Field of the invention:

The present invention relates to an improved process for the preparation of antidepressant drug i.e., 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la represented by the following structural formula:

Further the present invention relates to novel crystalline forms of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 and its pharmaceutically acceptable salts.

Back ground of invention:

US 5,532,241 (hereafter referred to as "241") first disclosed 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide and its hydrochloride salt compound of formula-la which is commonly known as Vilazodone hydrochloride, an antidepressant agent, which acts as a serotonin reuptake inhibitor.

"241" first disclosed the process for the preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide and its hydrochloride salt compound of formula-la by reacting 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylic acid with 2-chloro-l-methylpyridinium methanesulfonate in the presence of N-methyl pyrrolidine and ammonia gas to provide compound of formula-1 as free base. Further, free base of compound of formula-1 is dissolved in propanolic hydrochloric acid solution to precipitate hydrochloride salt of compound of formula-la.

The major drawback of the "241" process is that, it involves reaction of 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylic acid in the presence of 2-chloro-l-methylpyridinium methanesulfonate to provide compound of formula-1 with low yield and purity. Whereas, the said 2-chloro-l-methylpyridinium methanesulfonate is an expensive reagent, not suitable for commercial scale-up process. Moreover, the said process requires tedious work-ups to provide compound of formula-1. So far, vilazodone free base as crystalline solid was not reported in the literature.

In view of the forgoing, there are still remains an unmet need for a process for preparation of vilazodone hydrochloride with high yield and also applicable for multi-kilogram production. The process of the present invention is inexpensive, environmental-friendly having straight forward workups, rendering it amenable to the large-scale production of vilazodone hydrochloride with high yield and purity.

Brief description of the invention:

The first aspect of the present invention is to provide a process for the preparation of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la, comprising of following steps;

a) Reacting lH-indole-5-carbonitrile compound of formula-2 with para toluene sulfonyl chloride in the presence of a suitable base in a suitable solvent to provide 1-tosyl-1H-indole-5-carbonitrile compound of formula-3,

b) reacting the compound of formula-3 with 4-chlorobutanoyl chloride compound of formula-4 in the presence of a suitable lewis acid in a suitable solvent to provide 3-(4-chlorobutanoyl)-1 -tosyl-1 H-indole-5-carbonitrile compound of formula-5,

c) reducing the compound of formula-5 with a suitable reducing agent in the presence of a suitable acid in a suitable solvent to provide 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

d) treating the compound of formula-6 with a suitable base in a suitable solvent to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7,

e) treating the ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-10a with a suitable base in a suitable solvent to provide free base of formula-10, which on in-situ condensation with 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7 in the presence of a suitable base and a suitable catalyst in the presence or absence of a suitable phase transfer catalyst to provide ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate compound of formula-11,

f) treating the compound of formula-11 with aqueous hydrochloric acid in a suitable solvent to provide ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride of compound formula-1 la,

g) amidating the compound of formula-1 la with a suitable amidation agent in the presence of a suitable base in a suitable solvent to provide 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1,

h) optionally isolating the compound of formula-1 as a solid,

i) treating the compound of formula-1 with a hydrochloric acid source in a suitable solvent to provide hydrochloride salt of compound of formula-la.

The second aspect of the present invention is to provide novel crystalline form herein after designated as form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

The third aspect of the present invention is to provide a process for the preparation of crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprising of, amidating the ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate compound of formula-11 with a suitable amidation agent in the presence of a suitable base in a suitable solvent to provide crystalline from-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

The fourth aspect of the present invention is to provide crystalline 1,4-dioxane solvate form hereinafter designated as form-M of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride.

The fifth aspect of the present invention is to provide process for the preparation of crystalline 1,4-dioxane solvate form-M of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride.

The sixth aspect of the present invention is to provide a process for the preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7, comprising of reacting 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6 with a suitable base in a suitable solvent to provide compound of formula-7.

The seventh aspect of the present invention is to provide novel crystalline form herein after designated as form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb.

The eighth aspect of the present invention is to provide a process for the preparation of crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb.

Brief description of figures:

Figure 1: Illustrates the PXRD pattern of crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3- yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

Figure 2: Illustrates the DSC thermogram of crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

Figure 3: Illustrates the PXRD pattern of crystalline 1,4-dioxane solvate form of 5-[4-[4-(5- cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride.

Figure 4: Illustrates the PXRD pattern of crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3- yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methane sulfonate compound of formula-lb.

