The Synthesis of a Novel Inhibitor of B-Raf Kinase

Autor:	David Bryant Batt, Run-Ming B. Wang, Peng Geng, Markus Bänziger, Tim Ramsey, Lawrence Blas Perez, Francis Taplin, Richard William Versace, David Cesarz, Wolfgang Marterer, Walter Michael, Naeem Yusuff, Donatienne Denni-Dischert
Rok vydání:	2005
Předmět:	Negishi coupling Chemistry Stereochemistry Kinase Yield (chemistry) Organic Chemistry Amine gas treating Raf kinase Physical and Theoretical Chemistry
Zdroj:	Organic Process Research & Development. 10:70-77
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op0501601
Popis:	A scaleable synthetic route to [4,7‘]bis-isoquinolinyl-1-yl-(2-tert-butyl-pyrimidine-5-yl)amine (1), an inhibitor of B-Raf kinase is described. The key step in the synthesis is the Pd-catalyzed Negishi coupling of 4-bromo-1-chloroisoquinoline with trifluoromethanesulfonic acid isoquinoline-7-yl ester to yield 1-chloro[4,7‘]bis-isoquinolinyl. This intermediate is transformed to the desired drug substance in one additional step, by reaction with 2-tert-butyl-5-aminopyrimidine in the presence of NaH. A special focus was put on the finally successful removal of traces of Zn and Pd in the drug substance, which came from the Negishi coupling.
Databáze:	OpenAIRE
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