Optimized synthesis process of tofacitinib citrate
10.11665/j.issn.1000-5048.20220606
- VernacularTitle:枸橼酸托法替尼的合成工艺改进
- Author:
Li LIU
1
;
Zijin LIU
;
Jun TANG
;
Guangwei HE
;
Weizhong LIU
Author Information
1. 安徽医学高等专科学校
- Publication Type:Journal Article
- Keywords:
tofacitinib citrate;
JAK3 inhibitor;
synthesis;
optimization
- From:
Journal of China Pharmaceutical University
2022;53(6):685-689
- CountryChina
- Language:Chinese
-
Abstract:
In order to improve the yield and simplify the operation, the synthesizing process of JAK3 inhibitor tofacitinib citrate was improved based on the analysis of the methods previously published.Using 2, 4-dichloro-7H-pyrrolo [2, 3-d] pyrimidine and (3R, 4R)-1-benzyl-N, 4-dimethylpiperidin-3-amine dihydrochloride as starting materials, tofacitinib citrate was obtained through four steps of nucleophilic substitution, catalytic transfer hydrogenation, cyanide acetylation and citrate salt, and its crystal form was consistent with the original research.After optimization, the yield was better than those reported in literature, and the mild reaction conditions were suitable for industrial production.
