Synthesis of novel 1,2,4-oxadiazole heterocyclic compounds containing 2-H pyranopyridine-2-one moiety and related compounds

Abstract

7-Hydroxy/Amino-5-methyl-6-(5-substituted-[1,2,4]oxadiazol-3-yl)-2-oxo-2H-pyrano[2,3-b]pyridine-3-carboxylic acid amides 5a-c and 6a-c have been prepared starting from ethyl 2H-pyrano [2,3-b] pyridine-3-carboxylate 1 and 2, compounds 1 and 2 are treated with aqueous ammonia solution to afford 2H-pyrano[2,3-b] pyridine-3-carboxamide 3a-b, which are converted to 6-carboxamidoxime 2H-pyrano [2,3-b] pyridine-3-carboxamide 4a-b by treating with hydroxyl amine in refluxing ethanol. Carboxamidoximes 4a-b are treated with various acid chlorides to obtain 1,2,4-oxadiazole derivatives 5a-c and 6a-c. Carboxamide 3a is reacted with triethyl orthoformate to give 4-amino-5-methyl pyrano [3",2':5,6] pyrido [2,3-d] pyrimidine-7-carboximde 7. Carboxamidoxime 4a is allowed to react with N,N-dimethyl formamide dimethyl acetal under reflux to obtain N-(6-carbonyl-4-methyl-7-oxo-1,7-dihydropyrano[2,3-b]pyrazolo[4,3-e]pyri¬dine-3-yl)methanamide 8. These compounds are expected to have better hypertensive activity.