反应详情

A solution of 6-methyl-5-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D77) (assumed 0.14 mmol—crude material) in dichloromethane (2 mL) was treated with tetrahydro-4H-pyran-4-one (1.4 mmol, 140 mg, 10 eq) and triethylamine (1.4 mmol, 141.7 mg, 10 eq) at room temperature under argon, then sodium triacetoxyborohydride (1.4 mmol, 296.8 mg, 10 eq) was added and the mixture was allowed to stir for 3 h and to stand overnight. The mixture was diluted with dichloromethane and treated with aqueous sodium hydroxide so that the pH was maintained around 12. The aqueous phase was extracted, the organics were combined, washed with aqueous sodium hydroxide solution (pH˜12), dried and concentrated under reduced pressure. The residue was purified by chromatography (methanol/dichloromethane, 0-10% 5CV) to give a gum, which was dissolved in dichloromethane and methanol, treated with ethereal hydrogen chloride, then concentrated under reduced pressure to give the title compound as its hydrochloride salt-white solid (0.071 mmol, 29 mg, 51% yield). M+H 374.1.

1. waitto stand overnight
2. temperaturewas maintained around 12
3. extractionThe aqueous phase was extracted
4. washwashed with aqueous sodium hydroxide solution (pH˜12)
5. customdried
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by chromatography (methanol/dichloromethane, 0-10% 5CV)
8. customto give a gum, which
9. concentrationconcentrated under reduced pressure