Synthesis And Process Improvement Of Bicalutamide

In the prostate,prostate cancer is an epithelial malignant tumor,It is a relative common male genitourinary malignancy that has been suffering from men.Since the development of Bicalutamide,prostate cancer has been alleviated,but anti-prostate cancer drugs is still the current research hot spots.In recent years,Bicalutamide has an increasing market share in the global anti-prostate cancer drug market,so the development of Bicalutamide has a very good market prospects.This paper is mainly studied the synthesis route of Bicalutamide and 4-amino-2-trifluoromethylbenzonitrile.It determine the optimal route of bicalutamide and process improvement of the route.The structural characterization of Bicalutamide and its intermediates was confirmed,and final the Bicalutamide contents of the two methods were determined.Make 2-bromobenzotrifluoride as material in this route,after nitration reaction to get 2-bromo-5-nitrobenzotrifluoride(7),after cyanidation reaction to get 4-nitro-2-trifluoromethylbenzonitrile(8),after the reduction reaction to get its intermediates of 4-Amino-2-Trifluoro-methylbenzonitrile(3),and then through the acylation reaction of 2-methacryloyl chloride(2)to get N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-methacrylamide(4),after epoxidation to get N-[4-Cyano-3-(Trifluoro-methyl)Phenyl]-2-Methyl-2-Oxirane Carboxamide(5),after the condensation reaction of 4-fluorothiophenol to get N-[4-cyano-3-(trifluoromethyl)-phenyl]-3-(4-fluorophenyl)sulfur-2-hydroxy-2-methyl-propanamid(6),after oxidation to get N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methy-l-propanami d(1).And in this experiment,the reaction ingredients ratio,reaction temperature,reaction time,catalyst,solvent,reactant concentration and reagents drop order and other factors to discuss one by one,and finally determine the most optimized synthesis process,which yield reached 57.6% to suitable for industrial production.The chemical structures of the target products and intermediates were confirmed by 1H NMR and LC / MS.