Detailed description of invention:
As used herein the "suitable solvent" is selected from "alcoholic solvent" 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-butylether, 1,4-dioxane and the like; "hydrocarbon solvents" such as toluene, xylene, cyclohexane, hexane, heptane, n-pentane and the like; "chloro solvents" such as methylene chloride, ethylene dichloride, carbon tetrachloride, chloroform and the like; "polar aprotic solvents" such as dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like; "nitrile solvents" such as acetonitrile and the like; "ketone solvents" such as acetone, methyl isobutyl ketone, methyl ethyl ketone; polar solvent such as water and the like.

As used herein the "base" is selected from inorganic bases like alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and the like; alkali metal alkoxides such as sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and the like; alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate and the like; and organic bases such as triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropylethylamine, piperidine, pyridine, tributyl amine, 4-dimethylaminopyridine, N-methyl morpholine and the like.

As used herein the "reducing agent" is selected from DIBAL-H, lithium aluminiumhydride, sodiumborohydride, lithium borohydride, NaBH3CN, sodium borohydride/BF3-etherate, vitride, sodiumborohydride/aluminium chloride or borane/aluminium chloride, sodiumborohydride/iodine, 9-BBN and trifluoroacetic acid/sodiumborohydride.

As used herein the "amidation agent" is 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 tartrate, ammonium triflate, ammonium thiocyanate, ammonium dihydrogen phosphate, urea, methyl carbamate, ethyl carbamate, propyl carbamate or t-butyl carbamate and alkyl or aryl amines.

As used herein the "phase transfer catalyst" is 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.

As used herein, the suitable "acid" is selected from "organic acids" such as oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphorsulfoic acid, ethane sulfonic acid, gluconic acid, glutamic acid, methanesulfonic acid, mucic acid, pamoic acid, pantothenic acid, paratoluene sulfonic acid and "inorganic acids" such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid and phosphoric acid.

The first aspect of the present invention is to provide a process for the preparation of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la, comprising of the following steps;

a) Reacting lH-indole-5-carbonitrile compound of formula-2 with para toluene sulfonyl chloride in the presence of a suitable base in a suitable solvent to provide 1-tosyl-1H-indole-5-carbonitrile compound of formula-3,

b) reacting the compound of formula-3 with 4-chlorobutanoyl chloride compound of formula-4 in the presence of a suitable lewis acid in a suitable solvent to provide 3-(4-chlorobutanoyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-5,

c) reducing the compound of formula-5 with a suitable reducing agent in the presence of a suitable acid in a suitable solvent to provide 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

d) treating the compound of formula-6 with a suitable base in a suitable solvent to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7,

e) treating the ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-10a, with a suitable base in a suitable solvent to provide its free base compound of formula-10, which on in-situ condensation with 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7 in the presence of a suitable base and a suitable catalyst in the presence or absence of suitable phase transfer catalyst to provide ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate compound of formula-11,

f) treating compound of formula-11 with aqueous hydrochloric acid in a suitable solvent to provide ethyl 5-(4-(4-(5-cyano-1 H-indol-3-yl)butyl)piperazin-1 -yl)benzofuran-2-carboxylate hydrochloride compound of formula-1 la,

g) amidating the compound of formula-1 la with a suitable amidation agent in the presence of a suitable base in a suitable solvent to provide 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1,

h) optionally, isolating the compound of formula-1 as a solid,

i) treating the compound of formula-1 with a suitable hydrochloric acid source in a suitable solvent to provide its hydrochloride salt of compound of formula-la. Wherein;

in step-a) the suitable base is selected from inorganic or organic bases and suitable solvent is selected from chloro solvents, ester solvents and hydrocarbon solvents.

in step-b) the suitable lewis acid is aluminium chloride and suitable solvent is selected from ester solvents, chloro solvents and keto solvents.

in step-c) the suitable suitable reducing agent is sodium borohydride and suitable acid is trifluoroacetic acid and suitable solvent is selected from chloro solvents, hydrocarbon solvents, alcoholic solvents, ether solvents and ester solvents.

in step-d) the suitable base is selected from inorganic or organic base and suitable solvent is selected from ether solvents, alcoholic solvents, chloro solvents and mixture thereof.

in step-e) the suitable base is selected from inorganic and organic base and suitable catalyst is potassium iodide and suitable phase transfer catalyst is selected from terra butyl ammonium bromide (TBAB), tetrapropyl ammonium bromide, tributyl benzyl ammonium bromide, tetraoctyl ammonium bromide, terra butyl ammonium iodide, tetra butyl ammonium hydrogen sulfate, benzyl trimethyl ammonium chloride, benzyl triethyl ammonium chloride and suitable solvent is selected from nitrile solvents, keto solvents and mixture thereof.

