A Greener Approach for the Large-Scale Synthesis of 1,4,5-Trisubstituted Pyrazole, AZD8329

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• 作者：Paramashivappa Rangappa ; Avipsa Ghosh ; Smitha Chitrapadi ; Gajanan Kantikar ; Vinod Kumar CH ; Sureshkumar Sythana ; Sulur G Manjunath ; Sudhir Nambiar ; Sridhran R
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：August 15, 2014
• 年：2014
• 卷：18
• 期：8
• 页码：947-951
• 全文大小：235K
• ISSN：1520-586X

文摘

The development of a convenient, safe and scalable process for AZD8329 manufacturing is reported here. Synthesis was achieved in a two-step telescopic process with an excellent overall yield of 75%. In the first step enamine (6) was synthesized with 90% yield through three chemical transformations. In the next step AZD8329 was synthesized from the reactions of 6 and 4-hydrazinobenzoic acid hydrochloride 7 through two chemical transformations. The process is very efficient and economical, and AZD8329 was manufactured in multikilogram scale. A greener approach is demonstrated through usage of a minimum number of solvents and energy and with process mass intensity (PMI) <60 in the manufacturing process.