WO2014061004A2 - Procédé pour la préparation de vilazodone ou de sel pharmaceutiquement acceptable de celui-ci - Google Patents

Procédé pour la préparation de vilazodone ou de sel pharmaceutiquement acceptable de celui-ci Download PDF

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Publication number
WO2014061004A2
WO2014061004A2 PCT/IB2013/059518 IB2013059518W WO2014061004A2 WO 2014061004 A2 WO2014061004 A2 WO 2014061004A2 IB 2013059518 W IB2013059518 W IB 2013059518W WO 2014061004 A2 WO2014061004 A2 WO 2014061004A2
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WIPO (PCT)
Prior art keywords
formula
benzofuran
compound
carboxamide
solvent
Prior art date
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PCT/IB2013/059518
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English (en)
Other versions
WO2014061004A3 (fr
Inventor
Prasenjit Das
Bindu Srivastava
Nitin Maheshwari
Hashim Nizar Poovanathil Nagoor Meeran
Mohan Prasad
Sudershan Kumar Arora
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Ranbaxy Laboratories Limited
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Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2014061004A2 publication Critical patent/WO2014061004A2/fr
Publication of WO2014061004A3 publication Critical patent/WO2014061004A3/fr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/84Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D307/85Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention provides a novel intermediate of vilazodone and its process of preparation.
  • the present invention further provides a process for preparing vilazodone or a pharmaceutically acceptable salt thereof using said novel intermediate.
  • Vilazodone hydrochloride is indicated for the treatment of major depressive disorder (MDD).
  • MDD major depressive disorder
  • Processes for the preparation of vilazodone free base and its different intermediates are purportedly described in U.S. Patent Nos. 5,532,241, 5,723,614, and 5,977,112 and European Patent No. 0 648 767.
  • the present invention provides a novel intermediate of vilazodone and its process of preparation.
  • the present invention further provides a process for preparing vilazodone or a pharmaceutically acceptable salt thereof using said novel intermediate.
  • the invention relates to a novel intermediate compound of Formula III.
  • the invention relates to a process for the preparation of 5-amino-l-benzofuran-2-carboxamide of Formula III
  • the process includes the steps of:
  • Embodiments of the process may include one or more of the following features.
  • the compound of Formula IV may be converted to the compound of Formula V in step a) in the presence of formamide, a base, and a solvent.
  • the compound of Formula IV may be converted to the compound of Formula V in step a) in the presence of formamide, a base, and a solvent.
  • the solvent may be selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • the solvent may be N-methyl pyrollidone.
  • the base may be selected from the group consisting of alkali metal alkoxide or organic bases.
  • the base may be sodium methoxide.
  • the compound of Formula V may be converted to the compound of Formula III in the presence of a reducing agent and a solvent.
  • the reducing agent may be selected from the group consisting of palladium/carbon, platinum/dioxide, or Raney-Nickel in the presence of ammonium formate.
  • the reducing agent may be palladium/carbon in the presence of ammonium formate.
  • the solvent may be selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • the invention relates to a process for preparing vilazodone free base of Formula I
  • larmaceutically acceptable salts thereof which comprises: converting ethyl 5-nitro-l-benzofuran-2-carboxylate of Formula IV
  • Embodiments of the process may include one or more of the following features.
  • the compound of Formula IV may be converted to the compound of Formula V in step a) in the presence of formamide, a base, and a solvent.
  • the compound of Formula IV may be converted to the compound of Formula V in step a) in the presence of formamide, a base, and a solvent.
  • the solvent may be selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • the solvent may be N-methyl pyrollidone.
  • the base may be selected from the group consisting of alkali metal alkoxide or organic bases.
  • the base may be sodium methoxide.
  • the compound of Formula V may be converted to the compound of Formula III in the presence of a reducing agent and a solvent.
  • the reducing agent may be selected from the group consisting of palladium/carbon, platinum/dioxide, or Raney-Nickel in the presence of ammonium formate.
  • the reducing agent may be palladium/carbon in the presence of ammonium formate.
