Judicious Application of Allyl Protecting Groups for the Synthesis of 2-Morpholin-4-yl-4-oxo-4H-chromen-8-yl Triflate, a Key Precursor of DNA-Dependent Protein Kinase Inhibitors

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• 作者：Sonsoles Rodriguez Aristegui ; Marine Desage El-Murr ; Bernard T. Golding ; Roger J. Griffin ; Ian R. Hardcastle
• 刊名：Organic Letters
• 出版年：2006
• 出版时间：December 21, 2006
• 年：2006
• 卷：8
• 期：26
• 页码：5927 - 5929
• 全文大小：49K
• 年卷期：v.8,no.26(December 21, 2006)
• ISSN：1523-7052

文摘

2-Morpholin-4-yl-4-oxo-4H-chromen-8-yl 2,2,2-trifluoromethanesulfonate is a key intermediate for the synthesis of the DNA-dependent proteinkinase (DNA-PK) inhibitor 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441). Two improved methods for the synthesis of thistriflate have been developed: (A) in 35% overall yield, through modification of the published route, and (B) in 15% overall yield, by a new routeemploying a Baker-Venkataraman rearrangement to enable generation of the chromenone scaffold. Both syntheses depend on the judicioususe of allyl protecting groups.