FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention - PROCESS FOR THE PREPARATION OF VILAZODONE
2. Applicant(s)
(a) NAME: ALEMBIC PHARMACEUTICALS LIMITED
(b) NATIONALITY: An Indian Company.
(c) ADDRESS: Alembic Campus, Alembic Road.
Vadodara-390, 003, Gujarat, India
3. PREAMBLE TO THE DESCRIPTION The following specification describes the invention and the manner in which is to be performed :

Field of the invention
The present invention relates to an improved, commercially viable and industrially advantageous process for the preparation of Viiazodone or a pharmaceutically acceptable salt thereof in high yield and purity. More specifically the present invention relates to an improved and industrially advantageous process for the preparation of Viiazodone.
Background of the invention
Viiazodone is 5-(4-[4-(5-cyano-lH-indol-3-yl) butyl] piperazin-l-yl) benzofuran-2-carboxamide and represented by formula (I).

The product is marketed in the form of Hydrochloride salt. The current pharmaceutical product containing this drug is being sold by Merck using the trade name Viibryd. Viiazodone is an SSRT antidepressant developed by Clinical Data for the treatment of major depressive disorder.
Viiazodone was first described in US patent 5532241. Example 4 of Said patent described process for preparing viiazodone by reacting l-[4-{5-cyanoindol-3-yl)butyl]-4-{2-carboxybenzofuran-5-yl)-piprazine at first with 2-chloro-1-methylpyridinium methanesulfonate in N-methylpyrrolidine and then with dried ammonia. Customary working up gives the free base viiazodone. Which is further converted in to Viiazodone hydrochloride.

Org. Process Res. Dev., 2012. 16 (9), pp 1552-1557 discloses process as per below scheme.

Journal of Medicinal Chemistry (2004), 47(19), 4684-4692 disclose process for preparation of vilazodone as per below scheme.

The main problem associated with these processes is that it involves use of less economical reagent such as 2-chloro-l-methylpyridinium methane sulphonate and solvent such as N-methyl pyrrolidine.
Zhongguo Yaowu Huaxue Zazhi (2012). 22(1). 74-75. 81 discloses many possible ways for synthesis of vilazodone.
None of the prior art disclosing direct conversion of ester to amide. All prior art references shows first conversion of ester of compound of formula II in to corresponding acid and then reaction of acid with ammonia in presence of solvent and catalyst to prepare vilazodone.

Org. Process Res. Dev., 2012. 16 (9), pp 1552-1557 article disclose that no vilazodone was obtained during direct conversion of ester to amide.
The above processes for preparation of Vilazodone require many numbers of steps and involve unfriendly reagents. The process is less economical, relatively less safe and time-consuming. Hence such technology is not readily suitable for commercial production.
Based on the aforementioned drawbacks, prior art processes found to be unsuitable for preparation of vilazodone at lab scale and commercial scale operations. Hence, a need still remains for an improved and commercially viable process of preparing pure vilazodone or a pharmaceutically acceptable salt thereof that will solve the aforesaid problems associated with process described in the prior art and will be suitable for large-scale preparation, in lesser reaction time, in terms of simplicity, purity and yield of the product. Therefore, the present invention provides a process in which directly ester converts in to amide.
Summary of the invention
The present inventors have focused on the problems associated with the prior art processes and have developed an improved process for the preparation of vilazodone.
As a whole, a process such as the one provided by the present invention has the advantage of high yields is achieved with very simple steps. Likewise, said process is not toxic and allows starting from inexpensive and non-hazardous reactants, providing vilazodone, with a good yield and pharmaceutical quality. All of this contributes in reducing the overall cost of the process, making it commercially interesting and allowing it to be put into practice on an industrial level.
Therefore, in one aspect the present invention provides a process for preparing vilazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II.


Therefore, in another aspect the present invention provides a process for preparation of vilazodone a compound of formula (I) or a salt thereof, comprising a step of reacting compound of formula II with source of ammonia to get a compound of formula (1).

Therefore, in another aspect the present invention provides a process for preparation of vilazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II in presence of source of ammonia and any suitable solvent.

