1. An Efficient Method for Synthesis of Tofacitinib Citrate.
- Author
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Zhi, Shuang, Liu, Dengke, Liu, Ying, Liu, Bingni, Wang, Donghua, and Chen, Ligong
- Subjects
CITRATES ,CHEMICAL synthesis ,METHYLPYRIDINE ,PYRIMIDINES ,CARBONYLATION - Abstract
An efficient and mild synthetic method was developed for tofacitinib citrate from 3-amino-4-methylpyridine and 4-chloro-7 H-pyrrolo[2,3-d]pyrimidine. The related reactions were systematically optimized. Sodium hydride instead of potassium tert-butoxide employed in the methoxycarbonylation reaction of compound 9 made the reaction proceed effectively to present compound 8 in a better yield. The replacement of benzaldehyde with benzyl bromide simplified the protection process of amino group. Red-Al provided a cost-effective method for the . The introduction of tosyl group into compound 10 enhanced the of 10 with compound 4 dramatically. Thus, under the optimized conditions, tofacitinib citrate was obtained in 13.3% yield (based on compound 9) with a purity of 99.9%, much better than the reported yield 8.6%. This cost-effective and environmental friendly process is more suitable for scale-up production. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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