Palladium-catalyzed Cyclization of 5-(o-Aminoaryl) 1,2,3-Triazoles with Isocyanides to Construct Triazolo [1,5-c]Quinazolines

Abstract

A series of triazoloquinazoline derivatives were synthesized by insertion cyclization of 5-(o-aminoaryl) 1,2,3-triazoles with isocyanides under palladium catalysis. This method features the construction of tricyclic-fused 1,2,3-triazoles involving two C–N bond formations in one simple manipulation. The system is suitable for a variety of 1,2,3-triazoles and isocyanides with good functional group compatibility, and even for other types of nitrogen-containing heterocyclic compounds such as 1,2,4-triazole, pyrazole, tetrazole, imidazole, and indole.

Keywords

Isocyanide - 1,2,3-Triazole - Insertion - Triazoloquinazoline - Tricyclic-fused triazoles

Publication History

Received: 10 September 2025

Accepted after revision: 29 November 2025

Article published online:
13 January 2026

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• 19 Synthesis of N-(tert-butyl)-[1,2,3] triazolo [1,5-c] quinazolin-5-amines 3: General Procedure. A 10-mL test tube equipped with a magnetic stir bar was charged with palladium acetate (10 mol%), amines 1 (0.3 mmol), potassium carbonate (0.6 mmol), 30 % hydrogen peroxide aqueous solution (0.3 mmol), t-butyl isocyanide 2 (0.45 mmol), and acetonitrile (1 mL), and then sealed with a rubber plug. The solution was stirred at 80 °C for 4 h. After the reaction was completed, the solvent was evaporated under vacuum, and the crude product was purified by column chromatography on silica gel (EtOAc/Petrol = 1:6) to give the pure product 3. N-(tert-butyl)-[1,2,3]triazolo[1,5-c]quinazolin-5-amine 3aa White solid, yield (85%). ¹H NMR (600 MHz, CDCl₃) δ 8.31 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 6.43 (s, 1H), 1.67 (s, 9H). ¹³C NMR (151 MHz, CDCl₃) δ 142.3, 139.7, 134.1, 130.8, 126.6, 126.4, 123.9, 123.7, 114.0, 52.7, 29.0. HRMS (ESI): mass found: 242.1401, calcd mass for C₁₃H₁₅N₅ ⁺ [M+H]⁺: 242.1400.