A convenient route for the synthesis of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-b][1,6]naphthyridine and pyrazolo[3,4-b]quinoline derivatives

Abstract

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

Vilsmeier reagent-mediated synthesis of 6-[(formyloxy)methyl]-pyrazolopyrimidines via a one-pot multiple tandem reaction

“…On the other hands, Morgan-Walls cyclization reaction has been widely used for C-C bond formation to build various nitrogen ring systems. [24][25][26] However, the reported synthetic manipulation for their preparation requires harsh conditions, long reaction times, complex synthetic procedures, and tedious purification steps. Other synthesis approaches of pyrazolopyrimidines were also found through heterocyclization reaction using 5-amino-4-formypyrazoles, 22 5-amino-1H-4-pyrazolcarbonitriles, 23 5-amino-1H-4-pyrazolcarboxamides 23 or other similar chemical reagents as the starting substrates.…”

New one‐step synthesis of pyrazolo[1,5‐a]pyrimidine and pyrazolo[1,5‐a]quinazoline derivatives via multicomponent reactions

“…MCR strategies offer significant advantages over conventional linear type synthesis [ 22–24]. As a part of our continued interest [25–27] in the synthesis of novel heterocyclic compounds, we have reported the synthesis of pyrazolo[3,4‐ b ]pyridines, pyrazolo[3,4‐ b ]quinolines, pyrazolonaphthyridines and pyrazolopyridopyrimidines by Friedlander condensation of 5‐aminopyrazole‐4‐carbaldehyde with various reactive methylene compounds and the synthesis of fused pyrimidines [28] by using 2‐aminoheterocycles and cyclic β‐formylesters in ammonium acetate at 120°C. We have also reported the study of fluorescence properties of benzo[ h ]quinolines and dipyrazolopyridines [29, 30].…”

A novel synthesis of benzo[h]quinolines and study of their fluorescence properties

“…We have recently reported facile synthetic routes towards benzo [h]quinolines, fused quinolines, pyrazolopyridine, pyrazoloquinoline and pyrazolopyridopyrimidine derivatives, [12][13][14][15]. Here in we are reporting synthesis and study of photophysical properties of benzo- [h]quinolines.…”