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‐trisubstituted pyrimidines on solid support. Thus, polymer‐boun J thiouronium salt 2 reacted in high yield in a cyclocondensation reaction with the 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‐pyrrolidinylpyrimidine‐4‐carboxylic acids 6a‐c in high yields and purities without further purification (Scheme 1). Alternatively, acid 4a was subjected to an Ugi four‐component condensation which gave the polymer‐bound Ugi products 9a‐e in good yields (Scheme 2). Multidirectional cleavage reaction of sulfone 8a with different nucleophiles resulted in the clean formation of pyrimidine‐4‐carboxamides 10–13 (Scheme 3). This strategy combines efficiently solid‐phase chemistry with a multicomponent reaction and a multidirectional cleavage step to form highly diverse pyrimidines in a parallel array.