反应详情

温度

170 °C

6-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Example 14, 100 mg, 0.339 mmol), (R)-(−)-3-fluoropyrrolidine hydrochloride (220 mg, 1.696 mmol) and KF (99 mg, 1.696 mmol) were suspended in NMP (1.5 mL). N-Ethyldiisopropylamine (296 μL, 1.696 mmol) was then added and the RM was stirred at 170° C. for 4 h. The mixture was diluted with EtOAc and extracted with 1 M HCl (3×). The aqueous layer was washed with TBME (2×) and then adjusted to pH 10 with 2 M NaOH. The solution was extracted with DCM (3×). The organic layer was washed with water (2×), dried over sodium, filtered and concentrated. The residue was purified by flash chromatography (Flashmaster) and triturated in DCM to afford the title compound as a yellow foam (tR 4.14 min (conditions 4), MH+=348.5, 1H-NMR in DMSO-d6: 8.84 (m, 1H); 8.29 (m, 1H); 7.93 (m, 2H); 7.81 (d, 1H); 7.76 (m, 1H); 7.49 (dd, 1H); 7.43 (s, 1H); 6.81 (d, 1H); 5.46 (m, 1H); 4.38 (s, 2H); 3.62 (m, 4H); 2.20 (m, 2H)).

1. extractionextracted with 1 M HCl (3×)
2. washThe aqueous layer was washed with TBME (2×)
3. extractionThe solution was extracted with DCM (3×)
4. washThe organic layer was washed with water (2×)
5. dry with materialdried over sodium
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by flash chromatography (Flashmaster)
9. customtriturated in DCM