A solid phase approach to substituted pyrimidines and their conversion into condensed heterocycles for potential use in combinatorial chemistry

A novel general synthesis of substituted pyrimidine 3 has been carried out on solid support. The C-atoms carring the cyano, amino, carboxamido, as well as anchoring site have exploited to generate libraries of compounds 6-8, 10, 13, 15, 17, 19, 21, 23, 25 and 27. A novel strategy to cleave the resin to resin-site unsubstituted system has been developed and it provides 5,6-disubstituted pyrimidines 6-8. In addition, synthesis of 2,5,6-trisubstituted pyrimidines of prototype 10 were carried out by nucleophilic displacement of the anchor by various amines. Further investigations were directed toward the solid phase synthesis of pyrimido[4,5-d]pyrimidines 12, 16, 20 and 24 in which C-atoms carring the oxo, thio, amino, anchoring site as well as NH could be introduced as center of diversity to generate libraries of compounds for potential use. 4-Aminopyrimido[4,5-d]pyrimidines 13 and 17 were obtained from fusion of 3a with urea or thiourea followed by cleavage of support while 3-phenylpyrimido[4,5-d]pyrimidines 21 and 27 were synthesized from cyclisation of 4 with phenyl isocyanate or isothiocyanate followed by release of resin. 7-substituted pyrimido[4,5-d]pyrimidines 15, 19, 23 and 27 were obtained by oxidation of 12, 16, 20 and 24 followed by aminolytic cleavage of support.