Studies On Synthetic Process For Gefitinib

Gefitinib is a quinazoline derivative, the epidermal growth factor receptor (EGFR) inhibitor, research shows that it has significant effect on the treatment of advanced lung cancer, which is a new anti-tumor product developed by Astra Zeneca, mainly used for the treatment of non-small cell lung cancer, with good prospects. The study on its synthetic method of Gefitinib is of great importance.Through accessing relevant literature, summarizing the advantages and disadvantag-es of synthetic routes, the final choice is that gefitinb was prepared from 3-hydroxy-4-methoxybenzaldehyde by a six-step way including substitution, nitration, reduction and cyclization. There is no hydroxyl protection or separation, or the use of high-risk and highly-contaminated halide reagents in this method. The route reduced environme-ntal pollution and simplified the steps. The process of reaction was optimized. In the nitr ation step, the mixed acid of 80% concentrated nitric acid and 80% concentrated sulf uric acid was adopted as nitrating agent, the yield was 80%, the reaction time was re duced by half. The total yield was improved to 45.1%.The structure of the synthetic products were characterized by measuring melting point, infrared(IR), mass spectra(MS) and 1H nuclear magnetic resonance(NMR). The results proved: the structures and performance indexes of the products conformed to the designed requirement, this can prognosticate the synthesis design of using the original raw material (3-hydroxy-4-methoxybenzaldehyde) was practical and effective.