Solution-phase synthesis of a library of 3,5,7-trisubstituted 3H-[1,2,3]triazolo[4,5-d]pyrimidines

An efficient solution-phase parallel synthesis of a library of 3,5,7-tri substituted [12,3]triazolo[4,5-d]-pyrimidines is described. Monosubstituted amidines may be converted to 2-substituted 5-amino-4,6-dihydroxypyrimidines in four steps. Treatment with a primary amine followed by cyclization yields the 7-chloro-3,5-disubstituted [1,2,3]triazolo[4,5-d]pyrimidines as penultimate intermediates. Final nucleophilic Substitution of the 7-chloro group with an excess of a primary or secondary amine, a hydrazine or a O-alkylhydroxylamine proceeds efficiently. Scavenging of the excess amine with a resin-bound isocyanate in the presence of resin-bound piperidine as a base affords the desired 3,5,7-tri substituted [1,2,3]triazolo[4,5-d]pyrimidines in good yields and purities.