in step-f) the suitable solvent is selected from chloro solvents, keto solvents, ether solvents and ester solvents.

in step-g) the suitable amidation agent is selected from 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 tartrate, ammonium triflate, ammonium thiocyanate, ammonium dihydrogen phosphate, urea and suitable base is selected from inorganic base or organic base and suitable solvent is selected from polar aprotic solvents, alcoholic solvents, ester solvents, ether solvents, keto solvents, chloro solvents and hydrocarbon solvents or mixture thereof.

in step-i) the suitable hydrochloride source is selected from HC1 gas, aqueous HC1, dry HC1, ethylacetate-HCl, IPA-HC1 and ethanol-HCl; and the suitable solvent is selected from alcoholic solvents, ether solvents, ester solvents, chlorosolvents, hydrocarbon solvents, polar solvents or mixture thereof.

The preferred embodiment of the present invention provides a process for the preparation of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la, comprising of following steps;

a) Reacting lH-indole-5-carbonitrile compound of formula-2 with para toluene sulfonyl chloride in the presence of dimethylamino pyridine in methylene chloride provides 1-tosyl-1H-indole-5-carbonitrile compound of formula-3,

b) reacting the compound of formula-3 with 4-chlorobutanoyl chloride compound of formula-4 in the presence of aluminium chloride in methylene chloride provides 3-(4-chlorobutanoyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-5,

c) reducing the compound of formula-5 with sodium borohydride in the presence of trifluoroacetic acid in methylene chloride provides 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

d) treating the compound of formula-6 with potassium carbonate in methanol and tetrahydrofuran provides 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7,

e) treating the ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-10a with potassium carbonate in acetonitrile to provide free base of formula-10, which on in-situ condensation with 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7 in the presence of triethylamine and potassium iodide in the presence or absence of tetrabutylammonium bromide provides ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate compound of formula-11,

f) treating the compound of formula-11 with aqueous hydrochloric acid in acetone provides ethyl 5-(4-(4-(5-cyano-1 H-indol-3-yl)butyl)piperazin-1 -yl)benzofuran-2-carboxylate hydrochloride compound formula-1 la,

g) amidating the compound of formula-lla with formamide in the presence of a base in dimethylformamide and methanol provides 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1,

h) optionally isolating the compound of formula-1 as a solid,

i) treating the compound of formula-1 with hydrochloric acid in a suitable solvent or mixture of solvents provides 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la.

The crystalline solid of compound of formula-1, on treatment with aqueous hydrochloric acid provides crystalline form-VIII of compound of formula-la.

The second aspect of the present invention provides novel crystalline form hereinafter designated as form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, characterized by:

a) its X-ray diffractogram having peaks at about 5.2, 7.6, 10.5, 14.3, 14.9, 15.3, 16.0, 17.7, 18.5, 19.7, 20.5, 21.0, 22.0, 22.9, 24.2, 24.8, 26.1, 28.8, 29.6, 30.9, 33.0, 33.3 and 34.5 ± 0.2 degrees of two-theta as illustrated in figure-1.

b) its DSC thermogram showing endotherm at 207.77°C as illustrated in figure-2.

The third aspect of the present invention is to provide a process for the preparation of crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprising of:

a) adding a suitable solvent to ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-1 la,

b) cooling the reaction mixture,

c) adding amidation agent to the reaction mixture,

d) adding a suitable base and a suitable solvent to the reaction mixture,

e) stirring the reaction mixture,

f) adding water to the reaction mixture and stirring the reaction mixture at 25-30°C,

g) filtering the precipitated solid and drying to get crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1. Wherein, the suitable amidation agent is defined as above and suitable base is selected from inorganic base or organic base and suitable solvent is selected from polar aprotic solvents, alcoholic solvents, ester solvents, ether solvents, keto solvents, chloro solvents and hydrocarbon solvents or mixture thereof; The step-(b), (c), (d) and (e) are carried out at a temperature ranges from -10 to 20°C.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprising of:

a) adding dimethylformamide to ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-1 la,

b) cooling the reaction mixture to 0-10°C,

c) adding formamide to the reaction mixture at 0-10°C,

d) adding sodium methoxide and methanol to the reaction mixture at 0-10°C,

e) stirring the reaction mixture at 0-10°C,

f) adding water to the reaction mixture and stirring the reaction mixture at 25-30°C,

g) filtering the precipitated solid and drying to get crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

US 5,532,241 discloses a process for the preparation of compound of formula-1 by the reaction of 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylic acid with 2-chloro-l-methylpyridinium methane sulfonate and N-methyl pyrrolidine in the presence of ammonia gas. However the said process involves the usage of expensive and complex reagent which leads to tedious and complicated workup process to provide compound of formula-1 with low yield. Further, the obtained free base of compound of formula-1 is dissolved in isopropanolic hydrochloric acid solution to precipitate hydrochloric acid salt of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la with melting point of 269-272°C.

