Potassium Iodide → 1-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 2230519Notes

Reaction equation

HRID 2230519 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].I.[CH2:34]([O:36][CH2:37][CH2:38][N:39]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:41]=[C:40]1[N:48]1[CH2:54][CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[CH3:35].[I-].[K+].C(N(CC)CC)C>C(#N)C.CO.ClCCl>[CH3:32][O:31][C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:51]2[CH2:52][CH2:53][CH2:54][N:48]([C:40]3[N:39]([CH2:38][CH2:37][O:36][CH2:34][CH3:35])[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)[CH2:49][CH2:50]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 184646303,4,5-Trimethoxybenzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidineHCID 865838874-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl) [1,4]diazepane hydriodic acid salt

Product 1

HCID 184644711-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt)(1.83 g, 3.94 mmol), 4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic acid salt (2.04 g, 3.75 mmol), potassium iodide ((0.62 g, 3.75 mmol), and triethylamine (1.15 mL, 8.25 mmol) in acetonitrile (54 mL). Heat to reflux. After 43 hours, evaporate in vacuo, dilute the evaporated reaction mixture with dichloromethane, extract with a saturated aqueous sodium bicarbonate solution, water, and then with brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with dichloromaethane, then 10% methanol/dichloromethane to give the title compound.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. additiondilute
  4. customthe evaporated reaction mixture with dichloromethane
  5. extractionextract with a saturated aqueous sodium bicarbonate solution, water
  6. dry with materialDry the organic layer over MgSO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-7c97c8a0163841d0af68bec24a53072a
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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