A Scalable Synthesis of a 1,7-Naphthyridine Derivative, a PDE-4 Inhibitor

A six-step synthesis of a 4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]- trans -cyclohexanecarboxylic acid with an overall yield of 27% starting from 2-cyano-3-methylpyridine, cyclohexane-1,4-dicarboxylic acid dimethyl ester, and 3-fluorophenylboronic acid is described. The trans stereochemistry in the cyclohexane moiety was achieved through a series of equilibration steps at different stages of the synthesis.