Process Development and Large-Scale Synthesis of a c-Met Kinase Inhibitor
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- 作者：Gavin W. Stewart ; Karel M. J. Brands ; Sarah E. Brewer ; Cameron J. Cowden ; Antony J. Davies ; John S. Edwards ; Andrew W. Gibson ; Simon E. Hamilton ; Jason D. Katz ; Stephen P. Keen ; Peter R. Mullens ; Jere
- 刊名：Organic Process Research & Development
- 出版年：2010
- 出版时间：July 16, 2010
- 年：2010
- 卷：14
- 期：4
- 页码：849-858
- 全文大小：279K
- 年卷期：v.14,no.4(July 16, 2010)
- ISSN：1520-586X
文摘
A highly convergent synthesis of c-Met kinase inhibitor 1 has been demonstrated on a multikilogram scale using three key fragments: dihalotricyclic core 2, chiral sulfamide side chain 3, and pyrazole boronic ester 4. The chirality in sulfamide side chain 3 was installed using the cheap and readily available starting material (S)-epichlorohydrin. A total of 2.71 kg of 1 were isolated in seven steps (the longest linear sequence).