Hydrochloric Acid → HCID 136176942, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde (45.0 mg, 0.14 mmol), hydroxylamine hydrochloride (100 mg, 1.45 mmol) and pyridine (129 μL, 1.59 mmol) in ethanol (1 mL) was heated at 100° C. for 3 minutes in the microwave. 1 mL 2 M HCl and 5 mL DCM were added. A precipitate was formed, which was found to be the desired product. The remaining solution was extracted with DCM (5×3 mL). The DCM layer was filtered through a phase separator and concentrated together with the precipitate to give the raw product. To this was added thionyl chloride (3 mL) and the mixture was stirred at room temperature for 2 h and concentrated. Dry DCM (1 mL) and BF3.Me2S (1 M solution in DCM, 0.5 mL, 0.5 mmol) were added and stirred at room temperature over night. The mixture was concentrated and MeOH was added to quench the reaction The crude product was purified on silica gel to give 4-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (30.5 mg, 0.01 mmol, 68%), and 3-(3-chloro-4-hydroxyphenyl)-4-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrazole-5-carbonitrile (6.0 mg, 0.018 mmol, 13%).

Provenance & Evidence