Sodium hydride → 2-Oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid

HRID 1670185Notes

Reaction equation

HRID 1670185 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:9]([C:10]([O:12]C)=[O:11])=[CH:8][CH:7]=[CH:6][N:5]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CS(C)=O>[O:3]=[C:4]1[C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=[CH:6][N:5]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 59852857Methyl 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylate

Product 1

HCID 210815852-Oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The heterocyclic amide derivatives 100 and 105 can be prepared according to the synthetic routes described in Schemes 18 and 19. To this end, methyl 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylate (97) can be obtained in a two step process beginning with commercially available (E)-dimethyl 2-(3-methoxyallylidene)malonate (95) (Scheme 18). Thus, treatment of compound 95 with aniline at room temperature can provide intermediate 96, which can then cyclized in the presence of a base, such as sodium hydride in dimethylsulfoxide to generate 97. Hydrolysis of intermediate 97 under basic conditions can provide 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid (98). The carboxylic acid 98 can then be coupled with the aniline derivative 99 in the presence of a coupling reagent, such as 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and hydroxybenzotriazole (HOBt) in DMF to furnish the desired compound 100.

Sources & evidence

ORD record
ord-24c95e3d80834e4cbc59b67cf1e29264
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

Loading…