Dimethylformamide → 4-(1H-Imidazol-1-yl)-N-[[4-phenyl-1-(phenylmethyl)piperazin-2-yl]methyl]benzamide

HRID 1588970Notes

Reaction equation

HRID 1588970 reaction equation
CN(C)C=O.[N:6]1([C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=2)[CH:10]=[CH:9][N:8]=[CH:7]1.[C:20]1([N:26]2[CH2:31][CH2:30][N:29]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:28]([CH2:39][NH2:40])[CH2:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(Cl)Cl>C(N(CC)CC)C.CO>[N:6]1([C:11]2[CH:12]=[CH:13][C:14]([C:15]([NH:40][CH2:39][CH:28]3[CH2:27][N:26]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:31][CH2:30][N:29]3[CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:17])=[CH:18][CH:19]=2)[CH:10]=[CH:9][N:8]=[CH:7]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 7365294-(1-Imidazolyl)benzoic AcidHCID 11044210C-(1-Benzyl-4-phenyl-piperazin-2-yl)-methylamine

Product 1

HCID 149987954-(1H-Imidazol-1-yl)-N-[[4-phenyl-1-(phenylmethyl)piperazin-2-yl]methyl]benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

To N,N-dimethylformamide (200 mL) under nitrogen atmosphere add 4-(1H-imidazol-1-yl)benzoic acid (7.0 g, 37 mmol) and 1,1-carbonyldiimidazole (6.0 g, 37 mmol) and stir for 1 h. Add 4-phenyl-1-(phenylmethyl)-2-piperazinemethanamine (9.5 g, 34 mmol) and stir. Monitor the progress of the reaction by thin-layer chromatography. Upon completion of the reaction remove the solvent in vacuo. To the oil add water (100 mL), a saturated solution of sodium bicarbonate (30 mL) and methylene chloride (200 mL) and stir for 1 h. Separate the layers and extract the aqueous layer with methylene chloride. Concentrate the combined organic layers to give an oil. Flash chromatograph the oil on silica (1000 g) with a mixture of methylene chloride, methanol, triethylamine (97/2/1). Combine and concentrate the fractions containing product. Recrystallize the solid from ethyl acetate/hexane to provide the title compound.

Workup

  1. customMonitor the progress of the reaction by thin-layer chromatography
  2. customUpon completion of the reaction remove the solvent in vacuo
  3. additionTo the oil add water (100 mL)
  4. stirringa saturated solution of sodium bicarbonate (30 mL) and methylene chloride (200 mL) and stir for 1 h
  5. customSeparate the layers
  6. extractionextract the aqueous layer with methylene chloride
  7. concentrationConcentrate the combined organic layers
  8. customto give an oil
  9. concentrationCombine and concentrate the fractions
  10. additioncontaining product
  11. customRecrystallize the solid from ethyl acetate/hexane

Sources & evidence

ORD record
ord-71a99ab021a44405b7b64a9fb123f402
Source dataset
uspto-grants-1993_06
Patent number
US05223623

Reaction notes

Loading…