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

…, J Hynes Jr, H Wu, L Parlanti, R Discordia…

Index: Shi, Zhongping; Kiau, Susanne; Lobben, Paul; Hynes Jr., 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 Organic Process Research and Development, 2012 , vol. 16, # 10 p. 1618 - 1625

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Citation Number: 6

Abstract

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.

~68%

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An efficient electrophilic N-amination utilizing in situ gen...

[Bhattacharya, Apurba; Patel, Nitin C.; Plata, Robert Erik; Peddicord, Michael; Ye, Qingmei; Parlanti, Luca; Palaniswamy, Venkatapuram A.; Grosso, John A. Tetrahedron Letters, 2006 , vol. 47, # 30 p. 5341 - 5343]

Pyrrolopyridazine MEK inhibitors

[Chen, Zhong; Kim, Soong-Hoon; Barbosa, Stephanie A.; Huynh, Tram; Tortolani, David R.; Leavitt, Kenneth J.; Wei, Donna D.; Manne, Veeraswamy; Ricca, Carolyn S.; Gullo-Brown, Johnni; Poss, Michael A.; Vaccaro, Wayne; Salvati, Mark E. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 3 p. 628 - 632]