Efficient and Selective Method for the Synthesis of Dihydrodipyridopyrazines Based on the Pd‐Catalysed Amination of Halopyridines

• Published in: European Journal of Organic Chemistry 2009-08, Vol.2009 (22), p.3753-3764
• Main Authors: Patriciu, Oana‐Irina, Fînaru, Adriana‐Luminiţa, Massip, Stéphane, Léger, Jean‐Michel, Jarry, Christian, Guillaumet, Gérald
• Format: Article
• Language: English
• Subjects: Catalysis; Catalysts: preparations and properties; Chemistry; Cross‐coupling; Cyclization; Dihydrodipyridopyrazines; Exact sciences and technology; General and physical chemistry; 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; Organic chemistry; Pd catalysis; Preparations and properties; Reduction; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200900404

A novel methodology for the efficient and selective synthesis of isomers A and B of N‐substituted dihydrodipyridopyrazines was developed. The key step is the intermolecular coupling of aminopyridines and halonitropyridines/dihalopyridines in the presence of a catalyst system composed of Pd(OAc)2/Xantphos. This system displays good functional group compatibility and the desired C–N bond‐forming process proceeds in good yields. Cyclization of suitable nitro‐substituted N,N′‐dipyridinylamines produces monosubstituted dihydrodipyridopyrazines, which can easily be alkylated to give a large variety of unsymmetrical 5,10‐dialkyl‐5,10‐dihydrodipyrido[2,3‐b:2′,3′‐e]pyrazines (isomers A) and 5,10‐dialkyl‐5,10‐dihydrodipyrido[2,3‐b:3′,2′‐e]pyrazines (isomers B). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) Specific syntheses of each of the unsymmetrically substituted dihydrodipyridopyrazine isomers A and B have been completed. The novel strategy that was developed for their syntheses featured Pd catalysis for key couplings, followed by a substitution/reduction/cyclization/substitutionsequence of suitable nitro‐substituted N,N′‐dipyridinylamine products.