Acetic Acid → 4-(2-Bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine

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Reaction Steps

To a solution of potassium tert-butoxide (0.41 g, 3.3 mmol) in THF (20 mL) at 0° C. was added a solution of 1-(2-bromo-4-fluorophenyl)-2-propanone (i.e. the product of Step A) (0.70 g, 3.0 mmol) in THF (10 mL) over 5 minutes. Stirring was continued for 1 h and then the temperature was reduced to −10° C. A solution of 1-chloro-3-fluoro-2-isothiocyanatobenzene (i.e. the product of Step B) (0.57 g, 3.0 mmol) in THF (10 mL) was added over 6 minutes, and stirring was continued for 15 minutes. Iodomethane (0.54 g, 3.8 mmol) was added, and the cooling bath was removed to provide a reaction mixture containing the intermediate compound α-acetyl-2-bromo-N-(2-chloro-6-fluorophenyl)-4-fluorobenzene-ethanethioamide. After 5 min, water (0.2 mL, 11 mmol), glacial acetic acid (0.53 mL, 9.1 mmol) and methylhydrazine (0.81 mL, 15 mmol) were added in rapid succession, and the reaction mixture was heated to reflux for 6 h. The crude reaction mixture was then concentrated under reduced pressure and purified by MPLC (0 to 100% ethyl acetate in hexanes as eluent) to provide the title product, a compound of the present invention, as an off-white solid (0.55 g).

Provenance & Evidence