Synthesis of 2-chloro-6-methoxypyridine-4-carbonitrile (25F): to a solution of 2,6-dichloro-4-cyanopyridine (24, 2.0 g, 11.6 mmol) in methanol (20 mL) was added sodium methanolate (628 mg, 11.6 mmol, 1.0 equiv). The reaction mixture was heated and stirred at 60°C for 6 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. Water (300 mL) was added to the residue and the aqueous phase was extracted with ethyl acetate (3 × 25 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-chloro-6-methoxypyridine-4-carbonitrile (25F) as a clear viscous oil (1.95 g, quantitative yield).1H NMR (DMSO-d6, 200 MHz) δ 3.80 (s, 3H), 7.17 (s, 1H), 7.90 (s, 1H).
