Potassium Iodide → 2-(2-(3-(((3-((2-methoxyethyl)amino)-3-oxopropyl)(methyl)amino)-methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-isonicotinamide

Participants

Reaction Conditions

Reaction Steps

Into a 8-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)-isonicotinamide 42a (250 mg, 0.31 mmol, 1.00 equiv, 80%) in N,N-dimethylformamide (6 mL), N-(2-methoxyethyl)-3-(methylamino)propanamide (185 mg, 1.04 mmol, 3.00 equiv, 90%), potassium carbonate (106 mg, 0.77 mmol, 2.00 equiv), and potassium iodide (32 mg, 0.19 mmol, 0.50 equiv). The resulting solution was stirred for 5 h at 60° C. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 1×20 mL of 10% sodium bicarbonate. The resulting mixture was washed with 1×20 mL of brine, dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with water:methanol (0.05% TFA) (10:90). The product was obtained as 63.7 mg (23%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.87 (d, J=6 Hz, 1H), 8.29 (m, 2H), 8.06 (m, 2H), 7.70 (m, 8H), 7.31 (d, J=9 Hz, 1H), 4.70 (s, 2H), 4.50 (m, 2H), 3.43 (m, 2H), 3.39 (m, 6H), 2.89 (s, 3H), 2.76 (m, 2H), 1.86 (m, 4H), 1.73 (m, 2H). MS (ES, m/z): 731 [M+H]+.

Provenance & Evidence