WO2016170542A1 - Process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof - Google Patents

Process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof Download PDF

Info

Publication number
WO2016170542A1
WO2016170542A1 PCT/IN2015/050044 IN2015050044W WO2016170542A1 WO 2016170542 A1 WO2016170542 A1 WO 2016170542A1 IN 2015050044 W IN2015050044 W IN 2015050044W WO 2016170542 A1 WO2016170542 A1 WO 2016170542A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
ammonium
solvents
compound
solvent
Prior art date
Application number
PCT/IN2015/050044
Other languages
English (en)
French (fr)
Inventor
Satyanarayana Reddy BHEMIREDDY
Venkat Reddy YARAPATHI
V. Vara Prasada Reddy Paidimarla
Original Assignee
Nosch Labs Private Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nosch Labs Private Limited filed Critical Nosch Labs Private Limited
Publication of WO2016170542A1 publication Critical patent/WO2016170542A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/12—Heterocyclic 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 invention relates to a process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof. More particularly, the invention relates to a process for preparation of Vilazodone. Invention also relates to novel intermediates for synthesis of Vilazodone. The invention also relates to novel crystalline form of Vilazodone hydrochloride and a process for preparation of the same.
  • CN 103304547 A discloses a process for Vilazodone as shown in below Scheme- 2:
  • Scheme-2 CN103570697 discloses various routes for synthesis of Vilazodone.
  • 5-(piperazin-l-yl) benzofuran-2-carboxamide reacts with 4-bromo-l-butene to give an intermediate 5- (4- (3- butenyl) piperazin-l-yl) benzofuran-2- carboxamide, which further reacts with 3- iodo-l-tosyl-indole-5- carbonitrile to give 5- (4- (4- (5-cyano-l-tosyl-indol-3-yl) -3-butenyl) piperazin -1- yl) benzofuran -2-carboxamide.
  • X halogen F, CI, Br, I; preferably Br
  • US Patent 8802851 B2 describes a process for preparation of Vilazodone free base and subsequent conversion to Vilazodone HC1 comprising the steps of: (a) reacting 3-(4-chloro-l-hydroxy-butyl)-lH-indol-5-carbonitrile of formula (I) with 5-piperazin-l-yl-benzofuran-2-carboxylate methyl hydrochloride of formula (II) to give 5- ⁇ 4-[4-(5-cyano-lH-indol-3-yl)-4-hydroxybutyl]-piperazin-l- yl ⁇ benzofuran-2-carboxylate methyl of formula (III); (b) treating the compound of formula (III), obtained from step (a), with an acidification agent to obtain 5- ⁇ 4-[4- (5-cyano-lH-indol-3-yl)-4-hydroxy-butyl]-piperazin-l-yl ⁇ benzofuran-2- carboxylate methyl of formula (IV);
  • the primary object of the invention is to provide a novel process for the preparation of Vilazodone.
  • Another object of the invention is to provide novel intermediates for the synthesis of Vilazodone.
  • Another object of the invention is to provide a novel crystalline form of Vilazodone hydrochloride.
  • a further object of the invention is to provide a process for preparing novel crystalline form of Vilazodone hydrochloride.
  • the present invention provides a process for preparation of Vilazodone and novel intermediates for synthesis of Vilazodone.
  • the invention also provides novel crystalline form of Vilazodone hydrochloride and process for preparing the same.
  • the invention provides a process for preparation of Vilazodone comprising the steps of:
  • Ts Tosyl
  • X represents a leaving group selected from halogen (CI, Br and I), O-tosyl, O-mesyl, O-benzenesulfonyl, O-trifluoromethane sulfonyl; preferably X is halogen, more preferably CI.
  • Et represents ethyl (-C 2 Hs).
  • the suitable reducing agent in step-(a) may be selected from sodiumborohydride, lithium borohydride, NaBH 3 CN, DIBAL-H, lithium aluminiumhydride, vitride, borane-THF, sodiumborohydride/ iodine, 9-BBN; preferably sodiumborohydride.
  • the suitable reducing agent used in step-(a) is sodiumborohydride .
  • the solvent used in step-(a) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec -butyl acetate, isopropyl acetate and the like; "ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene dichloride, ethylene dichloride, carbon tet
