Pyridine → N1-methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)phenyl)isophthalamide

Participants

Reaction Steps

Into a 50-mL round bottom flask, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)benzamide (287 mg, 0.64 mmol, 1.00 equiv) in dichloromethane (3 mL), and pyridine (406 mg, 5.13 mmol, 8.00 equiv). This was followed by dropwise addition of a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride (300 mg, 0.97 mmol, 1.50 equiv) in dichloromethane (2 mL) with stirring. The resulting solution was stirred for 1 h at room temperature, then diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 1×20 mL of hydrogen chloride (1 N) and 2×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (300 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 120 mg (20%) of as a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 12.89 (s, 1H), 10.93 (s, 1H), 9.79 (s, 1H), 8.26 (m, 2H), 8.00 (m, 4H), 7.69 (m, 4H), 7.53 (s, 1H), 7.27 (d, J=8.7 Hz, 1H), 4.01 (s, 2H), 3.85 (s, 2H), 3.63 (s, 4H), 3.44 (s, 2H), 3.17 (m, 6H), 2.99 (s, 3H), 1.70 (m, 6H). MS (ES, m/z): 721 [M+H]+.

Provenance & Evidence