Methyl 6-formylpyridine-3-carboxylate → HCID 67980582, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 6-formylnicotinate (0.200 g, 1.21 mmol) in tetrahydrofuran (8 mL) containing activated molecular sieves was added 4′-(trifluoromethyl)biphenyl-4-amine (316 mg, 1.33 mmol). The reaction was heated to 90° C. and stirred overnight. The reaction was concentrated to dryness and the residue was dissolved in tetrahydrofuran (8 mL). The solution was cooled to 0° C. Zinc chloride (3.52 mL, 1M in diethyl ether, 3.52 mmol) was added, followed by isobutylmagnesium bromide (1.47 mL, 2.0M in THF, 3.52 mmol). The reaction was stirred at 0° C. for 2 hours. The reaction was quenched with saturated ammonium chloride. The mixture was diluted with dichloromethane and water. The layers were separated and the aqueous was extracted again with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by column chromatography gave methyl 6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-ylamino)butyl)nicotinate (210 mg, 39%) as a yellow oil. 1H NMR (400 MHz, CD3OD, δ): 9.09 (s, 1H), 8.31 (d, 1H), 7.72-7.57 (m, 5H), 7.41 (d, 2H), 6.65 (d, 2H), 4.61-4.52 (m, 1H), 3.94 (s, 3H), 1.92-1.73 (m, 2H), 1.1.72-1.61 (m, 1H), 1.05 (d, 3H), 0.91 (d, 3H).

Provenance & Evidence