Approaches to combinatorial synthesis of heterocycles: Solid phase synthesis of pyridines and pyrido[2,3-d]pyrimidines

An efficient solid phase synthesis of diverse pyridines and pyrido[2,3-d]pyrimidines is described. O-Immobilized keto esters 2 react with aldehydes to afford Knoevenagel derivatives 3. These undergo Hantzsch-condensation with alpha-ore enamines to generate I,l-dihydropyridines 4 that me oxidized with CAN to produce immobilized pyridines 5. The method has been extended to synthesis of fused pyrido[2,3-d]pyrimidines employing 6-aminouracils as the alpha-oxo enamine component. The course of the reaction on solid phase was studied by gel-phase C-13 NMR spectrosopy. The synthesis is designed to be amenable for combinatorial libraries preparation. Copyright (C) 1996 Elsevier Science Ltd