American Chemical Society
co8b00145_si_001.pdf (1.29 MB)

Traceless Solid-Phase Synthesis of 1′H‑Spiro[Pyrrolidine-3,2′-quinazolin]-2-ones and 1′H‑Spiro[Piperidine-3,2′-quinazolin]-2-ones via Lactamization of 1,2-Dihydroquinazoline-2-carboxylates

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Version 2 2018-12-20, 16:04
Version 1 2018-11-29, 21:43
journal contribution
posted on 2018-11-28, 00:00 authored by Jana Pospíšilová, Viktor Krchňák, Eva Schütznerová
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.