Hydrogen Peroxide → HCID 90409125, compound

HRID 589022Notes

Reaction equation

HRID 589022 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:12]4[C:23](=[O:25])[NH:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:26])[O:4][N:3]=1.[OH:27]O>O1CCCC1.O.CCOC(C)=O.C[Re](=O)(=O)=O>[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N+:18]=4[O-:27])[N:12]4[C:23](=[O:25])[NH:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:26])[O:4][N:3]=1

Participants

7

Reactant 2

HCID 784Hydrogen PeroxideHCID 86298851HCID 86298851, compound

Product 1

HCID 90409125HCID 90409125, compound

Reagents, catalysts & solvents 4

HCID 178477782HCID 178477782, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Methyltrioxorhenium(VII) (2 mg, 0.008 mmol) was added to a solution of 7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (20 mg, 0.06 mmol) from Example 15, in tetrahydrofuran (2 mL) at room temperature and then 3.0 M hydrogen peroxide in water (0.04 mL) was added. The reaction mixture was heated to 80° C. for 20 min. allowed to cool and was diluted with water and EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by preparative HPLC on a C-18 column eluting with a water:MeCN gradient buffered pH 10 to give the title compound as a white amorphous solid (0.007 g, 30%). LCMS calc. for C19H17N4O4 (M+H)+: m/z=365.1. found: 365.1. 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.37 (d, J=5.8 Hz, 1H), 7.39 (td, J=7.2, 6.5, 2.0 Hz, 1H), 7.25 (td, J=7.7, 0.9 Hz, 1H), 6.84 (d, J=8.1 Hz, 1H), 6.77 (d, J=8.0 Hz, 1H), 6.63 (dd, J=7.9, 2.0 Hz, 1H), 5.84 (d, J=2.2 Hz, 1H), 4.78 (dd, J=11.6, 1.3 Hz, 1H), 4.36 (dd, J=11.6, 3.4 Hz, 1H), 2.17 (s, 3H), 2.00 (s, 3H).

Workup

  1. temperatureto cool
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThe product was purified by preparative HPLC on a C-18 column
  8. washeluting with a water

Sources & evidence

ORD record
ord-03efa697a6164d4db2c4175b2c897ff2
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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