Methanol → 3-Methyl-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester

In a 250 mL pear-shaped flask, N-phenyl-N-(3-propionyl-6-trifluoromethyl-pyridin-2-yl)-oxalamic acid methyl ester (1.74 g, 4.58 mmol) was combined with methanol (25 mL) to give a yellow solution. Potassium carbonate (3.8 g, 27.5 mmol) was added and the reaction mixture was refluxed for 2 hr. The reaction mixture was cooled, diluted with H2O (75 mL) and extracted with ethyl acetate (3×75 mL). The organic layers were combined, washed with brine (1×50 mL), dried over MgSO4, and concentrated in vacuo to give 1.7 g crude product as a yellow solid. The crude material was purified by flash chromatography (silica gel, 120 g, 20% to 50% ethyl acetate in hexanes) to give 3-methyl-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (0.89 g, 3.7%) as an off-white solid. 1H NMR (DMSO-d6) δ ppm 8.84 (d, J=8.2 Hz, 1H) 7.91 (d, J=8.2 Hz, 1H) 7.32-7.70 (m, 5H) 3.51 (s, 3H) 2.01 (s, 3H). MS calcd. for C18H13F3N2O3 [(M+H)+] 363.0, obsd. 363.0.