Triethylamine → 5,6-dimethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

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Reaction Steps

5,6-Dimethyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D32) (330 mg, 0.6 mmol) as suspension in dichloromethane (10 ml) was treated under argon at room temperature with triethylamine (4.2 mmol, 425 mg, 7 eq) and tetrahydro-4H-pyran-4-one (4.2 mmol, 420 mg, 7 eq). Then sodium triacetoxyborohydride (4.2 mmol, 890 mg, 7 eq) was added and the mixture was stirred overnight. Then 7 eq of fresh borohydride and the ketone were added again and stirred for 2 h 15 min. Methanol (3 mL) was added and stirred for 2 h. 7 eq of borohydride and the ketone were added again and stirred for 3.5 h. Then sodium cyanoborohydride (3 mmol, 188 mg, 5 eq) was added and the mixture was allowed to stand overnight. The mixture was loaded on an SCX cartridge, washed with methanol and eluted with 2M ammonia in methanol and dichloromethane. The eluate was concentrated under reduced pressure and chromatographed to give 5,6-dimethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one as a white solid, which was transformed into the corresponding HCl salt. M+H=330.10,

Provenance & Evidence