title: Traceless solid-phase synthesis of bicyclic dihydropyrimidones using multidirectional cyclization cleavage.
abstract: Solid-phase and solution-phase protocols for the synthesis of furo[3,4-d]pyrimidines, pyrrolo[3,4-d]pyrimidines, and pyrimido[4,5-d]pyridazines are reported. The multistep solid-phase sequence involves the initial high-speed, microwave-promoted acetoacetylation of hydroxymethylpolystyrene resin with methyl 4-chloroacetoacetate. The immobilized 4-chloroacetoacetate precursor was subsequently subjected to three-component Biginelli-type condensations employing urea and a variety of aromatic aldehydes. The resulting 6-chloromethyl-functionalized resin-bound dihydropyrimidones served as common chemical platforms for the generation of the desired heterobicyclic scaffolds using three different traceless cyclative cleavage strategies. The corresponding furo[3,4-d]pyrimidines were obtained by microwave flash heating in a rapid, thermally triggered, cyclative release. Treatment of the chloromethyl dihydropyrimidone intermediates with a variety of primary amines followed by high-temperature microwave heating furnished the anticipated pyrrolo[3,4-d]pyrimidine scaffolds via nucleophilic cyclative cleavage. In a similar way, reaction with monosubstituted hydrazines resulted in the formation of pyrimido[4,5-d]pyridazines. All compounds were obtained in moderate to good overall yields and purities.
authors.affiliation: Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
authors.forename: Rolando
authors.initials: R
authors.lastname: Pérez
authors.forename: Tetyana
authors.initials: T
authors.lastname: Beryozkina
authors.forename: Oleksandr I
authors.initials: OI
authors.lastname: Zbruyev
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Haas
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Kappe