反应详情

In a solution of 3.86 g of 2-amino-5-chloropyrimidine in 100 mL of pyridine, 10.0 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methylbenzoyl-chloride synthesized in Step 4 of Synthetic Example 1 was added at room temperature with stirring, and stirred at the same temperature for 23 hours. The solvent was distilled off under reduced pressure, the residue was dissolved in 30 mL of 1,4-dioxane, a solution of 3.02 g of potassium hydroxide in 20 mL of water was added and stirred at room temperature for 1.5 hour. After the completion of the reaction, the reaction mixture was diluted with 380 mL of water, precipitated crystal was filtered off, and washed with 150 mL of water. The resulting crude product was dissolved in 50 mL of ethyl acetate with heating, and 50 mL of 2N hydrochloric acid was added and stirred for 1 hour, and then 50 mL of toluene was added, and precipitated crystal was filtered off. Thereafter, the reaction mixture was washed with 50 mL of water, and then with 50 mL of toluene to obtain 7.95 g of the aimed product as white crystal. Melting point 137.0 to 141.0° C.

1. stirringstirred at the same temperature for 23 hours
2. distillationThe solvent was distilled off under reduced pressure
3. dissolutionthe residue was dissolved in 30 mL of 1,4-dioxane
4. additiona solution of 3.02 g of potassium hydroxide in 20 mL of water was added
5. stirringstirred at room temperature for 1.5 hour
6. customAfter the completion of the reaction
7. customprecipitated crystal
8. filtrationwas filtered off
9. washwashed with 150 mL of water
10. dissolutionThe resulting crude product was dissolved in 50 mL of ethyl acetate
11. temperaturewith heating
12. addition50 mL of 2N hydrochloric acid was added
13. stirringstirred for 1 hour
14. addition50 mL of toluene was added
15. customprecipitated crystal
16. filtrationwas filtered off
17. washThereafter, the reaction mixture was washed with 50 mL of water