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

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Reaction Steps

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.

Provenance & Evidence