反应详情

温度

85 °C

A mixture of 6-(2-chlorophenyl)-3-methyl-4-oxo-4,5,6,7-tetrahydroindazole (1.14 g), 1-amino-3-hydroxyguanidine p-toluenesulfonate (1.26 g) and concentrated hydrochloric acid (0.44 ml) in ethanol (12 ml) was stirred at 85° C. (bath temperature) for 1 hour. The reaction solution was concentrated under reduced pressure, and to the residue were added ethyl acetate (50 ml), tetrahydrofuran (20 ml) and an aqueous solution (20 ml) of anhydrous potassium carbonate (1.4 g). The mixture was shaken, and the separated upper layer was washed with an aqueous solution (10 ml) of anhydrous potassium carbonate (0.7 g) and water (10 ml, thrice). To the upper layer was added 2 N hydrochloric acid (2.3 ml), and the mixture was concentrated under reduced pressure. To the residue was added a mixture of ether (30 ml) and ethanol (15 ml), and the mixture was stirred at room temperature for 15 hours to give solidified powder. The powder was stirred in ethanol (4 ml) at 90° C. (bath temperature) for 1 hours, and precipitated crystals were filtered off. The filtrate was concentrated under reduced pressure, and the residue was dissolved in ethanol (12 ml). The solution was stirred at 90° C. (bath temperature) for 14 hours. The reaction solution cooled, and crystals precipitated while stirring were filtered, washed with ethanol and dried to give 6-(2-chlorophenyl)-4-(1-hydroxyguanidin-3-yl)imino-3-methyl-4,5,6,7-tetrahydroindazole hydrochloride (Compound 93) (604 mg) as pale yellow crystals.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. additionto the residue were added ethyl acetate (50 ml), tetrahydrofuran (20 ml)
3. stirringThe mixture was shaken
4. washthe separated upper layer was washed with an aqueous solution (10 ml) of anhydrous potassium carbonate (0.7 g) and water (10 ml, thrice)
5. additionTo the upper layer was added 2 N hydrochloric acid (2.3 ml)
6. concentrationthe mixture was concentrated under reduced pressure
7. additionTo the residue was added
8. additiona mixture of ether (30 ml) and ethanol (15 ml)
9. stirringthe mixture was stirred at room temperature for 15 hours
10. customto give
11. customprecipitated crystals
12. filtrationwere filtered off
13. concentrationThe filtrate was concentrated under reduced pressure
14. dissolutionthe residue was dissolved in ethanol (12 ml)
15. stirringThe solution was stirred at 90° C. (bath temperature) for 14 hours
16. temperatureThe reaction solution cooled
17. customcrystals precipitated
18. stirringwhile stirring
19. filtrationwere filtered
20. washwashed with ethanol
21. customdried