The synthesis and regioselective functionalization of rare 2,4‐disubstituted‐pyrido[1′,2′:1,5]pyrazolo[3,4‐d]pyrimidine derivatives is reported. C‐4 aminations were performed by chlorine nucleophilic substitution SNAr reactions, and their efficiencies were compared with those for direct one‐pot amide C–O activation with bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP) as a reagent. The latter method was used to perform palladium‐catalyzed C‐4 (het)arylation. Finally, two C‐4 amino and aryl derivatives were prepared on a large scale and engaged in desulfurative Liebeskind–Srogl‐type reactions under microwave irradiation to afford the envisioned compound library. Each step was optimized, and the results are discussed.
The 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.