- C?H Cyanation of 6-Ring N-Containing Heteroaromatics
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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.
- 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.
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supporting information
p. 14733 - 14737
(2017/10/07)
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- Zinc cyanide mediated direct α-cyanation of isonicotinic acid N-oxide. Application to the synthesis of FYX-051, a xanthine oxidoreductase inhibitor
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Reaction of isonicotinic acid N-oxide 1a with dimethylcarbamoyl chloride and zinc cyanide in CH3CN at 120 °C gave the corresponding 2-cyanoisonicotinamide 2a in a good yield. This strategy was applied to the synthesis of FYX-051·TsOH 8, a xanthine oxidoreductase inhibitor.
- Huo, Zhibao,Kosugi, Teruo,Yamamoto, Yoshinori
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p. 4369 - 4371
(2008/12/21)
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- Mild and general methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides
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New methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides have been developed, featuring sterically demanding, electron-rich phosphines. Highly challenging electron-rich aryl chlorides, in addition to electron-neutral and electron-deficient substrates, as well as nitrogen- and sulfur-containing heteroaryl chlorides can all undergo efficient cyanation under relatively mild conditions using readily available materials. In terms of substrate scope and temperature, these methods compare very favorably with the state-of-the-art cyanations of aryl chlorides.
- Littke, Adam,Soumeillant, Maxime,Kaltenbach III, Robert F.,Cherney, Robert J.,Tarby, Christine M.,Kiau, Susanne
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p. 1711 - 1714
(2008/02/02)
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- Site-Selectivity in the Cyanation of 3-Substituted Pyridine 1-Oxides with Trimethylsilanecarbonitrile
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The cyanation of 3-halo-, 3-methoxy-, and 3-dimethylaminopyridine 1-oxide with trimethylsilanecarbonitrile gave predominantly the corresponding 3-substituted 2-pyridinecarbonitriles.The deoxygenation of nitropyridine 1-oxides to nitropyridines with the same reagent is also described.Keywords - site-selective reaction; trimethylsilanecarbonitrile; pyridine 1-oxide; 2-pyridine-carbonitrile; nitropyridine 1-oxide; deoxygenation; aromatic amine N-oxide; cyanation
- Sakamoto, Takao,Kaneda, Soh-ichi,Nishimura, Sumiko,Yamanaka, Hiroshi
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p. 565 - 571
(2007/10/02)
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- An Electron Spin Resonance and Voltametric Investigation of Some 2-Mono- and 2,4-Di-substitued Pyridinyl Radicals
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The chemical reduction of some 2-monosubstitued and 2,4-disubstitued pyridinium ions has been investigated by means of e.s.r. spectroscopy and the result compared with those of an electrochemical study on the same species.By combining the electrochemical and e.s.r. data, a scale of stability has been determined for the investigated pyridinyl radicals.N-Methyl-2-cyanopyridinyl, wich was found to be too unstable to be observed, eventually evolved to the 2,4-dicyano-substitued radical.E.s.r. studies have also been carried out on the structurally similar, although more persistent, N-germylpyridinyls.
- Greci, Lucedio,Alberti, Angelo,Carelli, Italo,Trazza, Antonio,Casini, Antonio
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p. 2013 - 2018
(2007/10/02)
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