N,N,N',N'-Tetramethylmethanediamine → 4,5-dihydro-3-(4-fluorophenyl)-4-(2-trifluoromethyl-5-thiazolyl)-1H-pyrazole

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A solution of 112 uL (microliters) (1.1 mmol) of acetic anhydride and 289 mg (milligram) (1.0 mmol) of 1-(4-fluorophenyl)-2-(2-trifluoromethyl-5-thiazolyl)ethanone in 2 mL of chloroform was added to a solution of 136 uL (12 mmol) of N,N,N',N',-tetramethyldiaminomethane in 3 mL of chloroform with stirring over a 5-min period. The resulting solution was stirred for 10 min and then 46 uL (1.5 mmol) of anhydrous hydrazine and one drop of trifluoroacetic acid were added sequentially. The mixture was heated at reflux with stirring for 20-30 min and then was cooled and diluted to 20 mL with dichloromethane. The resulting solution was washed with 2×10 mL of water, dried over sodium sulfate, and filtered to obtain 4,5-dihydro-3-(4-fluorophenyl)-4-(2-trifluoromethyl-5-thiazolyl)-1H-pyrazole. 4-Trifluoromethylphenyl isocyanate (143 uL, 1.0 mmol) was then added and the mixture was heated at reflux for 15 min, cooled, and concentrated by evaporation under reduced pressure. The residue was purified by medium pressure liquid chromatography eluting with a 90:10 mixture of hexane and ether to obtain 297 mg (63. percent of theory) of the title compound as a white foamy solid. An analytical sample prepared by recrystallization from a mixture of hexane and acetone was a white solid melting at 174°-176° C.

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