Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity

Autor:	Thomas Andrew Brandt, David B. Damon, David A. Griffith, Lulin Wei, Peter Robert Rose, Brian C. Vanderplas, Arun Ghosh, Sandeep Kedia, Stephane Caron, John A. Ragan, Joseph DiBrino
Rok vydání:	2009
Předmět:	chemistry.chemical_classification Ketone Stereochemistry Aryl Organic Chemistry Antagonist Condensation reaction Biochemistry Chemical synthesis chemistry.chemical_compound chemistry Suzuki reaction 1 3 5-Triazine Drug Discovery Moiety
Zdroj:	Tetrahedron. 65:3292-3304
ISSN:	0040-4020
DOI:	10.1016/j.tet.2008.10.067
Popis:	CE-178,253 benzenesulfonate (1) is a CB1 antagonist discovered by Pfizer medicinal chemists. Two syntheses of this compound are described. The first, based on the discovery synthesis, involves assembly of an aryl-substituted pyrazolotriazine core onto which the second aryl moiety is installed by a Suzuki coupling; this route has been scaled to provide up to 6 kg of API. A second, more convergent route is also described, which installs the pyrazolotriazine containing both aryl substituents by condensation of a bromoketone with a substituted thiosemicarbazide. This route has been demonstrated on laboratory scale and is viewed as the preferred bond-forming sequence.
Databáze:	OpenAIRE
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