反应详情

To a solution of N-(5-bromo-2-methylpyridin-3-yl)acetamide (8.28 g, 36 mmol) in chloroform (550 mL) at ambient temperature was added potassium acetate (4.32 g, 43.6 mmol), acetic acid (2.5 mL, 43.6 mmol) and followed by acetic anhydride (6.86 mL, 72.6 mmol). The mixture was stirred at ambient temperature for 15 minutes before being heated to 40° C. Isoamylnitrite was then added dropwise. The reaction was then stirred at 60° C. for 48 hours. The reaction mixture was poured slowly into a saturated solution of sodium bicarbonate (500 mL) at 0° C. The organic phase was retained and the aqueous phase extracted with dichloromethane (500 mL). The combined organics were then concentrated to a brown oil which was dissolved in methanol (500 mL). Aqueous sodium hydroxide (2 M, 500 mL) was added at 0° C. and the mixture stirred at ambient temperature for 1 hour before the methanol was removed in vacuo. The aqueous mixture was then extracted with ethyl acetate (3×500 mL). The combined organics were dried over magnesium sulfate, filtered, and the solvent removed in vacuo to give 6-bromo-1H-pyrazolo[4,3-b]pyridine as a light brown solid (5.5 g, 77%). 1HNMR (400 MHz, CD3OD, δ): 8.55 (s, 1H), 8.24 (s, 1H), 8.21 (s, 1H).

1. temperaturebefore being heated to 40° C
2. stirringThe reaction was then stirred at 60° C. for 48 hours
3. extractionthe aqueous phase extracted with dichloromethane (500 mL)
4. concentrationThe combined organics were then concentrated to a brown oil which
5. dissolutionwas dissolved in methanol (500 mL)
6. additionAqueous sodium hydroxide (2 M, 500 mL) was added at 0° C.
7. stirringthe mixture stirred at ambient temperature for 1 hour before the methanol
8. customwas removed in vacuo
9. extractionThe aqueous mixture was then extracted with ethyl acetate (3×500 mL)
10. dry with materialThe combined organics were dried over magnesium sulfate
11. filtrationfiltered
12. customthe solvent removed in vacuo