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Synlett 2006(3): 0379-0382  
DOI: 10.1055/s-2006-926229
LETTER
© Georg Thieme Verlag Stuttgart · New York

A One-Pot Method for the Synthesis of Naphthyridines via Modified Friedländer Reaction

Pavel Zhichkin*, Catherine M. Cillo Beer, W. Martin Rennells, David J. Fairfax
Albany Molecular Research Inc., 21 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA
Fax: +1(518)8674381; e-Mail: PavelZ@albmolecular.com;
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Publication History

Received 12 October 2005
Publication Date:
06 February 2006 (online)

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Abstract

A one-pot method for the preparation of 1,8-naphthyridine derivatives is reported. The method involves the dimetalation of an appropriate N-2-pyridylpivalamide or tert-butylcarbamate ­followed by reaction with a β-dimethylamino or β-alkoxyacrolein derivative. This method is also applicable to 1,6-naphthyridines.

Key words

pyridines - directed ortho-metalation - cyclization - naphthyridines

    References and Notes

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9

For example, Hamada8b reported preparation of 4-methyl-1,8-naphthyridine in 38% yield. We repeatedly obtained 10-17% yield following his procedure, which is consistent with the yield reported by Paudler and Kress (17%).4b