反应详情

A mixture of 1-(3,4-dimethylphenyl)-3-methyl-4-(3-bromo-2-methoxyphenyl)hydrazono-5-pyrazolone (10 g) prepared as in Example 16, 3-carboxyphenylboronic acid (5.2 g), bis(triphenylphosphine)palladium(II)chloride [PdCl2(PPh3)2] (0.84 g), potassium hydroxide (6.72 g) in ethanol (200 mL) and water (15 mL) was heated to about reflux temperature under nitrogen atmosphere and stirred for about 8 hours. The reaction mixture was cooled to about 30° C. to about 35° C. and stirred for about 4 hours at about the same temperature. The reaction mixture was treated with Norit™ charcoal and filtered over celite bed. The filtrate was treated with EDTA and Scavenger Type 2S. The mixture was stirred at about 30° C. to about 40° C. for about 20 hours and filtered over celite bed. To the filtrate, hydrochloric acid was added to adjust the pH to about 3 to about 5. The mixture was stirred for about 2 hours at about 80° C. to about 85° C. The mixture was cooled to about 40° C. to about 45° C. and filtered. The wet cake was treated with potassium hydroxide in methanol and stirred to give a clear solution. The solution was treated with 50% tributylphosphene in ethyl acetate and stirred for about 20 hours at about room temperature. The pH of the solution was adjusted to about 2 to about 4 using hydrochloric acid and the solid obtained was filtered and purified using tetrahydrofuran. Yield: 9.3 g

1. temperaturewas heated
2. temperatureto about reflux temperature under nitrogen atmosphere
3. temperatureThe reaction mixture was cooled to about 30° C. to about 35° C.
4. stirringstirred for about 4 hours at about the same temperature
5. filtrationfiltered over celite bed
6. additionThe filtrate was treated with EDTA and Scavenger Type 2S
7. stirringThe mixture was stirred at about 30° C. to about 40° C. for about 20 hours
8. filtrationfiltered over celite bed
9. additionTo the filtrate, hydrochloric acid was added
10. stirringThe mixture was stirred for about 2 hours at about 80° C. to about 85° C
11. temperatureThe mixture was cooled to about 40° C. to about 45° C.
12. filtrationfiltered
13. additionThe wet cake was treated with potassium hydroxide in methanol
14. stirringstirred
15. customto give a clear solution
16. stirringstirred for about 20 hours at about room temperature
17. customthe solid obtained
18. filtrationwas filtered
19. custompurified