  • Step-(b) proceeds in presence of suitable solvents and or suitable acid binding agents and with or without suitable activating agents.
  • the solvent used in step-(b) may be selected from triethylamine (TEA), disiopropylethyl amine, toluene, diglyme, acetone, methanol, ethanol, isopropanol, n-butanol, tetrahydrofuran (THF), dioxane, water, dimethylformamide (DMF), dimethylacetamide, N- methylpyrrolidone, acetonitrile or mixtures thereof; preferably triethylamine (TEA).
  • TFA triethylamine
  • the suitable acid binding agents in step-(b) may be selected from an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide or alkali metal or alkali earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate or calcium carbonate or alkali metal or alkaline earth metal salt of a week acid, preferably a potassium, sodium or calcium salt, or an organic bases such as triethylamine, disiopropylethyl amine, dimethylaniline, pyridine or quinoline and the like or the mixtures thereof; preferably triethylamine.
  • the suitable activating agents in step-(b) may be metal halides and/or phase transfer catalysts.
  • Step-(b) is performed with or without presence of metal halides and with or without presence of phase transfer catalyst.
  • the metal halides in step-(b) may be selected from iodide and bromide of alkali metal or alkali earth metal; preferably sodium iodide or potassium iodide.
  • the phase transfer catalyst in step-(b) may be selected from tetra butyl ammonium bromide (TBAB), tetrapropyl ammonium bromide, tributyl benzyl ammonium bromide, tetraoctyl ammonium bromide, tetra butyl ammonium iodide, tetra butyl ammonium hydrogen sulfate, benzyl trimethyl ammonium chloride, benzyl triethyl ammonium chloride, tetra butyl ammonium acetate, tetra butyl ammonium iodide and ethyl triphenyl phosphonium bromide; preferably TBAB.
  • TBAB tetra butyl ammonium bromide
  • the suitable amidation agent in step-(c) may be selected from ammonia, formamide, ammonia gas, ammonium carbamate, ammonium formate, ammonium phosphate, ammonium acetate, ammonium fluoride, ammonium bromide, ammonium chloride, ammonium iodide, ammonium iodate, ammonium carbonate, ammonium citrate, ammonium chromate, ammonium dichromate, ammonium hydroxide, ammonium lactate, ammonium molybdate, ammonium nitrate, ammonium oxalate, ammonium sulfate, ammonium sulfide, ammonium tartarate, ammonium triflate, ammonium thiocyanate, ammonium dihydrogen phosphate, urea, methyl carbamate, ethyl carbamate, propyl carbamate or t-butyl carbamate, alkyl or aryl amines, magnesium
  • the suitable solvent in step-(c) may be selected from water, alcohols, ketones, diols, triols, esters, amides, ethers, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof.
  • Polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane; alcohols such as methanol, ethanol, propanol, butanol, glycerol, propylene glycol; polyglycols such as polyethylene glycol 200, polyethylene glycol 300 and polyethylene glycol 400; pyrrolidones such as N-methyl pyrrolidone and 2-pyrrolidone; glycol ethers such as propylene glycol monomethyl ether, dipropylene glycol monomethyl ether and diethylene glycol ethyl ether, ⁇ , ⁇ -dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like to toluene, xylene, heptane, cyclohexane and hexane; preferably the solvent selected from methanol or ethanol.
  • the suitable reducing agent in step-(d) may be used alone or in combination of suitable reagents; selected from DIBAL-H, lithium aluminiumhydride, sodiumborohydride, lithium borohydride, NaBH 3 CN, sodium borohydride/BF 3 - etherate, vitride, sodiumborohydride/aluminium chloride, borane/aluminium chloride, sodiumborohydride/iodine, 9-BBN, trifluoroacetic acid (TFA)/sodiumborohydride(SBH), Et 3 SiH/TFA; preferably combination of trifluoroacetic acid with sodiumborohydride is used.
  • suitable reagents selected from DIBAL-H, lithium aluminiumhydride, sodiumborohydride, lithium borohydride, NaBH 3 CN, sodium borohydride/BF 3 - etherate, vitride, sodiumborohydride/aluminium chloride, borane/aluminium chloride, sodiumborohydride/iodine, 9-BBN, tri
  • the solvent used in step-(d) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec -butyl acetate, isopropyl acetate and the like; "ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene dichloride, ethylene dichloride, carbon tet
