# US 7,745,628 B2 · Method for obtaining a pharmaceutically active compound, synthesis intermediates thereof and methods for obtaining them > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,628 B2 - Document ID: US7745628B2 - Status: Granted - Kind: B2 - Application number: 11/994,667 - Filed: 2006-06-26 - Published: 2008-08-14 - Granted: 2010-06-29 - Earliest claimed: 2005-07-06 - Assignees: Inke, S.A. - Inventors: Juan Antonio Perez Andres; Pere Dalmases Barjoan - Web page: https://patentgrep.com/patent/US7745628B2 ## CPC - C07D 451/06: Oxygen atoms - Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS ## Abstract The present invention relates to a method for obtaining Dolasetron that comprises: a) Esterification of the alcohol of formula (IV) with indole-3-carboxylic acid (compound (III)) or a reactive derivative thereof, to give a compound of formula (V), followed by step b) which includes Dieckmann reaction of the intermediate (V), by reaction with a strong organic or inorganic base, to give the intermediate (VI), and step c) which comprises dealcoxycarbonylation of the intermediate (VI) to give Dolasetron base and, if desired, a pharmaceutically acceptable salt thereof, hydrates or solvates of the base of said salt. The invention also relates to the intermediates (V) and (VI), and methods for obtaining them. With the method of the present invention Dolasetron is obtained at industrial scale with good yields, with decreased use of reactants and solvents, while said method is also of greater atomic efficiency. ## Claims ### Claim 1 Method for obtaining a pharmaceutically active compound, Dolasetron, characterised in that it comprises the following steps: a) Esterification of the alcohol of formula IV with indole-3-carboxylic acid (compound III) or a reactive derivative thereof, where R1 and R2 mean any linear or branched chain C1-C4 alkyl group, in which the indole group can optionally be protected with a protective group of indoles, to give a compound of formula V: b) Dieckmann reaction of intermediate V, by reaction with a strong organic or inorganic base, to give the intermediate VI: c) Dealcoxycarbonylation of the intermediate VI, and optionally deprotection of the indole group, to give Dolasetron base and, if desired, a pharmaceutically acceptable salt thereof, hydrates or solvates of the base or of said salt. ### Claim 2 (depends on 1) Method according to claim 1, characterised in that said indole protective group is selected from sulphonyl, alcoxycarbonyl or trialkylsilyl. ### Claim 3 (depends on 1) Method according to claim 1, characterised in that said reaction in step a) is carried out at a temperature between −50 and 100° C. and in the presence of an aprotic organic solvent. ### Claim 4 (depends on 3) Method according to claim 3, characterised in that said reaction is carried out between −10 and 30° C. ### Claim 5 (depends on 4) Method according to claim 4, characterised in that said reaction is carried out between 0° C. and 25° C. ### Claim 6 (depends on 3) Method according to claim 3, characterised in that said aprotic organic solvent is selected from dichloromethane, toluene and DMF. ### Claim 7 (depends on 1) Method according to claim 1, characterised in that said reaction in step a) is carried out in the presence of a catalyst. ### Claim 8 (depends on 7) Method according to claim 7, characterised in that said catalyst is DMAP. ### Claim 9 (depends on 1) Method according to claim 1, characterised in that said strong organic or inorganic base is potassium tert-butoxide. ### Claim 10 (depends on 1) Method according to claim 1, characterised in that said reaction in step b) is carried out at a temperature between −40° C. and 70° C., in an aprotic organic solvent. ### Claim 11 (depends on 10) Method according to claim 10, characterised in that it is carried out at a temperature between 0° C. and 25° C. ### Claim 12 (depends on 10) Method according to claim 10, characterised in that said aprotic organic solvent is THF. ### Claim 13 (depends on 1) Method according to claim 1, characterised in that the dealcoxycarbonylation of step c) is carried out by treating with an inorganic salt, in a polar aprotic organic solvent and at a temperature between 100° C. and 200° C. ### Claim 14 (depends on 13) Method according to claim 13, characterised in that it is carried out at a temperature between 130° C. and 150° C. ### Claim 15 (depends on 13) Method according to claim 13, characterised in that said inorganic salt is selected from LiCl, NaCl and NaBr. ### Claim 16 (depends on 15) Method according to claim 15, characterised in that said inorganic salt is LiCl. ### Claim 17 (depends on 13) Method according to claim 13, characterised in that said polar aprotic organic solvent has a high boiling point and is selected from DMF, DMSO or N-methylpyrrolidone. ### Claim 18 (depends on 1) Method according to claim 1, characterised in that steps b) and c) are carried out in a one-pot reaction.