Study on Synthesis and Optimization of Syn-thesis Technology of JAK Inhibitor Peficitinib

Abstract

Peficitinib is a novel Janus kinase 1 and Janus kinase 3 inhibitor developed by Astellas, a Japa-nese company. Peficitinib mainly treats the moderate or severe rheumatoid arthritis with in-刘珊 adequate response to methotrexate. At present, there are very few papers on the synthesis route of Peficitinib. In this paper, a complete synthesis route is designed, and then each step of the reaction is studied and optimized. Starting from 7-azindole, the target compound was obtained through seven steps including halogenation, substitution (upper protection), esterification, de-protection, ester hydrolysis, amidation and then substitution. By providing catalyst or changing other reaction conditions such as solvent, temperature and molar ratio of reactants, a reasona-ble route, high yield, short time and simple operation of Peficitinib synthesis process was suc-cessfully obtained, and the synthesis of Peficitinib can reach industrial production. The struc-tures of the target compounds and intermediates were confirmed by 1 H NMR, and the total yield of the route was 32.8%.