1,2-Dichloroethane → N-[(5,6-dimethoxypyridin-2-yl)methyl]-6-(2-fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxamide

Participants

Reaction Steps

To a solution of 6-(2-fluorophenyl)-5′-methyl-3,3′-bipyridine-5-carboxylic acid hydrochloride (3-4, 3.0 g, 8.70 mmol) in dimethylformamide (43 mL) cooled to 0° C., was added EDC (2.67 g, 13.92 mmol) and HOBt (2.13 g, 13.92 mmol) followed by 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 1.90 g, 11.31 mmol) and N-methylmorpholine (5.74 mL, 52.2 mmol). The reaction was allowed to warm to room temperature and stir overnight. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water and brine, then stripped to dryness. The crude product was taken up in DMF/DMSO (30 mL, 1:1), filtered and purified via reverse phase chromatography (5→65% acetonitrile in water with 0.1% TFA buffer). The clean fractions were pooled, partitioned between ethyl acetate and 2M sodium carbonate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (3-5) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.99 (d, J=2.5 Hz, 1H), 8.74 (d, J=2 Hz, 1H) 8.53 (s, 1H), 8.34 (d, J=2.5 Hz, 1H), 7.77 (s, 1H), 7.66 (m, 1H), 7.31 (m, 1H), 7.21 (t, J=14.6 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.92 (t, J=18.3 Hz, 1H), 6.73 (d, J=7.8 Hz, 1H), 6.46 (m, 1H), 4.44 (d, J=5 Hz, 2H), 3.87 (s, 3H), 3.81(s, 3H), 2.45 (s, 3H). HRMS [M+H] C26H23FN4O3 calc'd 459.1827, found 459.1830.

Provenance & Evidence