  • the solvent may be selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • the 5-amino-l-benzofuran-2-carboxamide compound of Formula III may be converted to the 5-(piperazin-l-yl)-l-benzofuran-2-carboxamide of Formula VI in step c) by reacting with bis-2-chloroethylamine in the presence of a solvent.
  • the solvent may be selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N- alkyl pyrollidone, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • the reaction of the compound of Formula VI and the compound of Formula VII in step d) may be carried out in the presence of a base and a solvent.
  • the solvent may be selected from the group consisting of water, organic solvents, or mixtures thereof.
  • Formula VII may be treated with hydrobromic acid before converting to vilazodone free base.
  • the pharmaceutically acceptable salt in step f) may be the hydrochloric acid salt.
  • a first aspect of the present invention provides an intermediate compound of
  • the intermediate compound of Formula III is chemically described as 5-amino-l- benzofuran-2-carboxamide.
  • a second aspect of the present invention provides a process for the preparation of 5-amino-l-benzofuran-2-carboxamide of Formula III
  • the compound of Formula IV may be prepared by methods known in literature, for example, by the process known from U.S. Patent No. 5,532,241.
  • the compound of Formula IV is converted to the compound of Formula V in the presence of formamide, a base, and a solvent.
  • the solvent is selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • Suitable alcoholic solvents are methanol, 2-propanol, or 1-propanol.
  • a suitable halogenated hydrocarbon solvent is
  • the preferred solvent is N-methyl pyrollidone.
  • the base is selected from the group consisting of alkali metal alkoxide or organic bases. Suitable alkali metal alkoxides are sodium methoxide or sodium i-butoxide. Suitable organic bases are ethyl amine, tri-n-butyl amine, diisopropyl ethyl amine, or methyl amine. The preferred base is sodium methoxide.
  • the conversion of the compound of Formula IV to the compound of Formula V is carried out at about 10°C to about 60°C, preferably at about 20°C to about 40°C.
  • the conversion of the compound of Formula IV to the compound of Formula V is carried out for about 3 hours to about 9 hours, preferably for about 5 hours to about 7 hours.
  • the compound of Formula V may optionally be isolated by filtration, concentration, precipitation, cooling, centrifugation, decantation, or a combination thereof.
  • the compound of Formula V is reduced to the compound of Formula III in the presence of a reducing agent and a solvent.
  • the reducing agent is selected from the group consisting of palladium/carbon, platinum/dioxide, or Raney-Nickel and is used in the presence of ammonium formate.
  • the preferred reducing agent is palladium/carbon in the presence of ammonium formate.
  • the solvent is selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, formamide, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • Suitable alcoholic solvents are methanol, 2-propanol, or 1-propanol.
  • a suitable halogenated hydrocarbon solvent is dichloromethane.
  • the preferred solvent is methanol.
  • the conversion of the compound of Formula V to the compound of Formula III is carried out at about 20°C to about 80°C, preferably at about 30°C to about 70°C.
  • the conversion of the compound of Formula V to the compound of Formula III is carried out for about 2 hours to about 7 hours, preferably for about 3 hours to about 5 hours.
  • the compound of Formula III may be isolated by filtration, concentration, precipitation, cooling, centrifugation, decantation, or a combination thereof.
  • a third aspect of the present invention provides a process for the preparation of vilazodone free base of Formula I
  • the compound of Formula IV may be prepared by methods known in the literature, for example, by the process known from U.S. Patent No. 5,532,241.
  • the compound of Formula IV is converted to the compound of Formula V as described in the second aspect.
  • the compound of Formula V may optionally be isolated by filtration,
  • the compound of Formula V is reduced to the compound of Formula III as described in the second aspect.
  • the compound of Formula III may be isolated by filtration, concentration, precipitation, cooling, centriiugation, decantation, or a combination thereof.
  • the 5-amino-l-benzofuran-2-carboxamide compound of Formula III is converted to 5-(piperazin-l-yl)-l-benzofuran-2-carboxamide of Formula VI by reacting with bis-2- chloroethylamine in the presence of a solvent.
