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

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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• 3For example, preparation of 2-methyl-1,8-naphthyridine from 2-amino-6-methylpyridine via EMME synthesis required five steps and afforded only 22% overall yield, see:
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9

For example, Hamada^8b 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