Toluene → Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)-isonicotinate (2.00 g, 5.48 mmol), 3-fluoro-4-methoxyphenylboronic acid (0.931 g, 5.48 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.316 g, 0.274 mmol) in a flask was flushed with nitrogen. Toluene (25 mL), MeOH (5 mL) and a 2 N aqueous solution of sodium carbonate (6.2 mL, 12.4 mmol) was added and the reaction was heated in a 125° C. oil bath for 2 hr. The reaction was partitioned between EtOAc and a saturated aqueous solution of sodium bicarbonate. The organic phase was separated and washed with a saturated aqueous solution of sodium bicarbonate and brine. It was dried with sodium sulfate and the solvents removed. Flash silica gel chromatography (elution with hexane containing 10% EtOAc) afforded methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate (1.8 g). MS (ESI) m/z 411.2 (M+H). 1H NMR (CDCl3) δ ppm 8.18 (2H, d, J=8.24 Hz), 8.06 (1H, s), 7.81 (2H, d, J=8.24 Hz), 7.74 (1H, dd, J=12.97, 1.98 Hz), 7.68 (1H, d, J=8.85 Hz), 6.99 (1H, t, J=8.70 Hz), 5.98 (2H, br. s.), 3.97 (3H, s), 3.96 (3H, s), 3.92 (3H, s).

Provenance & Evidence