Journal of medicinal chemistry-2004, 47, 4684-4692 discloses the reaction of 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylic acid with 2-chloro-l-methylpyridinium iodide in the presence of ethyl diisopropyl amine to provide compound of formula-1. Since the said process involves the usage of fairly expensive or unfriendly reagent like 2-chloro-l-methylpyridinium iodide, which leads to low yield of compound of formula-1 with complicated purification process.

Whereas, the present invention is carried out in the presence of formamide and sodium methoxide, which are cheaper reagents and are environmental user friendly reagents when compared to the prior art. Moreover the present invention also reduces the cycle time of the reaction and avoids tedious work up process to provide compound of formula-1 in crystalline solid with high yield and purity.

So far there is no clear teaching in the earlier document or any alternative route of synthesis that would generate crystalline solid of compound of formula-1. Further the present invention also involves the conversion of compound of formula-1 into hydrochloric acid salt of compound of formula-1 a.

The compound of formula-1 obtained according to the present invention having HPLC purity of greater than 99.95%, which is further useful in the preparation of highly pure compound of formula-1 a.

The fourth aspect of the present invention provides crystalline 1,4-dioxane solvate form herein after designated as form-M of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride characterized by its powder X-ray diffractogram having peaks at about 2.7, 10.6, 13.5, 13.8,14.6, 16.2, 17.2,18.0, 19.1,19.7, 20.3, 21.1, 21.8, 22.2, 22.8, 26.5,27.3,28.0 and 31.3 ± 0.2 degrees of two-theta as illustrated in figure-3.

The fifth aspect of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-1H-mdol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride, comprising of;

a) Dissolving the compound of formula-1 in 1,4-dioxane by heating to reflux temperature,

b) adding aqueous hydrochloric acid to the above reaction mixture,

c) filtering the precipitated solid and drying to get the crystalline form-M.

In another aspect of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride, comprising of;

d) Dissolving the compound of formula-1 in a mixture of 1,4-dioxane and ethanol by heating,

e) adding aqueous hydrochloric acid to the above reaction mixture,

f) filtering the precipitated solid and drying to get the crystalline form-M.

The 1,4-dioxane solvate crystalline form-M is useful for the preparation of pure 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la. The said crystalline form-M is converted into crystalline form-VIII compound of formula-1 a by treating with water.

The sixth aspect of the present invention provides a process for the preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7, comprising of:

a) adding a suitable solvent to 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

b) adding a suitable base and a suitable solvent to the reaction mixture,

c) stirring the reaction mixture,

d) distilling off the solvent from the reaction mixture and cooling to a suitable temperature,

e) adding water to the reaction mixture and stirring,

f) filtering the precipitated solid and adding a suitable solvent,

g) heating the reaction mixture to reflux temperature and stirring,

h) cooling the reaction mixture,

i) filtering the precipitated solid to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7.

Wherein, the suitable base is selected from inorganic base or organic bases as defined above and the suitable solvent is selected from ether solvents, alcoholic solvents, chloro solvents and mixture thereof and a suitable temperature is 25°C - 40°C.

The preferred embodiment of the present invention provides a process for the preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7, comprising of,

a) adding tetrahydrofuran to the 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

b) adding sodium methoxide and methanol to the reaction mixture,

c) stirring the reaction mixture at 30-35°C,

d) distilling off the solvent from the reaction mixture and cooling to 30-35°C,

e) adding water to the reaction mixture and stirring,

f) filtering the precipitated solid and adding cyclohexane to the solid,

g) heating the reaction mixture to reflux temperature and stirring,

h) cooling the reaction mixture to 30-35°C,

i) filtering the precipitated solid to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7.

The seventh aspect of the present invention provides novel crystalline form hereinafter designated as form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb characterized by its powder X-ray diffractogram having peaks at about 5.6, 6.3, 7.0, 7.4, 9.5, 10.3, 11.7, 12.6, 13.7, 14.2, 14.7, 15.0, 15.2, 16.3, 16.7, 17.1, 17.9, 18.4, 18.7, 19.1, 19.5, 19.8, 20.4, 20.8, 21.8, 22.4, 22.8, 23.7, 24.3, 24.6, 25.0, 25.8, 26.2, 26.5, 27.7, 28.5, 29.0, 30.9, 31.5, 32.3, 34.3, 35.3 and 42.5 ± 0.2 degrees of two-theta as illustrated in figure-4.

