Imidazole → tert-butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-(4,5-dihydro-1H-imidazol-2-ylcarbamoyl)-propoxy)phenyl)propionate

HRID 2297393Notes

Reaction equation

HRID 2297393 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH2:6].N1C=CN=C1.[I-].[Li+].[CH2:14]([O:21][C:22]([NH:24][C@@H:25]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][C:44](OCC)=[O:45])=[CH:36][CH:35]=1)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C=O>[CH2:14]([O:21][C:22]([NH:24][C@@H:25]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][C:44](=[O:45])[NH:6][C:2]2[NH:3][CH2:4][CH2:5][N:1]=2)=[CH:36][CH:35]=1)[C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])=[O:23])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 66321Lithium iodideHCID 1347844,5-Dihydro-1H-imidazol-2-amine2×HCID 11038228tert-Butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate

Product 1

HCID 11145802tert-butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-(4,5-dihydro-1H-imidazol-2-ylcarbamoyl)-propoxy)phenyl)propionateYield 23.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

340 mg of 4,5-dihydro-1H-imidazol-2-ylamine, 13.6 mg of imidazole and 26.8 mg of lithium iodide were added to a solution of 970 mg of tert-butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate (Example 1a) in 5 ml of absolute dimethylformamide. The solution was stirred at 40° C. for 4 hours, an additional 170 mg of 4,5-dihydro-1H-imidazol-2-ylamine were added and the solution stirred at 55° C. for further 3 hours. After removal of the solvent in vacuo, the residue was treated with ethyl acetate, filtered, extracted with 10% strength aqueous KHCO3 solution, dried over MgSO4, filtered, concentrated in vacuo and precipitated with diisopropyl ether. The crude product was purified by silica gel chromatography (dichloromethane/methanol/glacial acetic acid 90/10/1). 250 mg of an amorphous product were obtained.

Workup

  1. stirringthe solution stirred at 55° C. for further 3 hours
  2. customAfter removal of the solvent in vacuo
  3. additionthe residue was treated with ethyl acetate
  4. filtrationfiltered
  5. extractionextracted with 10% strength aqueous KHCO3 solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customprecipitated with diisopropyl ether
  10. customThe crude product was purified by silica gel chromatography (dichloromethane/methanol/glacial acetic acid 90/10/1)

Sources & evidence

ORD record
ord-68fd9977c3fa411190f369c552a2d2e8
Source dataset
uspto-grants-2002_12
Patent number
US06492356B1

Reaction notes

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