Diversity-oriented synthesis of novel benzo[h]quinoline and pyrimidine-tethered tri-substituted methane using L-proline as an effective bio-organo-catalyst

Abstract

We present the synthesis of a novel series of tri-substituted methane (TRSM) derivatives via an efficient one-pot, three-component reaction. This reaction combines 4-hydroxybenzo[h]quinolin-2(1H)-one, aromatic aldehydes, and 1,3-dimethyl-6-aminouracil, catalyzed by L-proline in ethanol. Our primary aim is to create a new TRSM scaffold by incorporating diverse pharmacophore moieties into a unified structure, providing a foundation for future drug discovery and medicinal chemistry studies. Key advantages of this approach include the use of an organocatalyst, a streamlined experimental process, and the absence of toxic byproducts. Notably, the methodology eliminates the need for time-consuming column chromatography, offering a cleaner, more efficient synthesis. The chemical structures of the products were confirmed through IR, NMR, mass spectrometry, and elemental analysis, validating the successful formation of the desired derivatives.