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

Author(s): Alexandra Kamlah, Franz Bracher*.

Journal Name: Letters in Organic Chemistry

Volume 16 , Issue 12 , 2019

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Graphical Abstract:


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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Article Details

VOLUME: 16
ISSUE: 12
Year: 2019
Page: [931 - 934]
Pages: 4
DOI: 10.2174/1570178616666181116110647
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