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

Organic Process Research and Development

Volumn 15, Issue 4, 2011, Pages 788-796

  Adam, Fiona M ^a   Bish, Gerwyn ^a   Calo, Frederick ^a   Carr, Christopher L ^a   Castro, Nieves ^a   Hay, Duncan ^a   Hodgson, Paul B ^a   Jones, Peter ^a   Knight, Craig J ^a   Paradowski, Michael ^a   Parsons, Gemma C ^a   Proctor, Katie J W ^a   Pryde, David C ^a   Rota, Filippo ^a   Smith, Mya C ^a   Smith, Nicholas ^a   Tran, Thien Duc ^a   Hitchin, James ^b   Dixon, Rachel ^b  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^b SRG   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BULK MATERIALS; CARBONYL GROUPS; LARGE SCALE SYNTHESIS; MEDICINAL CHEMISTRY; REGIO-SELECTIVE; REGIOSPECIFIC SYNTHESIS; TOLL-LIKE RECEPTORS;

CHLORINATION;

REGIOSELECTIVITY;

EID: 79960492508     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op200021a     Document Type: Article

References (12)

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2. Pryde, D. C., Tran, T. D., Jones, P., Parsons, G. C., Bish, G., Adam, F. M., Smith, M. C., Middleton, D. S., Smith, N. S., Calo, F., Hay, D., Paradowski, M., Proctor, K. J. W., Parkinson, T., Laxton, C., Fox, D. N. A., Horscroft, N. J., Ciaramella, G., Jones, H. M., Duckworth, J., Benson, N., Harrison, A., and Webster, R. Med. Chem. Commun., 2011, 2 (3), 185.
3. Substoichiometric copper sulphate-mediated displacements of poorly activated 2-chloropyridines with simple amines have been sparsely reported in the literature. For example: Maurel, J., Bonnaud, B., Ribet, J., and Vahcer, B. Patent Application WO 2002/064585 A1, 2002.
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8. An acid-catalysed cyclisation to 1,3-dihydro-2 H -imidazo[4,5-c ] pyridin-2-ones via a carbamate strategy had been recently reported in the literature: Fiksdahl, A.; Bakke, J. M.; Holt, J. J. Heterocycl. Chem. 2006, 43, 787
9. 3 have failed and higher temperatures are required: Robison, M. M. J. Am. Chem. Soc. 1958, 80, 5481
10. High yields of aromatic hydroxylamine can be obtained by hydrogenation over platinum in lower alcohols containing 1-2% dimethylsulfoxide: Rylander, P. Aldrichimica Acta 1979, 12, 53 Palladium catalysis has been used with hydrazine or phosphinic acid as the reductant: Rondestvedt, C. S., Jr.; Johnson, T. A. Synthesis 1977, 850
11. Entwistle, I. D.; Gilkerson, T.; Johnstone, R. A. W.; Telford, R. P. Tetrahedron 1978, 34, 213
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