The eighth aspect of the present invention provides a process for the preparation of crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb, comprising of:

a) Dissolving the compound of formula-1 in a suitable solvent by heating to reflux temperature,

b) adding methane sulfonic acid to the above reaction mixture,

c) cooling the reaction mixture and stirred for 3 hours,

d) filtering the precipitated solid and drying to get the crystalline form-N of compound of formula-lb.

Wherein, the suitable solvent used is selected from ether solvents, polar aprotic solvents, hydrocarbon solvents, ester solvents and chloro solvents.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methane sulfonate compound of formula-lb, comprising of:

a) Dissolving the compound of formula-1 in tetrahydrofuran by heating to reflux temperature,

b) adding methane sulfonic acid to the above reaction mixture,

c) cooling the reaction mixture and stirred for 3 hours,

d) filtering the precipitated solid and drying to get the crystalline form-N compound of formula-lb.

The crystalline form-S compound of formula-1 of the present invention can be useful in the preparation of salts of compound of formula-1 i.e., crystalline form-M and crystalline form-N. The crystalline form-M is also useful in the preparation of highly pure compound of formula- la. Further, the crystalline form-N of compound of formula-lb is useful in the preparation of highly pure compound of formula-1 a.

The compound of formula-la produced by the present invention can be further micronized or milled to get the desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements. Techniques that may be used for particle size reduction include, but not limited to ball, roller and hammer mills, and jet mills. Milling or micronization may be performed before drying, or after the completion of drying of the product.

HPLC Method of Analysis:

5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 and its hydrochloride salt:

Apparatus: A liquid chromatographic system is to be equipped with variable wavelength UV-detector; Column: Symmetry C18, 150 x 4.6mm, 3.5 mm (or) equivalent; Flow rate: 1.0 ml/min; Wavelength: 242 nm; Column Temperature: 40°C; Injection volume: 5 mL; Run time: 35 min; Diluent: Water : Isopropyl alcohol (1:1) v/v; Needle wash: Water : Isopropyl alcohol (1:1) v/v; Elution: Gradient; Mobile phase-A: Buffer (100%); Mobile phase-B: Acetonitrile: Buffer (70:30) v/v; Buffer: 2.72 grams of potassium dihydrogen phosphate and 3.0 grams of 1-Octane sulphonic acid in 1000 ml of water. Adjust pH to 2.0 with diluted orthophosphoric acid and filtered through 0.22um Nylon membrane filter paper and sonicate to degas it.
PXRD analysis of compound of formula-1 and its salts were carried out using BRUKER/AXS X-Ray diffractometer using Cu Ka radiation of wavelength 1.5406 A0 and continuous scan speed of 0.03°/min.

The process of the present invention is schematically represented as below:

The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.

Examples:

Example-1: Preparation of l-Tosyl-1H-indole-5-carbonitrile (Formula-3)

To a mixture of 5-cyanoindole (10 g) and dichloromethane (80 ml) added dimethylamino pyridine (25.8 g)at 25-30°C. Cooled the reaction mixture to 10 -15°C. Para toluene sulfonyl chloride (33.58 g) was added to the reaction mixture at 10 -15°C and the reaction mixture was stirred for 2 hours at 10-15°C. After completion of the reaction, quenched the reaction mixture with water. Separated the both aqueous layer and organic layer. Aqueous layer was extracted with dichloromethane. Both the organic layers were combined. Organic layer was washed with 2% hydrochloric acid solution and followed by water. Distilled off the solvent completely from organic layer. Co-distilled the crude with methanol. Methanol (40 ml) was added to the crude at 25-30°C and stirred for 2 hour at 25-30°C. Filtered the solid and washed with methanol and dried to get the title compound. Yield: 16.6 gm; Melting point: 122-127°C.

Example-2: Preparation of 3-(4-chlorobutanoyl)-l-tosyl-1H-indole-5-carbonitrile (Formula-5)

4-chloro butyryl chloride compound of formula-4 (28.6 g) was added to a mixture of dichloromethane (100 ml) and aluminium chloride (54.1 g) at 25-30°C and stirred the reaction mixture was stirred for 30 minutes at same temperature. Solution of l-tosyl-1H-indole-5-carbonitrile (10 g) in dichloromethane (100 ml) was added to the above reaction mixture at 25-30°C. Stirred the reaction mixture for 3 hours at 25-30°C. After completion of the reaction, the reaction mixture was slowly added to chilled water and stirred for 15 minutes. Separated both the organic and aqueous layers. Organic layer was washed with 5% sodium bicarbonate solution and followed by water. Distilled off the solvent completely from organic layer. Co-distilled the crude with methanol. The obtained compound was cooled to 25-30°C. Methanol (50 ml) was added to the crude compound at 25-30°C and stirred for 2 hour at 25-30°C. Filtered the solid and washed with methanol and dried to get the title compound. Yield: 9.3 gm. Melting point: 152-155°C.

