Development of a Practical and Reliable Synthesis of Laquinimod
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- 作者：Johan Wennerberg ; Anders Bjö ; rk ; Tomas Fristedt ; Bo Granquist ; Karl Jansson ; Ingela
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- 刊名：Organic Process Research & Development
- 出版年：2007
- 出版时间：July 2007
- 年：2007
- 卷：11
- 期：4
- 页码：674 - 680
- 全文大小：82K
- 年卷期：v.11,no.4(July 2007)
- ISSN：1520-586X
文摘
Laquinimod (5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide) is a drug candidatefor treatment of Multiple Sclerosis. A short and industriallyfeasible process for the preparation of laquinimod starting from2-amino-6-chlorobenzoic acid, in essentially four steps, is dis-cussed. The key step is a novel reaction in which a methyl esteris converted to an amide in very high yield and with excellentpurity. The present article elucidates the scale-up process alongwith safety aspects and the impurity profiles of the intermediates and product. Initial laboratory conditions are describedas well as the changes made on transfer to pilot-plant scale.