Regioselective Synthesis of 2,4-Substituted Pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidines through Sequential Pd-Catalyzed Arylation and SNAr Reactions

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 amid...

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Bibliographic Details
Published in:European journal of organic chemistry 2016-07, Vol.2016 (21), p.3550-3558
Main Authors: Belaroussi, Rabia, El Hakmaoui, Ahmed, Akssira, Mohamed, Guillaumet, Gérald, Routier, Sylvain
Format: Article
Language:English
Subjects:
Cross-coupling
Nitrogen heterocycles
Nucleophilic substitution
Palladium
Synthesis design
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Summary: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 synthesis and regioselective functionalization of rare 2,4‐disubstituted‐pyrido[1′,2′:1,5]pyrazole[3,4‐d]pyrimidine derivatives is reported. C‐4 amination or (het)arylations are performed by halogen displacement or by “one‐pot” amide C–O activation. Finally, desulfurative Liebeskind–Srogl reactions under microwave irradiation afford the envisioned C‐2 and C‐4 functionalized library.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201600356