  • the solvent is selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, ethers, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • Suitable alcoholic solvents are methanol, 2-propanol, or 1-propanol.
  • Suitable halogenated hydrocarbon solvent are dichlorome thane, 1,2-dichlorobenzene, or chlorobenzene.
  • Suitable aromatic hydrocarbon solvents are toluene or xylene.
  • the preferred solvent is N-methyl pyrollidone.
  • the conversion of the compound of Formula III to the compound of Formula VI is carried out in the presence of a base.
  • the base is selected from the group consisting of inorganic bases or organic bases.
  • Suitable inorganic bases are hydroxides or carbonates and bicarbonates of alkali or alkaline metal.
  • Suitable carbonates or bicarbonates of alkali or alkaline metal are sodium carbonate, potassium carbonate, magnesium carbonate, sodium bicarbonate, or potassium bicarbonate.
  • a preferable inorganic base is potassium carbonate.
  • Suitable organic bases are tributyl amine, ethyl amine, diisopropyl ethyl amine, triethyl amine, or methyl amine.
  • the preferred base is tributyl amine.
  • the conversion of the compound of Formula III to the compound of Formula VI is carried out at about -20°C to about 180°C, preferably at about 0°C to about 160°C.
  • the conversion of the compound of Formula III to the compound of Formula VI is carried out for about 2 hours to about 7 hours, preferably for about 3 hours to about 5 hours.
  • the compound of Formula VI may be isolated by filtration, concentration, precipitation, cooling, centrifugation, decantation, or a combination thereof.
  • the compound of Formula VI is converted to vilazodone free base or its salt by treating with the compound of Formula VII.
  • the treatment of the compound of Formula VI and the compound of Formula VII is carried out in the presence of a base and a solvent.
  • the solvent is selected from the group consisting of water, organic solvents, or mixtures thereof.
  • the organic solvent is selected from the group consisting of halogenated hydrocarbons, alcohols, ketones, N-alkyl pyrollidone, nitriles, aromatic and aliphatic hydrocarbons, or mixtures thereof.
  • a suitable halogenated hydrocarbon solvent is dichloromethane.
  • Suitable alcoholic solvents are methanol, 2-propanol, or 1-propanol.
  • Suitable ketone solvents are acetone or methyl isobutyl ketone.
  • a suitable nitrile solvent is acetonitrile.
  • Suitable amide solvents are N-methyl pyrrolidone or dimethyl formamide.
  • a suitable aromatic hydrocarbon solvent is toluene.
  • the preferred solvent is N-methyl pyrollidone.
  • the base is selected from the group consisting of organic bases or inorganic bases.
  • Suitable organic bases are tributyl amine, triethyl amine, diisopropyl amine, diisopropyl ethylamine, 4-dimethylaminopyridine, pyrollidine, or N-methyl morpholine.
  • the preferred organic base is tributyl amine.
  • Suitable inorganic bases are hydroxides, or carbonates or bicarbonates of alkali or alkaline metal. Suitable carbonates or bicarbonates of alkali or alkaline metal are sodium carbonate, potassium carbonate, magnesium carbonate, sodium bicarbonate, or potassium bicarbonate.
  • the preferred base is potassium carbonate.
  • the treatment of the compound of Formula VI and the compound of Formula VII is carried out in the presence of alkali metal halides, for example, sodium iodide.
  • the treatment of the compound of Formula VI and the compound of Formula VII is carried out at a temperature of about 5°C to about 130°C, preferably at about 20°C to about 120°C.
  • the treatment of the compound of Formula VI and the compound of Formula VII is carried for about 2 hours to about 35 hours, preferably for about 5 hours to about 30 hours.
  • the reaction mixture of the compound of the Formula VI and the compound of Formula VII is treated with hydrobromic acid before converting to vilazodone free base.
  • the hydrobromic acid may be dilute or concentrated.
  • the hydrobromic acid may be used in a solution or in gaseous form.
