Sodium 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 637039Notes

Reaction equation

HRID 637039 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].C(N(CC)CC)C.[I-].[Na+].I.[CH2:43]([O:45][CH2:46][CH2:47][N:48]1[C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=2[N:50]=[C:49]1[N:57]1[CH2:63][CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1)[CH3:44]>C(#N)C.CO.ClCCl.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:60]2[CH2:61][CH2:62][CH2:63][N:57]([C:49]3[N:48]([CH2:47][CH2:46][O:45][CH2:43][CH3:44])[C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=4[N:50]=3)[CH2:58][CH2:59]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 5238Sodium 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 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent2×

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) (1.43 g, 3.1 mmol), triethylamine (2.05 mL, 14.75 mmol), sodium iodide (0.46 g, 3.1 mmol), and 4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic acid salt (1.6 g, 2.95 mmol) in acetonitrile (40 mL). Heat to reflux. After 40 hours, evaporate in vacuo to give a residue. Partition the residue between dichloromethane and water. Separate the layers and extract the organic layer with a saturated aqueous sodium bicarbonate solution, water, and then 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 dichloromethane, 5% methanol/dichloromethane, and then 10% methanol/dichloromethane to give the title compound.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto give a residue
  4. customPartition the residue between dichloromethane and water
  5. customSeparate the layers
  6. extractionextract the organic layer with a saturated aqueous sodium bicarbonate solution, water
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue

Sources & evidence

ORD record
ord-e70bfa6dc1114e229c369d835deaeca9
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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