反应详情

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine from Example 8 (199 mg, 0.984 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 then partitioned between DCM (50 mL) and a saturated solution of NaHCO3. The organic layer was dried (Na2SO4) and concentrated in vacuo and the resulting residue was dissolved in AcOH (10 mL) and stirred for 18 h at 70° C. After cooling to RT, volatiles were evaporated in vacuo and the residue was partitioned between DCM (50 mL) and a saturated 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) affording (S)-tert-butyl 1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propylcarbamate as a beige solid (234 mg, 64%). LCMS: RT 3.82 min [M+H]+ 370.5

1. customThe reaction mixture was then partitioned between DCM (50 mL)
2. dry with materialThe organic layer was dried (Na2SO4)
3. concentrationconcentrated in vacuo
4. dissolutionthe resulting residue was dissolved in AcOH (10 mL)
5. stirringstirred for 18 h at 70° C
6. temperatureAfter cooling to RT
7. customvolatiles were evaporated in vacuo
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)