Convenient and Practical One-Pot Synthesis of 4-Chloropyrimidines via a Novel Chloroimidate Annulation
Organic Process Research & Development2010Vol. 15(4), pp. 918–924
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Thomas Storz, Richard Heid, Joseph Zeldis, Steven M. Hoagland, Vito Rapisardi, Susan Hollywood, George Morton
Abstract
Reaction of aromatic or heteroaromatic 2-acyl(amino)nitriles with phosphorus pentachloride triggers a novel chloroimidate cyclization, leading directly to the corresponding annullated 4-chloropyrimidines in good to excellent yields. The reaction lends itself to the telescoped one-pot construction of 4-functionalized pyrimidines from the corresponding (hetero)aromatic 2-aminonitriles. For a pyrazolopyrimidine development intermediate, this reaction was scaled up to multikilogram scale with excellent results. A total of 10 examples with different substrates are provided. This one-pot reaction provides an attractive and sustainable alternative to the commonly used multistep methodology for this transformation.
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