反应详情

温度

60 °C

3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole (100 mg, 0.27 mmol), 3-bromopentane (70 mg, 0.46 mmol), potassium carbonate (45 mg, 0.33 mmol) and N,N-dimethylformamide (2 mL) were added to a 1-necked flask. The mixture was heated to 60° C. for 6 hours, then slowly cooled to room temperature and stirred for a further 48 hours. A further equivalent of 3-bromopentane (41 mg, 0.27 mmol) was then added, and the reaction was heated to 120° C. After cooling to room temperature, water and ethyl acetate were added. The product was extracted once with ethyl acetate, and washed with water and brine. The combined organics were dried, and filtered and concentrated. The reside was purified by column chromatography on silica gel (eluting using 50% ethyl acetate in hexanes for 10 minutes and then a linear gradient to 100% ethyl acetate in hexanes at 20 minutes) to give 4.4 mg (3.7%) of 3-ethyl-2-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-2H-indazole. LC/MS (EI) tR 4.36 (Method C), m/z 437.1 (M++1), 1H NMR (CDCl3) δ 0.6 (t, 3H), 1.4 (t, 2H), 1.8 (m, 2H), 1.9 (m, 2H), 3.0 (m, 6H), 4.0 (m, 1H), 6.5 (s, 1H), 7.0 (d, 1H), 7.1 (s, 1H), 7.5 (d, 2H), 7.7 (m, 1H), 7.8 (s, 1H), 7.8 (d, 2H). 13 mg (11%) of the corresponding isomer (3-ethyl-1-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole) was also isolated.

1. temperatureslowly cooled to room temperature
2. temperaturethe reaction was heated to 120° C
3. temperatureAfter cooling to room temperature
4. extractionThe product was extracted once with ethyl acetate
5. washwashed with water and brine
6. customThe combined organics were dried
7. filtrationfiltered
8. concentrationconcentrated
9. customThe reside was purified by column chromatography on silica gel (
10. washeluting
11. customfor 10 minutes