反应详情

Methyl (3-amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)carbamate (185 mg, 0.590 mmol) and DMAP (15 mg, 0.118 mmol) were dissolved in 10 mL of DCM. Trimethylacetyl chloride (0.080 mL, 0.649 mmol) was added dropwise and the solution was stirred at rt for 2 h. The solution was washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The solvent was concentrated. The residue was dissolved in 4 mL of DCE and P2O5 (catalytic) was added and the solution was heated at 125° C. for 1 h using a Personal Chemistry microwave apparatus. The solution was washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by silica gel flash chromatography using 50 to 75% EtOAc/hexanes. Yield: 122 mg (54%); 1H NMR (400 MHz, CHLOROFORM-D): δ 1.43-1.52 (m, 2H), 1.55 (s, 9H), 1.57-1.66 (m, 2H), 1.67-1.74 (m, 2H), 2.08-2.18 (m, 3H), 3.79 (s, 3H), 4.19 (d, J=7.42 Hz, 2H), 6.63 (br.s, 1H), 7.23 (d, J=8.79 Hz, 1H), 7.37-7.46 (m, 1H), 7.62 (d, J=1.76 Hz, 1H).

1. washThe solution was washed with aqueous NaHCO3 solution, brine
2. dry with materialdried over anhydrous MgSO4
3. concentrationThe solvent was concentrated
4. dissolutionThe residue was dissolved in 4 mL of DCE
5. additionP2O5 (catalytic) was added
6. temperaturethe solution was heated at 125° C. for 1 h
7. washThe solution was washed with aqueous NaHCO3 solution, brine
8. dry with materialdried over anhydrous MgSO4
9. customThe crude product was purified by silica gel flash chromatography