反应详情

To a homogeneous mixture of 4-(4-amino-2,5-difluorophenoxy)picolinamide (0.15 g, 0.57 mmol) in THF (5 mL) was added diisopropylethylamine (0.10 mL, 0.57 mmol). The mixture was stirred for two minutes at ambient temperature before 2-(4-fluorophenyl)acetyl isocyanate (Compound D of Example 11, 0.36 M in toluene, 2.0 mL, 0.72 mmol) was added. After 3.5 hours, 2-(4-fluorophenyl)acetyl isocyanate (0.36 M in toluene, 2.0 mL, 0.72 mmol) was added to the reaction mixture. After an additional two hours, 2-(4-fluorophenyl)acetyl isocyanate (0.36 M in toluene, 2.0 mL, 0.72 mmol) was added to the reaction mixture. The mixture was then stirred for 16 hours before being concentrated in vacuo. The residue was treated with Et2O and sonication and the resultant white solid was removed by filtration. The solid was treated with Et2O and sonication two more times before vacuum filtration afforded a white solid (0.23 g, 91%). 1H NMR (DMSO-d6) δ 11.29 (s, 1H), 10.92 (s, 1H), 8.56 (d, 1H, J=5.6 Hz), 8.21-8.26 (m, 1H), 8.16 (br s, 1H), 7.76 (br s, 1H), 7.66-7.71 (m, 1H), 7.12-7.44 (m, 6H), 3.77 (s, 2H); MS(ESI+) m/z 445 (M+H)+.

1. additionwas added
2. waitAfter an additional two hours
3. concentrationbefore being concentrated in vacuo
4. additionThe residue was treated with Et2O and sonication
5. customthe resultant white solid was removed by filtration
6. additionThe solid was treated with Et2O and sonication two more times before vacuum filtration