反应详情

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (450 mg, 2.2 mmol), (S)-2-tertbutoxycarbonylamino-3-methoxypropionic acid (525 mg, 2.4 mmol), HOAt (330 mg, 2.4 mmol), 4-methylmorpholine (0.53 mL, 4.8 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (460 mg, 2.4 mmol) in DCM (10 mL) was stirred at RT for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic phase was washed with brine, dried (MgSO4) concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(S)-1-(4-fluoro-2-phenylaminophenylcarbamoyl)-2-methoxyethyl]carbamic acid tert-butyl ester (0.655 g, 74%). A solution of the compound thus obtained (0.655 g) in AcOH (10 mL) was heated at 70° C. for 56 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford the title compound (227 mg, 28%). LCMS (Method J): RT 3.59 and 3.70 min [M+H]+ 386.2

1. customThe reaction mixture was partitioned between DCM
2. washThe organic phase was washed with brine
3. dry with materialdried (MgSO4)
4. concentrationconcentrated in vacuo
5. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)