Ammonium Chloride → 4-isopropyl-6-methoxy-2-[1-(3-chloropyridazin-6-yl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-(3-chloropyridazin-6-yl)-3-trifluoromethyl-5-hydroxypyrazole (264 mg; 1 mmol) in DMF under nitrogen was added 96 mg (1.66 mmol) of KF and the mixture was stirred at 20° C. for 10 minutes. To the resulting mixture was added 2-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (289 mg, 0.83 mmol) and the resulting mixture was stirred at room temperature (20° C.) for 1 hour and poured into saturated ammonium chloride solution/ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×), the combined organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (silica gel; 20% ethyl acetate in hexane) and recrystallized from ether/hexane to afford 337 mg (77%) of 4-isopropyl-6-methoxy-2-[1-(3-chloropyridazin-6-yl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =3-Cl-6-pyridazinyl; R2 =CF3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OCH3) as a white solid, m.p. 110°-1110° C.

Provenance & Evidence