New Pyrazolyl‐Nicotinic Acids, Methyl Esters, and 1,3,4‐Oxadiazolyl‐pyrazolyl‐pyridine Tricyclic Scaffold Derivatives from 6‐Hydrazinylnicotinic Acid Hydrazide Hydrate

Abstract

This paper describes an efficient approach for the synthesis of a new series of 6‐[3‐alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl]nicotinic acids (where alkyl = CH3; aryl = Ph, 4‐OCH3Ph, 4,4′‐BiPh; and heteroaryl = 2‐Furyl) from the hydrolysis reaction of alkyl(aryl/heteroaryl)substituted 2‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐5‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐1‐carbonylpyrazol‐1‐yl)pyridines, under basic conditions and at 70–95% yields. In a subsequent step, the esterification reaction of pyrazolyl‐nicotinic acids done in thionyl chloride and methanol led to the isolation of a series of methyl 6‐[alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl] nicotinates as stable hydrochloride salts at 64–84% yields, which could be easily converted to hydrazides to give new oxadiazolyl‐pyrazolyl‐pyridine tricyclic scaffolds at good yields from a [4 + 1] cyclocondensation reaction with 1,1,1‐triethoxyethane and 1‐(triethoxymethyl)benzene as the reagent/solvent.

Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole Bearing Oxadiazole Derivatives

“…1,3,4‐Oxadiazole ( 1 ) is a thermally stable aromatic heterocycle and exists in two partially reduced forms: 2,3‐dihydro‐1,3,4‐oxadiazole(1,3,4‐oxadiazoline) ( 2 ) and 2,5‐dihydro‐1,3,4‐oxadiazole(1,3,4‐oxadiazoline) ( 3 ), depending on the position of the double bond. The completely reduced form of the 1,3,4‐oxadiazole is known as 2,3,4,5‐tetrahydro‐1,3,4‐oxadiazole (1,3,4‐oxadiazolidine) ( 4 ) (Fig. ).…”