A Practical and Scalable Method for Manufacturing JAK Inhibitor ASP3627

ASP3627 (1) is a potent Janus kinase inhibitor discovered and developed by Astellas Pharma Inc. Here, we report the development of a practical and scalable method for manufacturing ASP3627 featuring a six-reaction telescoping process consisting of DIBAL reduction, hydrolysis, Wittig reaction, cyclization, and a two-step sequence to remove the SEM group. In addition, a simple palladium removal procedure using l-cysteine is described. This method was used to successfully perform the first multikilogram synthesis of ASP3627, producing 30 kg with high purity in excellent overall yield.