Example-3: 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile (Formula-6)

Trifluoroacetic acid (100 ml) was added to a mixture of dichloromethane (50 ml) and 3-(4-chlorobutanoyl)-l-tosyl-1H-indole-5-carbonitrile (10 g) at 25-30°C. The reaction mixture was cooled to 0 - 10°C and sodium borohydride (5.54 g) was added to the reaction mixture at 0-5°C.

Stirred the reaction mixture at 10 - 15°C for 5 hours. After completion of the reaction, quenched the reaction mixture with hydrochloric acid solution. Stirred the reaction mixture for 1 hour at 30-35°C. Filtered the precipitated solid and washed with water and dried to get the title compound. Yield: 9.1 gm; Melting point: 96-100°C.

Example-4: Preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (Formula-7)

3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile (10 g) was dissolved in tetrahydrofuran (100 ml) at 25-30°C. Cesium carbonate (16.9 g) and methanol (50 ml) was added to the reaction mixture at 25-30°C. Stirred the reaction mixture for 3 hours at 25-30°C. After completion of the reaction, distilled off the solvent completely. Added water (70 ml) to the crude compound and stirred for 1 hour at 25-30°C. Filtered the precipitated solid and washed with water. Cyclohexane (70 ml) was added to the wet compound and heated to reflux temperature and stirred for 1 hour. Cooled the reaction mixture to 30-35°C and stirred for 1 hour. Filtered the precipitated solid and washed with cyclohexane and dried to get the title compound. Yield: 4.5 gm; Melting point: 78-84°C.

Example-5: Preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (Formula-7)

A mixture of methanol (82.5 ml) and sodium methoxide (21.8 ml) were added to 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile (32.0 g) at 25-30°C. Heated the reaction mixture to 40-45°C and stirred for 2 hours at the same temperature. After completion of the reaction mixture, cooled the reaction mixture to 25-30°C and added water (82.5 ml) to the reaction mixture. Stirred the reaction mixture for 30 minutes at 25-30°C. Filtered the precipitated solid, washed with water and dried to get the title compound. Yield: 17.0 gms; Melting point: 78-84°C. Purity by HPLC:95%.

Example-6: Preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (Formula-7)

Potassium carbonate (0.36 g) was added to a mixture of 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile (1 g), methanol (5 ml) and tetrahydrofuran (10 ml) and heated to 50-55°C. The reaction mixture was stirred for 3 hours at 50-55°C. After completion of the reaction, the reaction mixture was cooled to 25-35°C and water was added to it. The reaction mixture was stirred further about 45 minutes at 25-35°C. Filtered the reaction mixture and then dried to get title compound. Yield: 0.5 g

Example-7: Preparation of ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride (Formula-10)

To a mixture of n-butanol (400 ml) and ethyl 5-aminobenzofuran-2-carboxylate (50 g) was added potassium carbonate (33.7 g) 25-30°C. Bis(2-chloroethyl)amine hydrochloride (43 g) was added to the reaction mixture. The reaction mixture was heated to 110-120°C and stirred for 48 hours. After completion of the reaction, the reaction mixture was cooled to 25-30°C and stirred for 1 hour. Filtered the reaction mixture and washed with methanol. The obtained wet compound was dissolved in methanol (500 ml) at 25-30°C and heated to reflux temperature and then stirred for 45 minutes. Filtered the reaction mixture and washed with methanol. Dissolved the wet compound in methanol at 25-30°C and heated to reflux temperature and then stirred for 45 minutes. Filtered the reaction mixture and then combined both n-butanol filtrate and methanol filtrates. Distilled off the solvent completely under reduced pressure. The obtained compound was dissolved in methanol (100 ml), cooled the reaction mixture to 0 - 10°C and stirred for 1 hour. Filtered the precipitated solid and washed with chilled methanol and dried to get the title compound. Yield: 37.5 gm; Melting point: 236-240°C.

