反应详情

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (199 mg, 0.98 mmol), (S)-2-tertbutoxycarbonylaminobutyric acid (219 mg, 1.08 mmol), HOAt (147 mg, 1.08 mmol), 4-methylmorpholine (0.238 mL, 2.16 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (207 mg, 1.08 mmol) in DCM (5 mL) was stirred at RT for 2 h. The reaction mixture was partitioned between DCM (50 mL) and a saturated solution of NaHCO3. The organic layer was dried (Na2SO4), concentrated in vacuo and the resulting residue dissolved in AcOH (10 mL) and stirred for 18 h at 70° C. After cooling to RT, the volatiles were evaporated under reduced pressure and the residue was partitioned between DCM (50 mL) and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a beige solid (234 mg, 64%). LCMS (Method C): RT 3.82 min [M+H]+ 370.5.

1. customThe reaction mixture was partitioned between DCM (50 mL)
2. dry with materialThe organic layer was dried (Na2SO4)
3. concentrationconcentrated in vacuo
4. dissolutionthe resulting residue dissolved in AcOH (10 mL)
5. stirringstirred for 18 h at 70° C
6. temperatureAfter cooling to RT
7. customthe volatiles were evaporated under reduced pressure
8. customthe residue was partitioned between DCM (50 mL)
9. washThe organic layer was washed with brine
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)