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

HRID 2230733노트

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HRID 2230733 반응식
I.I.[N:3]1([C:10]2[N:14]([CH2:15][CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])[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(CC)CC)C>C(#N)C>[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][CH2:17][C:18]([F:21])([F:19])[F:20])[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

5

반응물 3

HCID 8471TriethylamineHCID 184644212-[1,4]diazepan-1-yl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole dihydroiodideHCID 86583904HCID 86583904, 화합물

생성물 1

HCID 599022611-(2-Methoxy-5-tetrazol-1-yl-phenyl)-1-[(R)-3-phenyl-3-(2-{4-[1-(4,4,4-trifluoro-butyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-pyrrolidin-1-yl]-methanone수율 106.2%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

Reflux a solution of 2-[1,4]diazepan-1-yl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole dihydroiodide (0.65 g, 1.12 immol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.50 g, 1.06 mmol, example 47.2), triethylamine (3.58 mmol) and acetonitrile (15 mL) for 20 hours. Cool and concentrate in vacuo. Dilute with dichloromethane (150 mL), wash the organic phase with NaHCO3 solution (3×30 mL), dry (Na2SO4) the organic phase, filter and evaporate. Purify the residue by flash chromatography (silica gel, 7×15 cm) eluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane and concentrate the appropriate fractions to afford 0.79 g of the title compound as a cream colored foam, Rf=0.46 (silica gel, 1.0% methanol/0.1% ammonium hydroxide solution in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

후처리

  1. temperatureCool
  2. concentrationconcentrate in vacuo
  3. additionDilute with dichloromethane (150 mL)
  4. washwash the organic phase with NaHCO3 solution (3×30 mL)
  5. dry with materialdry (Na2SO4) the organic phase
  6. filtrationfilter
  7. customevaporate
  8. customPurify the residue by flash chromatography (silica gel, 7×15 cm)
  9. washeluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane
  10. concentrationconcentrate the appropriate fractions

출처 및 근거

ORD 기록
ord-1d85fe1d48604d4abe63fc979fb6265b
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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