A general strategy for the synthesis of difluoromethyl-containing pyrazoles, pyridines and pyrimidines

• Published in: Tetrahedron Vol. 67; no. 31; pp. 5663 - 5677
• Main Authors: Iaroshenko, Viktor O., Specowius, Verena, Vlach, Katharina, Vilches-Herrera, Marcelo, Ostrovskyi, Dmytro, Mkrtchyan, Satenik, Villinger, Alexander, Langer, Peter
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 05.08.2011; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Cyclizations; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydrazines; N-Heterocycles; Organic chemistry; Organofluorine compounds; Physical Sciences; Preparations and properties; Purine isosteres; Pyrazole; Pyridines; Pyrimidines; Radicals; Regioselectivity; Science & Technology; Strategy; Synthesis (chemistry); Tetrahedrons; Organofluorine compounds; N-Heterocycles; Cyclizations; Regioselectivity; Purine isosteres; POTENT; EFFICACY; VIVO; PHARMACOKINETICS; DRUGS; INHIBITORS; ANTAGONISTS; Purine derivatives; Nitrogen heterocycle; Isostere; Purine base; Diketone; Free radical reaction; Pyridine derivatives; Amidine; Pyridine; Cyclization; Pyrazole derivatives; Pyrimidine derivatives; Fluorine Organic compounds; Hydrazine; Chemical synthesis
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.05.085

Difluoromethyl-containing heteroannulated pyridines, pyrimidines and pyrazoles are prepared by a two step method. The regioselective cyclizations of electron-excessive aminoheterocycles, hydrazines and amidines with CF 2Cl-substituted 1,3-dicarbonyl compounds provide the corresponding CF 2Cl-substituted heterocycles. Subsequent radical reactions with trimethylstannane or allyltrimethylstannane gave difluoromethyl-containing heteroannulated pyridines, pyrimidines and pyrazoles, respectively. [Display omitted]