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 thermal Curtius rearrangement. 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 bio-pharmacological appraisals.

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

OSTACOLO, CARMINE;NOVELLINO, ETTORE;
2014

Abstract

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 thermal Curtius rearrangement. 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 bio-pharmacological appraisals.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/580217
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