  • the suitable base used in step-(e) may be selected from an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide; or alkali metal or alkaline earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate and calcium carbonate; or alkali metal or alkaline earth salt of weak acid, preferably a potassium, sodium or calcium salt; or an organic base such as triethylamine, dimethylaniline, pyridine or quinoline and the like; ammonia or mixtures thereof; preferably the base is sodium hydroxide (NaOH) and potassium hydroxide (KOH); more preferably the base used is
  • the suitable solvent used in step-(e) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; “ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene chloride, ethylene dichloride, carbon tetrach
  • the invention provides a process for preparation of Vilazodone comprising the steps of:
  • the invention provides novel intermediate compounds of general Formula-II, Formula-IV and Formula-V as follows:
  • Ts Tosyl
  • X represents a leaving group selected from halogen (CI, Br and I), O-tosyl, O-mesyl, O-benzenesulfonyl and 0-trifluoromethane sulfonyl with the exception that when Z is Ts (tosyl), X is not CI and when X is CI, Z is not
  • Et represents ethyl (-C 2 H 5 ).
  • Ts represents tosyl and Et represents ethyl.
  • a further aspect of the invention is to provide a novel crystalline form of Vilazodone hydrochloride of Formula VIII characterized by X-ray powder diffraction spectrum having peaks at 8.98, 14.44, 18.75, 19.36, 20.01, 20.34, 20.97, 24.56 and 25.34 + 0.2 degrees 2 ⁇ values as shown in Figure-1.
  • the invention provides a process for preparation of novel crystalline form of Vilazodone hydrochloride of Formula VIII comprising the step of:
  • novel crystalline form of Vilazodone HCl of Formula VIII is obtained by the above described process for Vilazodone hydrochloride.
  • Figure- 1 XRPD spectrum of novel crystalline form of Vilazodone hydrochloride.
  • Figure-2 Table showing the list of XRPD peaks of novel crystalline form of Vilazodone hydrochloride.
  • the present invention provides a process for preparation of Vilazodone of Formula- VII.
  • the invention provides a process for preparation Vilazodone as shown in below Scheme- A:
  • Ts Tosyl
  • X represents a leaving group selected from halogen (CI, Br and I), O-tosyl, O-mesyl, O-benzenesulfonyl, O-trifluoromethane sulfonyl; preferably X is halogen, more preferably CI.
  • Et represents ethyl (-C 2 H 5 ).
  • the invention provides a process for preparation Vilazodone comprising the steps of:
  • Step-(a) of the process in Scheme-A comprises a process for the preparation of intermediate compound of Formula-II by reduction of starting compound of
  • the suitable reducing agent in step-(a) may be selected from sodiumborohydride, lithium borohydride, NaBH 3 CN, DIBAL-H, lithium aluminiumhydride, vitride, borane-THF, sodiumborohydride/ iodine, 9-BBN; preferably sodiumborohydride.
  • the suitable reducing agent used in step-(a) is sodiumborohydride .
  • the solvent used in step-(a) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec -butyl acetate, isopropyl acetate and the like; "ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene dichloride, ethylene dichloride, carbon tet
  • Z is tosyl (Ts) and X is chlorine (- CI).
  • Ts tosyl
  • X chlorine
  • the compound of Formula- la reacts with the reducing agent sodiumborohydride in presence of solvent methanol to give intermediate com ound of Formula-IIa as shown below:
  • Step-(b) of the process in Scheme-A comprises a process for the preparation of novel intermediate compound of Formula-IV by coupling of the compound of Formula- II obtained in ste -(a) with a compound of Formula-Ill as shown below:
  • Step-(b) proceeds in presence of suitable solvents and or suitable bases/reagents.
  • the suitable solvent used in step-(b) may be selected from triethylamine (TEA), toluene, diglyme, acetone, methanol, ethanol, isopropanol, n-butanol, tetrahydrofuran (THF), dioxane, water, dimethylformamide (DMF), dimethylacetamide, N-methylpyrrolidone, acetonitrile or mixtures thereof; preferably triethylamine (TEA).
