反应详情

温度

40 °C

To a solution of 5-bromo-1H-indazole (10.0 g, 51.2 mmol) in DMSO (120 mL) was added 2-bromoacetaldehyde dimethyl acetal (12.1 mL, 103 mmol) and Cs2CO3 (66.8 g, 205 mmol). The reaction mixture was stirred at 40° C. for 18 h; then the reaction mixture was diluted with H2O (100 mL) and EtOAc (175 mL). The aqueous layer was extracted with EtOAc (4×175 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated. Purification by flash chromatography (ISCO 330 g column, 95:5 hexanes/EtOAc to hexanes/EtOAc 50:50, 60 min, 40 mL/min) gave the title compound (8.52 g, 46%) as a light orange solid: 1H NMR (300 MHz, CDCl3) 7.94 (s, 1H), 7.85 (d, J=1.2, 1H), 7.48-7.42 (dd, J=8.9, 1.7 Hz, 1H), 7.37 (d, J=8.9 Hz, 1H), 4.71 (t, J=5.4 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.33 (s, 6H).

1. extractionThe aqueous layer was extracted with EtOAc (4×175 mL)
2. washThe combined organics were washed with brine (2×100 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by flash chromatography (ISCO 330 g column, 95:5 hexanes/EtOAc to hexanes/EtOAc 50:50, 60 min, 40 mL/min)