Synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones by the condensation of cyclohexanone derivatives with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one

Abstract

The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure of the 7-acetyl-2, 4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-1-one obtained was proved by X-ray diffraction analysis.On the basis of tetrahydroisoquinoline a series of compounds used in medicine as drugs has been synthesized [1, 2]. Besides, the isoquinoline framework is a part of many alkaloids exhibiting pharmacological effect [3][4][5]. In turn, among the pyrazoloizoquinolines some kinase inhibitors were identified, which were taken as the base to develop drugs for the treatment of osteoarthritis, rheumatoid arthritis and asthma [6]. Therefore, the development of the methods of synthesis and production of new compounds of this class is relevant and promising in terms of finding new biologically active substances.In the present study, we investigated a reaction of 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones (Ia-Ig) with 3-amino-1-phenyl-1H-pyrazol-5H-one (II). We found that at reflux in the presence of sodium ethoxide a formation occurs of new derivatives of the tricyclic system 6-aryl(heteryl)-7-acetyl-2,4, 6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-1H-pyrazolo[3,4-c]isoquinolin-1-ones (IIIa-IIIg), apparently as a result of intramolecular cyclization of intermediates (A).Structure of compounds obtained is confirmed by spectral studies (see Experimental). However, unambiguous choice between the prototropic tautomers III and IV was impossible. Therefore, the structure of 7-acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-1-one IIIf was studied by the X-ray diffraction analysis (see the figure and Tables 1, 2).

Regioselective alkylation of substituted 1H-pyrazolo[3,4-c]isoquinolin-1-ones

“…IR spectrum, ν, cm -1 : 3392 (OH), 1709 (C=O). 1 The IR spectra were recorded in KBr on a Perkin Elmer Spectrum One spectrometer. The 1 H and 13 C NMR spectra were measured on a Bruker Avance instrument at 399.95 and 100 MHz, respectively, using DMSO-d 6 as solvent and tetramethylsilane as internal reference.…”

“…According to the X-ray diffraction data [1], molecules 1a and 1b in crystal are largely contributed by zwitterionic structure A. Compounds 1a and 1b in DMF in the presence of aqueous potassium hydroxide are likely to generate anion B which exists in tautomeric equilibrium with oxygen-centered anion C. The reaction of anion B with alkyl halides 2a and 2b yields N-alkylpyrazolo [3,4-c]isoquinolines 3a-3c.…”

One-pot synthesis of functionalized pyrazolo[3,4-c]pyrazoles by reaction of 2-cyano-N-methyl-acrylamide, aryl aldehyde, and hydrazine hydrate

“…1,2 Also, monocyclic pyrazoles are useful scaffolds for the synthesis of larger fused heterocyclic systems. Among them, we can mention pyrazolo-fused pyrimidines, 3 quinolines, 4 pyridines, 5 thiazoles, 6 isoquinolines, 7 imidazoles, 8 diazepines, 9 and triazines. 10 Fused pyrazoles are important classes of heterocycles with effective biological activity such as antitumor, 11 antioxidant, 2 antimicrobial, 12 antiviral, 13 and as immunostimulatory agents.…”

The Reaction of 5-Amino-3-(cyanomethyl)-1H-pyrazol-4-carbonitrile with beta-Cycloketols

“…However, the heterocyclization reactions of β-cycloketols are not well studied. Thus, the literature describes the preparation of isoquinolines 2 [3][4][5][6][7], indazoles 3 [8][9][10], benzo[c]isoxazoles 4 [9,10], [1,2,4]triazolo [3-b]quinazolines 5 [11] and pyrazolo[3-c]isoquinolines 6 [12] (Scheme 1) by reactions of beta-cycloketols with various 1,2-and 1,3-dinucleophilic agents. Despite the large attention paid to reactions of aminoazoles with 1,3-dielectrophilic agents (see reviews [13,14]), only a few examples of reactions involving β-cycloketols were found in the literature.…”