Imidazole → 1-(t-butoxycarbonyl)-4-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

HRID 637149Notes

Reaction equation

HRID 637149 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[C:8]([O:12][C:13]([N:15]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]2[N:26]([CH2:27][CH2:28]OS(C)(=O)=O)[C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]=3[N:23]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].CO.ClCCl>CN(C)C=O>[C:8]([O:12][C:13]([N:15]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]2[N:26]([CH2:27][CH2:28][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)[C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]=3[N:23]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:10])([CH3:11])[CH3:9]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 18464661HCID 18464661, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 184648321-(t-butoxycarbonyl)-4-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Combine imidazole (0.08 g, 1.2 mmol) and dimethylformamide (2 mL). Cool in an ice bath and add sodium hydride (0.04 g, 60% i oil, 1.2 mmol). After 30 minutes, warm to ambient temperature. Add a solution of 1-(t-butoxycarbonyl)-4-(1-(2-methanesulfonyloxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (0.35 g, 0.80 mmol) in dimethylformamide (2 mL). Heat to 75° C. After 12 hours, partition the reaction mixture between water and dichloromethane. Extract the organic layer twice with water, dry over Na2SO4, filter, and concentrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia to give 1-(t-butoxycarbonyl)-4-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf=0.44 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Workup

  1. temperatureCool in an ice bath
  2. temperatureHeat to 75° C
  3. waitAfter 12 hours
  4. custompartition the reaction mixture between water and dichloromethane
  5. extractionExtract the organic layer twice with water
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-7e369b7cf6aa4b15a1e3f9bcb6d521e1
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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