Hydrogen Peroxide → 5-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-3-[4-(phenylsulfinyl)-phenyl]-1,2,4-oxadiazole

HRID 2400592Notes

Reaction equation

HRID 2400592 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([S:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:22][CH:21]=3)[N:16]=2)[CH:3]=1.[OH:33]O.O>C1COCC1.[Cl-].[Cl-].[Cl-].[V+3]>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)[N:5]=[C:4]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([S:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[O:33])=[CH:22][CH:21]=3)[N:16]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 784Hydrogen Peroxide2×HCID 962WaterHCID 595047135-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-3-[4-(phenylsulfanyl)phenyl]-1,2,4-oxadiazole

Product 1

HCID 595047045-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-3-[4-(phenylsulfinyl)-phenyl]-1,2,4-oxadiazole

Reagents, catalysts & solvents 2

HCID 178478626HCID 178478626, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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.

Sources & evidence

ORD record
ord-ef18a28ec0534a288c8c85083fa42e3c
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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