Elbert Bryony L, Farley Alistair J M, Gorman Timothy W, Johnson Tarn C, Genicot Christophe, Lallemand Bénédicte, Pasau Patrick, Flasz Jakub, Castro José L, MacCoss Malcolm, Paton Robert S, Schofield Christopher J, Smith Martin D, Willis Michael C, Dixon Darren J
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Global Chemistry, UCB New Medicines, UCB Biopharma sprl, 1420, Braine-L'Alleud, Belgium.
Chemistry. 2017 Oct 20;23(59):14733-14737. doi: 10.1002/chem.201703931. Epub 2017 Sep 22.
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C-H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one-pot protocol is simple to perform, is applicable to a broad range of decorated 6-ring N-containing heterocycles, and has been shown to be suitable for late-stage functionalization of complex drug-like architectures.
杂芳腈是药物研发中的重要化合物，这既归因于它们在临床中的广泛存在，也源于它们能够进行的多样转化。因此，获得它们的高效且可靠的方法在合成化学和生物医学科学领域具有产生深远影响的潜力。在此，我们报道了一种通过三氟甲磺酸酐活化、氰化物的亲核加成，随后消除三氟甲磺酸盐以再生氰化杂芳环来实现杂芳环C-H氰化的方法。这个一锅法操作简单，适用于多种带有取代基的六元含氮杂环，并且已被证明适用于复杂类药物结构的后期官能团化。
