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

HRID 2230710노트

반응식

HRID 2230710 반응식
I.I.[CH:3]1([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[N:16]2[CH2:22][CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:5][CH2:4]1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH:35]=[N:34][N:33]=[N:32]2)=[CH:27][C:26]=1[C:36]([N:38]1[CH2:42][CH2:41][C@:40]([CH2:49][CH2:50]OS(C)(=O)=O)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:39]1)=[O:37].C(N(CC)CC)C.C(#N)C>ClCCl>[OH-:24].[NH4+:7].[CH:3]1([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[N:16]2[CH2:22][CH2:21][CH2:20][N:19]([CH2:50][CH2:49][C@:40]3([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH2:41][CH2:42][N:38]([C:36]([C:26]4[CH:27]=[C:28]([N:31]5[CH:35]=[N:34][N:33]=[N:32]5)[CH:29]=[CH:30][C:25]=4[O:24][CH3:23])=[O:37])[CH2:39]3)[CH2:18][CH2:17]2)[CH2:4][CH2:5]1

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 184646651-cyclopropylmethyl-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydroiodideHCID 86583904HCID 86583904, 화합물

생성물 2

HCID 14923Ammonium Hydroxide수율 30%HCID 599022641-((R)-3-{2-[4-(1-Cyclopropylmethyl-1H-benzoimidazol-2-yl)-[1,4]diazepan-1-yl]-ethyl}-3-phenyl-pyrrolidin-1-yl)-1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanone수율 130%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Reflux a mixture of 1-cyclopropylmethyl-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydroiodide (0.60 g, 1.14 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.53 g, 1.12 mmol, example 47.2), triethylamine (0.65 mL, 4.66 mmol) and acetonitrile (10 mL) for 8 hours. Cool and dilute with dichloromethane (150 mL), wash the organic phase with NaHCO3 (30 mL) and saturated brine solution (30 mL), dry (MgSO4) the organic phase, filter and evaporate. Purify the residue by silica gel chromatography (4×41 cm) eluting with dichloromethane:methanol:30% ammonium hydroxide (95:5:0.05} to afford 0.47 g of the title compound, Rf=0.32 (silica gel, dichloromethane:methanol:30% ammonium hydroxide solution. 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 NaHCO3 (30 mL) and saturated brine solution (30 mL)
  4. dry with materialdry (MgSO4) the organic phase
  5. filtrationfilter
  6. customevaporate
  7. customPurify the residue by silica gel chromatography (4×41 cm)
  8. washeluting with dichloromethane

출처 및 근거

ORD 기록
ord-9cc1ed271fde4b80b7a45f002cc3e9f6
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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