Continuous Flow Synthesis of Thieno[2,3-c]isoquinolin-5(4H)-one Scaffold: A Valuable Source of PARP-1 Inhibitors

详细信息    查看全文

• 作者：Paolo Filipponi ; Carmine Ostacolo ; Ettore Novellino ; Roberto Pellicciari ; Antimo Gioiello
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：November 21, 2014
• 年：2014
• 卷：18
• 期：11
• 页码：1345-1353
• 全文大小：501K
• ISSN：1520-586X

文摘

An efficient multistep method for the continuous flow synthesis of thieno[2,3-c]isoquinolin-5(4H)-one-A (TIQ-A), an important pharmacological tool and building block for PARP-1 inhibitors, has been developed. The synthesis involves a Suzuki coupling reaction to generate 3-phenylthiophene-2-carboxylic acid which is transformed into the corresponding acyl azide and readily cyclized by a thermal Curtius rearrangement. A statistical design of experiments (DoE) was employed as a valuable support for decision-making of further experiments enabling the development of a robust and reliable protocol for large-scale preparation. As a result, the reactions are facile, safe, and easy to scale-up. The large-scale applicability of this improved flow method was tested by conducting the reactions on multigram scale to produce the desired product in high yield and quality for biopharmacological appraisals.