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Title
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Combining isocyanides with carbon dioxide in Palladium-catalyzed heterocycle synthesis : N3-substituted quinazoline-2,4(1H,3H)-diones via a three-component reaction
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Author
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Abstract
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| We report a Pd-catalyzed three-component reaction of 2-bromoanilines, carbon dioxide, and isocyanides. The combination of these two readily available C1-reactants, featuring a huge difference in kinetic and thermodynamic stability, is hitherto unprecedented in transition-metal catalysis. With this one-pot three-component reaction, N3-substituted quinazoline-2,4(1H,3H)-diones are obtained in moderate to high yields in a completely regio- and chemoselective manner. Our approach easily allows variation of the arene and N3-substitution pattern of the desired heterocycle. The formal synthesis of different APIs illustrates its practical applicability. In addition, the methodology also allows for a convenient and selective 13C-labeling through the use of 13CO2. This is illustrated for [2-13C]-2,4-dichloro-6,7-dimethoxyquinazoline synthesis, a key intermediate for several APIs. |
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Language
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English
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Source (journal)
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ACS catalysis. - -
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Publication
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2017
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ISSN
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2155-5435
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DOI
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10.1021/ACSCATAL.7B01503
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Volume/pages
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7
:8
(2017)
, p. 5549-5556
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ISI
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000407309100074
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Full text (Publisher's DOI)
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Full text (open access)
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