反应详情

A mixture of 1-(2-pyrimidinyl)-3-trifluoromethyl-5-hydroxypyrazole (314 mg; 1.37 mmol) and KF (132 mg; 2.3 mmol) in 8 ml of DMF was stirred under nitrogen at room temperature and then 2-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (400 mg, 1.14 mmol) was added. The reaction mixture was stirred at room temperature for 1.25 hours and diluted with cold saturated ammonium chloride solution. The mixture was extracted with ether (3×), the organic layer was dried over magnesium sulfate and then filtered and concentrated in vacuo. The yellow solid residue (495 mg) was dissolved in methylene chloride and was purified by column chromatography (silica gel; 20-40% ethyl acetate/hexane) and recrystallized from ether/hexane to afford 330 mg (60%) of 4-isopropyl-6-methoxy-2-[1-(2-pyrimidinyl)-3-(trifluoro methyl)pyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =2-pyrimidinyl; R2 =CF3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OCH3) as a white solid, m.p. 133°-134.5° C.

1. stirringThe reaction mixture was stirred at room temperature for 1.25 hours
2. extractionThe mixture was extracted with ether (3×)
3. dry with materialthe organic layer was dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe yellow solid residue (495 mg) was dissolved in methylene chloride
7. customwas purified by column chromatography (silica gel; 20-40% ethyl acetate/hexane)
8. customrecrystallized from ether/hexane