Source of ammonia is selected from ammonia gas, liquid ammonia, aqueous ammonia, ammonium hydroxide, magnesium nitride and formamide with base; more preferably ammonia gas. Suitable solvent is 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, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like toluene. xylene, heptane, cyclohexane and hexane; more preferably DMSO.
Therefore, in another aspect the present invention provides a process for preparation of vilazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II in presence suitable solvent under ammonia gas pressure.
Therefore, in another aspect the present invention provides a novel compound ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride.
Therefore, in another aspect the present invention provides a novel compound ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate hydrobromide.
Therefore, in another aspect the present invention provides a process for preparation of ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride comprises reaction of compound of formula (VI) with Bis (2-chloroethyl) amine hydrochloride in presence of suitable base, suitable solvent and phase transfer catalyst.

Phase transfer catalyst is one selected from the group consisting of quaternary ammonium cations, quaternary phosphonium cations, and cyclic polyethers such as tricaprylylmethylammonium chloride, methyl tributyl ammonium chloride, methyl tributyl ammonium fluoride, tetrabutyl ammonium bromide, tetrabutyl ammonium fluoride, tetrabutyl ammonium hydrogen sulfate, triethyl benzyl ammonium chloride, tetrabutyl phosphonium bromide, tetrabutyl phosnhonium chloride, tetraoctylphosphonium bromide, and mixtures

thereof. Suitable solvent is selected from water, alcohols, ketones, diols, triols, esters, amides. erhers, 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; polygiycols 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, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like toluene, xylene, heptane, cyclohexane and hexane, more preferably DMSO. Suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate,
Therefore, in another aspect the present invention provides a process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base with any suitable solvent and suitable base optionally in presence of water, wherein suitable solvent is selected from group of polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane, DMAC. NMF etc. Suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate, wherein the suitable base is selected from NaOH, KOH, LiOH, NaHC03, KHC03, LiHC03, Na2C03j K2C03, Li2C03, Mg(OH)2, Ca(OH)2; CaC03, MgCOj, Ba(OH)2, Be(OH)2, BaC03, SrC03 and the like or mixtures thereof.
Therefore, in another aspect the present invention provides a process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base by treatment of vilazodone base with DMF and aqueous sodium hydroxide solution.
Therefore, in another aspect the present invention provides a novel compound process for preparation of vilazodone or a salt thereof, comprising crystallizing vilazodone base from DMSO and water.
Therefore, in another aspect the present invention provides a process having a content of 5-(4-[4-(5-cyano-lH-indol-3-yl) butyl] piperazin-1-yl) benzofuran-2-carboxylic acid is less than 1% by mole; more preferably les than 0.5% by mole; more specifically less than 0.15% by mole.

Therefore, in another aspect the present invention provides a novel compound novel crystalline form A of Vilazodone.
Therefore, in another aspect the present invention provides a novel compound Crystalline form A of Vilazodone, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 5.8, 13.9, 18.6, 20.9, 21.9 + 0.3.
Therefore, in another aspect the present invention provides a process for preparing crystalline form A of vilazodone base, comprising the steps of: : (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing crystalline form A to precipitate from the solution obtained in step (a), and (c) isolating the crystalline form A obtained in step (b).
Therefore, in another aspect the present invention provides a novel compound amorphous vilazodone base.
Therefore, in another aspect the present invention provides a process for preparing amorphous vilazodone base, comprising the steps of: (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing an amorphous solid to precipitate from the solution obtained in step (a), and (c) isolating the amorphous solid obtained in step (b).
Therefore, in another aspect the present invention provides a novel crystalline form If of ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl) butyl) piperazin-1-yl) benzofuran-2- carboxylate hydrochloride.
Therefore, in another aspect the present invention provides a novel compound Crystalline form II of ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl) butyl)piperazin-I-yl)benzofuran-2-carboxylate hydrochloride, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 11.7, 18.86, 22.75, 23.3, 24.7± 0.3.
Therefore, in another aspect the present invention provides a process for preparation of
vilazodone comprises condensation of compound of formula (VII) or salt thereof with
compound of formula (VIII) to get compound of formula (II) or salt thereof in presence of
triethyl amine and tetrabutyl ammonium bromide.

