HCID 59504717, compound → HCID 25121168, compound

HRID 2400583Notes

Reaction equation

HRID 2400583 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:15][O:14][C:13]([C:16]3[CH:20]=[C:19]([CH3:21])[N:18]([CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)[N:17]=3)=[N:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1.[O-2].[O-2].[Mn+4]>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:12]=[C:13]([C:16]3[CH:20]=[C:19]([CH3:21])[N:18]([CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)[N:17]=3)[O:14][CH:15]=2)=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 59504717HCID 59504717, compound

Product 1

HCID 25121168HCID 25121168, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(4-tert-butylphenyl)-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-4,5-dihydro-1,3-oxazole (Example 70, 100 mg, 0.26 mmol) in THF (2 mL) was treated with manganese dioxide (45 mg, 0.52 mmol), and the resultant mixture was stirred to reflux. Further portions of manganese dioxide (45 mg and 90 mg) were added after 2.5 and 4.5 h. After a total of 6.5 h, the mixture was cooled to rt, diluted with 2 ml THF and filtered over a pad of celite. The filtrate was concentrated in vacuo, re-disolved in dichloromethane and successively washed with aqueous HCl (1.0 N) and water, dried (MgSO4), filtered, and concentrated to dryness. The crude material was purified by flash chromatography (silica) eluting with cyclohexane/ethyl acetate 2:1. The combined product fractions were then further purified by preparative HPLC to afford the title compound as a white solid (49 mg, 50%): 1H NMR (400 MHz, DMSO-d5) δ 8.58 (s, 1H), 7.75 (d, 2H), 7.47 (d, 2H), 7.18 (d, 2H), 7.08 (d, 2H), 6.67 (s, 1H), 5.37 (s, 2H), 2.29 (s, 3H), 2.28 (s, 3H), 1.31 (s, 9H); ES-MS m/z 386, HPLC RT (Method E) 2.81 min.

Workup

  1. temperatureto reflux
  2. filtrationfiltered over a pad of celite
  3. concentrationThe filtrate was concentrated in vacuo, re-disolved in dichloromethane
  4. washsuccessively washed with aqueous HCl (1.0 N) and water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified by flash chromatography (silica)
  9. washeluting with cyclohexane/ethyl acetate 2:1
  10. customThe combined product fractions were then further purified by preparative HPLC

Sources & evidence

ORD record
ord-53fd4497227340aaac5ebb6944a8c15e
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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