反应详情

温度

80 °C

To a solution of KOH (1.5 g, 26 mmol) in 20 mL ethanol were added 3-methyl-1H-indazole-5-carbaldehyde (see Note 1 for synthesis) (0.850 g, 5.3 mmol) and commercially available N-(4-acetyl-3-methylphenyl)acetamide (1.0 g, 5.3 mmol). The reaction mixture was heated to 80° C. for 24 hours and then cooled down to room temperature. After acidification with 1N HCl, the mixture was brought to pH 8 with saturated aqueous NaHCO3 and extracted twice with ethyl acetate (2×100 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The product was purified by SiO2 flash chromatography (60:40 to 50:50 hexanes/ethyl acetate) to afford (E)-1-(4-amino-2-methylphenyl)-3-(3-methyl-1H-indazol-5-yl)prop-2-en-1-one (0.500 g, 32%). 1H NMR (400 MHz, d6-DMSO): δ 12.8 (s, 1H), 8.12 (s, 1H), 7.81 (dd, 1H), 7.78 (d, 1H), 7.61 (d, 2H), 7.48 (d, 1H), 6.45 (m, 2H), 5.88 (br s, 1H), 3.06 (s, 3H), 2.42 (s, 3H); MS (EI) for C18H17N3O: 292.3 (MH+).

1. temperaturecooled down to room temperature
2. extractionextracted twice with ethyl acetate (2×100 mL)
3. washThe combined organic phases were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe product was purified by SiO2 flash chromatography (60:40 to 50:50 hexanes/ethyl acetate)