Synthesis and Electrophilic Substitutions of Novel Pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines

Kamal F.M Atta

doi:10.3390/molecules16087081

Abstract

5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4- triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic reagents gave the respective 6-substituted derivatives 3-5 rather than the 7-isomeric products. Formylation of the key compounds 1 with ethyl formate yielded the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7. Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and nitration gave the monosubstituted derivatives 9 and 10, respectively. Also, treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives 11. The structure of synthesized products was confirmed by elemental analyses, IR, 1H NMR and MS spectra.

Highlights

The pyrazolo[1,5-c]pyrimidine ring represents a biologically and synthetically important class of compounds
In the last few decades, the chemistry of 1,2,4-triazoles and their fused heterocyclic derivatives has received considerable attention owing to their synthetic and effective biological importance. 1,2,4Triazole moieties have been incorporated into a wide variety of therapeutically interesting drug candidates, e.g., triazolam [8], alprazolam [9], etizolam [10], and furacylin [11], including antiinflammatories, central nervous system stimulants, sedatives, anti-anxiety compounds, antimicrobial agents [12,13,14,15] and antimycotic ones such as fluconazole, intraconazole, voriconazole [16,17]
The target pyrazolotriazolopyrimidine compounds were synthesized from 5-aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1a-d that were prepared via a sequence of reactions from ethyl phenylpropiolate [2,22]

Summary

Introduction

The pyrazolo[1,5-c]pyrimidine ring represents a biologically and synthetically important class of compounds. In the last few decades, the chemistry of 1,2,4-triazoles and their fused heterocyclic derivatives has received considerable attention owing to their synthetic and effective biological importance. 1,2,4Triazole moieties have been incorporated into a wide variety of therapeutically interesting drug candidates, e.g., triazolam [8], alprazolam [9], etizolam [10], and furacylin [11], including antiinflammatories, central nervous system stimulants, sedatives, anti-anxiety compounds, antimicrobial agents [12,13,14,15] and antimycotic ones such as fluconazole, intraconazole, voriconazole [16,17]. The above mentioned therapeutic activity has prompted the present investigation to synthesize the pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines ring system 2 and a new series of 7-acetylhydrazino5-aryl-2-phenylpyrazolo[1,5-c]pyrimidine derivatives 7

Results and Discussion

General

Synthesis of Compounds

Conclusions