塞普替尼合成路线综述  

Review of synthetic routes of selpercatinib

作　　者：陈龙 胡伟 黄璐 范昭泽[1] CHEN Long;HU Wei;HUANG Lu;FAN Zhaoze(Wuhan Jiuzhou Yumin Pharmacutical Technology Co.,Ltd,Wuhan 430071,China;School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China;School of Pharmacutical Sciences,Wuhan University,Wuhan 430072,China)

机构地区：[1]武汉九州钰民医药科技有限公司,湖北武汉430071 [2]武汉工程大学化工与制药学院,湖北武汉430205 [3]武汉大学药学院,湖北武汉430072

出　　处：《武汉工程大学学报》2024年第1期1-6,共6页Journal of Wuhan Institute of Technology

基　　金：武汉东湖国家自主创新示范区2021年度“3551光谷人才计划”项目(武新管人才[2021]3号)。

摘　　要：塞普替尼是一种高选择性的转染重排(RET)酪氨酸激酶抑制剂,是全球首个获批上市的专门针对携带RET基因突变的癌症患者的靶向药。对塞普替尼及其中间体的合成路线进行了综述,对7条塞普替尼合成路线进行了对比分析,通过对比收率、工艺危险性和产业化可行性,提出分别以3-溴-5-甲氧基吡啶、3,5-二溴吡啶和3-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-3,6-二氮杂双环[3.1.1]庚烷-6-羧酸叔丁酯为起始原料的3条合成路线更具有工业化生产前景,与其他合成路线相比,该3条合成路线的工艺原料易得,操作简单,收率高,成本低。Selpercatinib is a rearranged during transfection(RET)tyrosine kinase inhibitor with high selectivity,and is the first approved targeted drug specifically for cancer patients with RET gene mutations in the world.This article reviews the synthetic routes of selpercatinib and its intermediates,and makes a comparative analysis of seven synthetic routes of selpercatinib,and compares the yield,process hazards,and industrial feasibility.It is proposed that the three synthetic routes starting from 3-bromo-5-mrthoxypyridine,3,5-dibromopyridine and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-azabicyclo[3.1.1]heptane-6-carboxylate respectively are more suitable for industrial production.Compared with the other four synthetic routes,these three synthetic routes have the advantages of available raw materials,simple operation,high yield and low cost.

关 键 词：塞普替尼 转染重排酪氨酸激酶抑制剂 合成路线 靶向药 

分 类 号：R914.5[医药卫生—药物化学]