Ethyl Acrylate → 7-Fluoro-1,5-naphthyridin-2(1H)-one

HRID 385490

Reaction equation

HRID 385490 reaction equation
Br[C:2]1[C:7]([NH2:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12]>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.C(N(CC)CC)C>[NH2:8][C:7]1[C:2](/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13])=[N:3][CH:4]=[C:5]([F:9])[CH:6]=1.[F:9][C:5]1[CH:6]=[C:7]2[C:2]([CH:12]=[CH:11][C:10](=[O:13])[NH:8]2)=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 8821Ethyl AcrylateHCID 404273672-Bromo-5-fluoropyridin-3-amine

Product 2

HCID 469008017-Fluoro-1,5-naphthyridin-2(1H)-oneHCID 68105283ethyl (2E)-3-(3-amino-5-fluoropyridin-2-yl)acrylate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
147.5 °C

Procedure

To 0.99 g of 2-bromo-5-fluoropyridin-3-amine, 0.67 mL of ethyl acrylate, 3.5 mL of triethylamine, and 0.13 g of bis(tri-tert-butylphosphine)palladium(0) were added, and the mixture was stirred at an external temperature of 145 to 150° C. for 5 hours in a sealed tube. The reaction mixture was cooled to room temperature and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with chloroform:methanol=100:0 to 90:10 to obtain 0.37 g of ethyl (2E)-3-(3-amino-5-fluoropyridin-2-yl)acrylate and 0.15 g of 7-fluoro-1,5-naphthyridin-2(1H)-one as light brown solids.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. distillationthe solvent was distilled off under reduced pressure
  3. customThe resultant residue was purified by flash silica gel column chromatography
  4. washelution with chloroform

Sources & evidence

ORD record
ord-d2f3bbce24b54a4fa176006bd43234d3
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Linked notes

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