A Practical Synthesis of the Dual Matrix Metalloprotease/Tumor Necrosis Factor Inhibitor MMP090
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- 作者：Joel S. Slade ; James A.Vivelo ; David J. Parker ; Joginder Bajwa ; Hui Liu ; Michael Girgis ; David T. Parker ; Oljan Repi
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- 刊名：Organic Process Research & Development
- 出版年：2005
- 出版时间：September 2005
- 年：2005
- 卷：9
- 期：5
- 页码：608 - 620
- 全文大小：160K
- 年卷期：v.9,no.5(September 2005)
- ISSN：1520-586X
文摘
A practical 9-step synthesis of the dual matrix metalloprotease/tumor necrosis factor inhibitor MMP090, trans-(R)-[[N-(4-ethoxyphenylsulfonyl)-N-(4-pyridinylmethyl)]amino]-N-hydroxy-4-propoxy cyclohexaneacetamide 10, was accomplished in 12%overall yield from D-4-hydroxyphenylglycine. Highlights include: (1) selective hydrogenation of D-hydroxyphenylglycineto afford predominantly the trans isomer without racemization;(2) virtually complete removal of the undesired cis diastereoisomer by fractional recrystallization of a TBS ether derivativeof the functionalized cyclohexylglycine; (3) direct conversionof the TBS ether into the n-propyl ether in the presence of acatalytic amount of bismuth bromide in high yield; and (4)conversion of the carboxylic acid into the hydroxamic acid usingan aqueous solution of hydroxylamine.