  • the suitable acid binding agents in step-(b) may be selected from an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide or alkali metal or alkali earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate or calcium carbonate or alkali metal or alkaline earth metal salt of a week acid, preferably a potassium, sodium or calcium salt, or an organic bases such as triethylamine, dimethylaniline, pyridine or quinoline and the like or the mixtures thereof; preferably triethylamine.
  • an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide or alkali metal or alkali earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate or calcium carbonate or alkali metal or alkaline earth metal salt of a week acid, preferably a potassium, sodium or calcium salt, or an organic bases such as triethylamine, dimethylaniline, pyridine or
  • the suitable activating agents in step-(b) may be metal halides and/or phase transfer catalysts. Step-(b) is performed with or without presence of metal halides and with or without presence of phase transfer catalyst.
  • the metal halides in step-(b) may be selected from iodide and bromide of alkali metal or alkali earth metal; preferably sodium iodide or potassium iodide.
  • the phase transfer catalyst in step-(b) may be selected from tetra butyl ammonium bromide (TBAB), tetrapropyl ammonium bromide, tributyl benzyl ammonium bromide, tetraoctyl ammonium bromide, tetra butyl ammonium iodide, tetra butyl ammonium hydrogen sulfate, benzyl trimethyl ammonium chloride, benzyl triethyl ammonium chloride, tetra butyl ammonium acetate, tetra butyl ammonium iodide and ethyl triphenyl phosphonium bromide; preferably TBAB.
  • TBAB tetra butyl ammonium bromide
  • the compound of Formula- Ila reacts with the compound of Formula-Ill in presence of solvent triethyl amine (TEA) and acid binding agent TEA, optionally in presence of phase transfer catalyst TBAB and metal halide potassium iodide (KI) to give novel intermediate compound of Formula- IVa as shown below:
  • Step-(c) of the process in Scheme-A comprises amidation of intermediate compound of Formula- IV obtained in above step-(b) by treating with an suitable amidation agent in presence of suitable solvent to give novel intermediate compound of Formula- V as shown below:
  • the suitable amidation agent in step-(c) may be selected from ammonia, formamide, ammonia gas, ammonium carbamate, ammonium formate, ammonium phosphate, ammonium acetate, ammonium fluoride, ammonium bromide, ammonium chloride, ammonium iodide, ammonium iodate, ammonium carbonate, ammonium citrate, ammonium chromate, ammonium dichromate, ammonium hydroxide, ammonium lactate, ammonium molybdate, ammonium nitrate, ammonium oxalate, ammonium sulfate, ammonium sulfide, ammonium tartarate, ammonium triflate, ammonium thiocyanate, ammonium dihydrogen phosphate, urea, methyl carbamate, ethyl carbamate, propyl carbamate or t-butyl carbamate, alkyl or aryl amines, magnesium
  • the suitable solvent in step-(c) may be selected from water, alcohols, ketones, diols, triols, esters, amides, ethers, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof.
  • Polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane; alcohols such as methanol, ethanol, propanol, butanol, glycerol, propylene glycol; polyglycols such as polyethylene glycol 200, polyethylene glycol 300 and polyethylene glycol 400; pyrrolidones such as N-methyl pyrrolidone and 2-pyrrolidone; glycol ethers such as propylene glycol monomethyl ether, dipropylene glycol monomethyl ether and diethylene glycol ethyl ether, ⁇ , ⁇ -dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like to toluene, xylene, heptane, cyclohexane and hexane; preferably the solvent selected from methanol or ethanol.
  • Step-(d) of the process in Scheme-A comprises reduction of hydroxyl group of the compound of Formula-V obtained in step-(c) by treating with suitable reducing agent(s) in presence of suitable solvent to give a compound of Formula- VI as shown below:
  • the suitable reducing agent in step-(d) may be used alone or in combination of suitable reagents; selected from DIBAL-H, lithium aluminiumhydride, sodiumborohydride, lithium borohydride, NaBH 3 CN, sodium borohydride/BF 3 - etherate, vitride, sodiumborohydride/aluminium chloride, borane/aluminium chloride, sodiumborohydride/iodine, 9-BBN, trifluoroacetic acid (TFA)/sodiumborohydride(SBH), Et 3 SiH/TFA; preferably combination of trifluoroacetic acid with sodiumborohydride is used.
