Diastereoselective synthesis of fluorinated piperidine quinazoline spirocycles as iNOS selective inhibitors

作者：Walpole Chris^*; Liu Ziping; Lee Ernest E; Yang Hua; Zhou Fei; Mackintosh Nicole; Sjogren Magnus; Taylor David; Shen Jinyu; Batey Robert A

来源：Tetrahedron Letters, 2012, 53(24): 2942-2947.

DOI：10.1016/j.tetlet.2012.03.050

• Spirocycle
• Lewis acid
• Difluorobenzamidine
• Piperidine
• Piperidone

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 center dot OEt2, ZnCl2, InCl3, etc.) accelerated the coupling reaction to afford the desired fluorospirocycies 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.

• 出版日期2012-6-13