Therefore, in another aspect the present invention provides a process for preparation of vilazodone comprises condensation of compound of formula (VII) hydro bromide salt with compound of formula (VIII) to get compound of formula (II).
Therefore, in another aspect the present invention provides a process for the preparation of vilazodone or a salt thereof which comprises,
a.reacting 5-nitro salicaldehyde of formula (III) with 2-bromo diethyl malonate of formula (IV) to get compound of formula (V),

b.reducing compound of formula (V) to get compound of formula (VI)

c.converting compound of formula (VI) to compound of formula (VII),

d.Condensing compound of formula (VII) or salt thereof with compound of formula (VIII) to get compound of formula (II) or salt thereof,

e.reacting compound of formula (II) with source of ammonia to get compound of formula (I)

Brief Description of the Drawing
Figure 1 shows an X-ray diffraction pattern of novel form II of ethyl 5-(4-(4-(5-cyano-lH-
indoI-3-yI) butyl) piperazin-1-yl) benzofuran-2-carboxylate hydrochloride prepared by
inventors.
Figure 2 shows an X-ray diffraction pattern of novel form A of vilazodone prepared by
inventors.
Detailed description of the invention:
The present invention provides a process for preparing vilazodone or a salt thereof. comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II.

Therefore, in one embodiment the present invention provides a process for preparation of vilazodone a compound of formula (I) or a salt thereof, comprising a step of reacting compound of formula II with source of ammonia to get a compound of formula (I).


Therefore, in another embodiment the present invention provides a process for preparation of viiazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II in presence of source of ammonia and any suitable solvent.

Source of ammonia is selected from ammonia gas, liquid ammonia, aqueous ammonia, ammonium hydroxide, magnesium nitride and formamide with base; more preferably ammonia gas. Suitable solvent is 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, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like toluene. xylene, heptane, cyclohexane and hexane; more preferably DMSO.
Therefore, in another embodiment the present invention provides a process for preparation of viiazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt

there of, from compound of formula II in presence suitable solvent under ammonia gas pressure.
Therefore, in another embodiment the present invention provides a novel compound ethyl 5-{l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride.
Therefore, in another embodiment the present invention provides a novel compound ethyl 5-(1 -piperazinyl)-benzofuran-2-carboxylate hydrobromide.
Therefore, in another embodiment the present invention provides a process for preparation of ethyl 5-(I-piperazinyl)-benzofuran-2-carboxyIate dihydrochloride comprises reaction of compound of formula (VI) with Bis (2-chloroethyl) amine hydrochloride in presence of suitable base, suitable solvent and phase transfer catalyst.

Phase transfer catalyst is one selected from the group consisting of quaternary ammonium cations, quaternary phosphonium cations, and cyclic polyethers such as tricaprylylmethylammonium chloride, methyl tributyl ammonium chloride, methyl tributyl ammonium fluoride, tetrabutyl ammonium bromide, tetrabutyl ammonium fluoride, tetrabutyl ammonium hydrogen sulfate, triethyl benzyl ammonium chloride, tetrabutyl phosphonium bromide, tetrabutyl phosnhonium chloride, tetraoctylphosphonium bromide, and mixtures thereof. Suitable solvent is 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, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like toluene, xylene, heptane, cyclohexane and hexane, more preferably DMSO. Suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate.

Therefore, in another embodiment the present invention provides a process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base with any suitable solvent and suitable base optionally in presence of water, wherein suitable solvent is selected from group of polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane. DMAC, NMP etc. Suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate, wherein the suitable base is selected from NaOH, KOH, LiOH, NaHC03, KHCO3 LiHC03, Na2C03, K2C03, Li2C03, Mg(OH)2, Ca(OH)2, CaC03, MgC03, Ba(OH)2; Be(OH)2, BaC03, SrC03 and the like or mixtures thereof.
Therefore, in another embodiment the present invention provides a process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base by treatment of vilazodone base with DMF and aqueous sodium hydroxide solution.
Therefore, in another embodiment the present invention provides a novel compound process for preparation of vilazodone or a salt thereof, comprising crystallizing vilazodone base from DMSO and water.
Therefore, in another embodiment the present invention provides a process having a content of 5-(4-[4-(5-cyano-l.H-indol-3-yl) butyl] piperazin-1-yl) benzofuran-2-carboxylic acid is less than 1% by mole; more preferably les than 0.5% by mole; more specifically less than 0.15% by mole.
Therefore, in another embodiment the present invention provides a novel compound novel crystalline form A of Vilazodone.
Therefore, in another embodiment the present invention provides a novel compound Crystalline form A of Vilazodone, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 5.8, 13.9, 18.6,20.9, 21.9 ±0.3.
Therefore, in another embodiment the present invention provides a process for preparing crystalline form A of vilazodone base, comprising the steps of: : (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing crystalline form A to precipitate from the solution obtained in step (a), and (c) isolating the crystalline form A obtained in step (b).

