AbstractWe describe a versatile novel approach for the synthesis of 2, 4, 6‐trisubstituted pyrimidines on solid support. Thus, polymer‐boun J thiouronium salt2reacted in high yield in a cyclocondensation reaction with the acetylenic ketones3to form, aftertert‐butyl‐ester cleavage, the polymer‐bound carboxylic acids4, which were cleaved by oxidation with 3‐chloroperbenzoic acid and pyrrolidine to form the 2‐pyrrolidinylpyrimidine‐4‐carboxylic acids6a‐cin high yields and purities without further purification (Scheme 1). Alternatively, acid4awas subjected to anUgifour‐component condensation which gave the polymer‐boundUgiproducts9a‐ein good yields (Scheme 2). Multidirectional cleavage reaction of sulfone8awith different nucleophiles resulted in the clean formation of pyrimidine‐4‐carboxamides10–13(Scheme 3). This strategy combines efficiently solid‐phase chemistry with a multicomponent reaction and a multidirectional cleavage step to form highly divers