Example-8: Preparation of ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride (Formula-11)

Potassium carbonate (22.2 g) was added to a mixture of acetonitrile (600 ml) and ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride (50 g) at 30-35°C and stirred for 15 minutes. Potassium iodide (5.3 g), tetrabutyl ammonium bromide (5.2 g) and triethyl amine (16.3 g) was added to the reaction mixture. 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7 (34 g) was added to the reaction mixture and the reaction mixture was heated to reflux temperature. Stirred the reaction mixture for 48 hours. After completion of the reaction, distilled off the solvent and water was added to the obtained residue. Extracted the product with ethyl acetate and washed the ethyl acetate layer with 10% sodium bicarbonate solution. Further washed the organic layer with 0.5% aqueous hydrochloric acid solution and distilled off the solvent completely from organic layer. The obtained compound was dissolved in acetone (250 ml). pH of the reaction mixture was adjusted to 2 by using 2N aqueous hydrochloric acid solution and water was added to the reaction mixture. Stirred the reaction mixture for 1 hour and then filtered the precipitated solid and washed with water. The obtained compound was dissolved in dimethylformamide (125 ml) by heating and then cooled to 25-30°C. Stirred the reaction mixture for 2 hours at 25-30°C. Filtered the precipitated solid and washed with dimethylformamide and dried to get the title compound. Yield: 35 gm.

Example-9: Preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (Formula-1)

Mixture of dimethylformamide (450 ml) and ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride (30.0 g) was cooled to 0-5°C and stirred for 20 minutes. Formamide (48.7 g) and followed by sodium methoxide in methanol (51.6 g) was added to reaction mixture at 0-5°C and stirred the reaction mixture for 1 hour at same temperature. After completion of the reaction, water (900 ml) was added to the reaction mixture and stirred for 45 minutes at 25-30°C. Filtered the precipitated solid, washed with water and dried to get the title compound as crystalline solid. Yield: 25.7 gm; Melting point: 203-209°C. Purity by HPLC: 99.5%.

The PXRD of the obtained compound is shown in figure-1.

Example-10: Preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyI]-2-benzofuran carboxamide hydrochloride (Formula-la)

Mixture of dioxane (50 ml) and 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (2.0 g) was heated to 80-90°C and stirred for 30 minutes. 20% aqueous hydrochloric acid solution (4 ml) was added to the reaction mixture at 80-90°C and stirred for 30 minutes at the same temperature, Reaction mixture was cooled to 50-55°C, filtered the precipitated solid, washed with 1,4-dioxane and dried to get the title compound. Yield: 1.8 gm; Melting point: 280-284°C. Purity by HPLC: 99.95%.

The PXRD of the obtained compound is shown in figure-3.

Example-11: Preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride (Formula-la)

20% hydrochloric acid (5 ml) was added to a mixture of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (1 gm) and water (20 ml) at 25-30°C. The reaction mixture was heated to 80-90°C and stirred for 20 minutes. Cooled the reaction mixture to 25-30°C and stirred for 15 minutes. Filtered the solid and washed with water and then dried to get the title compound. Purity by HPLC: 99.0%. Yield: 1 g; Melting point: 272-275°C.

Example-12: Preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride: (Formula-la)

A mixture of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (4 gms), 1,4-dioxane (50 ml) and ethanol (50 ml) was heated to 55-60°C and stirred for 30 minutes at the same temperature. Hydrochloride acid (8.8 ml) was added to the reaction mixture at the same temperature and stirred for 20 minutes. Filtered the precipitated solid and dried to get the title compound. Yield: 3.6 gms; Melting point: 274-276°C. Purity by HPLC: 99.0%.

The PXRD of the obtained compound is shown in figure-3.

Example-13: Preparation of 5-[4-[4-(5-cyano-1H-indoI-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate (Formula-lb)

Mixture of tetrahydrofuran (24 ml) and 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (2 g) was heated to 60-65°C and stirred for 30 minutes. Methane sulfonic acid (0.4 ml) was added to the reaction mixture at 60-65°C and then cooled the reaction mixture to 25-30°C. Stirred the reaction mixture for 3 hours at same temperature. Filtered the precipitated solid and washed with tetrahydrofuran and dried to get the title compound. Yield: 1.8 gms. Purity by HPLC: 99.93%.

The PXRD of the obtained compound is shown in figure-4.

We Claim:

1. A process for the preparation of crystalline 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprising of amidating the ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1 -yl)benzofuran-2-carboxylate hydrochloride compound of formula-1 la with a suitable amidation agent in the presence of a suitable base in a suitable solvent at a suitable temperature to provide crystalline 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

2. The process according to claim-1 wherein, the suitable amidation agent is selected from 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 tartrate, ammonium triflate, ammonium thiocyanate, ammonium dihydrogen phosphate, urea, methyl carbamate, ethyl carbamate, propyl carbamate or t-butyl carbamate and alkyl or aryl amines and the suitable base is selected from inorganic or organic base and the suitable solvent is selected from polar aprotic solvents, alcoholic solvents, ester solvents, ether solvents, keto solvents, chloro solvents and hydrocarbon solvents or mixture thereof and the suitable temperature is -10°C to 20°C.

