Solid-Phase Synthesis of 2-Alkyl-4,6-diamino- and 2,4,6-Triaminopyrimidines

Significance

Solid-phase synthesis of 2-alkyl-4,6-diaminopyrimidines and 2,4,6-triaminopyri­midines was demonstrated. 2-(4-Formyl-3-methoxyphenoxy)ethyl polystyrene resin 1 was coupled with several primary aliphatic amines to give supported secondary amine 2. Pyrimidine 3 was attached to resin 2 to give 4-chloropyrimidine derivatives 4. Resin 4 was loaded with various aliphatic amines by aromatic nucleophilic substitution reaction. The resulting compounds 5 were converted via cleavage of PS-supports with TFA into 2-alkyl-4,6-di­aminopyrimidines or 2,4,6-triaminopyrimidines 6 of 80-99% purity in 57-96% overall yields (19 examples).