反应详情

There was dissolved, in tetrahydrofuran (4 mL), 3-amino-4-phenyl-pyrazole (208 mg, 1.31 mM), then malonyl chloride (153 μL, 1.57 mM) was added to the solution with ice-cooling and the mixture was stirred at room temperature for 30 minutes. To the reaction solution, there was added malonyl chloride (15 μL, 0.16 mM) and the mixture was further stirred at room temperature for 30 minutes. This reaction liquid was diluted with a 1M aqueous sodium hydroxide solution, washed with ethyl acetate, the aqueous phase was acidified (pH 2) by the addition of hydrochloric acid and then it was extracted with ethyl acetate. The extracts thus obtained were combined, dried over anhydrous sodium sulfate, the solvent was then distilled off and the resulting solid was washed with diethyl ether. Phosphoryl chloride (4 mL) was added to the resulting solid with ice-cooling, and then the resulting suspension was stirred for 6 hours while refluxing the same with heating. The phosphoryl chloride was distilled off from the reaction liquid, ethanol was added to the resulting residue with ice-cooling and the mixture was stirred for 15 minutes. After the reaction liquid was concentrated, the concentrate was diluted with water and then extracted with methylene chloride. The extracts were combined, dried over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by the silica gel column chromatography (ethyl acetate/hexane=1:10) to thus give the title compound (47.7 mg, overall yield of these two steps: 14%).

1. temperaturecooling
2. stirringthe mixture was further stirred at room temperature for 30 minutes
3. customThis reaction liquid
4. washwashed with ethyl acetate
5. additionby the addition of hydrochloric acid
6. extractionit was extracted with ethyl acetate
7. customThe extracts thus obtained
8. dry with materialdried over anhydrous sodium sulfate
9. distillationthe solvent was then distilled off
10. washthe resulting solid was washed with diethyl ether
11. additionPhosphoryl chloride (4 mL) was added to the resulting solid with ice-
12. temperaturecooling
13. stirringthe resulting suspension was stirred for 6 hours
14. temperaturewhile refluxing the same
15. temperaturewith heating
16. distillationThe phosphoryl chloride was distilled off from the reaction liquid, ethanol
17. additionwas added to the resulting residue with ice-
18. temperaturecooling
19. stirringthe mixture was stirred for 15 minutes
20. customAfter the reaction liquid
21. concentrationwas concentrated
22. additionthe concentrate was diluted with water
23. extractionextracted with methylene chloride
24. dry with materialdried over anhydrous sodium sulfate
25. distillationthe solvent was distilled off
26. customthe resulting residue was purified by the silica gel column chromatography (ethyl acetate/hexane=1:10)