Transition-metal-catalyzed synthesis of quinazolines: A review

Abstract

Quinazolines are a class of nitrogen-containing heterocyclic compounds with broad-spectrum of pharmacological activities. Transition-metal-catalyzed reactions have emerged as reliable and indispensable tools for the synthesis of pharmaceuticals. These reactions provide new entries into pharmaceutical ingredients of continuously increasing complexity, and catalysis with these metals has streamlined the synthesis of several marketed drugs. The last few decades have witnessed a tremendous outburst of transition-metal-catalyzed reactions for the construction of quinazoline scaffolds. In this review, the progress achieved in the synthesis of quinazolines under transition metal-catalyzed conditions are summarized and reports from 2010 to date are covered. This is presented along with the mechanistic insights of each representative methodology. The advantages, limitations, and future perspectives of synthesis of quinazolines through such reactions are also discussed.

One-Pot Reactions of Triethyl Orthoformate with Amines

“…The synthesis of quinazoline derivatives has also attracted great attention in recent years, and numerous synthetic procedures for their formation have been developed [38][39][40][41][42][43]. It is currently in numerous accepted drugs and biologically active compounds, like erlotinib, gefitinib, prazosin, rutaecarpine and many others, as well as in clinical candidates and biologically active molecules [44][45][46]. Pyrimidines and their derivatives are an important class of heteroaromatic systems found in natural products, used as key intermediates in medicinal chemistry to generate new chemical structures with a diverse range of pharmacological activities, and are gaining attention due to their structural similarity to the purines [47].…”

KOtBu Mediated Alcohol Dehydrogenation Strategy: Synthesis of 2‐Aryl Quinazolinones

“…[9] Over the past few decades transition-metalcatalyzed direct coupling of aminobenzamides with carbonyl compounds have been successfully explored to synthesize quinazolinone derivatives. [10] Transition-metal-catalyzed threecomponent couplings of 2-aminobenzamides, aryl halides or equivalents, and isocyanides are important examples of catalytic synthesis of quinazolinones. [11] Acceptorless dehydrogenative coupling (ADC) reactions [12,13] offer a direct approach for the synthesis of diverse heterocyclic compounds from relatively inexpensive and readily available starting materials.…”

“…Lately, emphasis has been devoted to the development of catalytic coupling methods to increase the efficiency and selectivity in the construction of quinazolinone core structures [9] . Over the past few decades transition‐metal‐catalyzed direct coupling of aminobenzamides with carbonyl compounds have been successfully explored to synthesize quinazolinone derivatives [10] . Transition‐metal‐catalyzed three‐component couplings of 2‐aminobenzamides, aryl halides or equivalents, and isocyanides are important examples of catalytic synthesis of quinazolinones [11] …”

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

“…Aromatic nucleophilic substitution [ 8 ] or metal-catalyzed reactions [ 9 – 10 ] are commonly employed for quinazoline modification ( Scheme 1 ). Existing literature underscores the reactivity of the C4 position in aromatic nucleophilic substitutions of quinazolines I while achieving regioselective replacement at the C2 position poses challenges [ 11 ].…”

“…Conse-quently, ongoing efforts focus on advancing methodologies for synthesizing established quinazoline-based drugs and acquiring novel modified quinazoline derivatives for pharmaceutical or materials science purposes. Aromatic nucleophilic substitution [8] or metal-catalyzed reactions [9,10] are commonly employed for quinazoline modification (Scheme 1). Existing literature underscores the reactivity of Scheme 1: Approaches for quinazoline modifications at the C2 and C4 positions.…”