Diisopropylethylamine → 1-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-(1H-tetrazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 2230625Notes

Reaction equation

HRID 2230625 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.[N:34]1([CH2:39][CH2:40][N:41]2[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=3[N:43]=[C:42]2[N:50]2[CH2:56][CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)[CH:38]=[N:37][N:36]=[N:35]1.C(N(CC)C(C)C)(C)C.CO.ClCCl>C(#N)C.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:53]2[CH2:54][CH2:55][CH2:56][N:50]([C:42]3[N:41]([CH2:40][CH2:39][N:34]4[CH:38]=[N:37][N:36]=[N:35]4)[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=4[N:43]=3)[CH2:51][CH2:52]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 81531DiisopropylethylamineHCID 184646303,4,5-Trimethoxybenzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidineHCID 21226129Dichloromethane methanolHCID 865838964-(1-(2-(1H-tetrazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic Acid Salt

Product 1

HCID 184645061-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-(1H-tetrazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.34 g, 0.72 mmol), 4-(1-(2-(1H-tetrazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic acid salt (0.41 g, 0.72 mmol), and N,N-diisopropylethylamine (0.33 g, 2.53 mmol) in acetonitrile (10 mL). Heat to reflux. After 12 hours, cool to ambient temperature and dilute the reaction mixture with dichloromethane and extract with twice water. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia). Combine the product containing fractions, evaporate in vacuo, dissolve in dichloromethane, and extract with water, dry over Na2SO4, filter, and evaporate invacuo to to give the title compound: Rf=0.30 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Workup

  1. temperatureHeat to reflux
  2. extractionextract with twice water
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. customevaporate in vacuo
  6. customto give a residue
  7. additionCombine the product containing fractions
  8. customevaporate in vacuo
  9. dissolutiondissolve in dichloromethane
  10. extractionextract with water
  11. dry with materialdry over Na2SO4
  12. filtrationfilter
  13. customevaporate invacuo

Sources & evidence

ORD record
ord-006ef19051bc43c4995fc5c6b2f64825
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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