1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 2405953노트

반응식

HRID 2405953 반응식
[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([OH:5])=O.CCN=C=NCCCN(C)C.C1C=CC2[N:42]([OH:43])N=NC=2C=1.[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1NO>C(Cl)Cl.O>[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([NH:42][O:43][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)=[O:5]

참가 물질

7

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 13168123Tetrahydropyranyl hydroxylamineHCID 708175182-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid

생성물 1

HCID 867102522-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide수율 6%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid (304.6 mg, 0.945 mmol, 1 eq) in DCM (10 mL) was added TEA (172 mg, 1.70 mmol, 0.237 mL, 1.80 eq), EDCI (254 mg, 1.32 mmol, 1.4 eq), HOBT (260 mg 1.70 mmol, 1.80 eq) and O— tetrahydro-2-H-pyran-2-ylhydroxylamine (166 mg, 1.42 mmol, 1.5 eq). The reaction was allowed stir at RT overnight. The reaction mixture was diluted with DCM and water. The aqueous layer was extracted several times with DCM and the combined organic layers were dried (MgSO4), filtered and concentrated. The crude product mixture was absorbed onto silica gel and purified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient to give 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (24 mg, 6% yield). LC-MS M+H+422.6.

후처리

  1. extractionThe aqueous layer was extracted several times with DCM
  2. dry with materialthe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product mixture was absorbed onto silica gel
  6. custompurified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient

출처 및 근거

ORD 기록
ord-2235fbe2387e4b26a8fd0a1bbea7beec
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809333B2

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