tert-Butyl hydroperoxide → tert-Butyl (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-2-carboxylate

HRID 589083Notes

Reaction equation

HRID 589083 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][C@H:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:12]4[C:23]([CH:25]=[O:26])=[N:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:27])[O:4][N:3]=1.Cl.CNC.C(=O)([O-])[O-].[Ca+2].[C:37]([O:41]O)([CH3:40])([CH3:39])[CH3:38].CCCCCCCCCC>C(#N)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][C@H:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:12]4[C:23]([C:25]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:26])=[N:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:27])[O:4][N:3]=1

Participants

8

Reactant 5

HCID 6410tert-Butyl hydroperoxideHCID 10112Calcium CarbonateHCID 10473Dimethylamine, hydrochlorideHCID 15600DecaneHCID 90409512(4S)-7-(3,5-Dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-2-carbaldehyde

Product 1

HCID 86299167tert-Butyl (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 24463Copper sulfate pentahydrateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

(4S)-7-(3,5-Dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine-2-carbaldehyde (15 mg, 0.042 mmol) and dimethylamine hydrochloride (0.0041 g, 0.050 mmol) [Aldrich, cat. #126365] were dissolved in acetonitrile (1.5 mL) at room temperature. To the resulting mixture, copper(II) sulfate pentahydrate (0.0005 g, 0.002 mmol) [Aldrich, cat. #209198], calcium carbonate (0.0046 g, 0.046 mmol) [Aldrich, cat. #C6763] and 6.0 M tert-butyl hydroperoxide in decane (0.0076 mL, 0.046 mmol) [Aldrich, cat. #416665] were added. The reaction vessel was capped, degassed, and allowed to stir at 40° C. for 10 hours. After filtration through Celite, the solution was concentrated and the resulting residue was purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) afforded the following three compounds:

Workup

  1. customThe reaction vessel was capped
  2. customdegassed
  3. filtrationAfter filtration through Celite
  4. concentrationthe solution was concentrated
  5. customthe resulting residue was purified by preparative LCMS (XBridge C18 column
  6. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)
  7. customafforded the following three compounds

Sources & evidence

ORD record
ord-fc5bd1ff553c4e6d85b50fa83fd67138
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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