特班布林药物的优化合成研究  

Study on Optimization and Synthesis of Tirbanibulin

作　　者：刘加艳 任宇鹏 LIU Jiayan;REN Yupeng(Henan Vocational College of Applied Technology,Henan Zhengzhou 450042,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042

出　　处：《广州化工》2024年第19期38-40,共3页GuangZhou Chemical Industry

基　　金：河南应用技术职业学院校级项目(No:2023-KJ-55)。

摘　　要：创新并优化了一种特班布林的合成方法,采用2,5-二溴吡啶、溴乙酸乙酯为原料经三步合成。以得率为指标,考察原料1、原料2、原料3添加量对每步产物得率的影响。从单因素考虑,第一步中,化合物1、溴乙酸乙酯的投料当量比为1∶1.2时,化合物2得率较好;第二步中化合物2、苄胺的投料当量为1∶1.1时,化合物3得率较好;第三步中,化合物3、化合物4、催化剂Pd(dppf)Cl 2投料当量比为1∶1.05∶0.01时,特班布林得率最高,终产物HPLC纯度98.34%。A synthesis method for tirbanibulin was innovated and optimized,using 2,5-dibromopyridine and ethyl bromoacetate as raw materials through a three-step synthetic method.Using yield as an indicator,the effect of the addition amount of raw materials 1,2,and 3 on the yield of each product step was studied.From single-factor perspective,in the first step,when the equivalence ratio of compound 1 to ethyl bromoacetate was 1∶1.2,the yield of compound 2 was better.In the second step,when the feed equivalent of compound 2 and benzylamine was 1∶1.1,the yield of compound 3 was better.In the third step,when the equivalence ratio of compound 3,compound 4,and Pd(dppf)Cl 2 was 1∶1.05∶0.01,the yield of tirbanibulin was best,and HPLC purity of tirbanibulin was 98.34%.

关 键 词：特班布林 Negishi偶联反应 SUZUKI偶联反应 优化合成 2 5-溴吡啶 

分 类 号：TQ463.5[化学工程—制药化工]