Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C, N-diheteroarylcarbamidines

Pavel S Silaichev; Tetyana V Beryozkina; Vsevolod V Melekhin; Valeriy O Filimonov; Andrey N Maslivets; Vladimir G Ilkin; Wim Dehaen; Vasiliy A Bakulev

doi:10.3762/bjoc.20.3

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C, N-diheteroarylcarbamidines

Beilstein J Org Chem. 2024 Jan 5:20:17-24. doi: 10.3762/bjoc.20.3. eCollection 2024.

Authors

Pavel S Silaichev¹, Tetyana V Beryozkina², Vsevolod V Melekhin^{3

4}, Valeriy O Filimonov¹, Andrey N Maslivets¹, Vladimir G Ilkin², Wim Dehaen⁵, Vasiliy A Bakulev²

Affiliations

¹ Department of Organic Chemistry, Perm State University, 15 Bukireva st., Perm 614990, Russia.
² TOS Department, Ural Federal University, 19 Mira st., Yekaterinburg 620002, Russia.
³ Innovation Center for Chemical and Pharmaceutical Technologies, Ural Federal University, 19 Mira st., Yekaterinburg 620002, Russia.
⁴ Department of Medical Biology and Genetics, Ural State Medical University, 3 Repina st., Yekaterinburg 620028, Russian.
⁵ Sustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

Abstract

A novel and efficient base-catalyzed, transition-metal-free method for the synthesis of diheterocyclic compounds connected by an amidine linker, including apart from the common 1,2,3-triazole ring, either an additional pyrimidinedione, 4-nitroimidazole, isoxazole, 1,3,4-triazole, 2-oxochromone or thiazole ring, has been developed. The process was facilitated by a strong base and includes the cycloaddition reaction of 3,3-diaminoacrylonitriles (2-cyanoacetamidines) to heterocyclic azides followed by a Cornforth-type rearrangement to the final products. The reaction is tolerant to various N-monosubstituted 3,3-diaminoacrylonitriles and to different heterocyclic azides. The developed method has a broad scope and can be applied to obtain a variety of N-heteroaryl-1,2,3-triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N¹ position .

Keywords: 1,2,3-triazole; 3,3-diaminoacrylonitriles; Cornforth rearrangement; cycloaddition reactions; heterocyclic azides.

Grants and funding

Design and elaboration of a novel tandem process, synthesis of starting building blocks and 21-st target compounds was made by chemistry team and founded by Russian Science Foundation, project number 23-13-00248. The study of cytotoxic effect of 7 compounds was financially supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of the Program of the Development of the Ural Federal University named after the first President of Russia B.N. Yeltsin under the Federal Academic Leadership Program “Priority 2030”.