Hydrochloric Acid → 6-Methyl-5-[(1-methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064219노트

반응식

HRID 2064219 반응식
[CH3:1][C:2]1[C:3]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:6]=2[CH:17]=1.[O:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[ClH:52]>ClCCl.CO>[ClH:52].[CH3:1][C:2]1[C:3]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:12][CH2:13][N:14]([CH:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)[CH2:15][CH2:16]3)[C:6]=2[CH:17]=1

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 598501546-Methyl-5-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one

생성물 1

HCID 691282956-Methyl-5-[(1-methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매3회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9e66d5ead34549a3a35c159fcb3edd8d
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288412B2

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