Therefore, in another embodiment the present invention provides a novel compound amorphous vilazodone base.
Therefore, in another embodiment the present invention provides a process for preparing amorphous vilazodone base, comprising the steps of: (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing an amorphous solid to precipitate from the solution obtained in step (a), and (c) isolating the amorphous solid obtained in step (b).
Therefore, in another embodiment the present invention provides a novel crystalline form II of ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl) butyl) piperazin-1-yl) benzofuran-2- carboxylate hydrochloride.
Therefore, in another embodiment the present invention provides a novel compound Crystalline form II of ethyl 5-(4-(4-(5-cyano-lH-indoi-3-yl) butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 11.7, 18.86, 22.75, 23.3, 24.7+ 0.3.
Therefore, in another embodiment the present invention provides a process for preparation of vilazodone comprises condensation of compound of formula (VII) or salt thereof with compound of formula (VIII) to get compound of formula (II) or salt thereof in presence of triethyl amine and tetrabutyl ammonium bromide.

Therefore, in another embodiment the present invention provides a process for preparation of vilazodone comprises condensation of compound of formula (VII) hydrobromide salt with compound of formula (VIII) to get compound of formula (II).
Therefore, in another embodiment the present invention provides a process for the preparation of vilazodone or a salt thereof which comprises,


b. reducingcompound of formula(V)to get compound of formula(VI)

c. converting compound of formula (VI) to compound of formula (VII).

a. reacting 5-nitro salicaldehyde of formula (III) with 2-bromo diethyl malonate of formula (IV) to get compound of formula (V),
d. Condensing compound of formula (VII) or salt thereof with compound of formula (VIII) to get compound of formula (II) or salt thereof.

e. reacting compound of formula (II) with source of ammonia to get compound of formula (I)

The embodiments of present invention are shown in below given scheme.


Vilazodone is converted into one of its acid-addition salts by treatment with an acid.
In another embodiment present invention provides a process for preparation of 3-(4-
chlorobutyl)-lH-indole-5-carbonitrile.


The present invention further illustrated in detail by the below examples which are however not limit to the scope of the invention.
Examples:
Example-1: Preparation of ethyl 5-nitro-l-benzofuran-2-carboxylate
To a solution of DMF (400ml), K2C03 powder (124.1g) and 5-nitro salicylaldehyde (l00g) was slowly added Diethyl bromomalonate (171.7g) at 30-40°C under Nitrogen atmosphere. The reaction mixture was stirred at 85-90°C under Nitrogen atmosphere for 15 hours. Cool the reaction mix to 80-85°C. Cyclohexane (500ml) was added to the reaction mix at 70-85°C within 1 hour and then stirred the reaction mix at 80-85°C for 15-30 minutes. The reaction mixture was cooled to 15-20°C and process water (1000ml) was added to the reaction mixture at 15-20°C within 1 hour. The reaction mixture was stirred at 20-30°C for 1-2 hour and then the solid was filtered and washed with process water (100ml x 5). Dried at 55-60°C. for 8-10 hours. Yield: 95.2%
Example-2: preparation of ethyl-5-amino-l-benzofuran-2-carboxylate
To a solution of ethyt-5-nitro-l-benzofuran-2-carboxylate (lOOg) in Ethyl acetate (800ml) was added 10% palladium on carbon (4.0g). The reaction mixture was stirred under an atmosphere of hydrogen at 33-38°C with 4-5kg/cm2 hydrogen pressure for 4-6 hrs. After completion of the reaction, reaction mixture was filtered through hyflo, washed with ethyl acetate. The filtrate was concentrated in vacuo to give ethyl-5-amino-l-benzofuran-2-carboxylate yield: 100%
Example-3: preparation of ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride.
ethyl-5-amino-l-benzofuran-2-carboxyIate obtained in above step was dissolved in o-Xylene (1500ml) and then Bis (2-chloroethyl) amine hydrochloride (113.8g), Potassium carbonate powder (108.6g) and TBAB (5.0g) at 20-30°C was added in the reaction mixture. The reaction mixture was maintained for 32 hrs at 135-140°C. After completion of the reaction solid was filtered and washed it with o-Xyiene [100ml x 3], suck it dry. The wet cake was charged in the saturated brine solution under stirring and ammonia solution (100ml) was added in the reaction mixture at 10-15°C under stirring. The product was extracted in MDC

