Reaction Steps
To a solution of TEA (0.091 mL, 0.654 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (100 mg, 0.654 mmol) in DCM (2 mL) was added 4-fluorobenzoyl chloride (0.064 mL, 0.545 mmol) dropwise, and the reaction was stirred at RT for 30 minutes. After 30 minutes, the suspension was added to a solution of cis-4-(2-amino-6-morpholino-1H-benzo[d]imidazol-1-yl)-N-isopropylcyclohexanecarboxamide (210 mg, 0.545 mmol) in DCM (5 mL). The reaction was stirred at RT. After 3 days, the reaction mixture was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-10% MeOH in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-morpholino-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a grey powder (95 mg, 34.4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (s, 1H), 8.29 (dd, J=6.1, 8.8 Hz, 2H), 7.73 (d, J=7.5 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J=8.7 Hz, 1H), 7.24 (dd, J=8.8 Hz, 8.8 Hz, 2H), 6.87, (d, J=8.8 Hz, 1H), 4.94 (brs, 1H), 3.90-3.99 (m, 1H), 3.78 (t, J=4.7 Hz, 4H), 3.18 (t, J=4.8 Hz, 4H), 2.74-2.84 (m, 2H), 2.55 (brs, 1H), 2.03-2.11 (m, 2H), 1.67-1.78 (m, 2H), 1.54-1.63 (m, 2H), 1.10 (d, J=6.5 Hz, 6H). MS, m/z (C28H34FN5O3): calcd, 507.3. found, 507.9 [M+H].
