反应详情

温度

100 °C

O-(7-Azabenzotriazol-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (100 mg, 0.27 mmol) was added to a mixture of 3-(2,4-Bis-benzyloxy-5-chloro-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-4carboxylic acid and 3-(2,4-Bis-benzyloxy-5-chloro-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-4-carboxylic acid (150 mg, 0.27 mmol). N,N-dimethylformamide (2.5 ml) was added, followed by 4-aminoacetophenone (43 mg, 0.32 mmol) and diisopropylethylamine (0.14 ml, 0.81 mmol). The reaction mixture was heated at 100° C. for 5 minutes using microwave heating and stood at ambient temperature for 2 hours. Solvents were removed in vacuo and the residue was partitioned between dichloromethane (8 ml) and aqueous sodium chloride solution (5 ml). Mixture was stirred vigorously for 10 minutes and the phases were separated. The organic phase was dried over anhydrous sodium sulphate and filtered and filtrate solvents were removed in vacuo to afford a brown oil. The crude amide product was re-dissolved in dichloromethane (2 ml) and placed under a nitrogen atmosphere. Boron trichloride (1.0M solution in dichloromethane, 1.35 ml, 1.35 mmol) was added drop-wise and a brown precipitate forms. Reaction mixture was stirred overnight then quenched by the cautious addition of saturated aqueous sodium bicarbonate solution (4 ml). Reaction mixture was extracted with ethyl acetate and phases separated. The organic phase was washed with brine then dried over sodium sulphate, filtered and filtrate solvents were removed in vacuo to afford brown solid which was purified by preparative HPLC to afford 3-(5-chloro-2,4-dihydroxy-phenyl)-1H-pyrazole-4-carboxylic acid (4-acetyl-phenyl)-amide (3 mg) as off-white solid.

1. temperatureheating
2. customSolvents were removed in vacuo
3. customthe residue was partitioned between dichloromethane (8 ml) and aqueous sodium chloride solution (5 ml)
4. customthe phases were separated
5. dry with materialThe organic phase was dried over anhydrous sodium sulphate
6. filtrationfiltered
7. customfiltrate solvents were removed in vacuo
8. customto afford a brown oil
9. customReaction mixture
10. stirringwas stirred overnight
11. customthen quenched by the cautious addition of saturated aqueous sodium bicarbonate solution (4 ml)
12. customReaction mixture
13. extractionwas extracted with ethyl acetate and phases
14. customseparated
15. washThe organic phase was washed with brine
16. dry with materialthen dried over sodium sulphate
17. filtrationfiltered
18. customfiltrate solvents were removed in vacuo
19. customto afford brown solid which
20. customwas purified by preparative HPLC