Purines, pyrimidines, and imidazoles. Part XXVI. Active esters of some 5-aminoimidazole-4-carboxylic acids and their use in the preparation of 5-aminoimidazole-4-carboxyamides and their nucleoside and nucleotide derivatives

Abstract

p-Nitrophenyl 5-amino-1-cyclohexylimidazole-4-carboxylate, prepared by reaction of the corresponding acid with p-nitrophenol and dicyclohexylcarbodi-imide, with a variety of amines and amino-acid esters gave aminoimidazole carboxyamides. The more reactive 2,4-dinitrophenyl esters of the cyclohexylimidazole and of 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxylic acid were prepared from 1-fluoro-2,4-dinitrobenzene and the appropriate sodium salts in dimethylformamide, and readily gave aminoimidazole carboxyamides with amines or amino-acid esters. The ribosyl ester was also used for the synthesis of 5-amino-1-β-D-ribofuranosylimidazole-4-N-methylcarboxyamide 5′-phosphate and related N-diethyl and N-succino (SAICAR) carboxyamide derivatives by amidation followed by phosphorylation with pyrophosphoryl chloride. The related unsubstituted carboxyamide (AICAR) was also obtained by phosphorylation of the dinitrophenyl ester and reaction of the resulting ester phosphate with ammonia.