Methanol → 7-fluoro-4-methyl-1,5-naphthyridin-2(1H)-one

HRID 1510715Notes

Reaction equation

HRID 1510715 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9](=[O:13])[C:10]([CH3:12])=C)=[CH:6][C:5]([F:14])=[CH:4][N:3]=1.O.[CH:16](Cl)(Cl)Cl.CO>CN(C)C=O.C(N(CC)CC)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:14][C:5]1[CH:6]=[C:7]2[C:2]([C:12]([CH3:16])=[CH:10][C:9](=[O:13])[NH:8]2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 962WaterHCID 6212ChloroformHCID 57815236N-(2-chloro-5-fluoropyridin-3-yl)-2-methylacrylamide

Product 1

HCID 578151987-fluoro-4-methyl-1,5-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalyst3×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 1.1 g of N-(2-chloro-5-fluoropyridin-3-yl)-2-methylacrylamide in 10 mL of N,N-dimethylformamide, 1.5 mL of triethylamine and 0.13 g of bis(tri-tert-butylphosphine)palladium(0) were added, and the mixture was stirred at 110° C. for 3 hours 40 minutes under a nitrogen flow. Thereto was further added 0.13 g of bis(tri-tert-butylphosphine)palladium(0), and the mixture was stirred for 2 hours. Thereto was further added 0.13 g of bis(tri-tert-butylphosphine)palladium(0), and the mixture was stirred for 2 hours. The reaction mixture was cooled to room temperature, the solvent was then distilled off under reduced pressure, and diisopropyl ether and ethyl acetate were added to the resultant residue, the solid was filtered off, and washed with ethyl acetate, to the solid thus obtained, water, chloroform and methanol were added, the organic layer was separated and the aqueous layer was extracted with chloroform. 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. To the resultant residue, diisopropyl ether was added, and the solid was filtered off to obtain 0.25 g of 7-fluoro-4-methyl-1,5-naphthyridin-2(1H)-one as a light brown solid.

Workup

  1. stirringthe mixture was stirred for 2 hours
  2. stirringthe mixture was stirred for 2 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. distillationthe solvent was then distilled off under reduced pressure, and diisopropyl ether and ethyl acetate
  5. additionwere added to the resultant residue
  6. filtrationthe solid was filtered off
  7. washwashed with ethyl acetate, to the solid
  8. customthus obtained
  9. customthe organic layer was separated
  10. extractionthe aqueous layer was extracted with chloroform
  11. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. additionTo the resultant residue, diisopropyl ether was added
  14. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-4673990e416e44c8b78b820cfdf73647
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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