Hydrogen Bromide → HCID 447721, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester(12.5 gm, 0.0195 mole) in dichloromethane (170 mL) at 0° C., under argon, was slowly added 30% hydrogen bromide in acetic acid (170 mL). The solution was allowed to stir for 1.5 h at 0° C. and then diluted with diethyl ether (2.0 L). The resulting solid was filtered under argon, washed with diethyl ether (500 ml) and sucked dry under argon. The solid was then dissolved in dichloromethane (500 mL) and 10% aqueous sodium bicarbonate (500 mL) and mixed well. The dicholormethane solution was removed and the aqueous layer washed with dichloromethane (200 mL). The dichloromethane extracts were dried over anhydrous sodium sulfate, concentrated and the resulting foam (9.6 gm) chromatographed on silica using (dichloromethane/methanol/acetic acid/water--90/10/1/1). The resulting product containing fractions were washed with 10% aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated to give (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine (9.4 gm). The solid was dissolved in ethyl acetate (400 ml) filtered and then treated with a solution of hydrochloric acid/ethyl acetate (84 mL, 0.033 gm HCl/mL, 4 eq.). The resulting solid was filtered, dissolved in water (100 ml) and lyophilized to give (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine trihydrochloride (12.0 gm).

Provenance & Evidence