1,8-Naphthyridine → 2,6-Dichloro-5-fluoro-4-methylpyridine-3-carboxylic acid

Participants

Reaction Steps

The introduction of the methyl group on the 1,8-naphthyridine substrate was accomplished by the formation of the di-anion of 2,6-dichloro-5-fluoronicotinic acid, preferably with lithium diisopropylamide in THF between -70° C. and -50° C. The di-anion was quenched with iodomethane and the target acid 2, 6-dichloro-5-fluoro-4-methylnicotinic acid is obtained after acidification. The remaining portion of the naphthyridine nucleus was elaborated using previously developed methodology.

Provenance & Evidence