Acetonitrile → 1-(2-Methoxy-5-tetrazol-1-yl-phenyl)-1-[(R)-3-phenyl-3-(2-{4-[1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-pyrrolidin-1-yl]-methanone

HRID 2230719노트

반응식

HRID 2230719 반응식
I.I.[N:3]1([C:10]2[N:14]([CH2:15][CH2:16][N:17]3[CH:21]=[CH:20][CH:19]=[N:18]3)[C:13]3[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=3[N:11]=2)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[CH:30][C:29]=1[C:39]([N:41]1[CH2:45][CH2:44][C@:43]([CH2:52][CH2:53]OS(C)(=O)=O)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:42]1)=[O:40].C(N(C(C)C)CC)(C)C.C(#N)C>ClCCl>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[CH:30][C:29]=1[C:39]([N:41]1[CH2:45][CH2:44][C@@:43]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([CH2:52][CH2:53][N:6]2[CH2:7][CH2:8][CH2:9][N:3]([C:10]3[N:14]([CH2:15][CH2:16][N:17]4[CH:21]=[CH:20][CH:19]=[N:18]4)[C:13]4[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=4[N:11]=3)[CH2:4][CH2:5]2)[CH2:42]1)=[O:40]

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 184648602-[1,4]diazepan-1-yl-1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazole dihydroiodideHCID 86583904HCID 86583904, 화합물

생성물 1

HCID 599022731-(2-Methoxy-5-tetrazol-1-yl-phenyl)-1-[(R)-3-phenyl-3-(2-{4-[1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-pyrrolidin-1-yl]-methanone수율 50.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Reflux a mixture of 2-[1,4]diazepan-1-yl-1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazole dihydroiodide (0.48 g, 0.84 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.40 g, 0.84 mmol, example 47.2), diisopropylethylamine (0.44 g, 3.37 mmol) and acetonitrile (20 mL) for 12 hours. Cool and dilute with dichloromethane (150 mL), wash the organic phase with water (2×10 mL), dry (MgSO4) the organic phase, filter and evaporate. Purify the residue by silica gel chromatography eluting with 0.5% methanol in dichloromethane to afford 0.29 g of the title compound, Rf=0.18 (silica gel, 0.5% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

후처리

  1. temperatureReflux
  2. temperatureCool
  3. washwash the organic phase with water (2×10 mL)
  4. dry with materialdry (MgSO4) the organic phase
  5. filtrationfilter
  6. customevaporate
  7. customPurify the residue by silica gel chromatography
  8. washeluting with 0.5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-fb211f43fdf84ccab88209a53133e171
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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