Abstarct: In recent years, there has been considerable attention to the green synthesis of organic heterocyclic compounds as drug molecules. Pyrimidine derivatives are important compounds in organic chemistry and medicine. They have a wide range of biological activities, such as anticancer, antiviral, antimicrobial, anti-inflammatory, analgesic, antioxidant, and antimalarial. Therefore, the synthesis of pyrimidine derivatives is an important research area in organic synthesis. Pyrano-[2,3-d]pyrimidines compounds are of this category that have medicinal properties. Pyranopyrimidines are a group of heterocyclic compounds that consist of a pyrimidine cycle containing two nitrogen atoms at the "1,3-positions" merged with a pyran ring that has one oxygen atom. In this research, new heterocyclic compounds baxsed on pyrano-[2,3-d]pyrimidine were synthesized using multicomponent reactions as follows: In the first study, green synthesis of pyrano-[2,3-d]pyrimidine compounds was performed using magnetized distilled water as a solvent. In the second study, novel 6-iodo-pyrano-[2,3-d]pyrimidin-4-ones were synthesized via one-pot multicomponent reactions in water. Green and efficient methods for the synthesis of pyrano-[2,3-d]pyrimidine derivatives were developed using water as a solvent. The structures of the synthesized compounds were confirmed by spectroscopic data including 1H NMR, 13C NMR, FT-IR and MASS.