Development of a Practical Synthesis of a p38 Kinase Inhibitor via a Safe and Robust Amination

The development of a practical synthesis for a p38 kinase inhibitor is described. The key advances include an improved route to the key intermediate, a substituted pyrrole, and a subsequent animation utilizing O -(4-nitrobenzoyl)hydroxylamine, which provides a safe, scalable, and robust amination method. The new protocol was successfully demonstrated to generate 1.6 kg of API in seven steps and 26% overall yield.