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

被引:12
作者
Belaroussi, Rabia [1 ,2 ]
El Hakmaoui, Ahmed [2 ]
Akssira, Mohamed [2 ]
Guillaumet, Gerald [1 ]
Routier, Sylvain [1 ]
机构
[1] Univ Orleans, CNRS, Inst Chim Organ & Analyt, UMR 7311, BP 6759, F-45067 Orleans 2, France
[2] Univ Hassan II Mohammedia Casablanca, Lab Chim Phys & Chim Bioorgan, BP 146, Mohammadia 28800, Morocco
关键词
Synthesis design; Cross-coupling; Nucleophilic substitution; Nitrogen heterocycles; Palladium; CROSS-COUPLING REACTIONS; P38 KINASE INHIBITORS; ARYL BORONIC ACIDS; HETEROAROMATIC THIOETHER; TAUTOMERIZABLE HETEROCYCLES; CONVENIENT SYNTHESIS; EFFICIENT ACCESS; PYBROP; DERIVATIVES; PYRIMIDINES;
D O I
10.1002/ejoc.201600356
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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.
引用
收藏
页码:3550 / 3558
页数:9
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