Ammonium formate → HCID 178457838, compound

Participants

Reaction Steps

To a solution of cis-4-(5-fluoro-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (123 mg, 0.380 mmol) in EtOH (5 mL) was added ammonium formate (240 mg, 3.80 mmol) and 10% palladium on carbon (40.5 mg, 0.038 mmol). The reaction was stirred at RT for 1 hour. The reaction mixture was filtered through Celite® brand filter aid (washed with MeOH), concentrated, and redissolved in DCM (10 mL). The solution was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford cis-4-(2-amino-5-fluorophenylamino)-N-isopropylcyclohexanecarboxamide as a purple oil that crystallized upon standing. The diamine was dissolved in THF (5 mL), cooled to 0° C., and 4-fluorobenzoyl isothiocyanate (97 mg, 0.534 mmol) was added. The reaction was stirred at 0° C. for 15 minutes, and then DIPEA (0.100 mL, 0.573 mmol) and EDC (110 mg, 0.573 mmol) were added, and the reaction was stirred for 1 hour at 60° C. The reaction mixture was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(6-fluoro-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as an off-white powder (137 mg, 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (d, J=6.7 Hz, 6H), 1.55-1.80 (m, 4H), 2.04-2.12 (m, 2H), 2.53 (br. s., 1H), 2.68-2.82 (m, 2H), 3.94-4.08 (m, 1H), 4.86 (br. s., 1H), 7.02-7.12 (m, 1H), 7.25 (dd, J=8.9 Hz, 8.9 Hz, 2H), 7.53 (dd, J=8.8, 4.9 Hz, 1H), 7.60 (dd, J=9.5, 1.9 Hz, 1H), 7.70 (d, J=7.4 Hz, 1H), 8.32 (dd, J=8.8, 5.9 Hz, 2H), 12.82 (s, 1H). MS, m/z (C24H26F2N4O2): calcd, 440.2. found, 440.7 [M+H].

Provenance & Evidence