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Isoquinoline and pyrimidine are valuable heterocyclic compounds that play a crucial role in the development of new drug molecules. The combination of isoquinoline and pyrimidine moieties in hybrid structures has provided exciting possibilities for various applications, leading to the discovery of pyrimidoisoquinoline (PyIsoQ) compounds, such as pyrimido[4,5-c]isoquinolines and pyrimido[5,4-c]isoquinolines, which exhibit intriguing properties. Pyrimido[4,5-c]isoquinolines (Py[4,5-c]IsoQs) can be synthesized from functionalized pyrimidine or isoquinoline. This review focuses on the synthesis of PyIsoQs4,5-c from 3,4-difunctionalized isoquinolines through several chemical reactions, including Suzuki–Miyaura, Stille coupling, and Pictet–Spengler reactions.
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