One-pot synthesis of triazines as potential agents affecting cell differentiation

Abstract

Abstract: This paper outlines the synthesis of a number of structural analogs of 3-[(4,6-diphenoxy-1,3,5-triazin-2-yl)amino]benzoic acid which represent compounds with potential cardiogenetic activity. A one-pot protocol was developed for swift functionalization of the 1,3,5-triazine core without the need of isolating intermediates. The developed route starts from readily available 2,4,6-trichloro-1,3,5-triazine, displacing the chlorine atoms sequentially by aryloxy, arylamino, or arylthio moieties to enable access to molecules with three different substituents of this type in good yields. To facilitate purification, tert-butyl, methyl, and ethyl ester derivatives of the target compounds were initially synthesized. The tert-butyl esters could be readily hydrolyzed to the desired compounds, while reduction of the methyl and ethyl esters gave the corresponding benzylic alcohols in high yields, thereby expanding the substrate scope for future relevant cell assays. Graphical abstract: [Figure not available: see fulltext.].