(1000ml) and washed subsequently with dilute acetic acid and water. Cone. HC1 (100.5g) was charged in MDC layer and then MDC was removed atmospherically up-to 50°C. Ethanol (700ml) was charged to the residue and raise the temperature of the suspension to 55-60°C. The reaction mass was cooled for 1-2 hours at 20-30°C and filtered the solid, washed it with Ethanol [100ml x3]. Dried at 55-60°C for 12 hours. Yield: 81.3%
Example-4: preparation of ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate hydrobromide.
ethyl-5-amino-l-benzofuran-2-carboxylate obtained in above step was dissolved in o-Xylene (1500ml) and then Bis (2-chloroethyl) amine hydrochloride (113.8g), Potassium carbonate powder (108.6g) and TBAB (5.0g) at 20-30°C was added in the reaction mixture. The reaction mixture was maintained for 32 hrs at 135-140°C. After completion of the reaction solid was filtered and washed it with o-Xylene [100ml x3], suck it dry. The wet cake was charged in the saturated brine solution under stirring and ammonia solution (100ml) was added in the reaction mixture at 10-15°C under stirring. The product was extracted in MDC (1000ml) and washed subsequently with dilute acetic acid and water. Aqueous HBr was charged in MDC layer and then MDC was removed atmospherically up-to 50°C. Ethanol (700ml) was charged to the residue and raise the temperature of the suspension to 55-60DC. The reaction mass was cooled for 1-2 hours at 20-30°C and filtered the solid, washed it with Ethanol [100ml x3]. Dried at 55-60°C for 12 hours. Yield: 81.3%
Example-5: preparation of ethyl 5-(4-[4-(5-cyano-lH-indo|-3- yl) butyl] piperazin-1-yl) benzofuran -2-car boxylate hydrochloride
A mixture of ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride (100g). 3-(4-chiorobutyl) -IH-indofe-5-carbonitrile(63.7g), triethyl amine (400ml) and TBAB(88.3g) were heated at 85-90°C (reflux) under stirring for 10 hrs. After completion of the reaction Acetone (400ml) was charged to the residue and reflux the reaction mass at 55-60°C under stirring for 30-45 minutes. The reaction mass was cooled to 45-50°C and activated carbon (5.0g) was charged to reaction mass and again refluxed for 15-30 minutes. The reaction mass was cooled to 15-20°C and filtered through hyflo and washed with acetone. IPA.HC1 (-100ml) was added to the solution at 50-55°C in more than 30 minutes to adjust the pH 2.0 under stirring and maintained for 45-60 minutes at reflux. The reaction m\x was cooled to 20-30°C under

stirring for 2-3 hours and then maintained at 0-5°C for 45-60 minutes under stirring. The solid was filtered and washed with Acetone. Dried at 55-60°C for 4-6 hours. Yield: 83%
Example-6: preparation of ethyl 5-(4-[4-(5-cyano-lH-indol-3- yl) butyl] piperazin-1-yl) benzofuran -2-carboxylate hydrochloride
A mixture of ethyl 5-(l-piperazinyI)-benzofuran-2-carboxylate hydrobromide (100g). 3-(4-chlorobutyl) -lH-indole-5-carbonitrile(63.7g), triethyl amine (400ml) and TBAB(88.3g) were heated at 85-90°C (reflux) under stirring for 10 hrs. After completion of the reaction Acetone (400ml) was charged to the residue and reflux the reaction mass at 55-60°C under stirring for 30-45 minutes. The reaction mass was cooled to 45-50°C and activated carbon (5.0g) was charged to reaction mass and again refluxed for 15-30 minutes. The reaction mass was cooled to 15-20°C and filtered through hyflo and washed with acetone. IPA.HC1 (~100ml) was added to the solution at 50-55°C in more than 30 minutes to adjust the pH 2.0 under stirring and maintained for 45-60 minutes at reflux. The reaction mix was cooled to 20-30°C under stirring for 2-3 hours and then maintained at 0-5°C for 45-60 minutes under stirring. The solid was filtered and washed with Acetone. Dried at 55-60°C for 4-6 hours. Yield: 83%
Example-7: preparation of Vilazodone
To a solution of DMSO (400ml) and Stage-II (l00g) in the Hydrogenator at 20-30°C Ammonia gas was charged with 5-6kg pressure. The reaction mix was maintained to 30-35°C at 5-6kg Ammonia pressure for 16-18 hours. After completion of the reaction ammonia gas was released the temperature of reaction mass was raised to 50-55°C. Activated carbon (5.0g) was charged to the reaction mass at 50-55°C and maintained at 55-60°C for 15-30 minutes. The reaction mixture was filtered through hyflo and washed with hot (50-55°C) DMSO (75ml). Charged the filtrate in hot DM Water (2000ml) at 80-85°C within 1 hour. The reaction mix was maintained at 80-85°C for 30-45 minutes. The solid was filtered and washed with hot water. Suck dried it. The wet cake (75g) was charged with DMF (450ml) and the temperature of reaction mix was raised to 50-55°C. Sodium hydroxide solution (dissolve 9.8g NaOH in 10ml DM Water) was added to the reaction mass and activated carbon (3.75g) at 50-55°C. The reaction mix was maintained at 50-55°C for 30-45 minutes. The reaction mix was filtered through hyflo and washed with hot (50-55°C) DMF: DM Water mix [(38.5ml+l9.2ml) x 2]. The reaction mixture was cooled for 2-3 hours at 20-30oC and

