A Novel and Efficient Approach for the Combinatorial Synthesis of Structurally Diverse Pyrimidines on solid support

Abstract

Abstract 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.