反应详情

温度

180 °C

(rac)-6-chloro-3-(1-(4,6-difluoro-1-isopropyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine (Intermediate U, 56.4 mg, 0.15 mmol), KF (44.5 mg, 0.75 mmol) and piperazin-2-one (46.4 mg, 0.45 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: 5-28% 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, crystallized in EtOAc to afford the title compound as a white solid (tR 3.98 min (conditions 5), MH+=440.3, 1H-NMR in DMSO-d6: 8.09 (s, 1H); 7.80 (d, 1H); 7.53 (s, 1H); 7.41 (d, 1H); 7.05 (d, 1H), 4.86 (m, 2H); 4.03 (d, 1H); 3.74 (d, 1H); 3.54 (d, 2H); 3.17 (m, 2H); 1.79 (d, 3H); 1.41 (m, 6H)).

1. custompurified by reverse phase chromatography (Büchi MPLC: 5-28% CH3CN, 0.1% HCOOH)
2. concentrationconcentrated
3. extractionextracted with EtOAc
4. filtrationfiltered
5. concentrationconcentrated
6. customcrystallized in EtOAc