A Practical Synthesis of 5-Lipoxygenase Inhibitor MK-0633
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- 作者：Francis Gosselin ; Robert A. Britton ; Ian W. Davies ; Sarah J. Dolman ; Danny Gauvreau ; R. Scott Hoerrner ; Gregory Hughes ; Jacob Janey ; Stephen Lau ; Carmela Molinaro ; Christian Nadeau ; Paul D. O’ ; Sh
- 刊名：Journal of Organic Chemistry
- 出版年：2010
- 出版时间：June 18, 2010
- 年：2010
- 卷：75
- 期：12
- 页码：4154-4160
- 全文大小：900K
- 年卷期：v.75,no.12(June 18, 2010)
- ISSN：1520-6904
文摘
Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).