Dichloromethane → 4-[5-(4-Cyanobenzyl)imidazol-1-ylmethyl]-1-phenyl-2-piperidinone hydrochloride

Participants

Reaction Conditions

Reaction Steps

The product from Step D (0.205 g, 1.00 mmol) and the product from Step E (0.425 g, 1.00 mmol) were dissolved in methylene chloride (2 mL) containing diisopropylethylamine (0.191 mL, 1.10 mmol) and cooled to -78° C. under argon. Trifluoromethane sulfonic anhydride was added (0.173 mL, 1.03 mmol) and the reaction stirred at -78° C. for 1 h, followed by warming to room temperature over 2 h. The solvent was evaporated, and the residue dissolved in methanol. After refluxing for 30 min, the methanol was evaporated, and the residue is partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase is washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The free base product was chromatographed on silica gel with 3% methanol in methylene chloride follwed by 7% 9:1 methanol:ammonium hydroxide in methylene chloride. The title compound was obtained after conversion to the hydrochloride salt. FAB ms: 371 (M+1). Anal. Calc for C23H22N4O·HCl·H2O, C, 65.01; H, 5.93; N,13.19. Found: C, 64.77; H, 5.89; N, 13.11.

Provenance & Evidence