Microwave-Assisted Regioselective Suzuki Coupling of 2,4-Dichloropyrimidines with Aryl and Heteroaryl Boronic Acids

Ana Dolšak,Kristjan Mrgole,Matej Sova

doi:10.3390/catal11040439

Ana Dolšak, Kristjan Mrgole + Show 1 more

Open Access

https://doi.org/10.3390/catal11040439

Copy DOI

Journal: Catalysts (Basel, Switzerland)	Publication Date: Mar 30, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: University of Ljubljana

Abstract

Suzuki coupling reaction has been often used for the preparation of a diverse set of substituted pyrimidines. In this study, the Suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation led to a very efficient and straightforward synthetic procedure providing C4-substituted pyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) are the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of substituted pyrimidine rings.

Highlights

Substituted pyrimidine rings as scaffolds are of great interest for medicinal chemists being a part of many biologically active compounds [1,2]
Substituted pyrimidine rings represent an attractive scaffold, which has been often present in compounds with diverse biological activities
In the present study we developed a quick, efficient, and regioselective procedure for preparation of C4-substituted pyrimidines from commercially available 2,4-dichloropyrimidines

Summary

Introduction

Substituted pyrimidine rings as scaffolds are of great interest for medicinal chemists being a part of many biologically active compounds [1,2]. Cyclocondensation between guanidine, amidine or thiourea derivatives and 1,3-diketones or 1,3-diesters is the most classical method for the synthesis of the main pyrimidine core [15,17], whereas one of the approaches to prepare substituted pyrimidine rings is via halogenated pyrimidines [18,19,20], which are greatly commercially available. The most common reactions involving various halogenated pyrimidines are cross-coupling reactions since pyrimidine ring is an electron-deficient aromatic system being far more reactive in comparison with analogous benzene halides [17,20]. Suzuki coupling of halogenated pyrimidines with boronic acids has been a commonly used approach for the preparation of a diverse set of substituted pyrimidines [20]

Methods

Results

Conclusion