Development of a Practical Synthesis of Toll-like Receptor Agonist PF-4171455: 4-Amino-1-benzyl-6-trifluoromethyl-1,3-dihydroimidazo [4,5-c] pyridin-2-one

Autor:	Craig J. Knight, Katie J. W. Proctor, Nicholas Smith, David C. Pryde, Christopher L. Carr, Peter Jones, Gerwyn Bish, Nieves Castro, Hodgson Paul Blaise, Filippo Rota, Frederick Calo, Duncan Hay, Mya C. Smith, James Hitchin, Tram T. Tran, Rachel Dixon, Michael Paradowski, Fiona M. Adam, Gemma C. Parsons
Rok vydání:	2011
Předmět:	Agonist chemistry.chemical_compound Nitropyridone Trifluoromethyl Stereochemistry medicine.drug_class Chemistry Organic Chemistry medicine Regioselectivity Physical and Theoretical Chemistry Combinatorial chemistry Carbonyl group
Zdroj:	Organic Process Research & Development. 15:788-796
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op200021a
Popis:	The development and implementation of a scalable process for the manufacture of the Toll-like receptor (TLR7) agonist PF-4171455 (1) is described. Initial routes used to synthesise 1 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the transfer between Medicinal Chemistry and Research-API, collaboration provided a fit for purpose route for the kilo-scale synthesis of 1. Key aspects of the synthesis included (i) a safe and practical synthesis of a key nitropyridone intermediate 7 over four steps, (ii) a sequential regioselective chlorination to selectively functionalise 7 and (iii) use of a carbamate as a tethered carbonyl group, allowing an efficient regiospecific synthesis of 1.
Databáze:	OpenAIRE
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