filtered the solid. Suck dried it completely. Then again wet cake was dissolved in DMSO (350ml) at 50-55°C and charged this clear solution in hot water (1500ml) at 80-85°C within 1 hour. Maintain the reaction mix was maintained at 80-85°C for 30-45 minutes and the solid was filtered and washed with DM Water (75mlx3) at 80-85°C. Suck it dried. Dried it at 55-60°C. Yield: 81.6%
Example-8: preparation of ViJazodone hydrochloride
Formic acid (500ml) and vilazodone base (100g) and 20%w/w hydrochloric acid were mixed at 20-30°C under stirring. Activated carbon (5.0g) was added and reaction mass was stirred for 30-45 minutes at 30-35°C. The reaction mass was filtered hot and washed with hot (30-35°C) Formic acid (100ml). The spray dryer aspirator was set at 1400 rpm (vacuum at 50-120mm), inlet temperature 125-130°C, and air pressure at 3-4 Kg /cm2 and feed pump rate of 2-3 rpm. Then filtrate was spray dried. The material was unloaded and dried in VTD at 85-90°C for 20-24 hours. Yield: 83.3%

Claims:
1. A process for preparation of vilazodone a compound of formula (I) or a salt thereof, comprising a step of reacting compound of formula II with source of ammonia to get a compound of formula (I).

2. A process for preparation of vilazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II in presence of source of ammonia and any suitable solvent.

3. A process claimed in claim 1 and 2 wherein source of ammonia is selected from ammonia gas, liquid ammonia, aqueous ammonia, ammonium hydroxide, magnesium nitride and formamide with base, more preferably ammonia gas.
4. A process chimed in claim 2 wherein suitable solvent is selected from water, alcohols, ketones, diols, triols. esters, amides, ethers, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof.
5. A suitable solvent claimed in claim 4 wherein 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, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents tike toluene, xylene, heptane, cyclohexane and hexane. more preferably DMSO.
6. A process for preparation of vilazodone or a salt thereof, comprising a step of obtaining a compound of formula I or a salt there of, from compound of formula II in presence suitable solvent under ammonia gas pressure.
7. Ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride.
8. Ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate hydro bromide.
9. A process for preparation of ethyl 5-(l-piperazinyl)-benzofuran-2-carboxylate dihydrochloride comprises reaction of compound of formula (VI) with Bis (2-chloroethyl) amine hydrochloride in presence of suitable base, suitable solvent and phase transfer catalyst.

10. A process as claimed in claim 9 wherein phase transfer catalyst is one selected from the group consisting of quaternary ammonium cations, quaternary phosphonium cations, and cyclic polyethers such as tricaprylylmethylammonium chloride, methyl tributyl ammonium chloride, methyl tributyl ammonium fluoride, tetrabutyl ammonium bromide, tetrabutyl ammonium fluoride, tetrabutyl ammonium hydrogen sulfate, triethyl benzyl ammonium chloride, tetrabutyl phosphonium bromide, tetrabutyl phosnhonium chloride, tetraoctylphosphonium bromide, and mixtures thereof.
11. A process claimed in claim 9 wherein suitable solvent is selected from water, alcohols, ketones, diols, triols, esters, amides, ethers, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof.

