Solution- and Solid-Phase Synthesis of Combinatorial Libraries of Trisubstituted 1,3,5-Triazines

Abstract

A general synthesis of trisusbstituted 1,3,5-triazines of types ( 4) and ( 5) by condensation of amidines (2) and thiouronium salts (3) with dimethyl cyanoiminodithiocarbonate (1) was first established in solution (Scheme 1).Further investigations were directed toward a multidirectional cleavage procedure of the 2-alkylsulfinyl intermediates with different nucleophiles to form highly substituted 1,3,5-triazines of type (8) and ( 9).This methodology was successfully transferred onto solid support taking advantages of a sulfur-based safety catch linkage, using the polymerbound thiouronium salt (11) (Scheme 3).In addition, other compounds libraries were chemoselectively generated on solid support in good to excellent yields combining both solution-and solid-phase synthesis, starting from a resin-bound thiol (15) and cyanuric chloride (16) (Scheme 4).