PROCESS FOR PREPARING A PHARMACEUTICALLY ACTIVE COMPOUND (GRANISETRON)
(19)AUSTRALIAN PATENT OFFICE (54) Title PROCESS FOR PREPARING A PHARMACEUTICALLY ACTIVE COMPOUND (GRANISETRON) (51)6 International Patent Classification(s) C07D 451/14 (21) Application No: 2003208552 (22) Application Date: 2003.03.21 (87) WIPONo: WO03/080G0G (30) Priority Data (31) Number (32) Date P200200713 2002.03.26 (33) Country ES (43) Publication Date : 2003.10.08 (43) Publication Journal Date : 2003.11.13 (71) Applicant(s) LABORATORIOS VITA, S.A. (72) Inventor(s) DALMASES BARJOAN, Pere; PUIG TORRES, Salvador (H) Application NoAU2003208552 A1(19)AUSTRALIAN PATENT OFFICE (54) Title PROCESS FOR PREPARING A PHARMACEUTICALLY ACTIVE COMPOUND (GRANISETRON) (51)6 International Patent Classification(s) C07D 451/14 (21) Application No: 2003208552 (22) Application Date: 2003.03.21 (87) WIPONo: WO03/080G0G (30) Priority Data (31) Number (32) Date P200200713 2002.03.26 (33) Country ES (43) Publication Date : 2003.10.08 (43) Publication Journal Date : 2003.11.13 (71) Applicant(s) LABORATORIOS VITA, S.A. (72) Inventor(s) DALMASES BARJOAN, Pere; PUIG TORRES, Salvador The invention relates to a process for preparing granisetron, or a pharmaceutically acceptable salt thereof, which comprises: a) cyclisation of a compound of formula (I) in an inert solvent and at a temperature between 0-100° C., in the presence of a strong acid, in order to yield the compound of formula (II); b) methylation of the compound of formula (II), with an alkylating agent, in the presence of a base, in an inert solvent and at a temperature between 0° C.-160° C., and with optional formation of a pharmaceutically acceptable salt. The process of the invention yields a granisetron of high purity, preventing impurities due to demethylation, by carrying out the methylation after rather than before cyclisation and with a higher yield. Process for preparing granisetron, or a pharmaceutically acceptable salt thereof, characterised in that it comprises: a) cyclisation of a compound of formula (I): in an inert solvent and at a temperature between 0-100°C, in the presence of a strong acid, in order to yield the compound of formula (II): b) methylation of the compound of formula (II), with an alkylating agent, in the presence of a base, in an inert solvent and at a temperature between 0°C-160°C Process as claimed in Claim 1, characterised in that step a) is carried out in a protic solvent or mixture of protic solvents. Process as claimed in Claim 1, characterised in that step a) is carried out at a temperature between 10°C and 40°C. Process as claimed in Claim 1, characterised in that said alkylating agent is dimethyl sulphate. Process as claimed in Claim 1, characterised in that said alkylating agent is dimethyl carbonate. Process as claimed in Claims 1 and 4,characterised in that the solvent of step b) is selected from among methylene chloride, toluene or tetrahydrofuran. Process as claimed in Claims 1 and 4,characterised in that said base is sodium or potassium hydroxide in concentrated aqueous solution or in solid form. Process as claimed in Claims 1 and 4,characterised in that step b) is carried out in the presence of a phase transfer catalyst. Process as claimed in Claims 1 and 5,characterised in that the solvent of step b) is a polar aprotic solvent selected from either dimethylformamide (DMF) or N-methyl-2-pyrrolidonone (NMP). Process as claimed in Claims 1 and 5,characterised in that said base is an alkaline carbonate.