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

HRID 2064215노트

반응식

HRID 2064215 반응식
Cl.[CH3:2][C:3]1[C:4]([C:19]([F:22])([F:21])[F:20])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:7]=2[CH:18]=1.[O:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(N(CC)CC)C>[CH3:2][C:3]1[C:4]([C:19]([F:20])([F:22])[F:21])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:13][CH2:14][N:15]([CH:26]4[CH2:27][CH2:28][O:23][CH2:24][CH2:25]4)[CH2:16][CH2:17]3)[C:7]=2[CH:18]=1

참가 물질

6

반응물 3

HCID 121599Tetrahydro-4H-pyran-4-one2회HCID 5049666Sodium triacetoxyborohydride2회HCID 69171370HCID 69171370, 화합물

생성물 1

HCID 160711346-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매2회HCID 8471Triethylamine용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-ea2cdb18ae2d46b4b5644911bb00abc4
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288412B2

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