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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence