1-Bromo-3-methylbutane → 1-(3-Methylbutyl)-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dione

HRID 601102Notes

Reaction equation

HRID 601102 reaction equation
[H-].[Na+].[NH:3]1[C:8]2[N:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6](=[O:13])[O:5][C:4]1=[O:14].Br[CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19]>CC(N(C)C)=O>[CH3:19][CH:18]([CH3:20])[CH2:17][CH2:16][N:3]1[C:8]2[N:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6](=[O:13])[O:5][C:4]1=[O:14]

Participants

5

Reactant 3

HCID 78911-Bromo-3-methylbutaneHCID 24758Sodium hydrideHCID 109865823-Azaisatoic anhydride

Product 1

HCID 102361501-(3-Methylbutyl)-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dioneYield 51%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A suspension of sodium hydride (95%, 0.048 g, 2.0 mmol) in dimethylacetamide (2 mL) at 20° C. under nitrogen was reacted with the product of Example 1A (0.3 g, 1.83 mmol). The reaction mixture was stirred for ½ hour then treated with 1-bromo-3-methylbutane (0.3 g, 2.0 mmol) and stirred for an additional 16 hours. The reaction was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1) to give the title compound as a white solid (0.218 g, 51%). MS (ESI−) m/z 233 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.93 (s, 3H), 0.96 (s, 3H), 1.55 (m, 2H), 1.66 (m, 1H), 4.14 (t, J=7.72 Hz, 2H), 7.37 (dd, J=7.91, 4.96 Hz, 1H), 8.38 (dd, J=7.72, 1.84 Hz, 1H), 8.78 (dd, J=4.78, 1.84 Hz, 1H).

Workup

  1. stirringstirred for an additional 16 hours
  2. customThe reaction was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1)

Sources & evidence

ORD record
ord-02a358f276394455b1252c24087e4120
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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