Imidazole → (2S)-2-[3-(2-Hydroxyethyl)-3-isoamylureido]-N-methyl-3-phenylpropionamide

HRID 2297720Notes

Reaction equation

HRID 2297720 reaction equation
Cl.[CH3:2][NH:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6].[C:15](N1C=CN=C1)(N1C=CN=C1)=[O:16].N1C=CN=C1.[OH:32][CH2:33][CH2:34][NH:35][CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39]>O1CCCC1>[OH:32][CH2:33][CH2:34][N:35]([CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39])[C:15](=[O:16])[NH:6][C@@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:4]([NH:3][CH3:2])=[O:14]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 682631,1'-CarbonyldiimidazoleHCID 2784772-((3-Methylbutyl)amino)ethan-1-olHCID 13689669HCID 13689669, compound

Product 1

HCID 59923466(2S)-2-[3-(2-Hydroxyethyl)-3-isoamylureido]-N-methyl-3-phenylpropionamideYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In anhydrous tetrahydrofuran (7 ml) are suspended N-methyl-L-phenylalanine amide hydrochloride (Reference compound No. 8-2, 429 mg), 1,1′-carbonyldiimidazole (422 mg) and imidazole (136 mg) under a nitrogen atmosphere, and the suspension is stirred at room temperature for 20 minutes. A solution of N-(2-hydroxyethyl)isoamylamine (Reference compound No. 13-2, 525 mg) in anhydrous tetrahydrofuran (3 ml) is added to the reaction mixture, and the mixture is refluxed for 0.5 hour. The reaction mixture is concentrated under reduced pressure, a 10% aqueous citric acid solution is added to the concentrate, and the whole is extracted with ethyl acetate. The organic layer is washed with a 10% aqueous citric acid solution, water and saturated brine successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting oily matter is purified by silica gel column chromatography to give 626 mg (93%) of the titled compound (Compound No. 20-1).

Workup

  1. temperaturethe mixture is refluxed for 0.5 hour
  2. concentrationThe reaction mixture is concentrated under reduced pressure
  3. additiona 10% aqueous citric acid solution is added to the concentrate
  4. extractionthe whole is extracted with ethyl acetate
  5. washThe organic layer is washed with a 10% aqueous citric acid solution, water and saturated brine successively
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting oily matter is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-984c0863294b48eea9e93259aa72568f
Source dataset
uspto-grants-2002_12
Patent number
US06492370B1

Reaction notes

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