The dihydropyridine-4-carboxylic acid derivative (I) was activated as the pentafluorophenyl ester (II) using pentafluorophenol and DCC. Coupling of the active ester (II) with glutamic acid (III) furnished the N-acyl glutamic acid (IV). Alternatively, (IV) was obtained by coupling of glutamic acid (III) with the pyridine acid (I) via activation with DCC/HOBt. Diacid (IV) was finally treated with NaOH to produce the corresponding disodium salt.
In a related method for the preparation of (IV), acid (I) was activated as the mixed anhydride (V) using isobutyl chloroformate. Coupling of anhydride (V) with the silyl ester (VI), prepared from glutamic acid (III) and hexamethyldisilazane, provided amide (IV).