Process Development and Large-Scale Synthesis of a c-Met Kinase Inhibitor

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 a...

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Bibliographic Details
Published in:Organic process research & development 2010-07, Vol.14 (4), p.849-858
Main Authors: Stewart, Gavin W, Brands, Karel M. J, Brewer, Sarah E, Cowden, Cameron J, Davies, Antony J, Edwards, John S, Gibson, Andrew W, Hamilton, Simon E, Katz, Jason D, Keen, Stephen P, Mullens, Peter R, Scott, Jeremy P, Wallace, Debra J, Wise, Christopher S
Format: Article
Language:English
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Summary: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).
ISSN:1083-6160
1520-586X
DOI:10.1021/op100101q