Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

详细信息    查看全文

• 作者：Neil J. Kallman ; Chin Liu ; Matthew H. Yates ; Ryan J. Linder ; J. Craig Ruble ; Eugene F. Kogut ; Lawrence E. Patterson ; Dana L. T. Laird ; Marvin M. Hansen
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：April 18, 2014
• 年：2014
• 卷：18
• 期：4
• 页码：501-510
• 全文大小：507K
• 年卷期：v.18,no.4(April 18, 2014)
• ISSN：1520-586X

文摘

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 N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.