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Synlett 2004(5): 0795-0798  
DOI: 10.1055/s-2004-820020
LETTER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Rapid Analogue Syntheses of 1-Methyl-3,5-diarylpyrazoles via Palladium-catalysed Coupling to 3(5)-Pyrazolyl Nonaflates

Sylvie Bourrain, Mark Ridgill, Ian Collins*
Department of Medicinal Chemistry, The Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Terlings Park, Harlow, Essex CM20 2QR, UK
Fax: +44(2087)707899; e-Mail: Ian.Collins@icr.ac.uk;
Further Information

Publication History

Received 14 November 2003
Publication Date:
04 March 2004 (online)

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Abstract

Regioselective rapid analogue syntheses of 1-methyl-3,5-diarylpyrazoles were developed, based on Pd-catalysed couplings to 1-methyl-3(5)-arylpyrazole nonaflates, which offered an advantage in hydrolytic stability over the corresponding triflates. The new bifunctional reagent 1-methyl-3-bromo-pyrazol-5-yl nonaflate underwent highly chemoselective Pd-catalysed couplings to the nonaflate, followed by Suzuki couplings to the bromide, allowing sequential, regioselective introduction of the two aryl substituents.

Key words

regioselectivity - chemoselectivity - palladium - cross-coupling - heterocycles

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1

New address: I. Collins, CRUK Centre for Cancer Therapeutics, The Institute for Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, U.K.