A novel solid-phase approach to 2,4-diaminothiazoles

A novel solid-phase synthesis of a 2,4-diaminothiazole library starting fro m a polymer-bound thiouronium salt is described. The synthetic strategy inv olves formation of polymer-bound thioureido-thiourea intermediates 5 which by treatment with alpha -bromo-ketones 6 undergoes S-alkylation, followed b y a base-catalyzed intramolecular-ring closure/cleavage to give 2,4-diamino thiazoles 8. This strategy tolerates a wide range of functionality and prot ecting groups. The novel feature of our method is a polymer-supported auto- scavenging strategy (PSAS), which provides a clean, high-yielding, and trac eless synthesis to 2,4-diaminothiazoles.