  • suitable reagents selected from DIBAL-H, lithium aluminiumhydride, sodiumborohydride, lithium borohydride, NaBH 3 CN, sodium borohydride/BF 3 - etherate, vitride, sodiumborohydride/aluminium chloride, borane/aluminium chloride, sodiumborohydride/iodine, 9-BBN, tri
  • the solvent used in step-(d) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec -butyl acetate, isopropyl acetate and the like; "ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene dichloride, ethylene dichloride, carbon tet
  • Step-(e) of the process in Scheme-A comprises deprotection of the compound of Formula- VI using suitable bases in presence of suitable solvent to obtain Vilazodone of Formula- VII.
  • the suitable base used in step-(e) may be selected from an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide; or alkali metal or alkaline earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate and calcium carbonate; or alkali metal or alkaline earth salt of weak acid, preferably a potassium, sodium or calcium salt; or an organic base such as triethylamine, dimethylaniline, pyridine or quinoline and the like; ammonia or mixtures thereof; preferably the base is sodium hydroxide (NaOH) and potassium hydroxide (KOH); more preferably the base used is NaOH.
  • an alkali metal or alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide
  • alkali metal or alkaline earth metal carbonate or bicarbonate salts such as sodium carbonate, potassium carbonate and calcium carbonate
  • alkali metal or alkaline earth salt of weak acid preferably a potassium, sodium or calcium salt
  • the suitable solvent used in step-(e) may be selected from "alcoholic solvents” such as methanol, ethanol, isopropanol, n-propanol, n-butanol, iso-butanol, ethylene glycol and the like; "ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; “ether solvents” such as tetrahydrofuran, diethylether, methyl tert-butyl ether, 1,4- dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptanes, n-pentane and the like; "chloro solvents” such as methylene chloride, ethylene dichloride, carbon tetrach
  • the invention provides novel intermediates for the preparation of Vilazodone.
  • Ts Tosyl
  • X represents a leaving group selected from halogen (CI, Br and I), O-tosyl, O-mesyl, O-benzenesulfonyl and 0-trifluoromethane sulfonyl with the exception that when Z is Ts, X is not CI and when X is CI, Z is not Ts.
  • Et represents ethyl (-C 2 H 5 ).
  • a further aspect of the invention is to provide a novel crystalline form of Vilazodone hydrochloride of Formula VIII characterized by X-ray powder diffraction spectrum having peaks at 8.98, 14.44, 18.75, 19.36, 20.01, 20.34, 20.97, 24.56 and 25.34 + 0.2 de rees 2 ⁇ values.
  • the invention provides a process for preparation of novel crystalline form of Vilazodone hydrochloride of Formula VIII comprising the step of:
  • XRPD x-ray powder diffraction
  • Example-2 Preparation of intermediate compound of Formula- IVa (Step-(b)) To a solution of Formula-IIa (60 g, 148 mmol) in 385 mL of triethyl amine, compound of Formula-Ill (43.2 g, 157 mmol), TBAB (33.6 g, 104 mmol) and KI (24.7 g, 148 mmol) were added at room temperature. The total reaction mixture was heated to 80-85°C for 8hrs. Reaction was monitored by the HPLC. After completion of the reaction, the triethylamine was distilled out completely under reduced pressure.
  • Example-6 Preparation of crystalline form of Vilazodone hydrochloride of Formula- VIII To a clear solution of Vilazodone free base (100 g, 226.5 mmol) in 4 Lit of isopropanol, 50 mL of IPA-HC1 was added drop wise at 60 °C for 30 min. The total reaction mixture was stirred for 1 hr at same temperature. After short stirring the solid separated was cooled to RT, then cooled to 0 °C and stirred for 1 hr. The solid was filtered and washed with chilled isopropanol. The wet material was dried for 10 hrs at 60 °C to get the constant weight. Weight: 100 g, yield: 92.5%, purity by HPLC: 99.6%.
  • XRPD x-ray powder diffraction

