Multicomponent Facile Synthesis of Highly Substituted [1,2,4]Triazolo[1,5-a] Pyrimidines

Abstract

A simple and convenient method for one-pot synthesis of a series of potentially biologically active [1,2,4]triazolo[1,5- a]pyrimidine-6-carboxamide derivatives has been developed in solvent-free conditions using maltose as a commercially available, cheap and eco-friendly catalyst. The salient features of the present protocol are mild reaction conditions, good to excellent yields, high atom economy, benign environmental conditions, easy isolation of products without column chromatography and clean reaction profiles.

An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5‐a]pyrimidine Scaffold

“…Adrom et al. reported the cyclization reaction of 1 H ‐1,2,4‐triazol‐5‐amine ( R16 ) with benzaldehyde and 2,4‐dioxo‐4‐(phenylamino)butan‐1‐ylium in presence of catalytic amount of 25 mol.% of maltose to achieve P16 (5‐methyl‐ N ,7‐diphenyl‐4,7‐dihydro‐[1,2,4]triazolo[1,5‐ a ]pyrimidine‐6‐carboxamide) (route‐16) [34] . Kolosov and co‐workers obtained the desired final compound P17 (5,7‐dimethyl‐6‐(phenylsulfonyl)‐4,7‐dihydro‐[1,2,4]triazolo[1,5‐ a ]pyrimidine) via treating 1 H ‐1,2,4‐triazol‐5‐amine ( R17 ) with acetaldehyde and 1‐(phenylsulfonyl)propan‐2‐one in presence of DMF‐H 2 O under heat conditions (route‐17) [35] …”

“…(5-methyl-N,7-diphenyl-4,7-dihydro-[1,2,4]triazolo [1,5-a]pyrimidine-6-carboxamide) (route-16). [34] Kolosov and co-workers obtained the desired final compound P17 (5,7- in presence of acetic acid and hydrochloric acid to afford P18 under reflux conditions (route-18). [36] Massari et al ).…”

Different Synthetic Methods for the Preparation of Triazolopyrimidines and their Biological Profile

“…Different amines and aldehyhdes have been tested and the yields are high (Scheme 61). [71] N,7-diaryl-5-methyl-4,7-dihydro- [1,2,4]-triazolo[1,5-a]-pyrimidine-6-carboxamides 99 (90-95 %), under solvent-free conditions using maltose as a commercially available, cheap and eco-friendly catalyst, were prepared by Adrom et al [72] via one-pot, three-component reaction under stirring at 80 °C for the appropriate time (14-25 h) (Scheme 62).…”

α-Aminoazoles/azines: key reaction partners for multicomponent reactions

“…In this method, a mixture of 3-amino-1,2,4-triazole 25, aryl aldehyde 4 and acetoacetanilide 52 was heated with maltose as the acidic catalyst at 80 °C under solvent-free conditions ( Scheme 18 ). 58 The reaction was proposed to proceed through the usual pathway, in which the in situ formation of intermediate 54 from acetoacetamide 52 and activated aldehyde 4 occurred followed by nucleophilic attack of 3-amino-1,2,4-triazole 25 in the presence of the catalyst. The resulting species 55 upon cyclisation afforded the desired product.…”