Synthesis of 4-Tetrazolyl-Substituted 3,4-Dihydroquinazoline Derivatives with Anticancer Activity via a One-Pot Sequential Ugi-Azide/Palladium-Catalyzed Azide-Isocyanide Cross-Coupling/Cyclization Reaction

2022/07/26 by Jun Xiong, Huiting He, Hui-Ting He +20 · 8 citations
Chemistry · #Multicomponent Synthesis of Heterocycles #Quinazolinone synthesis and applications #Synthesis of Tetrazole Derivatives

paper · doi:10.1021/acs.joc.2c00382

Abstract

A new one-pot preparation of 4-tetrazolyl-3,4-dihydroquinazolines has been reported. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced azide intermediates without separation, which were treated with isocyanides to give 4-tetrazolyl-3,4-dihydroquinazoline derivatives through a sequential Palladium-catalyzed azide-isocyanide cross-coupling/cyclization reaction in moderate to good yields. The biological evaluation demonstrated that compound 6c inhibited breast cancer cells well and displayed broad applications for synthesis and medicinal chemistry.

Cited by

• Stereoselective Synthesis of 12-Tetrazolyl Substituted (E)-5H-Quinazolino[3,2-a]quinazolines via Sequential Ugi-Azide/Staudinger/aza-Wittig/Addition/Ag(I)-Catalyzed Cyclization
• Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 M Pro and PL Pro . [europepmc]
• Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs. [europepmc]
• Nitrene-transfer from azides to isocyanides: Unveiling its versatility as a promising building block for the synthesis of bioactive heterocycles. [europepmc]
• 2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives. [europepmc]
• One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction. [europepmc]
• Acid-Catalyzed, Metal- and Oxidant-Free C=C Bond Cleavage of Enaminones: One-Pot Synthesis of 3,4-Dihydroquinazolines. [europepmc]
• 2-Azidobenzaldehyde-Enabled Construction of Quinazoline Derivatives: A Review. [europepmc]

Related

• New Facile Synthesis of 3,4-Dihydroquinazoline-2(1H)-thiones by a Sequential Ugi-Azide/Staudinger/Aza-Wittig/Cyclization Reaction
• Stereoselective Synthesis of 12-Tetrazolyl Substituted (E)-5H-Quinazolino[3,2-a]quinazolines via Sequential Ugi-Azide/Staudinger/aza-Wittig/Addition/Ag(I)-Catalyzed Cyclization
• One-Pot Synthesis of [1,2,3]Triazolo[1,5-a]quinoxalin-4(5H)-ones by a Metal-Free Sequential Ugi-4CR/Alkyne–Azide Cycloaddition Reaction
• New Efficient Synthesis of 6,12-Dihydro-5H-quinazolino[3,2-a] quinazolin-5-ones via Ugi/Staudinger/Aza-Wittig/Addition/Nucleophilic Acyl Substitution Sequence
• 1,5-Disubstituted Tetrazoles as Promising Anticancer Resistance Agents: A Chemoinformatic Characterization