Synthesis of 1,4-disubstituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyridazines by means of SNAr and palladium-catalysed reactions

International audienceThe first efficient synthesis of various 1,4-disubstituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyridazines is reported. The reactivity toward chlorine release at the C-1 and C-4 positions was investigated. SNAr and palladium-catalysed cross-coupling reactions were carried out, and conditions were optimised for each procedure. 1,4-Bis(het)aryl derivatives were obtained under a Suzuki cross-coupling procedure whereas SNAr substitution was achieved mainly at C-1 in preference to C-4. The monosubstituted C-4 morpholino derivative was used as a starting material to provide dissymmetrical 1,4-diaminated or 1-(het)aryl-4-morpholino products