Chemical Insights Into the Synthetic Chemistry of Quinazolines: Recent Advances

Abstract

In medicinal chemistry, one of the most significant heterocyclic compounds are quinazolines, possessing broad range of biological properties such as anti-bacterial, anti-fungal, anti-HIV, anti-cancer, anti-inflammatory, and analgesic potencies. Owing to its numerous potential applications, in the past two decades, there is an increase in the importance of designing novel quinazolines, exploring promising routes to synthesize quinazolines, investigating different properties of quinazolines, and seeking for potential applications of quinazolines. The present review article describes synthesis of quinazolines via eco-friendly, mild, atom-efficient, multi-component synthetic strategies reported in the literature. The discussion is divided into different parts as per the key methods involved in the formation of quinazoline skeletons, aiming to provide readers an effective methodology to a better understanding. Consideration has been taken to cover the most recent references. Expectedly, the review will be advantageous in future research for synthesizing quinazolines and developing more promising synthetic approaches.

Quinazoline Based HDAC Dual Inhibitors as Potential Anti-Cancer Agents

“…Owing to its ubiquitous nature, synthetic versatility and widespread biological and pharmacological applications, numerous synthetic methods have come to light for the facile synthesis of quinazoline and its derivatives both for therapeutic and imaging purposes [ 15 ]. The most notable among them is the copper-catalyzed intramolecular N-arylation, Rhodium-catalyzed ortho-amidation, cyclocondensation, tetrabutyl ammonium fluoride promoted cyclization of N-imidoyl-o-alkynylanilines, Niementowski reaction, and benzotrizol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate (BOP)-mediated ring closures [ 8 , 17 , 20 ].…”

Late-stage diversification of indole skeletons through nitrogen atom insertion

“…Additionally, indoles bearing adjacent pyridine and benzofuran motifs, common heterocyclic handles, were efficiently transformed into the corresponding quinazoline moieties (8y, 8z). Despite their structural simplicity, most of these quinazolines are novel, as existing methods do not allow easy access to the 2-H quinazoline products (40). TBS-protected indoles featuring substituents on the 2-, 3-or 7position (8ab, 8ac, 8ad) as well as 2,3-disubstituted indoles (8ae) were successfully converted to the corresponding quinazoline motifs in good yields showing the reaction's tolerance to proximal substitutions (Fig.…”

Metal-Free Synthesis of 2-Substituted Quinazolines via Green Oxidation of o-Aminobenzylamines: Practical Construction of N-Containing Heterocycles Based on a Salicylic Acid-Catalyzed Oxidation System

“…This metal-free imine synthesis method not only enables the one-pot synthesis of important heterocyclic compounds, but also the highly selective one-pot reactions (e.g., the Ugi reaction) of multicomponent linkages ( Dong, et al, 2017 ; Kumazawa, et al, 2018 ; Dong et al, 2019 ; Yamamoto et al, 2021 ). To further elucidate the versatility of this metal-free imine synthesis method, we attempted one-pot synthesis for reactions that are typically multistep, and succeeded in the metal-free synthesis of quinazoline derivatives ( Wang and Gao, 2013 ; Faisal and Saeed, 2021 ), which are one of the heterocycles forming the basis of pharmaceuticals, agrochemicals, and functional materials (eq 2).…”