Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N 1-Methylindazole

…, MH Yates, RJ Linder, JC Ruble, EF Kogut…

Index: Kallman, Neil J.; Liu, Chin; Yates, Matthew H.; Linder, Ryan J.; Ruble, J. Craig; Kogut, Eugene F.; Patterson, Lawrence E.; Laird, Dana L. T.; Hansen, Marvin M. Organic Process Research and Development, 2014 , vol. 18, # 4 p. 501 - 510

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Citation Number: 8

Abstract

The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu- catalyzed cyclization to form an important N 1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a ...