4-Амінозаміщені 1,6-дигідропіразоло[3,4-e][1,4]діазепіни: синтез, ямр-спектральне та квантово-хімічне дослідження

• Main Authors: Kemskіі, S. V., Boyko, Yu. S., Bolbut, A. V., Suykov, S. Yu., Kyrylchuk, A. A., Vovk, M. V.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2016
• Subjects: 4-aminosubstituted 1; 6-dyhidropyrazolo[3; 4-e][1; 4]diazepines; structural modification; bioactive compounds; UDC 547.89 547.233; 4-аминозамещенные 1; 6-дигидропиразоло[3; 4] диазепины; структурная модификация; биоактивные соединения; УДК 547.89 547.233; 4-амінозаміщені 1; 6-дигідропіразоло[3; 4]діазепіни; структурна модифікація; біоактивні сполуки
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.16.896

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.