反应详情

To a solution of N-({3-[2-(4-morpholinyl)ethyl]-oxo-2,3-dihydro-1H-benzimidazol-1-yl}carbonyl)-L-tert-leucine (prepared according to the procedure described in step 1 of example 3 from methyl L-tert-leucinate hydrochloride) (0.18 g, 0.45 mmol) in DMF (1 mL) were added a solution of N-hydroxyethanimidamide (37 mg, 0.50 mmol, Hamze, A.; Hernandez, J.-F.; Fulcrand, P.; Martinez, J. J. Org. Chem. 2003, 68, 7316-7321.) in DMF (1 mL), triethylamine (0.26 mL, 1.8 mmol), HOBt (83 mg, 0.54 mmol) and WSC (0.10 g, 0.54 mmol) at rt. After 9 h, to this mixture were added N-hydroxyethanimidamide (20 mg, 0.26 mmol), triethylamine (0.10 mL, 0.70 mmol), HOBt (10 mg, 0.06 mmol) and WSC (20 mg, 0.10 mmol). After 13 h, the reaction was quenched by addition of sat. aq. sodium bicarbonate (10 mL) and extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with water (10 mL×2), brine (20 mL) and dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (10/1) to afford 0.12 g (57%) of the title compound.

1. customat rt
2. waitAfter 13 h
3. customthe reaction was quenched by addition of sat. aq. sodium bicarbonate (10 mL)
4. extractionextracted with ethyl acetate (20 mL×2)
5. washThe combined organic layers were washed with water (10 mL×2), brine (20 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (10/1)