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Synthesis of alkyl- and aryl-amino-substituted anthraquinone derivatives by microwave-assisted copper(0)-catalyzed Ullmann coupling reactions

Nature Protocols volume 5, pages 945–953 (2010)Cite this article

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Abstract

This protocol describes the efficient, generally applicable Ullmann coupling reaction of bromaminic acid with alkyl- or aryl-amines in phosphate buffer under microwave irradiation using elemental copper as a catalyst. The reaction leads to a number of biologically active compounds. As a prototypical example, the synthesis of a new, potent antagonist of human platelet P2Y12 receptors, which has potential as an antithrombotic drug, is described in detail. The optimized protocol includes a description of an appropriate reaction setup, thin layer chromatography for monitoring the reaction and a procedure for the isolation, purification and characterization of the anticipated product. The reaction is performed without the use of a glove box and there is no requirement for an inert atmosphere. The reaction typically proceeds within 2–30 min, the protocol, including workup, generally takes 1–3 h to complete.

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Figure 10: Purification of anthraquinone derivatives by reverse phase flash column chromatography.
Figure 11: HPLC trace, MS and UV chromatograms of compound 9 (a–f).

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Acknowledgements

Y.B. thanks the Deutscher Akademischer Austauschdienst (DAAD) for a PhD Fellowship. Support by the Deutsche Forschungsgemeinschaft (DFG, GRK804) is gratefully acknowledged. We would like to thank Ms. Marion Schneider for providing us with the LC-MS chromatogram.

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  1. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, Pharmaceutical Sciences Bonn (PSB), University of Bonn, Bonn, Germany

    Younis Baqi & Christa E Müller

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Y.B. planned and performed the experiments and prepared the first draft of the manuscript. C.E.M. designed the experiments, supervised the work and finalized the manuscript.

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Correspondence to Younis Baqi.

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Baqi, Y., Müller, C. Synthesis of alkyl- and aryl-amino-substituted anthraquinone derivatives by microwave-assisted copper(0)-catalyzed Ullmann coupling reactions. Nat Protoc 5, 945–953 (2010). https://doi.org/10.1038/nprot.2010.63

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