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 met...

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Bibliographic Details
Published in:Organic process research & development 2012-10, Vol.16 (10), p.1618-1625
Main Authors: Shi, Zhongping, Kiau, Susanne, Lobben, Paul, Hynes, John, Wu, Hong, Parlanti, Luca, Discordia, Robert, Doubleday, Wendel W, Leftheris, Katerina, Dyckman, Alaric J, Wrobleski, Stephen T, Dambalas, Konstantinos, Tummala, Srinivas, Leung, Simon, Lo, Ehrlic
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op300181r