反应详情

温度

95 °C

A mixture of 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline (Stage 173.1, 50 mg, 0.160 mmol), 1-[2-(2-methoxy-ethoxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 233.1, 47 mg, 0.160 mmol), Pd(PPh3)2Cl2 (6 mg, 0.008 mmol) and 2 M K2CO3 (216 μL, 0.432 mmol) in DME (1 mL) was stirred at 95° C. for 1 h. The mixture was diluted with EtOAc and washed with NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified twice by flash chromatography (CombiFlash® Companion System®, with a 4 g RediSep® silica gel column, DCM/(DCM/MeOH 19:1)=100:0→0:100) to afford the title compound as a foam (tR 3.56 min (conditions 3), MH+=447.1, 1H-NMR in DMSO-d6: 8.84 (m, 1H); 8.42 (s, 1H); 8.33 (d, 1H); 8.08 (m, 2H); 8.01 (d, 1H); 7.76 (d, 1H); 7.61 (s, 1H); 7.52 (d, 1H); 7.46 (dd, 1H); 4.55 (s, 2H); 4.31 (t, 2H); 3.79 (t, 2H); 3.50 (m, 2H); 3.36 (m, 2H); 3.15 (s, 3H)).

1. washwashed with NaHCO3 and brine
2. dry with materialThe organic layer was dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified twice by flash chromatography (CombiFlash® Companion System®