Design, Synthesis, and Molecular Docking Studies of Pyrazine Containing 1,2,3‐Triazole Derivatives

Abstract

Here, we demonstrate on the design and synthesis of novel pyrazine containing 1,2,3‐triazole derivatives (7a, 7b, 7c, 7d, 8a, 8b, 8c, 8d, and 12a, 12b, 12c, 12d) using various chemicals, bases, and catalysts synthesized with excellent yields (78–92%) as described in the procedures. The development of this methodology is simple, efficient, and easier to handle; milder reaction conditions and higher selectivity under versatile coupling reagent useful for both amide and ester bond formations have also been developed. The synthesis of amide coupling derivatives prepared by (6a, 6b, 6c, 6d) was coupled with N‐ethylpiperazine to afford (7a, 7b, 7c, 7d) and morpholine to afford (8a, 8b, 8c, 8d) by using 1‐[Bis(dimethylamino)methylene]‐1H‐1,2,3‐triazolo[4,5‐b]pyridinium 3‐oxid hexafluorophosphate (HATU) and N,N‐diisopropylethylamine (DIPEA) in dichloromethane at room temperature for 10 h. The derivatives (6a, 6b, 6c, 6d) were coupled with alcohol (11) by using N,N′‐dicyclohexylcarbodiimide and 4‐dimethylaminopyridine in dichloromethane (DCM) at room temperature for 16 h to give final compounds (12a, 12b, 12c, 12d). In silico docking approach has been applied to these compounds to screen their efficacy against selected drug targets of cancer and diabetes. The docking approach may facilitate the prediction of activity profile for future experimental findings.

Mechanistic Evaluation of Benzoin Catalysis Enabled by Triazolium Salt Application in the Preparation of Benzil and Heterocycles

“…[52][53][54][55][56] One of the most significant nitrogen-containing heterocycle molecules and adaptable building blocks for the synthesis of natural products, pharmaceuticals, and other biologically active compounds is based on quinoxaline, pyrazine, triazole, and imidazole core. [57][58][59][60][61][62] Herein, we'd like to report our modified condition for the synthesis of a wide range of pyrrolidine-based triazolium NHCs via mechanistic understanding with successful isolation of imine ether intermediates. We evaluated a key potential use for synthesised NHC organocatalysts in the benzoin condensation process with mechanistic understating to produce high yields of benzoin derivatives having an electron-withdrawing group.…”

“…The wide range of pharmaceutical and medicinal applications of quinoxaline and imidazole moiety has triggered the development of several synthetic methods for their important organic synthesis. [57][58][59][60][61][62] As a result, we are now reporting a gentle and practical method for making functionalized 1,2,4,5tetrasubstituted imidazoles using aryl amine, benzil, and ammonium acetate, all of which are easily accessible and bear the sensitive functionalities in the presence of an acid catalyst. [57] The 10 mol% meldrum's acid organocatalyzed preparation of highly substituted imidazoles moiety has been achieved from a mixture of benzil (1 equiv.…”

“…One of the most significant nitrogen‐containing heterocycle molecules and adaptable building blocks for the synthesis of natural products, pharmaceuticals, and other biologically active compounds is based on quinoxaline, pyrazine, triazole, and imidazole core [57–62] …”

New Bis-Cyclometalated Iridium(III) Complexes with β-Substituted Porphyrin-Arylbipyridine as the Ancillary Ligand: Electrochemical and Photophysical Insights

“…The access to new iridium(III) cyclometalated complexes is receiving much attention within the scientific community due to their promising applications in several fields [ 1 , 2 , 3 , 4 ]; their use in electron transfer arrays, photoelectrochemistry, (photo)catalysis, and electroluminescence, namely in organic light emitting diodes (OLEDs), are certainly of great significance [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. More recently, this type of compounds shows promising features to be used as alternatives to the platinum-based anti-tumor drugs, like cisplatin, which have demonstrated several disadvantages such as neurotoxicity, elevated blood pressure, induce hearing, kidney damage, nauseas, among others.…”