Diethyl {[(pyridin-3-yl)amino]methylidene}propanedioate → Ethyl 4-hydroxy-1,5-naphthyridine-3-carboxylate
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
Product 1
Reagents, catalysts & solvents 1
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.