反应详情

温度

100 °C

Triphenylphosphine (21 mg, 0.082 mmol), 2-aminophenylboronic acid hydrochloride (710 mg, 4.1 mmol), 2 M aqueous sodium carbonate (4.1 mL), n-propanol (4.8 mL), and water (1 mL) were added to 4-(4-bromo-5-cyano-2-ethyl-2H-pyrazol-3-yl)butyl acetate (0.86 mg, 2.7 mmol), and the flask was evacuated and backfilled with nitrogen five times before the addition of palladium (II) acetate (6.0 g, 0.027 mmol). The reaction was evacuated and backfilled with nitrogen three more times and then heated overnight at 100° C. An analysis by HPLC indicated that the reaction was incomplete. Additional triphenylphosphine (10 mg, 0.038 mmol), 2-aminophenylboronic acid hydrochloride (300 mg, 1.73 mmol), solid sodium carbonate (500 mg), and palladium (II) acetate (3.0 g, 0.013 mmol) were added at ambient temperature, and the reaction was heated at reflux for three hours and allowed to cool to ambient temperature. The reaction was diluted with brine and extracted with chloroform. The combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Methanol (10 mL) and sodium methoxide (2.2 mL of a 47% solution in methanol) were added to the resulting dark oil. The reaction was heated at reflux for three hours, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was diluted with water and extracted with chloroform. The combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge, eluting with chloroform/CMA in a gradient from 100:0 to 75:25) to provide an oil. The oil was crystallized from acetonitrile and recrystallized from acetonitrile to provide 250 mg of 4-(4-amino-2-ethyl-2H-pyrazolo[3,4-c]quinolin-1-yl)butan-1-ol as gold-colored crystals, mp 159-160° C.

1. customthe flask was evacuated
2. customThe reaction was evacuated
3. temperaturethe reaction was heated
4. temperatureat reflux for three hours
5. temperatureto cool to ambient temperature
6. extractionextracted with chloroform
7. dry with materialThe combined extracts were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. additionMethanol (10 mL) and sodium methoxide (2.2 mL of a 47% solution in methanol) were added to the resulting dark oil
11. temperatureThe reaction was heated
12. temperatureat reflux for three hours
13. temperatureto cool to ambient temperature
14. concentrationconcentrated under reduced pressure
15. additionThe residue was diluted with water
16. extractionextracted with chloroform
17. dry with materialThe combined extracts were dried over sodium sulfate
18. filtrationfiltered
19. concentrationconcentrated under reduced pressure
20. customThe crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge
21. washeluting with chloroform/CMA in a gradient from 100:0 to 75:25)
22. customto provide an oil
23. customThe oil was crystallized from acetonitrile
24. customrecrystallized from acetonitrile