多靶点酪氨酸激酶抑制剂Amuvatinib的合成  

Synthesis of Multi-targeted Tyrosine Kinase Inhibitor Amuvatinib

作　　者：陶燕[1] 吴安琪[1] 王前进 TAO Yan;WU An-qi;WANG Qian-jin(Shaanxi Energy Institute,Shaanxi Xianyang 712000,China)

机构地区：[1]陕西能源职业技术学院,陕西咸阳712000

出　　处：《广州化工》2024年第5期74-76,共3页GuangZhou Chemical Industry

基　　金：陕西省高校青年创新团队。

摘　　要：为了进一步研究和优化多靶点酪氨酸激酶抑制剂Amuvatinib的合成方法,以水杨腈为起始原料,经酯化、环化、关环、氯化反应得到关键中间体4-氯-苯并呋喃并[3,2-d]嘧啶;以1,3苯并二氧戊环-5-甲胺为原料,以N,N’-硫羰基二咪唑(TCDI)为硫代酰胺试剂,与哌嗪合成关键中间体N-(1,3-亚甲二氧基苯-5-甲基)-4-哌嗪-1-硫代酰胺;两个中间体经亲核取代得到最终产物Amuvatinib,总收率41.1%。该方法操作简便,反应后处理相对简单,产物结构经过1H NMR和MS确认,纯度可达99.18%。Using 2-hydroxy-benzonitril and(benzo[d][1,3]dioxol-6-yl)methylamine as starting materials,the intermediate 4-chloro-benzofuran[3,2-d]pyrimidine and N-(1,3-Benzodioxol-5-ylmethyl)-4-piperazine-1-carbothioamide were obtained in 2 steps and 4 steps,respectively.The Amuvatinib was synthesized by nucleophile substitution reaction with total yield of 41.1%.The method was easy to operate and the post-treatment of the reaction was relatively simple.The structure was confirmed by 1H NMR and MS.The purity can reach 99.18%.

关 键 词：Amuvatinib 酪氨酸激酶抑制剂 合成 

分 类 号：R914[医药卫生—药物化学]