Water → 1-(1,3-dioxolan-2-ylmethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

HRID 1510611Notes

Reaction equation

HRID 1510611 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:13])[NH:10]2)=[N:5][CH:4]=1.[H-].[Na+].Br[CH2:17][CH:18]1[O:22][CH2:21][CH2:20][O:19]1.O>CN(C)C=O.C(OCC)(=O)C>[O:19]1[CH2:20][CH2:21][O:22][CH:18]1[CH2:17][N:10]1[C:11]2[C:6](=[N:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[CH:7]=[CH:8][C:9]1=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 780681,3-Dioxolane, 2-(bromomethyl)-HCID 578154107-Methoxy-1,5-naphthyridin-2(1H)-one

Product 1

HCID 578152071-(1,3-dioxolan-2-ylmethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 0.23 g of 7-methoxy-1,5-naphthyridin-2(1H)-one in 3 mL of N,N-dimethylformamide, 79 mg of 60% sodium hydride was added at room temperature, the temperature was increased to 50° C., and the mixture was stirred for 15 minutes. Thereto was added 0.41 mL of 2-bromomethyl-1,3-dioxolan, the temperature of the reaction mixture was increased to 90 to 100° C., and the reaction mixture was stirred for 3 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with hexane:ethyl acetate=100:0 to 33:67, then gradient elution with chloroform:methanol=100:0 to 90:10 to obtain 0.11 g of 1-(1,3-dioxolan-2-ylmethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one as a light brown solid.

Workup

  1. additionwas added at room temperature
  2. temperaturethe temperature of the reaction mixture was increased to 90 to 100° C.
  3. stirringthe reaction mixture was stirred for 3 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe resultant residue was purified by flash silica gel column chromatography
  10. washelution with hexane
  11. washethyl acetate=100:0 to 33:67, then gradient elution with chloroform

Sources & evidence

ORD record
ord-ab130878035a4589bc2ef3c6471f9b0a
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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