p-Aminoacetophenone → HCID 178466755, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence