Solid-phase synthesis of the 2-aminobenzoxazole library using thioether linkage as the safety-catch linker

An efficient solid-phase methodology has been developed for the synthesis of 2-aminobenzoxazole derivatives. The key step in this procedure involves preparation of polymer-bound 2-mercaptobenzoxazole resins 3 by reaction of the Merrifield resin with 2-aminophenols and CS(2) in the presence of DIC in MeCN. Oxidation of the resulting resins followed by treatment with amines gives the desired 2-aminobenzoxazole products 5. Further diversification can be introduced to the key resin 11, derived from the nitro group containing resin 3c. This process produces the corresponding amine, which upon reaction with acid chlorides and isocyanates can be used to generate various 6-functionalized 2-aminobenzoxazole analogues 13 and 15.