Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

摘要

A straightforward synthesis of 6-substituted 1-phenyl-3-trifluoromethyl-1 H -pyrazolo[4,3- c ]pyridines and the corresponding 5-oxides is presented. Hence, microwave-assisted treatment of 5-chloro-1-phenyl-3-trifluoromethylpyrazole-4-carbaldehyde with various terminal alkynes in the presence of tert -butylamine under Sonogashira-type cross-coupling conditions affords the former title compounds in a one-pot multicomponent procedure. Oximes derived from (intermediate) 5-alkynyl-1-phenyl-3-trifluoromethyl-1 H -pyrazole-4-carbaldehydes were transformed into the corresponding 1 H -pyrazolo[4,3- c ]pyridine 5-oxides by silver triflate-catalyzed cyclization. Detailed NMR spectroscopic investigations (1H, 13C, 15N and 19F) were undertaken with all obtained products.