反应详情

To a mechanically stirred solution of 5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-3-[4-(phenylsulfanyl)phenyl]-1,2,4-oxadiazole (Example 114, 350 mg, 0.798 mmol) in THF (3 mL) was added vanadium trichloride (6 mg, 0.04 mmol) and hydrogen peroxide (30% in water, 82 μL, 0.798 mmol). The reaction mixture was stirred at rt for 5 h, before another 40 μL (0.4 mmol) of the hydrogen peroxide solution were added. Stirring was continued at rt over night. Then water (30 mL) was added, and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous sodium sulfate. After filtration and evaporation of the solvent, the crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 3:1), followed by precipitation using acetonitril/water 3:1 affording a first crop of the title compound (29 mg, 8%). A second crop was obtained from the mother liquor after preparative HPLC (26 mg, 7%): 1H NMR (400 MHz, DMSO-d6) 8.39 (s, 1H), 8.18 (d, 1H), 7.96 (d, 1H), 7.81 (d, 2H), 7.78-7.74 (m, 1H), 7.60-7.50 (m, 3H), 7.18 (d, 2H), 7.12 (d, 2H), 6.94 (s, 1H), 5.44 (s, 2H), 2.32 (s, 3H), 2.28 (s, 3H); ES-MS m/z 455, HPLC RT (Method D) 2.78 min.

1. additionwere added
2. waitwas continued at rt over night
3. extractionthe mixture was extracted with ethyl acetate (3×30 mL)
4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
5. filtrationAfter filtration and evaporation of the solvent
6. customthe crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 3:1)
7. customfollowed by precipitation
8. customA second crop was obtained from the mother liquor after preparative HPLC (26 mg, 7%)
9. customES-MS m/z 455, HPLC RT (Method D) 2.78 min.