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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Letter Article

A Short Synthesis of the Plant Alkaloid 4-Methyl-2,6-naphthyridine

Author(s): Alexandra Kamlah and Franz Bracher*

Volume 16, Issue 12, 2019

Page: [931 - 934] Pages: 4

DOI: 10.2174/1570178616666181116110647

Price: $65

Abstract

A new synthesis of the 2,6-naphthyridine alkaloid 4-methyl-2,6-naphthyridine from Antirrhinum majus has been developed. Key steps are a regioselective oxidation of 3-bromo-4,5- dimethylpyridine to the corresponding 4-formyl derivative, and the annulation of the second pyridine ring by Suzuki-Miyaura cross-coupling using (E)-2-ethoxyvinylboronic acid pinacol ester as a masked acetaldehyde equivalent. This protocol gives the alkaloid in four steps starting from commercially available 3,4-dimethylpyridine in 15% overall yield. This annulation protocol should be useful for the synthesis of other condensed pyridines as well.

Keywords: Alkaloid, naphthyridine, oxidation, annulation, Suzuki-Miyaura coupling, enol ether.

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