Development of a Manufacturing Process for Sibenadet Hydrochloride, the Active Ingredient of Viozan
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- 作者：Melvyn E. Giles ; Colin Thomson ; Stephen C. Eyley ; Andrea J. Cole ; Christopher J. Goodwin ; Paul A. Hurved ; Andrew J. G. Morlin ; James Tornos ; Sté ; phanie Atkinson ; Cecelia Just ; Janet C. Dean ; Joh
- 刊名：Organic Process Research & Development
- 出版年：2004
- 出版时间：July 2004
- 年：2004
- 卷：8
- 期：4
- 页码：628 - 642
- 全文大小：209K
- 年卷期：v.8,no.4(July 2004)
- ISSN：1520-586X
文摘
A process for commercial manufacture of the dual D2-
2receptor agonist sibenadet hydrochloride has been developed.The process relies upon introduction of operationally simplechemistry at the final stages where two key intermediates arereacted to assemble the final molecule, isolated by crystallization. A nine-stage sequence for synthesis of the key aminehydrochloride intermediate was developed, and modificationsto the original process are described. Major strategic improvements were made in definition of the final route to the "sidechain" precursor molecule, the second key intermediate, hingingaround a thiyl radical addition and subsequent high-yieldingtelescoped processes for synthesis of this highly crystallinebenzoate ester. Development of these chemistries is discussed,together with some issues surrounding definition of the finalvalidated commercial processes.
2receptor agonist sibenadet hydrochloride has been developed.The process relies upon introduction of operationally simplechemistry at the final stages where two key intermediates arereacted to assemble the final molecule, isolated by crystallization. A nine-stage sequence for synthesis of the key aminehydrochloride intermediate was developed, and modificationsto the original process are described. Major strategic improvements were made in definition of the final route to the "sidechain" precursor molecule, the second key intermediate, hingingaround a thiyl radical addition and subsequent high-yieldingtelescoped processes for synthesis of this highly crystallinebenzoate ester. Development of these chemistries is discussed,together with some issues surrounding definition of the finalvalidated commercial processes.