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 2230710ノート

反応式

HRID 2230710 の反応式
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

参加物

7

反応物 4

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

生成物 2

HCID 14923Ammonium Hydroxide収率 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)-methanone収率 130%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9cc1ed271fde4b80b7a45f002cc3e9f6
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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