N,2-Dimethoxy-N-methylpyridine-4-carboxamide → HCID 46183761, compound

Participants

Reaction Conditions

Reaction Steps

(2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methanone. A stirred mixture of 5-bromo-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-c]pyridin-2-amine (1.53 g, 4.28 mmol) in tetrahydrofuran (35 mL) was heated briefly with a heat gun under nitrogen until all solids dissolved. The resulting clear red solution was cooled with a dry ice acetone bath under nitrogen. n-Butyllithium (5.76 mL, 9.21 mmol, 1.6 M in hexane) was added dropwise slowly via syringe. During the addition the reaction became black-colored. After 40 min N,2-dimethoxy-N-methylisonicotinamide (4.61 mL, 9.21 mmol, 2 M in tetrahydrofuran) was added. The cold bath was removed and the resulting mixture was warmed to 0° C. over 15 min. After 30 min at 0° C., water (20 mL) was added and the resulting mixture was stirred vigorously at room temperature for 15 min. The resulting mixture was diluted with ethyl acetate and shaken in a separatory funnel. The layers were separated and the organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. The residue was dissolved in hot ethyl acetate and purified using flash chromatography (Biotage) (10-100% ethyl acetate in hexane). Fractions containing the desired product were combined and concentrated on a rotary evaporator down to ˜10 mL of ethyl acetate. Hexane (10 mL) was added. Solids were collected by vacuum filtration, washed with hexane, and dried under high vacuum to give the desired product (0.864 g, 2.090 mmol, 49% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.23 (s, 1H), 8.43 (d, J=5.47 Hz, 1H), 7.93 (dd, J=0.98, 8.79 Hz, 1H), 7.77 (dd, J=7.42, 8.98 Hz, 1H), 7.53-7.60 (m, 2H), 7.45-7.53 (m, 3H), 7.31 (dd, J=1.37, 5.27 Hz, 1H), 7.16 (s, 1H), 3.91 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ (ppm)-60.23 (s, 3F); MS (ESI) m/z 414.2 [M+1]+.

Provenance & Evidence