反应详情

6-Methyl-1-(4-piperidinyl)-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D60) (2.2 mmol), was dissolved in 1,2-dichloroethane (50 ml) and triethylamine (7 ml), tetrahydro-4H-pyran-4-one (7 eq., 15.4 mmol, 1.4 ml), sodium triacetoxyborohydride (7 eq., ˜3.2 g) were added in that order at room temperature and the mixture was stirred at room temperature for 2 hours. Reaction mixture was quenched with 10 ml of NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product. The crude obtained was dissolved again in 1,2-dichloroethane (50 ml) and triethylamine (7 ml), tetrahydro-4H-pyran-4-one (7 eq., 15.4 mmol, 1.4 ml), sodium triacetoxyborohydride (7 eq., ˜3.2 g) were added at room temperature and the mixture was stirred at room temperature for three hours. Reaction mixture was quenched with 10 ml of NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product that was purified by chromatography (methanol-NH3-dichloromethane) to afford 6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one, 240 mg, 30%, M++H=384, which was subsequently converted into the hydrochloride salt using HCl solution (1M in diethyl ether, 2 eq).

1. customReaction mixture
2. customwas quenched with 10 ml of NaHCO3 (saturated solution)
3. additiondiluted with dichloromethane
4. customthe two phases were separated
5. customthe organic solvent was evaporated
6. customto afford the crude product
7. customThe crude obtained
8. stirringthe mixture was stirred at room temperature for three hours
9. customReaction mixture
10. customwas quenched with 10 ml of NaHCO3 (saturated solution)
11. additiondiluted with dichloromethane
12. customthe two phases were separated
13. customthe organic solvent was evaporated
14. customto afford the crude product that
15. customwas purified by chromatography (methanol-NH3-dichloromethane)