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Synthesis 2009(5): 721-730  
DOI: 10.1055/s-0028-1083354
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 5,7-Dichloro-6-azaindoles and Functionalization via a Highly Selective Lithium-Chlorine Exchange

Nicolas Lachance*, Louis-Philippe Bonhomme-Beaulieu, Pascal Joly
Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe Claire-Dorval, QC, H9R 4P8, Canada
Fax: +1(514)4284900; e-Mail: nicolas_lachance@merck.com;
Further Information

Publication History

Received 8 October 2008
Publication Date:
02 February 2009 (online)

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Abstract

The synthesis of a range of novel 5,7-dichloro-6-azaindoles through the use of a Fischer cyclization with pyridine hydrochloride in N-methylpyrrolidin-2-one is described. Dichloro-6-azaindoles are versatile compounds that can be selectively substituted through a palladium-catalyzed cross-coupling reaction or a high-yielding lithium-chlorine exchange.

Key words

azaindole - pyrrolopyridine - Fischer cyclizations - metalations - palladium

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12

The use of a condenser is not recommended.

13

Typically, aminopyridine 1 was isolated in less than 5%.

22

Starting material 6 was observed in less than 5% on the ¹H NMR of the unpurified reaction mixture.