Potassium Iodide → (S)-2-(2-(3-((3-Acetamidopyrrolidin-1-yl)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

Participants

Reaction Conditions

Reaction Steps

Into a 50-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (100 mg, 0.15 mmol, 1.00 equiv) in N,N-dimethylformamide (10 mL), potassium carbonate (62 mg, 0.45 mmol, 2.92 equiv), potassium iodide (5 mg, 0.03 mmol, 0.20 equiv), and (S)—N-(pyrrolidin-3-yl)acetamide (38.5 mg, 0.30 mmol, 1.96 equiv). The resulting solution was stirred for 3 h at 70° C. in an oil bath. The resulting solution was diluted with 150 mL of water. The resulting solution was extracted with 4×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×200 mL of brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 38.7 mg (24%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.921-8.938 (d, J=5.1 Hz, 1H), 8.623-8.653 (d, J=9.0 Hz, 1H), 8.429 (s, 1H), 8.070-8.138 (m, 3H), 7.859-7.881 (m, 1H), 7.536-7.799 (m, 7H), 4.719 (s, 2H), 4.526-4.593 (m, 2H), 4.377-7.420 (m, 1H), 3.612-3.648 (t, J=5.4 Hz, 4H), 2.500 (m, 1H), 2.007-2.022 (m, 5H), 1.946 (s, 3H), 1.803-1.818 (m, 2H). MS (ES, m/z): 699 [M+H]+.

Provenance & Evidence