Optimization Of The Synthetic Route Of The Anti-arthritic Drug Baricitinib

Baricitinib is a selective JAK inhibitor that preferentially inhibits JAK1 and JAK2,primarily for the treatment of rheumatoid arthritis and other inflammatory diseases,with good safety and tolerance.Because it has good efficacy and smaller side effects,there will be a broader market prospects.This paper summarizes the existing synthetic methods of Baricitinib.Howecer,In these synthetic methods,raw materials are expensive,the operation is troublesome and the yield is low,not suitable for industrial production.A synthetic route for Baricitinib was selected on the basis of the existing synthetic route,and the benzoylamine and 4-chloropyrrolopyrimidine were used as starting materials.The synthesis was accomplished in ten steps starting from the benzoylamine and4-chloropyrrolopyrimidine,and the reaction conditions are optimized for each step.Compared with the existing synthesis methods,the reaction conditions are mild,this route is low-cost,easy purification,simplified operation and higher yield,the total yield is 13.2%,HPLC purityt is more than 99.7%.This program laid the foundation for pilot production.The structure of the target compound was confirmed by 1H NMR and MS.