Events The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics

Event submissions

Published

This submission belongs to the session S3. New Small Molecules as Drug Candidates of the event The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics

Published date

28 Oct, 2026

Academic Editor

Mary J. Meegan

Citation

Daria Andreyevna Likhobabina, Alexey Nikolaevich Noev, Nikita Vladimirovich Suvorov, Mikhail Aleksandrovich Grin, Optimization of the conditions for the nucleophilic aromatic substitution reaction of 2,4,5‑trichloropyrimidine, in Proceedings of The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics, 1 November–30 November 2026, MDPI: Basel, Switzerland

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$Optimization of the conditions for the nucleophilic aromatic substitution reaction of 2,4,5‑trichloropyrimidine$

Daria Andreyevna Likhobabina ¹

Alexey Nikolaevich Noev ^1,2

Nikita Vladimirovich Suvorov ¹

Mikhail Aleksandrovich Grin ¹

1. Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry named after N.A. Preobrazhensky, Institute of Fine Chemical Technologies named after M.V. Lomonosov, Federal State Budgetary Educational Institution of Higher Education "MIREA – Russian Technological University", Moscow, Russia

2. Department of Pharmacology of Biomedical Preparations, P.A. Herzen Moscow Oncology Research Institute – Branch of the Federal State Budgetary Institution "National Medical Research Center of Radiology" of the Ministry of Health of Russia, Moscow, Russia

Abstract

2,4,5-Trichloropyrimidine is an important reagent for the synthesis of various tyrosine kinase inhibitors; however, its reactivity decreases significantly with each substituted chlorine atom. Thus, the substitution of the second chlorine atom located in the fourth position is the limiting step in the synthesis of the target compounds. Currently, there are two main methods for replacing the second chlorine atom: 1) heating in alcohol without adding additional reagents, 2) heating in DMF with the use of palladium catalysts. To optimize the first method, reagents were used to create either basic or acidic conditions. Thus, carrying out the reaction in IPA without using additives did not yield a positive result; adding K 2 CO 3 or Et 3 N also did not lead to the formation of the target product, while adding HCl resulted in the production of product without Boc with a yield of 7 %. According to the second method, no product is formed in the absence of a catalyst, but when Pd(OAc) 2 was added, a reaction yield of 24 % was achieved. Other palladium catalysts will be considered for further optimization. The work was carried out with the support of the Ministry of Science and Higher Education of the Russian Federation (FSFZ-2026-0022).

Keywords

tyrosine kinase inhibitors

nucleophilic aromatic substitution

Poster

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