A NOVEL AND EFFICIENT APPROACH FOR THE COMBINATORIAL SYNTHESIS OF STRUCTURALLY DIVERSE PYRIMIDINES ON SOLID SUPPORT

We describe a versatile novel approach for the synthesis of 2,4,6-tris ubstituted pyrimidines on solid support. Thus, polymer-bound thiouroni um salt 2 reacted in high yield in a cyclocondensation reaction with t he acetylenic ketones 3 to form, after tert-butyl-ester cleavage, the polymer-bound carboxylic acids 4, which were cleaved by oxidation with 3-chloroperbenzoic acid and pyrrolidine to form the 2-pyrrolidinylpyr imidine-4-carboxylic acids 6a-c in high yields and purities without fu rther purification (Scheme I). Alternatively, acid 4a was subjected to an Ugi four-component condensation which gave the polymer-bound Ugi p roducts 9a-e in good yields (Scheme 2). Multidirectional cleavage reac tion of sulfone 8a with different nucleophiles resulted in the clean f ormation of pyrimidine-4-carboxamides 10-13 (Scheme 3). This strategy combines efficiently solid-phase chemistry with a multicomponent react ion and a multidirectional cleavage step to form highly diverse pyrimi dines in a parallel array.