反应详情

温度

85 °C

NaH (34 mg, 0.85 mmol) was suspended in NMP (1.5 mL) under argon. 3-Chloroaniline (108 μL, 1.017 mmol) was added and the RM was heated to 85° C. After 10 min, 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Example 14, 100 mg, 0.339 mmol) was added and the RM was stirred at 85° C. for 1 h. The mixture was then heated to 160° C. for 10 min. The mixture was diluted with EtOAc and washed with water (3×). The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (Flashmaster) and crystallized in Et2O to afford the title compound as a yellow solid (tR 4.99 min (conditions 4), MH+=386.1, 1H-NMR in DMSO-d6: 9.57 (s, 1H); 8.82 (m, 1H); 7.93 (m, 3H); 7.86 (m, 1H); 7.71 (m, 1H); 7.56 (s, 1H); 7.47 (dd, 1H); 7.43 (m, 1H); 7.25 (t, 1H); 6.99 (m, 1H); 6.85 (d, 1H); 4.50 (s, 2H)).

1. temperatureThe mixture was then heated to 160° C. for 10 min
2. washwashed with water (3×)
3. extractionThe aqueous layer was extracted with EtOAc (3×)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography (Flashmaster)
8. customcrystallized in Et2O