Regioselective Synthesis of New 2,4-(Het)aryl-3<i>H</i>-pyrido[1′,2′:1,5]pyrazolo[4,3-<i>d</i>]pyrimidines Involving Palladium-Catalyzed Cross-Coupling Reactions
Abdelaziz Ejjoummany,
Rabia Belaroussi,
Ahmed El Hakmaoui,
Mohamed Akssira,
Gérald Guillaumet,
Frédéric Buron,
Sylvain Routier
Affiliations
Abdelaziz Ejjoummany
Institut de Chimie Organique et Analytique, Univ Orleans, UMR CNRS 7311, BP 6759, F-45067 Orléans CEDEX 2, France
Rabia Belaroussi
Institut de Chimie Organique et Analytique, Univ Orleans, UMR CNRS 7311, BP 6759, F-45067 Orléans CEDEX 2, France
Ahmed El Hakmaoui
Laboratoire de Chimie Physique et Chimie Bioorganique, Université Hassan II-Casablanca, B. P. 146, 28800 Mohammedia, Morocco
Mohamed Akssira
Laboratoire de Chimie Physique et Chimie Bioorganique, Université Hassan II-Casablanca, B. P. 146, 28800 Mohammedia, Morocco
Gérald Guillaumet
Institut de Chimie Organique et Analytique, Univ Orleans, UMR CNRS 7311, BP 6759, F-45067 Orléans CEDEX 2, France
Frédéric Buron
Institut de Chimie Organique et Analytique, Univ Orleans, UMR CNRS 7311, BP 6759, F-45067 Orléans CEDEX 2, France
Sylvain Routier
Institut de Chimie Organique et Analytique, Univ Orleans, UMR CNRS 7311, BP 6759, F-45067 Orléans CEDEX 2, France
The design of some novel di-(het)arylated-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl sulfur release and C-O activation, respectively. The two regioselective and successive cross-coupling reactions were first carried out in C-4 by in situ C-O activation and next in C-2 by a methylsulfur release. Process optimization furnished conditions leading to products in high yields. The scope and limitations of the methodologies were evaluated and the final compounds characterized.