12. A suitable solvent claimed in claim ] 1 wherein polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane; alcohols such as methanol, ethanol, propanol, butanol, glycerol, propylene glycol; polyglycois such as polyethylene glycol 200, polyethylene glycol 300 and polyethylene glycol 400; pyrrolidones such as N-methyi pyrrolidone and 2-pyrrolidone; glycol ethers such as propylene glycol monomethyl ether, dipropylene glycol monomethyl ether and diethylene glycol ethy] ether, N,N,-dimethyl acetamide, PEG 300, propylene glycol; chloro solvents like methylene chloride, chloroform and ethylene chloride; hydrocarbon solvents like toluene, xylene. heptane, cyclohexane and hexane, more preferably DMSO.
13. A process claimed in claim 9 wherein suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate.
14. A process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base with any suitable solvent and suitable base optionally in presence of water.
15. A process claimed in claim 14 wherein suitable solvent is selected from group of polar aprotic solvents such as acetone, DMF, acetonitrile, DMSO, sulfolane, DMAC, NMP etc.
16. A process claimed in claim 14 wherein suitable base is selected from the group of alkali or alkaline earth metal hydroxide, carbonate, bicarbonate.
17. A process claimed in claim 16 wherein the suitable base is selected from NaOH, KOH, LiOH, NaHC03; KHCO3, LiHC03, Na2C03, K2C03, Li2CO3, Mg(OH)2, Ca(OH)2, CaC03, MgC03, Ba(OH)2j Be(OH)2, BaC03, SrC03 and the like or mixtures thereof.
18. A process for preparation of vilazodone or a salt thereof, comprising purification of vilazodone base by treatment of vilazodone base with DMF and aqueous sodium hydroxide solution.

19. A process for preparation of vilazodone or a salt thereof, comprising crystallizing vilazodone base from DMSO and water.
20. A process according to claim 18 for preparing vilazodone or salt thereof, having a content of 5-(4-[4-(5-cyano-1 H-indoi-3-yl)butyl]piperazin-1 -yI)benzofuran-2-carboxylic acid is less than \% by mole; more preferably les than 0,5% by mole ; more specifically less than 0.15% by mole.
21. A novel crystalline form A of Vilazodone.
22. Crystalline form A of Vilazodone as claimed in claim 21, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 5.8, 13.9. 18.6, 20.9.
21.9±0.3.
23. A process for preparing crystalline form A of vilazodone base, comprising the steps of: : (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing crystalline form A to precipitate from the solution obtained in step (a), and (c) isolating the crystalline form A obtained in step (b).
24. A process for preparing amorphous vilazodone base, comprising the steps of: (a) dissolving vilazodone base in one or more organic solvent(s), (b) causing an amorphous solid to precipitate from the solution obtained in step (a), and (c) isolating the amorphous solid obtained in step (b).
25. A novel crystalline form II of ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl) butyl)piperazin-1 -yl)benzofuran-2-carboxylate hydrochloride.
26. Crystalline form II of ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl) butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride as claimed in claim 26, having an X-ray diffraction pattern comprising at least five peaks selected from 2theta values 11.7, 18.86, 22.75, 23.3, 24.7± 0.3.
27. A process for preparation of vilazodone comprises condensation of compound of formula (VII) or salt thereof with compound of formula (VIII) to get compound of

formula (II) or salt thereof in presence of triethyl amine and tetrabutyl ammonium bromide.

28. A process for preparation of vilazodone comprises condensation of compound of formula (VII) hydro bromide salt with compound of formula (VIII) to get compound of formula (II).
29. A process for the preparation of vilazodone or a salt thereof which comprises,

b. reducing compound of formula (V) to get compound of formula (VI)

c. converting compound of formula (VI) to compound of formula (VII),

a. reacting 5-nitro salicaldehyde of formula (III) with 2-bromo diethyl malonate of formula (IV) to get compound of formula (V),
d. Condensing compound of formula (VII) or salt thereof with compound of formula (VIII) to get compound of formula (II) or salt thereof.


e. reacting compound of formula (II) with source of ammonia to get compound of formula (I)

30. Use of any of the compound as claimed in claim 7, 8, 21 and 25 as an intermediate in a process of preparation of Vilazodone hydrochloride.