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Practical and rapid construction of 2-pyridyl ketone library in continuous flow

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Abstract

2-Pyridyl ketones widely appear in bioactive molecules, natural products, and are employed as precursors of chiral 2-pyridine alky/aryl alcohols or 2-aminoalkyl pyridine ligands for asymmetric catalysis. Herein, a practical method for the rapid synthesis of 2-pyridyl ketone library in continuous flow is reported, in which the 2-lithiopyridine formed by Br/Li exchange reacts with commercially available esters to obtain 2-pyridyl ketones in a good yield at short reaction time. This protocol functions broadly on a variety of esters and has been applied to the synthesis of TGF-β type 1 receptor inhibitor LY580276 intermediate in an environmentally friendly method. It is rapid, reliable, and cost-efficient to afford diverse kinds of 2-pyridyl ketones in the compound library.

A practical method for therapid synthesis of 2-pyridyl ketones under continuous flow using simple estersand 2-bromopyridine was reported. This procedure iswidely applicable to aromatic esters, alkyl esters, N-Boc amino acidmethyl esters, α-bromoesters and dimethyl oxalate, leading to variousfunctionalized 2-pyridyl ketones with good yields

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Acknowledgements

This work was partially supported by Shanghai Post-doctoral Excellence Program, Shanghai Sailing Program (20YF1410400), National Natural Science Foundation of China (21572056), the Fundamental Research Funds for the Central Universities, 111 project (B07023), and the Open Project of State Key Laboratory of Chemical Engineering (SKL-ChE-17C01).

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Authors and Affiliations

  1. Engineering Research Centre of Pharmaceutical Process Chemistry, School of Pharmacy, Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China

    Maolin Sun, Jianchang Li, Chaoming Liang, Chao Shan, Xinyuan Shen, Yueyue Ma & Jinxing Ye

  2. School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Ruihua Cheng

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  1. Maolin Sun
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Sun, M., Li, J., Liang, C. et al. Practical and rapid construction of 2-pyridyl ketone library in continuous flow. J Flow Chem 11, 91–98 (2021). https://doi.org/10.1007/s41981-020-00120-7

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  • DOI: https://doi.org/10.1007/s41981-020-00120-7

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