4-Aminosubstituted 1,6-dyhidropyrazolo[3,4-e][1,4] diazepines: the synthesis, NMR-spectral and quantum-chemical study

Authors

  • S. V. Kemskіі Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • Yu. S. Boyko Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • A. V. Bolbut Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • S. Yu. Suykov Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • A. A. Kyrylchuk Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • M. V. Vovk Institute of Organic Chemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.16.896

Keywords:

4-aminosubstituted 1, 6-dyhidropyrazolo[3, 4-e][1, 4]diazepines, structural modification, bioactive compounds

Abstract

The role of the structural modification of 1,4-benzodiazepine systems with dialkylamino groups previously used successfully for a number of important derivatives possessing a complex of specific biological properties has been noted. This paper significantly expands the variety of hetero-annelated diazepines by developing a preparatively convenient synthetic route of new amino substituted pyrazol[3,4-e][1,4]diazepines. For this purpose, the reaction of 4-chloro-1,6-dihydropyrazolo[3,4-e][1,4]diazepines with the primary alkyl (aryl) amines and the secon- dary cycloalkylamines has been studied in detail. It has been found that this interaction occurs under 8-10 hour reflux in ethanol and for the primary and secondary alkylamines it leads to 4-amino-1,6-dihydropyrazolo[3,4-e] [1,4]diazepine hydrochlorides, and in case of aryl amines – to their corresponding free bases with high yields. The reaction of the secondary amines has been shown to be very sensitive to their steric parameters: dietyl- or diisopropylamines do not interact with 4-chloro derivatives of 1,6-dihydropyrazolo[3,4-e][1,4]diazepines. The structure of the compounds synthesized is consistent with the results of elemental analysis, LS/MS-, IR- and NMR-spectra. The COSY and EXSY methods were used for reliable identification of signals of cycloalkylamino substituents of 1,6 dihydropyrazolo[3,4-e][1,4]diazepines. Changes in NMR-spectra during protonation of 5-cycloalkylaminopyrazolodiazepines correspond to the results of quantum chemical simulations, according to them the preferred structure is the one with the protonated nitrogen atom in position 5 of the pyrazolodiazepine system.

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Published

2016-09-19

How to Cite

(1)
Kemskіі S. V.; Boyko, Y. S.; Bolbut, A. V.; Suykov, S. Y.; Kyrylchuk, A. A.; Vovk, M. V. 4-Aminosubstituted 1,6-dyhidropyrazolo[3,4-e][1,4] Diazepines: The Synthesis, NMR-Spectral and Quantum-Chemical Study. J. Org. Pharm. Chem. 2016, 14, 43-51.

Issue

Vol. 14 No. 3(55) (2016)

Section

Original Researches

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