“Green and Sustainable Synthesis of Thienopyrimidine Derivatives: A Review of Methods and Medicinal Applications”

Thienopyrimidines, purine-isosteric scaffolds of enduring interest, underpin discovery programs in oncology, inflammation, metabolic, and infectious diseases. In recent years, their synthesis has increasingly shifted toward greener approaches that minimize solvent use, energy demand, and chemical waste. This review highlights key advances in sustainable strategies for thienopyrimidines, including multicomponent condensations from simple building blocks, solvent-free and microwave-assisted cyclizations, and the use of benign or recyclable catalysts. Emerging green chemistry metrics, such as atom economy and process mass intensity, further demonstrate the scalability of these methods. The medicinal impact of such approaches is also considered, with recent examples of thienopyrimidines active against clinically relevant targets such as EGFR, PI3K, BTK, JAK3, and STAT3, as well as novel anti-infective candidates. Green synthesis not only reduces the environmental footprint but also accelerates library generation and design-make-test cycles in drug discovery. Future prospects include the integration of flow chemistry, mechanochemistry, and biobased catalytic systems to expand sustainable access to this privileged scaffold.