Recent green approaches for the synthesis of thienopyrimidine scaffolds: an overview (2007-2025)

Thienopyrimidines are considered purine bioisosteres as they consist of a thiophene ring fused with pyrimidine. Thienopyrimidines are present in three isomeric forms: thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines, and thieno[3,4-d]pyrimidines. They are of interest in drug discovery owing to their extensive pharmacological and biological activities. Several drugs incorporating the thienopyrimidine scaffold are marketed commercially, while others are presently in the experimental and development stages. Green chemistry, also known as sustainable chemistry, aims to minimize the environmental impact of chemical products and processes. Thus, applying green techniques has become a necessity in organic chemistry. The current review discusses the different synthetic approaches to obtain thienopyrimidine scaffolds using various green techniques, including microwave-assisted synthesis, green solvents, one-pot reactions, solvent-less reactions, and catalysis, published between 2007 and 2025. Additionally, a brief overview of the conventional synthetic routes is provided. This review emphasizes how green chemistry is becoming increasingly important in promoting the synthesis of bioactive heterocycles such as thienopyrimidines.