Process Development of the PDE IV Inhibitor 3-(Cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide

详细信息    查看全文

• 作者：David C. Cook ; Ronald H. Jones ; Humayun Kabir ; David J. Lythgoe ; Ian M. McFarlane ; Clive Pemberton ; Alan A. Thatcher ; David. M. Thompson ; and John B. Walton
• 刊名：Organic Process Research & Development
• 出版年：1998
• 出版时间：May 1998
• 年：1998
• 卷：2
• 期：3
• 页码：157 - 168
• 全文大小：160K
• 年卷期：v.2,no.3(May 1998)
• ISSN：1520-586X

文摘

Development of an industrial process for3-(cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide, a potentPDEIV type inhibitor, is described. The rapid identificationofscalable reaction conditions allowed pilot-scale synthesisofkilogramme quantities for early clinical evaluation.However,as more compound was demanded, better reaction conditionswere required in the interests of safety, economics, andenvironmental impact. This led to the derivation of ahigh-yielding and very robust procedure which included varioussafeguards to ensure that high-quality product wasobtainedand that new trace impurities were effectively removed.Thelarge-scale oxidation of a benzaldehyde derivative to thecorresponding benzoic acid using hydrogen peroxide underaqueous alkaline conditions is described.