Solution- and solid-phase synthesis of combinatorial libraries of trisubstituted 1,3,5-triazines

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 cy anoiminodithiocarbonate (1) was first established in solution (Scheme 1). F urther investigations were directed toward a multidirectional cleavage proc edure of the 2-alkylsulfinyl intermediates with different nucleophiles to f orm highly substituted 1,3,5-triazines of type (8) and (9). This methodolog y was successfully transferred onto solid support taking advantages of a su lfur-based safety catch linkage, using the polymer-bound thiouronium salt ( 11) (Scheme 3). In addition, other compounds libraries were chemoselectivel y generated on solid support in good to excellent yields combining both sol ution- and solid-phase synthesis, starting from a resin-bound thiol (15) an d cyanuric chloride (16) (Scheme 4).