反应详情

温度

80 °C

N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide (99 mg, 0.333 mmol), DIPEA (0.087 mL, 0.500 mmol), HATU (140 mg, 0.366 mmol) and 2,2-difluoropropionic acid (40 mg, 0.366 mmol) were stirred in 5 mL of DMF at rt for 1 h. The solvent was evaporated. The residue was dissolved in 3 mL of glacial AcOH and heated at 80° C. for 2 h. The solvent was evaporated. The product was dissolved in EtOAc and washed with aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by silica gel flash chromatography using EtOAc as eluent. Yield: 100 mg (81%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.39-1.52 (m, 2 H), 1.57-1.63 (m, 1 H), 1.64-1.71 (m, 3 H), 2.06-2.16 (m, 3 H), 2.22 (s, 3 H), 2.29 (m, 3 H), 4.25 (d, J=7.42 Hz, 2 H), 7.31 (s, 1 H), 7.35 (d, J=8.79 Hz, 1 H), 7.60 (dd, J=8.89, 1.86 Hz, 1 H), 7.86 (d, J=1.76 Hz, 1 H).

1. customThe solvent was evaporated
2. dissolutionThe residue was dissolved in 3 mL of glacial AcOH
3. customThe solvent was evaporated
4. dissolutionThe product was dissolved in EtOAc
5. washwashed with aqueous NaHCO3 solution, saturated aqueous NaCl solution
6. dry with materialdried over anhydrous Na2SO4
7. customThe product was purified by silica gel flash chromatography