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TitleDevelopment 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
Publication TypeJournal Article
Year of Publication2011
AuthorsAdam, F.M., Bish G., Calo F., Carr C.L., Castro N., Hay D., Hodgson P.B., Jones P., Knight C.J., Paradowski M., Parsons G.C., Proctor K.J.W., Pryde D.C., Rota F., Smith M.C., Smith N., Tran T.-D., Hitchin J., and Dixon R.
JournalOrganic Process Research and Development
Pagination788 - 796
Date Published2011
ISSN10836160 (ISSN)
KeywordsBulk materials, Carbonyl groups, Chlorination, Large scale synthesis, Medicinal chemistry, Regio-selective, Regioselectivity, Regiospecific synthesis, Toll-like receptors
AbstractThe 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. © 2011 American Chemical Society.

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