反应详情

To a solution of 4,5-dichloro-2-methylaniline (1.69 g, 9.6 mmol) in CHCl3 (25 ml) at 0° C. was slowly added acetic anhydride (2.09 ml, 22.1 mmol). The reaction mixture was warmed to room temperature and stirred for 1 h. A thick white precipitate had gradually formed. Potassium acetate (283 mg, 2.88 mmol) was added followed by slow addition of isoamyl nitrite (2.78 ml, 20.6 mmol). The reaction mixture was heated at reflux overnight. The homogeneous deep orange reaction mixture was cooled to room temperature and concentrated. Water (10 mL) was added and the mixture was reconcentrated to an orange solid. This solid was suspended in conc. HCl (15 mL) and heated at 60° C. for 2 h then cooled to 0° C. and neutralized with 50% NaOH. Extracted with EtOAc, dried over MgSO4 and concentrated to an orange solid. This solid was dissolved in THF/MeOH (1:1, 25 mL) and 10% NaOH (3 mL) was added. The deep maroon reaction mixture was stirred at room temperature for 5 min then neutralized with 1.0 M HCl and diluted with water. The mixture was extracted with EtOAc (2×) then dried over MgSO4 and concentrated. The residue was absorbed onto silica gel and purified by chromatography with 30% to 50% EtOAc/hexanes to afford 1.50 g (84%) of 5,6-dichloro-1H-indazole as a light orange solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.04 (s, 1H), 7.89 (s, 1H), 7.68 (s, 1H).

1. customat 0° C.
2. customA thick white precipitate had gradually formed
3. temperatureThe reaction mixture was heated
4. temperatureat reflux overnight
5. temperatureThe homogeneous deep orange reaction mixture was cooled to room temperature
6. concentrationconcentrated
7. additionWater (10 mL) was added
8. temperatureheated at 60° C. for 2 h
9. temperaturethen cooled to 0° C. and neutralized with 50% NaOH
10. extractionExtracted with EtOAc
11. dry with materialdried over MgSO4
12. concentrationconcentrated to an orange solid
13. dissolutionThis solid was dissolved in THF/MeOH (1:1, 25 mL)
14. addition10% NaOH (3 mL) was added
15. customThe deep maroon reaction mixture
16. stirringwas stirred at room temperature for 5 min
17. extractionThe mixture was extracted with EtOAc (2×)
18. dry with materialthen dried over MgSO4
19. concentrationconcentrated
20. customThe residue was absorbed onto silica gel
21. custompurified by chromatography with 30% to 50% EtOAc/hexanes