反应详情

温度

180 °C

6-Chloro-3-[(S)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Intermediate E, 66.0 mg, 0.2 mmol), KF (59.3 mg, 1.0 mmol) and piperazin-2-one (61.9 mg, 0.6 mmol) were suspended in NMP (0.5 mL). The RM was stirred at 180° C. for 3 h. The mixture was diluted with CH3CN and purified by reverse phase chromatography (Büchi MPLC: 5-24% CH3CN, 0.1% HCOOH). The fractions was combined, concentrated and neutralized with NaHCO3, extracted with EtOAc. The combined organics layers were tried over Na2SO4, filtered, concentrated to afford the title compound as a yellow foam (tR 3.53 min (conditions 4), (tR 8.25 (conditions 5), MH+=394.3, 1H-NMR in DMSO-d6: 8.04 (s, 1H); 7.92 (s, 1H); 7.81 (d, 1H); 7.50 (m, 1H); 7.46 (d, 1H); 7.06 (d, 1H); 4.78 (m, 1H); 3.95 (s, 3H); 3.95 (d, 1H); 3.80 (d, 1H); 3.58 (m, 2H); 3.22 (m, 2H); 1.71 (d, 3H)).

1. custompurified by reverse phase chromatography (Büchi MPLC: 5-24% CH3CN, 0.1% HCOOH)
2. concentrationconcentrated
3. extractionextracted with EtOAc
4. filtrationfiltered
5. concentrationconcentrated