One-pot solvent-free synthesis of pyrido[2,3-d:6,5-d′]-dipyrimidines catalyzed by MgFe2O4 magnetic nanoparticles under microwave irradiation

The development of multi-component reactions (MCRs) to produce biologically active compounds has become an important area of research in organic, combinatorial, and medicinal chemistry. MCRs leading attractive heterocyclic scaffolds are particularly useful for the creation of diverse chemical libraries of “drug-like” molecules, because, the combination of three or more small-molecular-weight building blocks in a single operation leads to high combinatorial efficacy in creating diversity [1]. The pyridopyrimidine scaffold is extensively described as heterocycles in many natural and synthetic biologically active compounds, as well as in different drug discovery programs. The properties of pyridopyrimidine depend on the position of the nitrogen atom in the fused ring scaffold. Pyrido[2,3-d:6,5-d′]pyrimidines occupy a special place in four possible isomeric structures and their structure has been the subject of medical research, because this scaffold is associated with a wide range of pharmacological properties and biological activities, such as dihydrofolate reductase inhibitory activity, antimicrobial activity, antitumor activity, anti-inflammatory, tyrosine kinase inhibition, calcium channel antagonists and fibroblast growth factor receptor inhibition. Some of the pharmaceutically important compounds containing pyrido[2,3-d]pyrimidine nucleus such as adenosine kinase inhibitor (I) and cyclin-dependent kinase inhibitors (II) [2-5]. In this project, a facile one-pot and four-component economical synthesis of pyrido[2,3-d:6,5-d]dipyrimidines using aldehyde, 2-thiobarbituric acid and ammonium acetate in the presence of MgFe2O4 NPs as magnetically heterogeneous catalyst in solvent free conditions under microwave irradiation is described. The current synthesis displays attractive characteristics such as; the use of magnetically recoverable and reusable catalyst, convenient one-pot operation, short reaction periods, high to excellent yields, solvent free conditions and is considered to be relatively environmentally benign.