone is the skeleton of FXIa inhibitors,and it is of great significance to explore the synthesis process of FXIa inhibitors.It is difficult to obtain chiral 1-substituted pyrimidinone by nucleophilic substitution reaction.1-substituted pyrimidinone with chiral center was obtained by direct condensation reaction of pyrimidinone with amino acid ester.The main factors affecting the yield of the product were also investigated,and the suitable reation conditions were determined as follows:acetonitrile as solvent,reaction temperature was 25℃,n(HATU):n(amino acid ester)=1.5:1.The yield of the product was 36%by this reaction condition.

关 键 词：FXIa抑制剂 1-取代的嘧啶酮 合成 缩合反应 

分 类 号：R914[医药卫生—药物化学]