The competitive N1-, N2-, O- and C-methylation of 3-trifluoromethyl-1H-pyrazol-5-ol for synthesis of analgesic compounds

Abstract We have found selective conditions for methylation of 3-trifluoromethyl-1 H -pyrazol-5-ol that allowed us to obtain mono-Me-substituted N 1 - and O-isomers as well N 1 ,N 2 -, N 1 ,O- and N 2 ,O-disubstituted isomers. A tautomeric structure of the parent pyrazole and its Me-substituted derivatives was investigated using quantum-chemical calculations, X-ray diffraction analysis, IR and NMR spectroscopy. Besides, the quantum-chemical calculations were used to explain the methylation direction. An analgesic activity and acute toxicity of some synthesized compounds were evaluated in vivo experiments.