:
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.
