Reaction Steps
To a 0° C. cooled solution of (E)-4-fluoro-N-(6-(hydroxymethyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (100 mg, 0.221 mmol) in DCM (2.5 mL) was added thionyl chloride (0.081 mL, 1.105 mmol) dropwise, and the reaction was stirred at 0° C. for 30 minutes. The solvent was removed at reduced pressure, and the residue was dried in vacuo for 5 minutes. The residue was resuspended in ACN (2 mL), cooled to 0° C., and 1H-1,2,4-triazole (153 mg, 2.210 mmol), potassium carbonate (305 mg, 2.210 mmol), and sodium iodide (33.1 mg, 0.221 mmol) were added. The reaction was stirred at RT. After 16 hours, the solvent was removed, and the residue was partitioned between water and DCM. The aqueous layer was neutralized (pH approximately 8) with 2 N aqueous HCl and extracted with DCM. The combined organic layers were concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-10% MeOH in DCM, to provide (E)-N-(6-((1H-1,2,4-triazol-1-yl)methyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-fluorobenzamide (35 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.80 (s, 1H), 8.69 (s, 1H), 8.33 (dd, J=6.0, 8.6 Hz, 2H), 7.95 (s, 1H), 7.76 (s, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.24 (dd, J=8.8 Hz, 8.8 Hz, 2H), 7.15, (d, J=8.2 Hz, 1H), 5.45 (s, 2H), 4.78 (brs, 1H), 4.02-4.14 (m, 1H), 2.74-2.85 (m, 2H), 2.54 (brs, 1H), 2.10-2.13 (d, J=12.8 Hz, 2H), 1.69-1.76 (m, 2H), 1.59-1.62 (m, 2H), 1.11 (d, J=6.6 Hz, 6H). MS, m/z (C27H30FN7O2): calcd, 503.2; found, 503.7 [M+H].
