Diastereoselective synthesis of fluorinated piperidine quinazoline spirocycles as iNOS selective inhibitors

Diastereoselective synthesis of fluorinated piperidine quinazoline spirocycles as iNOS selective inhibitors

A diastereoselective synthesis of fluoropiperidine quinazoline spirocycles has been developed through a silyl triflate mediated intermolecular coupling of difluorobenzamidine and racemic N-protected 3-fluoropiperidine dimethyl ketals or piperidones. Combination of the silyl reagents together with Le...

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Bibliographic Details
Published in:Tetrahedron letters Vol. 53; no. 24; pp. 2942 - 2947
Main Authors: Walpole, Chris, Liu, Ziping, Lee, Ernest E., Yang, Hua, Zhou, Fei, Mackintosh, Nicole, Sjogren, Magnus, Taylor, David, Shen, Jinyu, Batey, Robert A.
Format: Journal Article
Language:English
Published: Elsevier Ltd 13-06-2012
Subjects:
Chemical reactions
Difluorobenzamidine
Dimethyl
Inhibitors
Isomers
Joining
Lewis acid
Piperidine
Piperidone
Spirocycle
Synthesis (chemistry)
Tetrahedrons
Lewis acid
Difluorobenzamidine
Spirocycle
Piperidone
Piperidine
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Summary:A diastereoselective synthesis of fluoropiperidine quinazoline spirocycles has been developed through a silyl triflate mediated intermolecular coupling of difluorobenzamidine and racemic N-protected 3-fluoropiperidine dimethyl ketals or piperidones. Combination of the silyl reagents together with Lewis acids (such as BF3·OEt2, ZnCl2, InCl3, etc.) accelerated the coupling reaction to afford the desired fluorospirocycles in good yields (40–83%) and high diastereoselectivity. A ratio of the two diastereoisomers of up to 10:1 in favor of the desired isomer can be achieved.
Bibliography:ObjectType-Article-1
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content type line 23
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2012.03.050