Triethylamine → HCID 59850144, compound

Participants

Reaction Steps

5-Chloro-1-(4-piperidinyl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (0.228 mmol, 82 mg) was dissolved in dichloromethane (6 ml) and triethylamine (3 eq., 0.68 mmol, 50 microliters), tetrahydro-4H-pyran-4-one (7 eq., 1.6 mmol, 160 mg), sodium triacetoxyborohydride (7 eq., 1.6 mmol, 340 mg) were added at room temperature and the mixture was stirred at room temperature for 3 hours. More triethylamine (4 ml), tetrahydro-4H-pyran-4-one (3.5 eq, 0.8 mmol, 80 mg), sodium triacetoxyborohydride (3.5 eq, 0.8 mmol, 170 mg) were added at room temperature and the mixture was stirred at room temperature for two extra hours. The solvent was evaporated and the mixture was worked up with sodium bicarbonate and DCM. The solvent was evaporated and triethylamine (3 eq., 0.68 mmol, 50 microliters), tetrahydro-4H-pyran-4-one (7 eq, 1.6 mmol, 160 mg), sodium triacetoxyborohydride (7 eq, 1.59 mmol, 340 mg) and DCE (4 ml) were introduced and all mixed together for 1 hour at room temperature. The mixture was quenched with water/NaHCO3 (saturated solution) and DCM. The organic phase was separated from the aqueous phase (by hydrophobic filters) and the organic solvent was evaporated to afford the crude product that was purified by chromatography (MeOH—NH3-dichloromethane) to afford 5-chloro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-6-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one, 29 mg, 31%, M++H=403, which was subsequently converted into the mono-hydrochloride salt using HCl (2 eq. from a 1M solution of HCl in diethyl ether).

Provenance & Evidence