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Efficient Access to New Chemical Space Through Flow—Construction of Druglike Macrocycles Through Copper-Surface-Catalyzed Azide–Alkyne Cycloaddition Reactions

Authors

  • Andrew R. Bogdan,

    1. Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037 (USA), Fax: (+1) 8587847550
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  • Keith James

    Corresponding author
    1. Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037 (USA), Fax: (+1) 8587847550
    • Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037 (USA), Fax: (+1) 8587847550
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Abstract

A series of 12- to 22-membered macrocycles, with druglike functionality and properties, have been generated by using a simple and efficient copper-catalyzed azide–acetylene cycloaddition reaction, conducted in flow in high-temperature copper tubing, under environmentally friendly conditions. The triazole-containing macrocycles have been generated in up to 90 % yield in a 5 min reaction, without resorting to the high-dilution conditions typical of macrocyclization reactions. This approach represents a very efficient method for constructing this important class of molecules, in terms of yield, concentration, and environmental considerations.

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