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 2230733ノート

反応式

HRID 2230733 の反応式
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]

参加物

5

反応物 3

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

生成物 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]-methanone収率 106.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1d85fe1d48604d4abe63fc979fb6265b
出典データセット
uspto-grants-2002_07
特許番号
US06423704B1

反応ノート

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