Dichloromethane → 3-Bromo-N-{(2S)-2-(4-fluorophenyl)-4-[3-(6-oxooctahydro-2H-pyrido[1,2-a]pyrazin-2-yl)azetidin-1-yl]butyl}-N-methyl-5-(trifluoromethyl)benzamide dihydrochloride

Participants

Reaction Steps

To a solution of 3-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see Method 3; 100 mg, 0.22 mmol) and 2-azetidin-3-yloctahydro-6H-pyrido[1,2-a]pyrazin-6-one (see Method 4; 58 mg, 0.28 mmol) in methylene chloride (3 mL) were added DIPEA (116 mg, 0.90 mmol) and sodium triacetoxyborohydride (66 mg, 0.31 mmol). The reaction mixture was stirred under nitrogen at RT for 2 h. The solution was washed twice with aqueous NaHCO3 and the organic solvent dried by a phase separator column. The solvent was removed by evaporation and the product was purified by chromatography on silica gel (ammonia saturated methanol-methylene chloride 1% to 10%). The right fractions were combined and concentrated on a rotavapor and the residue was then dissolved in a small amount of acetonitrile/water. A few drops of diluted hydrochloric acid were added and the water was removed by freeze-drying. There was obtained 114 mg (70%) of the title compound as a white solid. 1H NMR (500 MHz, CDCl3): 1.4-3.8 (cm, 27H), 4.6 (d, 1H), 6.8-7.4 (cm, 6H), 7.7 (s, 1H); LCMS: m/z 640 (M+1)+.

Provenance & Evidence