Cu-catalyzed, ligand free syntheses of arylaminopyrimidines in aqueous solution and in silico investigation of their druglikeliness properties

A ligand free Cu(NO3)2·3H2O catalyzed synthetic protocol for arylaminopyrimidines starting from chloropyrimidines and aliphatic/aromatic amines in aqueous medium is being reported here. The procedure is quite general and was successful to deliver 22 numbers of arylaminopyrimidines including 5 novel compounds in good to excellent yield (54–97 %). The reaction protocol doesn't require dry solvents and inert atmosphere, and in comparison to existing reports, it worked under mild reaction temperature (80 °C). The developed methodology offers first application of ligand free Ullmann type coupling reactions for the synthesis of arylaminopyrimidine-2,4(1H,3H)-diones and arylaminopyrimidines. The aqueous medium containing the catalyst system can be reusable up to third run without significant decline in productivity. All the 22 synthesized compounds were computed to investigate their druglikeliness properties using SwissADME tool. 18 of those were found to obey all the criteria set for druglikeliness properties and 5 of those fulfilling completely the requirements of all the six parameters of bioavailability radar viz. lipophilicity, molecular weight, polarity, solubility, flexibility and saturation to be orally bioavailable. While all the compounds were predicted to have high gastrointestinal (GI) absorption, 16 of those have blood brain barrier (BBB) penetration ability.