We describe a versatile novel approach for the synthesis of 2,4,6-trisubstituted pyrimidines on solid support. Thus, polymer-bound thiouronium salt 2 reacted in high yield in a cyclocondensation reaction with the acetylenic ketones 3 to form, after terr-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-karboxylic acids 6a-e in high yields and purities without further purification (Scheme I ) . Alternatively, acid 4a was subjected to an Ugi four-component condensation which gave the polymer-bound Ugi products 9a-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. As a part of an ongoing project, devoted toward the development of efficient methodologies for a parallel version of the combinatorial synthesis of different molecularily diverse heterocyclic systems on solid support, we have focused our attention on pyrimidine derivatives, due to the broad range of useful properties they display [22] [23], and developed a new and general synthetic route on solid support toward these potentially interesting compounds. Our strategy efficiently combines a versatile cyclocondensation reaction of acetylenic ketones with a polymer-bound isothiourea, to form polymer-bound 2-(alkylthio)-4,6-disubstituted pyrimidines, with the nucleophilic displacement reaction of the 2-sulfonyl group of pyrimidines [24] [25] by various nucleophiles as the key cleavage reaction.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.