反应详情

To a solution of 1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid (0.25 g, 0.48 mmol) in DMF (2 mL) was added HOAt (0.065 g, 0.48 mmol), EDC (0.092 g, 0.48 mmol), DMAP (0.005 g, 0.041 mmol), Et3N (0.066 mL, 0.48 mmol). The reaction allowed to stir for 10 min at room temperature. To this mixture was added N′-(1-amino-cyclopropanecarbonyl)-hydrazinecarboxylic acid tert-butyl ester (0.10 g, 0.48 mmol) and the reaction was heated at 70° C. for 15 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc (3×50 mL). The combined extracts were washed with saturated NaHCO3, 2N HCl, brine and dried with MgSO4. The mixture was filtered and concentrated in vacuo to give N′-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl ester (0.33 g, 96%) as a yellow solid, m/z 721.9 [M+1]+.

1. temperaturethe reaction was heated at 70° C. for 15 h
2. temperatureThe mixture was cooled to room temperature
3. extractionextracted with EtOAc (3×50 mL)
4. washThe combined extracts were washed with saturated NaHCO3, 2N HCl, brine
5. dry with materialdried with MgSO4
6. filtrationThe mixture was filtered
7. concentrationconcentrated in vacuo