We present the solid-phase synthesis of 1,2-dihydroquinazoline-2-carboxylate derivatives with a quaternary carbon in position 2 and their subsequent cyclization in solution into compounds with unique 3D architectures and pharmacological relevance-spiroquinazolines, namely, 1' H-spiro[pyrrolidine-3,2'-quinazolin]-2-ones and 1' H-spiro[piperidine-3,2'-quinazolin]-2-ones. Acyclic precursors were prepared from commercially available building blocks: protected amino acids (2,4-diaminobutyric acid and ornithine), 2-nitrobenzensulfonyl chlorides and α-bromoacetophenones. The crucial step of the synthesis was a base-mediated tandem reaction including C-arylation followed by cyclization into indazole oxides, and the formation of a 5-membered heterocycle was accomplished by ring expansion into quinazolines. These derivatives were cyclized into spiro compounds in solution after cleavage from the resin.

Department of Organic Chemistry Faculty of Science Palacký University 17 listopadu 12 771 46 Olomouc Czech Republic

Department of Organic Chemistry Faculty of Science Palacký University 17 listopadu 12 771 46 Olomouc Czech Republic Department of Chemistry and Biochemistry University of Notre Dame 251 Nieuwland Science Center Notre Dame Indiana 46556 United States

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