Synthesis Of Prostate Cancer Drug Of Bicalutamide

Bicalutamide, (±)-N-[4-Cyano-3-(trifluoro-methyl)phenyl]-3-[(4-fluorophenyl) sulfonyl]-2-hydroxyl-2-methylpropanamide, is an effective drug in treatment of prostate cancer.It is reported in literature [14] that Bicalutamide is synthesised from methyl methacrylate via epoxidation, nucleophilic substitution, esterolysis, N-acylation and oxidation. The yield of each process respectively is 53%, 61.9%, 41% and 83.2%, The overall yield is 11.2%.A novel synthesis route was developed in this paper. Bicaluatmide is prepared by epoxidation of methyl methacrylate, N-acylation, nucleophilic substitution and oxidation. The yield of each process respectively is 75.2%, 72.8%, 74.7% and 84.3%, The overall yield is 34.5%.In the reaction of epoxidation, using peracetic acid generated from 50% aqueous hydrogen peroxide solution and acetic anhydride as oxidant in stead of m-chloroperoxybenzoic acid greatly reduces the cost. N-acylation takes place from ester as acylating agent and amine, which avoids the reaction of esterolysis and chlorination. Compared to the former method using irritant acyl chloride as acylating agent, this new process shortens the reaction steps and avoids pollution. Removing methanol through reacting distillation makes the equilibrium shift right and increase the conversion. Using ammonium percarbonate as oxidant in stead of m-chloroperoxybenzoic acid which is expensive and contaminative improves the selectivity and yield of oxidation of thioether.The process of synthesizing intermediate of 3-trifluoromethyl-4-cyanoaniline has also been studied. Pouring reaction solution of nitration into ice water simply makes' the product crystallize and avoids extraction using diethyl ether which is inflammable and unsafe. Recrystallization for substitution Choosing 50% ethanol can avoid column chromatograph. The overall yield of nitration, reduction and substitution is 40.8%.The structure of each product has been confirmed by analyzing, Thus we succeed in getting a new industrial route of Bicalutamide characterized by low cost, cheap and easily gained materials, convenient operate process and little pollution.