Trisubstituted pyrimidine derivatives from tetrafluoropyrimidine

• Published in: Tetrahedron Vol. 66; no. 32; pp. 6195 - 6204
• Main Authors: Parks, Emma L., Sandford, Graham, Yufit, Dmitry S., Howard, Judith A.K., Christopher, John A., Miller, David D.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 07.08.2010; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocycle; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Nucleophilic aromatic substitution; Organic chemistry; Physical Sciences; Polyfunctional pyrimidine; Preparations and properties; Pyrimidine; Scaffold; Science & Technology; Tetrafluoropyrimidine; Nucleophilic aromatic substitution; Polyfunctional pyrimidine; HZDBFEIBKDQBAG-UHFFFAOYSA-N; IOEIHOLDMXPRSE-UHFFFAOYSA-N; KWCKWUKVGSPAHA-UHFFFAOYSA-N; Heterocycle; Scaffold; KZMWBUVUQLGBBP-UHFFFAOYSA-N; Pyrimidine; Tetrafluoropyrimidine; BSBGJXDXHCBVEA-UHFFFAOYSA-N; DESIGN; RAPID ANALOG SYNTHESES; SYSTEMS; SCAFFOLDS; Polyfunctional compound; Regioselectivity; Nitrogen heterocycle; Amine; Pyrimidine derivatives; Fluorine Organic compounds; Nucleophilic substitution; Chemical synthesis; SNAr mechanism; Nucleophile
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.05.094

The use of tetrafluoropyrimidine as a scaffold for the synthesis of 2,4,6-trisubstituted pyrimidine derivatives by three sequential nucleophilic aromatic substitution processes is assessed. Reactions of tetrafluoropyrimidine with various amine nucleophiles followed by a series of nitrogen and oxygen centred nucleophilic species gave a range of 4,6-disubstituted-2,5-difluoropyrimidine systems regioselectively and in good yield. Displacement of a further fluorine atom from representative difluoropyrimidine derivatives proceeded to give trisubstituted pyrimidine derivatives although mixtures of products could be obtained depending upon the substrate. [Display omitted]