Triethylamine → N-{(2S)-2-(4-Fluorophenyl)-4-[3-(4-fluoropiperidin-1-yl)azetidin-1-yl]butyl}-N-methyl-3,5-bis(trifluoromethyl)benzamide

Participants

Reaction Steps

N-[(2S)-2-(4-Fluorophenyl)-4-oxobutyl]-N-methyl-3,5-bis(trifluoromethyl)benzamide (see Method 20; 189 mg, 0.43 mmol), 1-azetidin-3-yl-4-fluoropiperidine dihydrochloride (see WO 97/27185; 139 mg, 0.56 mmol) and triethylamine (154 mg, 1.52 mmol) were dissolved in methanol (10 mL). A methanol solution (5 mL) of sodium cyanoborohydride (191 mg, 3.04 mmol) and zinc chloride (178 mg, 1.30 mmol) was added and the mixture stirred at room temperature for 20 minutes. The solvent was removed by evaporation and the residue partitioned between water and ethyl acetate. The organic solution was washed with aqueous NaHCO3 (1 M) and then brine. The solution was dried over Na2SO4 and then the solvent was removed by evaporation. The product was chromatographed on silica gel using a gradient of methanol and CH2Cl2 (0% MeOH-20% MeOH). There was obtained 120 mg (48%) of the title compound as a gum. 1H NMR (500 MHz, CDCl3): 1.4-1.9 (cm, 6H), 2.1-2.4 (cm, 6H), 2.6-3.5 (cm, 10H), 3.6-3.8 (m, 1H), 4.6-4.8 (bd, 1H), 6.8-7.5 (m, 6H), 7.8 (s, 1H); LCMS: m/z 578 (M+1)+.

Provenance & Evidence