Unexpected synthesis of (trifluoroethyl)pyrimidines from the heterocyclisation of α-trifluoroacetylpropanenitriles (original) (raw)
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ACS Omega
This study reports two strategies for preparing O-alkyl derivatives of 6substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation, using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that the cyclocondensation strategy is not feasible; thus, the direct chemoselective O-alkylation was performed, and 18 derivatives of the targeted pyrimidines were obtained in 70−98% yields. The structure of the products was unambiguously determined via single crystal Xray analyses and two-dimensional nuclear magnetic resonance experiments.
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Synthesis, 2006
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