Diethyl {[(pyridin-3-yl)amino]methylidene}propanedioate → Ethyl 4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate

HRID 1497686Notes

Reaction equation

HRID 1497686 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][CH:8]=[C:9]([C:15]([O:17]CC)=O)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:2]=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[O:17]=[C:15]1[C:2]2[C:3](=[CH:4][CH:5]=[CH:6][N:1]=2)[NH:7][CH:8]=[C:9]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

3

Reactant 1

HCID 2313092Diethyl {[(pyridin-3-yl)amino]methylidene}propanedioate

Product 1

HCID 2763116Ethyl 4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylateYield 50.2%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent2×

Conditions

Temperature
246.5 °C

Procedure

To a hot (248° C., mantle and thermometer were used) and colorless solution of diphenyl ether (100 mL) was added dropwise a light brown solution of diethyl 2-((pyridin-3-ylamino)methylene)malonate (24) (3 g, 11.4 mmol) in diphenyl ether (4 mL, heated to dissolve) at 248° C. for 10 min. During the addition, the reaction mixture turned to a brown solution and then to a dark brown solution. The resulting brown reaction mixture was refluxed (inside temperature was 245 to 248° C.) for 1 h. Then, the heating was stopped and it was allowed to cool to approx. 80° C. at which time some solids started to precipitate and then the mantle was removed. The resulting suspension was poured into approx. 300 mL of hexanes and the brown solids were collected by filtration and washed with hexanes. 1H NMR and LCMS analysis of this solid indicated the presence of two regioisomers in a ratio of approx. 4:1. Then, the two peaks were separated by HPLC method and the desired ethyl 4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate (25) (1.25 g, 50% yield) was isolated as a brown solid.

Workup

  1. custom248° C.
  2. additionDuring the addition
  3. temperatureto cool to approx. 80° C. at which time some solids
  4. customto precipitate
  5. customthe mantle was removed
  6. additionThe resulting suspension was poured into approx. 300 mL of hexanes
  7. filtrationthe brown solids were collected by filtration
  8. washwashed with hexanes
  9. customThen, the two peaks were separated by HPLC method

Sources & evidence

ORD record
ord-b26fa53871284fe499374b8bd2e49a87
Source dataset
uspto-grants-2015_12
Patent number
US09199987B2

Reaction notes

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