Traceless solid-phase synthesis of bicyclic dihydropyrimidones using multidirectional cyclization cleavage / Pérez R., Beryozkina T., Zbruyev O.I., Haas W., Kappe C.O. // Journal of Combinatorial Chemistry. - 2002. - V. 4, l. 5. - P. 501-510.

ISSN:
15204766
Type:
Article
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.
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article
DOI:
10.1021/cc0200181
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Affiliations Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria
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Correspondence Address Kappe, C.O.; Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria; email: oliver.kappe@uni-graz.at
CODEN JCCHF
PubMed ID 12217023
Language of Original Document English
Abbreviated Source Title J. Comb. Chem.
Source Scopus