반응 #534965

반응 방정식

sodium triacetoxyborohydride

sodium triacetoxyborohydride

triethylamine

tetrahydro-4H-pyran-4-one

triethylamine

tetrahydro-4H-pyran-4-one

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

→

4-fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

용매

1,2-dichloroethane

dichloromethane

반응 조건

후처리

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature for one overnight
2. 2
   기타Reaction mixture
3. 3
   기타was quenched with NaHCO3 (saturated solution)
4. 4
   workup.ADDITIONdiluted with dichloromethane
5. 5
   기타the two phases were separated
6. 6
   기타the organic solvent was evaporated
7. 7
   기타to afford the crude product
8. 8
   기타The crude obtained
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature for 10 minutes
10. 10
    workup.STIRRINGthe mixture was stirred at room temperature for 3 extra hours
11. 11
    기타Reaction mixture
12. 12
    기타was quenched with NaHCO3 (saturated solution)
13. 13
    workup.ADDITIONdiluted with dichloromethane
14. 14
    기타the two phases were separated
15. 15
    기타the organic solvent was evaporated
16. 16
    기타to afford the crude product that
17. 17
    기타was purified by chromatography (methanol-NH3-dichloromethane)

실험 절차

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D5) (0.072 mmol, 21 mg) was dissolved in dichloromethane (2 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was added at room temperature and the mixture was stirred at room temperature for one overnight. Reaction mixture was quenched with 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 in 1,2-dichloroethane (3 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added again and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was subsequently added at room temperature and the mixture was stirred at room temperature for 3 extra hours. Reaction mixture was quenched with 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 4-fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 10 mg, 42%, M++H=334, which was converted to the HCl salt using 1M HCl in diethyl ether.

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