Antinociceptive pyrimidine derivatives: aqueous multicomponent microwave assisted synthesis

Pyrimidines and their oxo-derivatives are well researched due to their anti-inflammatory, analgesic, antimicrobial, antiviral, and interferon inducing activities. New pyrimidine derivatives are therefore frequently synthesized to build up small molecule libraries for the discovery of drug candidates. Synthesis of 2,6-diaryl-4-(3H)-pyrimidinones and 2,6-diaryl-4-aminopyrimidines is traditionally a 2-day laboratory effort carried out in two steps, always using ethanol as solvent, and triethylamine as base. In this Letter, we advance a one-step alternative synthetic method with a 40 min reaction time using a microwave reactor in an aqueous media with potassium carbonate as base. The average yields were also somewhat improved. This new method thus emerges as more eco-friendly, not only because it does not employ triethylamine as base, but also due to a much reduced usage of organic solvents, leading to less harmful residues. Using this method, we synthesized twenty pyrimidine derivatives with antinociceptive activities in satisfactory chemical yields.