反应详情

温度

10 °C

A suspension of methyl 3-cyano-1H-indazole-5-carboxylate (50.0 g, 249 mmol) in methanol (1 L) was cooled to 10° C. A solution of urea hydrogen peroxide (241 g, 2.49 mol) in sodium hydroxide (1 L of 2.5 N) and water (100 mL) was added dropwise, maintaining an internal temperature below 25° C. When the addition was complete, the ice bath was removed and the reaction was allowed to stir at room temperature for 16 hours. A small amount of unreacted starting material was observed by HPLC. The reaction was cooled to 15° C. and additional urea hydrogen peroxide (50 g) was added portionwise. Vigorous bubbling was noted. The reaction was allowed to stir for another 2 hours. The crude reaction was filtered to remove the solids present and the filtrate was concentrated to remove the methanol. The remaining solution was cooled in an ice bath and 6 N hydrochloric acid (420 mL) was added dropwise to adjust the pH to 4. The solution was stirred for 20 minutes and the resulting tan solid was collected by filtration and dried to give 57.2 g of crude product. To the crude was added acetonitrile (700 mL) and dichloromethane (700 mL) and the mixture was stirred at room temperature for 1 hour. The solid was collected by filtration, washed with 1:1 acetonitrile:dichloromethane (400 mL) and dried to give the title compound (39.5 g, 77%) as a tan solid. +ESI (M+H) 206.1; 1H NMR (400 MHz, DMSO-d6, δ): 13.81 (s, 1H), 12.85 (br. s., 1H), 8.82 (d, J=0.8 Hz, 1H), 7.93 (dd, J=8.8, 1.6 Hz, 1H), 7.79-7.85 (m, 1H), 7.64 (d, J=8.6 Hz, 1H), 7.44 (s, 1H).

1. temperaturemaintaining an internal temperature below 25° C
2. additionWhen the addition
3. customthe ice bath was removed
4. temperatureThe reaction was cooled to 15° C.
5. additionadditional urea hydrogen peroxide (50 g) was added portionwise
6. customVigorous bubbling
7. stirringto stir for another 2 hours
8. customThe crude reaction
9. filtrationwas filtered
10. customto remove the solids present
11. concentrationthe filtrate was concentrated
12. customto remove the methanol
13. temperatureThe remaining solution was cooled in an ice bath
14. addition6 N hydrochloric acid (420 mL) was added dropwise
15. stirringThe solution was stirred for 20 minutes
16. filtrationthe resulting tan solid was collected by filtration
17. customdried
18. customto give 57.2 g of crude product
19. stirringthe mixture was stirred at room temperature for 1 hour
20. filtrationThe solid was collected by filtration
21. washwashed with 1:1 acetonitrile
22. dry with materialdichloromethane (400 mL) and dried