反应详情

温度

90 °C

A suspension of the product of Example 1B (0.1507 g, 0.51 mmol) in POCl3 (4.0 mL, 42.9 mmol) was stirred at 90° C. for 90 minutes, cooled to room temperature and excess POCl3 was removed under vacuum. The resulting residue was treated with 4-tert-butylaniline (0.1027 g, 0.69 mmol) in tetrahydrofuran (3 mL), followed by the addition of a solution of triethylamine (0.25 mL, 1.79 mmol) in tetrahydrofuran (2 mL), and stirred at room temperature for 16 hours. The reaction mixture was quenched with saturated NaHCO3 (5 mL) and diluted with dichloromethane (5 mL). The isolated aqueous phase was extracted with dichloromethane (2×10 mL). The combined organic fractions were dried (MgSO4), filtered and concentrated. The residue was purified by silica gel column chromatography, eluted with ethyl acetate/dichloromethane to afford the title compound. MS (ESI+) m/z 426 (M+H)+; (ESI−) m/z 424 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 1.32 (s, 9H), 7.55 (m, 3H), 7.79 (m, 2H), 8.16 (dd, J=8.3, 1.5 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.30 (s, 1H), 8.60 (d, J=8.1 Hz, 1H), 8.71 (dd, J=4.7, 1.4 Hz, 1H), 10.94 (s, 1H).

1. temperaturecooled to room temperature
2. customexcess POCl3 was removed under vacuum
3. stirringstirred at room temperature for 16 hours
4. customThe reaction mixture was quenched with saturated NaHCO3 (5 mL)
5. additiondiluted with dichloromethane (5 mL)
6. extractionThe isolated aqueous phase was extracted with dichloromethane (2×10 mL)
7. dry with materialThe combined organic fractions were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by silica gel column chromatography
11. washeluted with ethyl acetate/dichloromethane