Ammonium Chloride → (R)-1-(1-acryloylpiperidin-3-yl)-2-(3-(trifluoromethyl)benzamido)-1H-benzo[d]imidazole-5-carboxamide

Participants

Reaction Steps

To a solution of Example 18 (50 mg, 0.1 mmol) and NH4Cl (7 mg, 0.11 mmol) in DMF (4 mL) were added hydroxybenzotriazole (15 mg, 0.11 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (21 mg, 0.11 mmol) and the mixture was stirred at room temperature for 14 h (completion of reaction monitored by TLC). The mixture was diluted with water and extracted with CH2Cl2 (3×20 mL). The combined organic phase was washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by column chromatography (10% MeOH in CH2Cl2) to afford the title compound (Example 19). 1H-NMR (400 MHz, DMSO-d6): ∂ 13.0 (br s, 1H), 8.47 (d, J=7.2 Hz, 2H), 8.06-7.73 (m, 6H), 7.35 (s, 1H), 6.92-6.79 (m, 1H), 6.17-6.13 (m, 1H), 5.75-5.60 (m, 1H), 4.81-4.60 (m, 2H), 4.29-4.10 (m, 1H), 2.84-2.72 (m, 1H), 2.17-1.94 (m, 3H), 1.65 (s, 2H); MS calculated for C24H23F3N5O3 (M+H+) 486.17. found 486.3.

Provenance & Evidence