  • the solution of hydrobromic acid may be aqueous or in an organic solvent.
  • the organic solvents are selected from the group consisting of methanol, ethanol, or 2-propanol.
  • the treatment of reaction mixture of the compound of Formula VI and the compound of Formula VII with hydrobromic acid is carried out in the presence of an organic solvent.
  • the organic solvent is selected from a group consisting of alcohols, ketones, esters, formamides, water, halogenated hydrocarbons, N-methyl pyrollidone, or combinations thereof.
  • Suitable alcoholic solvents are methanol, ethanol, 2- propanol, 1-propanol, or butanol.
  • the preferred solvent is N-methyl pyrollidone in combination with 2-propanol, methanol, or methylated ethanol.
  • the dissolution of the reaction mixture of the compound of Formula VI and the compound of Formula VII with hydrobromic acid is carried out at a temperature of about 10°C to about 40°C, preferably at about 20°C to about 35°C.
  • the dissolution of the reaction mixture of the compound of Formula VI and the compound of Formula VII with hydrobromic acid is carried out for about 5 minutes to about 25 hours, preferably for about 7 hours to about 18 hours.
  • the vilazodone hydrobromide salt may optionally be isolated by filtration, decantation, drying, vacuum drying, or a combination thereof.
  • the vilazodone hydrobromide is converted to vilazodone free base.
  • the conversion of vilazodone hydrobromide to vilazodone free base is carried out in the presence of a base and a solvent.
  • the base is selected from the group consisting of organic or inorganic bases.
  • the inorganic base is selected from the group consisting of carbonates, bicarbonates, or hydroxides.
  • the preferred base for the conversion of vilazodone hydrobromide to vilazodone free base is sodium bicarbonate.
  • the base used for the conversion of vilazodone hydrobromide to vilazodone free base may be used in the form of a solid or an aqueous solution.
  • the solvent for the conversion of vilazodone hydrobromide to vilazodone free base is selected from the group consisting of water, organic solvents, or combinations thereof.
  • the organic solvent is selected from the group consisting of alcohols, esters, halogenated hydrocarbons, ketones, amides, esters, or combinations thereof.
  • Suitable alcoholic solvents are methanol, ethanol, methylated ethanol, 2-propanol, 1-propanol, or butanol.
  • Suitable amide solvents are N-methyl pyrrolidone, dimethyl acetamide, or dimethyl formamide.
  • a suitable nitrile solvent is acetonitrile.
  • Suitable ketonic solvents are acetone or methyl isobutyl ketone.
  • a suitable chlorinated solvent is dichloromethane.
  • Suitable ester solvents are ethyl acetate, methyl acetate, or isopropyl acetate.
  • the preferred solvent is water in combination with methanol, ethanol, or 2-propanol.
  • the conversion of vilazodone hydrobromide to vilazodone free base is carried out at a temperature of about 10°C to about 100°C, preferably at about 20°C to about 85°C.
  • the dissolution of vilazodone free base with water and an alcoholic solvent is carried out for about 30 minutes to about 6 hours, preferably for about 1 hour to about 4 hours.
  • the vilazodone free base of Formula I may be isolated by filtration, concentration, precipitation, cooling, centrifugation, decantation, or a combination thereof.
  • the vilazodone free base obtained by the present invention can be converted to its pharmaceutically acceptable salt, for example, hydrochloric acid salt.
  • the vilazodone free base is treated with hydrochloric acid in the presence of water, alcohol, amide, halogenated hydrocarbon, esters, or mixtures thereof.
  • Suitable alcoholic solvents are methanol, ethanol, 2-propanol, 1-propanol, or butanol.
  • Suitable amide solvents are N- methyl pyrrolidone, dimethyl acetamide, or dimethyl formamide.
  • Suitable halogenated hydrocarbon solvents are dichloromethane or chloroform.
  • Suitable ester solvents are ethyl acetate, methyl acetate, or isopropyl acetate.
