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

摘要

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 = CH_3;aryl = Ph, 4-OCH_3Ph, 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.