反应详情

5-Amino-3-(1-methylethyl)pyrazole (12.5 g) was dissolved in methanol (40 ml) and to the resulting solution was added methyl 4-(p-nitrophenyl)butaneimidate hydrochloride (25.9 g) and the resulting mixture was stirred for 2 hours at room temperature. To this mixture was further added a methanol solution of hydroxylamine prepared by hydroxylamine hydrochloride (6.95 g) and a 28% methanol solution of sodium methoxide (19.3 g), and the resulting mixture was left to stand overnight at room temperature. After the solvent was distilled off under reduced pressure, the residue was added to water and extracted by ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (200 ml), and triethylamine (12.0 ml) was added and the resulting mixture was stirred in a water bath. p-Toluenesulfonic acid chloride (16.0 g) was gradually added to the mixture, and the resulting mixture was stirred for 1 hour without water bath. The insoluble matter was filtered off, and the filtrate was concentrated. The residue was dissolved in methanol (600 ml) and heated under refluxing for 3 hours. The methanol was distilled off under reduced pressure, and the residue was poured into water (1,000 ml) and extracted by ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated. The residue was separated by the silica gel column chromatography (eluate: chloroform/ethyl acetate=5/1). The eluate containing the intended Compound (C) was concentrated, and the residue was recrystallized from ethyl acetate to obtain 6.2 g (20%) of 6-(1-methylethyl)-2-[3-(4-nitrophenyl)propyl]-pyrazolo[1,5-b][1,2,4]triazole (C) as pale yellow crystals (m.p.: 188°-189° C.).

1. waitto stand overnight at room temperature
2. distillationAfter the solvent was distilled off under reduced pressure
3. additionthe residue was added to water
4. extractionextracted by ethyl acetate
5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in tetrahydrofuran (200 ml)
8. additiontriethylamine (12.0 ml) was added
9. stirringthe resulting mixture was stirred in a water bath
10. additionp-Toluenesulfonic acid chloride (16.0 g) was gradually added to the mixture
11. stirringthe resulting mixture was stirred for 1 hour without water bath
12. filtrationThe insoluble matter was filtered off
13. concentrationthe filtrate was concentrated
14. dissolutionThe residue was dissolved in methanol (600 ml)
15. temperatureheated
16. temperatureunder refluxing for 3 hours
17. distillationThe methanol was distilled off under reduced pressure
18. additionthe residue was poured into water (1,000 ml)
19. extractionextracted by ethyl acetate
20. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
21. concentrationconcentrated
22. customThe residue was separated by the silica gel column chromatography (eluate: chloroform/ethyl acetate=5/1)
23. additionThe eluate containing the intended Compound (C)
24. concentrationwas concentrated
25. customthe residue was recrystallized from ethyl acetate