A series of 1,3,6-trisubstituted and 1,3,5,6-tetrasubstituted pyrazolo[3,4-b]pyridines 5 has been synthesized by Friedländer condensation of 5-aminopyrazole-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 pyrazolo [3,4-b]pyridine derivatives 7 and 8. Condensation of 5-aminopyrazole-4-carbaldehydes 3 with CHacidic acylacetonitriles 9 and acylacetates 11 with piperidine as basic catalyst yielded pyrazolo [3,4-b] [7]. o-Aminoaldehydes are the key intermediates for the synthesis of various biologically active heterocycles e.g. [8,9] using the Friedländer reaction with ketones in a 4+2 cyclocondensation [10], which prompted us to investigate the reaction pathway of 5-aminopyrazole-4-carbaldehydes with α-methylene ketones to new 1,3,6-trisubstituted and 1,3,5,6-tetrasubstituted pyrazolo [3,4-b]pyridines, especially to 1,3,6-triarylpyrazolo[3,4-b]pyridines. A literature survey shows a few reports on the synthesis of pyrazolo [3,4-b]pyridines using the Friedländer condensation [11], however with substitution patterns different to ours.The required starting materials for the intendedFriedländer condensation, 5-aminopyrazole-4-carbaldehydes 3, were synthesized by cyclocondensation of p-substituted aroylacetonitriles, a class of compounds which was studied recently by us for other cyclization reactions [12]. p-Substituted aroylacetonitriles cyclize as 1,3-dicarbonyl synthons with arylhydrazines already on heating without catalysts according to known methods [13] and furnished in good to excellent yields 5-aminopyrazoles 1, which afforded on Vilsmeier-Haack formylation with excess dimethylformamide and phosphoryl chloride 4-formyl-pyrazolyl-dimethylimidoformamides 2. Thermal analysis of formamides 2 by differential scanning calorimetry (DSC) revealed that they are thermally stable compounds which showed thermal decomposition only above 350 °C. Hydrolysis of formamides 2 with refluxing ethanolic sodium hydroxide yielded the required 5-aminopyrazole-4-carbaldehydes 3 in good yield.

H 2 N-NHPh N N R NH 2 H O O O N N N R O + 9 a-b 10 a-b 11 a-b 12 a-b 11 a-b 1 a-b 1, 4, 9, 10, 11, 12 a-b R = Cl, Br 4 a-b Friedländer condensation of 5-aminopyrazole-4-carbaldehydes 1 with formamide 2a or benzamide 2b gave pyrazolo[3,4-d]pyrimidine derivatives 3. Cyclocondensation of 1 with cyclopentanone, N-benzyl-4piperidone and 6-methoxy-1-tetralone yielded cyclopenta[b]pyrazolo[4,3-e]pyridines 4, pyrazolo[3,4-b]-[1,6]naphthyridines 5 and benzo[h]pyrazolo[3,4-b]quinolines 6, respectively. Analogous condensation of cyclohexanone 7a or 2-methyl-1-cyclohexanone 7b with 1 afforded pyrazolo[3,4-b]quinoline derivatives 8a-d. Heating 1 with dimedone furnished pyrazolo[3,4-b]quinolinone derivatives 9. Vilsmeier-Haack formylation of 9 yielded a mixture of two compounds 10 and 11. Further bispyrazolo[3,4-b:4,3-f]quinolines 12a, b were obtained on cyclocondensation of 11a, b with phenyl hydrazine.Heterocyclic ring systems that containing the pyrazole ring fused to pyrimidine, quinoline or benzoquinoline rings are interesting classes of compounds both chem.ically and biologically. For example, pyrazolopyrimidines display significant chemical properties [1-7], whereas pyrazoloquinolines and pyrazolobenzoquinolines exhibit a wide range of biological properties [8][9][10][11][12][13][14][15]. Our ongoing interest in this area encouraged us to report the synthesis of title compounds.In a recent paper [16], we have reported the synthesis of pyrazolo fused pyridines using orthoaminoaldehyde 1 as a starting material. In this paper we extended this work towards the synthesis of several pyrazolo[3,4-d]pyrim-idine, pyrazolo[3,4-b]quinolines and pyrzolo[3,4-b]benzoquinolines from 1. Compound 1 was synthesized by the method reported in our previous communication [16]. The Friedlander condensation of ortho-aminoaldehyde 1 with amides was performed without catalyst or solvent. Thus a mixture of 1a or 1b and the corresponding formamide 2a or benzamide 2b was heated at 170-180°C to afford pyrazolo[3,4-d]pyrimidines 3a-d in 56-61% yield. However, similar condensation of 1a, or 1b with cyclic ketones was unsuccessful.According to our previous protocol [16], a mixture of 1a or 1b and cyclic ketones such as cylopetanone or Nbenzyl-1-piperidone, on refluxing in ethanolic potassium

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An elegant synthesis of highly fluorescent benzo[h]quinolines have been accomplished from readily available and highly economical 6‐methoxy‐1‐tetralone in high purity and excellent yield.