Piperidine → HCID 178501181, compound

Participants

Reaction Conditions

Reaction Steps

cis-Methyl 4-(2-(4-fluorobenzamido)-6-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (0.19 g, 0.447 mmol) was suspended in DCM (4.47 mL) and cooled to 0° C. under a nitrogen atmosphere. To this mixture was added thionyl chloride (0.652 mL, 8.93 mmol) dropwise, and the reaction mixture was stirred at 0° C. for 1 hour. The ice bath was removed, and the mixture was stirred at RT for 2 hours. The reaction mixture was concentrated under reduced pressure and dried under high vacuum to afford a yellow foam. The foam was suspended in 2 mL of DMSO and treated with piperidine (0.441 mL, 4.47 mmol) followed by TEA (0.248 mL, 1.786 mmol). The resulting mixture was stirred at RT for 2 hours. The reaction mixture was diluted with DCM (2-20 mL) and washed with water (2-20 mL). The organic layer was collected, dried over sodium sulfate, and concentrated. The residue was purified by HPLC (10-70% ACN/H2O; 0.1% TFA) to afford cis-methyl 4-((E)-2-(4-fluorobenzoylimino)-6-(piperidin-1-ylmethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate as a white solid (150 mg, 68.2% yield). MS m/z=493.2 [M+H]. Calc'd for C28H33FN4O3: 492.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.45 (m, 2H) 1.44-1.61 (m, 4H) 1.66-1.93 (m, 4H) 2.19-2.32 (m, 2H) 2.29-2.43 (m, 4H) 2.53-2.65 (m, 2H) 2.81-2.94 (m, 1H) 3.51 (s, 2H) 3.78 (s, 3H) 4.57-4.89 (m, 1H) 7.10-7.18 (m, 1H) 7.21-7.32 (m, 2H) 7.42-7.52 (m, 2H) 8.02-8.48 (m, 2H) 12.78 (s, 1H).

Provenance & Evidence