1,2-Dichloroethane → N-[(5,6-dimethoxy-2-pyridinyl)methyl]-2-(3-fluorophenyl)-5-(5-methyl-3-pyridinyl)pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-(3-fluorophenyl)-5′-methyl-3,3′-bipyridine-5-carboxylic acid hydrochloride (3-6, prepared by the method described above for the preparation of 3-4, 2.5 g, 7.25 mmol) in dimethylformamide (36 mL) cooled to 0° C., was added EDC (1.95 g, 10.2 mmol) and HOBt (1.67 g, 10.9 mmol) followed by 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 1.46 g, 8.7 mmol) and N-methylmorpholine (4.78 mL, 43.5 mmol). The reaction stirred for 15 minutes and then was allowed to warm to room temperature. After 3.5 hours the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water and brine, dried over Na2SO4/MgSO4, filtered and stripped to dryness. The crude product was recrystallized from chloroform/ethyl ether to afford the title compound (3-7) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.96 (d, J=2.2 Hz, 1H), 8.72 (d, J=1.7 Hz, 1H), 8.56 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 7.76 (s, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.40 (d, J=9.5 Hz, 1H), 7.24 (m, 1H), 6.99 (m, 2H), 6.74 (d, J=7.8 Hz, 1H), 6.33 (m, 1H), 4.44 (d, J=5.4 Hz, 2H), 3.88 (s, 3H), 3.76(s, 3H), 2.45 (s, 3H). HRMS [M+H] C26H23FN4O3 calc'd 459.1827, found 459.1832.

Provenance & Evidence