Incorporating coumarin nuclei into other heterocyclic scaffolds such as thienopyrimidine can significantly increase the photophysical and biological efficiency. Accordingly, we describe in this manuscript the synthesis of new heterocyclic derivatives containing combined coumarin and pyrimidine nuclei to maximize the application benefit of the target compounds. All of the synthesized derivatives were thoroughly characterized using spectral analyses such as FT-IR, NMR, and mass spectroscopy. The photophysical properties of four compounds in solution were investigated, where the substitutions had a significant effect even when the molecule conjugation was not included. Although having similar luminescent cores, two analog compounds showed different emission colors, blue and green. Uncommonly, one derivative showed a blue shift after aggregation. DFT simulations showed that adding a terminal group can significantly alter the electronic structure or molecular packing which affected directly the luminescence behavior.