  • the preferred solvent is 2-propanol, either alone or in combination with N-methyl pyrrolidone or water.
  • the treatment of vilazodone free base with hydrochloric acid is carried out at a temperature of about 50°C to about 100°C, preferably at about 70°C to about 85°C.
  • the treatment of the reaction mixture obtained in step c) with hydrochloric acid is carried out for about 30 minutes to about 2 hours, preferably for about 60 minutes to about 2 hours.
  • the hydrochloric acid may be dilute or concentrated.
  • the hydrochloric acid may be used in solution form or gaseous form.
  • the solution of hydrochloric acid may be aqueous or in an alcoholic solvent.
  • the alcoholic solvent used for the preparation of hydrochloric acid solution is 2-propanol.
  • the vilazodone hydrochloride salt may be isolated by filtration, distillation, evaporation, centriiugation, decantation, drying, vacuum drying, or a combination thereof.
  • the vilazodone hydrochloride prepared by the present invention may be characterized using an X-ray powder diffraction (XRPD) pattern.
  • Ethyl 5-nitro-l-benzofuran-2-carboxylate 100 g was added to N-methyl pyrollidone (250 mL) at 20°C to 25°C.
  • a solution of formamide (57.4 g) in N-methyl pyrollidone (250 mL) was added to the reaction mixture.
  • a solution of 30% sodium methoxide (230 g) was added to the reaction mixture over 1 hour at 20°C to 25°C.
  • the reaction mixture was stirred at 20°C to 25 °C for 1 hour.
  • the temperature of the reaction mixture was increased to 30°C to 35°C.
  • Deionized water (3 L) was added to the reaction mixture at 30°C to 35 °C for 1 hour.
  • the reaction mixture was filtered and washed with deionized water (500 mL x 6) to obtain the title compound.
  • step a) The solid obtained in step a) was added to methanol (1 L). A solution of 2.5% palladium/carbon (20 g) in deionized water (20 mL) was added to the reaction mixture. Ammonium formate (26.8 g x 4) was added to the reaction mixture at 30°C to 45°C. The reaction mixture was stirred at 40°C to 45 °C for 1 hour. The reaction mixture was filtered and washed with methanol (2 x 100 mL). Methanol was recovered under vacuum at 60°C to 65°C. Deionized water (200 mL) was added to the reaction mixture and the mixture stirred for 1 hour. The reaction mixture was filtered and washed with water (200 mL). The solid obtained was dried in air at 50°C to 55 °C to obtain the title compound.
  • 5-Amino-l-benzofuran-2-carboxamide (10 g; prepared according to Example 1) was added to N-methyl pyrollidone (50 mL).
  • Bis-2-chloroethylamine (12.2 g) was added to the reaction mixture.
  • the temperature of the reaction mixture was raised to 150°C to 155°C and the mixture stirred for 2 hours.
  • Tributyl amine (10.5 g) was added to the reaction mixture and stirred at 150°C to 155°C for 6 hours.
  • the reaction mixture was cooled to 25 °C to 30°C.
  • Deionized water 350 mL was added to the reaction mixture and the pH was adjusted to 12 with 20% sodium hydroxide solution (35 mL).
  • the reaction mixture was cooled to 0°C to 5°C and stirred for 2 hours.
  • the reaction mixture was filtered and washed with water (50 mL).
  • Deionized water (50 mL) was added to the reaction mixture and the pH was adjusted to 4.7 with concentrated hydrochloric acid (3.1 mL).
  • Activated carbon (1 g) was added to the reaction mixture and stirred for 45 minutes.
  • the reaction mixture was filtered and washed with deionized water (50 mL).
  • the pH of the filtrate was adjusted to 12.0 with 20% sodium hydroxide solution (4 mL).
  • the reaction mixture was cooled to 0°C to 5°C and stirred for 1 hour.
  • the reaction mixture was filtered and washed with deionized water (2 x 10 mL).
  • the solid obtained was dried in air at 50°C to 55°C to obtain the title compound.
