1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(3-{1-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenoxy)-propan-2-one

HRID 2230730노트

반응식

HRID 2230730 반응식
Cl.Cl.[CH2:3]([O:5][CH2:6][CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[N:17]1[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][CH2:25][C@:26]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:30][CH2:29][NH:28][CH2:27]2)[CH2:19][CH2:18]1)[CH3:4].[CH3:37][O:38][C:39]1[CH:47]=[CH:46][C:45]([O:48][CH2:49][C:50](=[O:52])[CH3:51])=[CH:44][C:40]=1[C:41](O)=[O:42].CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[CH2:3]([O:5][CH2:6][CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[N:17]1[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][CH2:25][C@:26]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:30][CH2:29][N:28]([C:41]([C:40]3[CH:44]=[C:45]([CH:46]=[CH:47][C:39]=3[O:38][CH3:37])[O:48][CH2:49][C:50](=[O:52])[CH3:51])=[O:42])[CH2:27]2)[CH2:19][CH2:18]1)[CH3:4]

참가 물질

7

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 184645202-Methoxy-5-(2-oxo-propoxy)-benzoic acidHCID 701481071-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride

생성물 1

HCID 599022651-(3-{1-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenoxy)-propan-2-one수율 85.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

Stir a mixture of 1-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride (0.33 g, 0.61 mmol, Preparation 12.1), 2-methoxy-5-(2-oxo-propoxy)-benzoic acid (0.14 g, 0.61 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.14 g, 0.73 mmol), 1-hydroxybenzotriazole hydrate (0.099 g, 0.73 mmol), diisopropylethylamine (0.25 mL, 1.2 mmol) and dichloromethane (10 mL) overnight at room temperature. Dilute the reaction mixture with dichloromethane, wash with saturated brine, dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the residue by column chromatography on silica gel eluting sequentially with ethyl acetate, 3% methanol in dichloromethane and 5% methanol in dichloromethane. Concentrate the appropriate fractions to afford 0.35 g of the title compound, Rf=0.48 (silica gel, 10% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

후처리

  1. washwash with saturated brine
  2. dry with materialdry (MgSO4) the organic phase
  3. filtrationfilter
  4. concentrationconcentrate the filtrate in vacuo
  5. customPurify the residue by column chromatography on silica gel eluting sequentially with ethyl acetate, 3% methanol in dichloromethane and 5% methanol in dichloromethane
  6. concentrationConcentrate the appropriate fractions

출처 및 근거

ORD 기록
ord-f5ed9fd8be6442c8b119d08ce20c9036
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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