Computational Elucidation of Novel Synthetic Scheme for Erlotinib

The current study focusses on the use of quantum chemistry to elucidate the novel synthetic route for erlotinib from methyl 4,5-dihydroxy-2-isocyanobenzoate, which includes oxidative coupling, nucleophilic addition, cyclization and Williamson’s ether synthesis. The overall reaction requires three intermediate and produces 13 transition states [TS]. Which are less than the earlier reported synthetic schemes. The energies of each reactant, intermediate and products were calculated using DFT (density functional theory) and B3LYP/6-311+G* as a basis set. The energies diagram obtained indicates the novel proposed scheme could follow the easy path to obtain the product, moreover, the energy barrier required to overcome the transition state is low indicating, very less activation energy is required for every reactant to take part in chemical reaction.