Abstract: A representative set of symmetric diacids was coupled onto deprotected TentaGel Rink Amide resin. The symmetric building blocks served as model to complete a synthesis protocol and to switch to a different synthesis paradigm consecutively. The reaction sequence continued in a non-combinatorial step by coupling of a bifunctional reagent (3-aminoacetophenone) to the remaining carboxyfunction of the symmetric diacid. The ketone served as model of a reagent prepared for combinatorial functional group transformation. The arylmethylketone was reacted with a set of aryl- and heteroarylaldehydes to give a,b-unsaturated ketones. Subsequently, guanidine, alkyl-, and arylcarboxamidines were introduced in combinatorial synthesis of substituted pyrimidines by reaction with the a,bunsaturated ketone functionality. The combination of symmetric building blocks and combinatorial functional group transformation created a versatile reaction sequence ideally suited for production of libraries from libraries with added diversity