Dimethylamine → HCID 66823658, compound

Participants

Reaction Steps

Oxalyl chloride (508 mg, 4.00 mmol) was added to a solution of acid 159 (496 mg, 3.00 mmol) in dry dichloromethane (6 mL) and the mixture was stirred at room temperature for 40 min. The solution was then evaporated under reduced pressure at room temperature to give an oil which was dissolved in dry THF (5 mL) and added to a stirred mixture of compound 8a (668 mg, 2.00 mmol), triethylamine (0.84 mL, 6.00 mmol), and ITT (15 mL) at 0° C. After 1 h another batch of acid chloride preformed from oxalyl chloride (508 mg, 4.00 mmol) and acid 9 (496 mg, 3.00 mmol) was added and stirred further at 0° C. for another 30 min. A mixture of 40% NHMe2 (15.2 mL, 12.0 mmol) and DMA (10 mL) was added and the reaction mixture was stirred at 0° C. to room temperature for 19 h. Volatiles were evaporated under reduced pressure at 25° C. to give a brown oil which was stirred with 1% sodium carbonate solution (100 mL) at 0° C. for 30 min. The solid thus formed was collected by filtration, washed with water several times, and dried. Column chromatography of this material on silica gel eluting with dichloromethane to dichloromethane/MeOH (15:1) gave (2E)-N-[4-(3-bromo-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)-2-butenamide (161) (400 mg, 45%) as a yellow/orange solid, mp 163-166° C.; 1H NMR δ [(CD3)2SO] 10.96 (s, 1H), 10.33 (s, 1H), 9.02 (br s, 1H), 8.99 (br s, 1H), 8.63 (s, 1H), 8.24 (dd, J=6.4, 2.6 Hz, 1H), 7.92-7.84 (m, 1H), 7.44 (t, J=8.8 Hz, 1H), 6.87 (dt, J=15.5, 6.0 Hz, 1H), 6.52 (br d, J=15.5 Hz, 1H), 3.09 (dd, J=6.0, 1.2 Hz, 2H), 2.19 (s, 6H). Anal. Calcd for C19H18BrFN6O.MeOH: C, 50.33; H, 4.65; N, 17.61%. Found C, 50.38; H, 4.31; N, 17.86%.

Provenance & Evidence