Eight series of pyrimidine‐5‐carboxamides were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR spectroscopies, HR‐MS and elemental analysis. To encourage experimental confirmations, molecular electronic structure calculations and harmonic vibrational frequencies of compounds (theoretical computations) were carried out with the DFT/B3LYP method at the 6–311G++(d,p) basis set. The selected important assignments‐computed harmonic vibrational wavenumbers of compounds were defined by using potential energy distribution (PED) analysis. The molecular electrostatic potential (MEP) surface analysis was examined to bring into the open nucleophilic and electrophilic reactive areas of the compounds. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals (HOMOs and LUMOs) analyses were theoretically used for definition of electronic transitions corresponding to UV‐Vis. electronic absorption wavelengths. Additionally, for these series non‐linear optical properties (NLO) were investigated based on urea. Finally, in this manuscript molecular docking studies between macromolecule (receptor) and ligand interactions were carried out by using AutoDock Vina program. Obtained all outputs of new compounds were explained in different sections in‐depth.