A new general three component solution-phase synthesis of 2-amino-1,3-thiazole and 2,4-diamino-1,3-thiazole combinatorial libraries

Abstract

A general procedure for the solution-phase synthesis of amino-1,3-thiazole libraries 9 and 10 is described. Their preparation is based on the condensation of amidines 1 and thiouronium salts 2 with isothiocyanates 3, affording amidino–thioureas and thioureido-thioureas of types 4 and 5. Subsequent treatment with α-bromo ketones 6 led to the S-alkylated intermediate, which yielded 1,3-thiazoles of types 9 and 10 via a base-catalysed ring closure process (Scheme 1) . In addition, this methodology tolerates a diverse range of functionality without recourse to protection.