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

Abstract

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.

Keywords

• pyridopyrazolopyrimidine
• pyBroP activation
• palladium cross-coupling