Friedländer condensation of 5-aminopyrazole-4-carbaldehydes with reactive α-methylene ketones: Synthesis of pyrazolo[3,4-<i>b</i>]pyridines

Abstract

A series of 1,3,6-trisubstituted and 1,3,5,6-tetrasubstituted pyrazolo[3,4-b]pyridines 5 has been synthesized by Friedlander condensation of 5-arninopyrazole-4-carbaldehydes 3 with α-methylene ketones such as acetone (4a) or acetophenones 4b-f with potassium hydroxide as basic catalyst. Condensation of 5-aminopyrazole-4-carbaldehydes 3 and unsymmetric dialkylketones 6 yielded mixtures of isomeric pyra-zolo[3,4-b]pyridine derivatives 7 and 8. Condensation of 5-aminopyrazole-4-carbaldehydes 3 with CH-acidic acylacetonitriles 9 and acylacetates 11 with piperidine as basic catalyst yielded pyrazolo[3,4-b]pyri-dine-5-carbonitriles 10 and pyrazolo[3,4-b]pyridine-5-carboxylates 12; with diethyl malonate 13 as CH-acidic component, pyrazolo[3,4-b]pyridin-6-ones 14 were obtained.