A GENERAL AND EFFICIENT SOLID-PHASE SYNTHESIS OF QUINAZOLINE-2,4-DIONES

An efficient solid phase synthesis of chiral quinazolinediones is desc ribed Immobilized amino acid based urea derivatives 3 undergo a racemi zation-free heterocyclization upon gentle heating in presence of tetra methylguanidine to afford fused pyrimidine-2,4-diones 6, which are smo othly N-1-alkylated under mild conditions to produce immobilized quina zolinediones 8. The method is amenable to combinatorial synthesis and offers broad scope for structural and chemical diversity, as illustrat ed by preparation of fused thieno[2,3-d]pyrimidine-2,4-dione 10 and hy droxamate pharmacophore bearing quinazolinedione derivative 11. (C) 19 97 Elsevier Science Ltd.