Cesium fluoride → Methyl 3-amino-6-bromo-6'-methoxy-2,3'-bipyridine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-amino-2,6-dibromoisonicotinate (300 mg, 0.97 mmol), 6-methoxypyridin-3-ylboronic acid (163 mg, 1.07 mmol), tetrakis(triphenylphosphine)-palladium(0) (56 mg, 0.048 mmol) and cesium fluoride (323 mg, 2.13 mmol) in a vial was flushed with nitrogen. Dimethoxyethane (4.8 mL) was added and the reaction was heated at 80° C. overnight. It was partitioned between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic phase was separated, washed with brine, and dried with sodium sulfate. The solvent removed and the major product was isolated by silica gel radial chromatography (step gradient with hexane containing 5 to 20% ethyl acetate). This gave methyl 3-amino-6-bromo-6′-methoxy-2,3′-bipyridine-4-carboxylate (165 mg, 50% yield) as a yellow solid. MS (ESI) m/z 338 and 340 (M+H). 1H NMR (CDCl3) δ ppm 8.45 (1H, d, J=2.14 Hz), 7.82 (1H, dd, J=8.55, 2.44 Hz), 7.80 (1H, s), 6.85 (1H, d, J=8.55 Hz), 5.91 (2H, br. s.), 3.97 (3H, s), 3.92 (3H, s).

Provenance & Evidence