摘要
来曲唑是治疗晚期乳腺癌的临床一线药物。以对氰基氯苄、1,2,4-三氮唑为起始原料,合成中间体4-((1H-1,2,4-三-1-唑)甲基)苯腈(I),再将其与对氟苯腈反应合成来曲唑,工艺总产率达76.5%。为了有效地去除中间体中1,3,4-三唑基异构体(II),采用分步降温结晶的方法,降温至20℃,先析出其异构体杂质盐酸盐,过滤后再继续降温析晶,得到高纯度的中间体,从而为下一步高纯度来曲唑的获得提供了可能性。终产品来曲唑经核磁(1H-NMR)、质谱(MS)确证结构。该工艺操作简单且产率高,适合应用于工业化生产。
Letrozole is a clinical first-line drug for the treatment of advanced breast cancer. A novel two- step synthesis process for letrozole was reported. In this process, chlorobenzonitrile and 1,2,4-triazole were the starting material. First, 4-[ 1-（ 1,2,4-triazolyl） methyl ] -benzontrile was synthesized by 4- （chloromethyl） benzonitrile and 1,2,4-triazo under heating, then reacted with fluorobenzonitrile. The overall yield was 76. 5%. In order to effectively remove the intermediate 1 ,3 ,4-triazolyl isomers （II）,the fractional cooling crystallization method was used. Isomer impurity hydrochloride was precipitated when temperature was cooled to 20 With further decrease of temperature,high purity of intermediates I was obtained. The structures of the compound were confirmed by 1H - N M R and M S . It is an easy operation process and suitable for industrial production.
出处
《生物加工过程》
CAS
2017年第2期41-44,共4页
Chinese Journal of Bioprocess Engineering
基金
国家自然科学基金面上项目(21476113)
关键词
来曲唑
1
3
4-三唑基异构体
合成
乳腺癌
letrozole
1,3,4-triazolyl isomers
synthesis process
breast cancer