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/IN2015/050044 2015-04-23 2015-06-10 Process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof WO2016170542A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2092/CHE/2015 2015-04-23
IN2092CH2015 IN2015CH02092A (enrdf_load_stackoverflow) 2015-04-23 2015-06-10

Publications (1)

Publication Number Publication Date
WO2016170542A1 true WO2016170542A1 (en) 2016-10-27

Family

ID=54396384

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2015/050044 WO2016170542A1 (en) 2015-04-23 2015-06-10 Process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof

Country Status (2)

Country Link
IN (1) IN2015CH02092A (enrdf_load_stackoverflow)
WO (1) WO2016170542A1 (enrdf_load_stackoverflow)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109627237A (zh) * 2017-10-09 2019-04-16 北京济美堂医药研究有限公司 一种维拉唑酮盐酸盐的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103304547A (zh) * 2012-03-13 2013-09-18 中国药科大学 一种抗抑郁药维拉唑酮的制备方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103304547A (zh) * 2012-03-13 2013-09-18 中国药科大学 一种抗抑郁药维拉唑酮的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MICHAEL B. SMITH ET AL.: "March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 2007, ISBN: 978-0-471-72091-1, article "Oxidations and Reductions - Chapter 19", pages: 1703 - 1869, XP055323966 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109627237A (zh) * 2017-10-09 2019-04-16 北京济美堂医药研究有限公司 一种维拉唑酮盐酸盐的制备方法

Also Published As

Publication number Publication date
IN2015CH02092A (enrdf_load_stackoverflow) 2015-05-29

Similar Documents

Publication Publication Date Title
US20220081385A1 (en) Novel salts and polymorphic form of bempedoic acid
US20100292480A1 (en) Process and intermediates for preparing integrase inhibitors
JP2024023340A (ja) グルホシネートアンモニウムの調製方法
WO2016141003A1 (en) Processes and intermediates for the preparation of pimavanserin
CN107922352B (zh) 制备蛋白质脱乙酰酶抑制剂的方法
CN108424395B (zh) 一种甲磺草胺的制备方法
EP1845084B1 (en) Process for producing (z)-1-phenyl-1-(n,n-diethylaminocarbonyl)idomethylcyclopropane
WO2016142952A1 (en) Process for preparation of vilazodone and its novel intermediates
US20040014983A1 (en) Method for preparing benzisoxazole methane sulfonyl chloride and its amidation to form zonisamide
WO2022241188A1 (en) Enantioselective synthesis of aminotropane compound
KR101135088B1 (ko) 1,3-프로펜설톤의 제조방법
WO2016170542A1 (en) Process for preparation of vilazodone, novel intermediates thereof and novel crystalline form thereof
JP7582997B2 (ja) 殺有害生物化合物の調製方法
JP3831954B2 (ja) ４−ヒドロキシ−２−ピロリドンの製法
CZ2011835A3 (cs) Zpusob prípravy chránených chirálních sulfon - diolu
US11434224B2 (en) Processes for preparing a diaminopyrimidine derivative or acid addition salt thereof
US9399624B2 (en) Process for preparing (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate
CN110498762A (zh) 一种(2s,5r)-5-[(苄氧基)氨基]-哌啶-2-甲酸乙酯的合成方法
KR100630041B1 (ko) 벤조티오펜카복실산 아미드 유도체의 제조방법
AU1081801A (en) Process to prepare aryltriazolinones and novel intermediates thereto
KR20200116118A (ko) 2-클로로-4-니트로이미다졸 유도체의 제조 방법
JP2022035954A (ja) Ｎ－Ｂｏｃ－ラクタム誘導体及びその製造方法、並びに、環状アミン誘導体の製造方法
CN110655491B (zh) 一种2-氨基嘧啶-5-甲酸酯的简便制备方法
SK8052000A3 (en) Process for the preparation of isopropyl-methyl-[2-(3-n-propoxyphenoxy)ethyl]amine
WO2022218734A1 (en) A process for preparation of substituted enamine compounds

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15889798

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15889798

Country of ref document: EP

Kind code of ref document: A1