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

Article abstract of DOI:10.1016/0040-4039(96)00923-9

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 α-oxo enamines to generate 1,4-dihydropyridines 4 that are 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 α-oxo enamine component. The course of the reaction on solid phase was studied by gel-phase ¹³C NMR spectroscopy. The synthesis is designed to be amenable for combinatorial libraries preparation.