  • Example 2 3-(4-chloro butyl)-lH-indole-5-carbonitrile (5.7 g) were added to N- methyl pyrollidone (25 mL). The temperature of the reaction mixture was increased to 110°C to 120°C and stirred for 2 hours. Tributyl amine (3.77 g) was added to the reaction mixture and stirred at 110°C to 120°C for 4 hours. The reaction mixture was cooled to 20°C to 35°C. Hydrobromic acid (2.5 mL) and 2-propanol (50 mL) were added to the reaction mixture. Vilazodone hydrobromide seed (0.005 g) was added to the reaction mixture and stirred at 0°C to 5°C for 1 hour. The reaction mixture was filtered, and then washed with cooled 2-propanol (25 mL).
  • reaction mixture was added to a mixture of N-methyl pyrollidone (25 mL) and hydrobromic acid (0.5 mL).
  • 2-Propanol (50 mL) was added to the reaction mixture and stirred for 2 hours.
  • the reaction mixture was filtered and washed with 2-propanol (10 mL).
  • the reaction mixture was added to 2-propanol (100 mL) and deionized water (50 mL).
  • the temperature of the reaction mixture was increased to 80°C to 82°C.
  • Activated carbon (1 g) was added to the reaction mixture and stirred for 1 hour.
  • the reaction mixture was filtered and washed with 2-propanol (20 mL) and deionized water (10 mL).
  • the pH of the filtrate was adjusted to 7.2 with 7% sodium bicarbonate solution (9 mL).
  • the reaction mixture was filtered and washed with deionized water (20 mL) and 2- propanol (20 mL).
  • the solid obtained was dried in air at 50°C to 55°C to obtain the title compound.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouvel intermédiaire de vilazodone et son procédé de préparation. La présente invention concerne en outre un procédé de préparation de vilazodone ou d'un sel pharmaceutiquement acceptable de celui-ci à l'aide dudit nouvel intermédiaire.
PCT/IB2013/059518 2012-10-19 2013-10-21 Procédé pour la préparation de vilazodone ou de sel pharmaceutiquement acceptable de celui-ci WO2014061004A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3248DE2012 2012-10-19
IN3248/DEL/2012 2012-10-19

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WO2014061004A2 true WO2014061004A2 (fr) 2014-04-24
WO2014061004A3 WO2014061004A3 (fr) 2014-06-19

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0648767A1 (fr) 1993-09-30 1995-04-19 MERCK PATENT GmbH Dérivés de piperidine et piperazine qui puissent agir sur le "CNS"
US5723614A (en) 1995-04-20 1998-03-03 Merck Patent Gesellschaft Mit Beschrankter Haftung Benzofurans

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005019670A1 (de) * 2005-04-26 2006-11-02 Merck Patent Gmbh Verfahren zur Herstellung von (5-(4-[4-(5-Cyano-3-indolyl)-butyl)-1-piperazinyl)-benzofuran-2-carboxamid
CN102863413A (zh) * 2011-07-08 2013-01-09 上海泛凯生物医药科技有限公司 一种5-哌嗪基苯并呋喃-2-甲酰胺及其盐的制备方法
CN103159749A (zh) * 2011-12-13 2013-06-19 南京友杰医药科技有限公司 抗抑郁药维拉佐酮(vilazodone)的合成方法
WO2013175499A2 (fr) * 2012-04-20 2013-11-28 Cadila Healthcare Limited Forme polymorphe du 5-(4-[4-(5-cyano-1h-indol-3-yl)butyl]pipérazin-1-yl)benzofurane-2-carboxamide

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0648767A1 (fr) 1993-09-30 1995-04-19 MERCK PATENT GmbH Dérivés de piperidine et piperazine qui puissent agir sur le "CNS"
US5532241A (en) 1993-09-30 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Piperidines and piperazines
US5723614A (en) 1995-04-20 1998-03-03 Merck Patent Gesellschaft Mit Beschrankter Haftung Benzofurans
US5977112A (en) 1995-04-20 1999-11-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Process of making substituted benzofurans

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