3. A process for the preparation of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7, comprising of,

a) adding a suitable solvent to the 3-(4-chlorobutyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-6,

b) adding a suitable base and a suitable solvent to the reaction mixture,

c) stirring the reaction mixture at a suitable temperature,

d) distilling off the solvent from the reaction mixture and cooling to a suitable temperature,

e) adding water to the reaction mixture and stirring,

f) filtering the precipitated solid and adding suitable solvent to the solid,

g) heating to reflux temperature and stirring, h) cooling the reaction mixture to a suitable temperature,

i) filtering the precipitated solid to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7.

4. A process for the preparation of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la, comprising of the following steps;

a) Reacting lH-indole-5-carbonitrile compound of formula-2, with para toluene sulfonyl chloride in the presence of dimethylaminopyridine in methylene chloride to provide l-tosyl-1H-indole-5-carbonitrile compound of formula-3,

b) reacting the compound of formula-3 with 4-chlorobutanoyl chloride compound of formula-4 in the presence of aluminium chloride in methylene chloride to provide 3-(4-chlorobutanoyl)-l-tosyl-1H-indole-5-carbonitrile compound of formula-5,

c) reducing the compound of formula-5 with sodium borohydride in the presence of trifluoroacetic acid in methylene chloride to provide 3-(4-chlorobutyl)-l-tosyl-1H-indole- 5-carbonitrile compound of formula-6,


d) treating the compound of formula-6 with potassium carbonate in a mixture of tetrahydrofuran and methanol to provide 3-(4-chlorobutyl)-1H-indole-5-carbonitrile compound of formula-7,

e) treating ethyl 5-(piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-10a, with potassium carbonate in acetonitrile to provide free base of formula-10, which on in- situ condensation with compound of formula-7 in the presence of triethylamine and potassium iodide in the presence or absence of tetrabutylammonium bromide to provide ethyl 5-(4-(4-(5-cyano-1 H-indol-3-yl)butyl)piperazin-1 -yl)benzofuran-2-carboxylate compound of formula-11,

f) treating the compound of formula-11 with aqueous hydrochloric acid in acetone to provide ethyl 5-(4-(4-(5-cyano-1 H-indol-3-yl)butyl)piperazin-1 -yl)benzofuran-2- carboxylate hydrochloride of compound formula-1 la,


g) amidating the compound of formula-11a with formamide in the presence of a base in dimethyl formamide at a suitable temperature to provide 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1,

h) treating the compound of formula-1 with hydrochloric acid in a suitable solvent or mixture of solvents to provide 5-4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-la.

5. Crystalline form-S of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 characterized by:

a) its X-ray diffractogram having peaks at about 5.2, 7.6, 10.5, 14.3, 14.9, 15.3, 16.0, 17.7, 18.5, 19.7, 20.5, 21.0, 22.0, 22.9, 24.2, 24.8, 26.1, 28.8, 29.6, 30.9, 33.0, 33.3 and 34.5 ± 0.2 degrees of two-theta as illustrated in figure-1.

b) its DSC thermogram showing endotherm at 207.77°C.

6. Crystalline 1,4-dioxane solvate form-M of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride characterized by its powder X-ray diffractogram having peaks at about 2.7, 10.6, 13.5, 13.8, 14.6, 16.2, 17.2, 18.0, 19.1, 19.7, 20.3, 21.1, 21.8, 22.2, 22.8, 26.5, 27.3, 28.0 and 31.3 ± 0.2 degrees of two-theta as illustrated in figure-3.

7. Crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb characterized by its powder X-ray diffractogram having peaks at about 5.6, 6.3, 7.0, 7.4, 9.5, 10.3, 11.7, 12.6, 13.7, 14.2, 14.7, 15.0, 15.2, 16.3, 16.7, 17.1, 17.9, 18.4, 18.7, 19.1, 19.5, 19.8, 20.4, 20.8, 21.8, 22.4, 22.8, 23.7, 24.3, 24.6, 25.0, 25.8, 26.2, 26.5, 27.7, 28.5, 29.0, 30.9, 31.5, 32.3, 34.3, 35.3 and 42.5 ± 0.2 degrees of two-theta as illustrated in figure-4.

8. A process for the preparation of crystalline form-N of 5-[4-[4-(5-cyano-1H-indol-3- yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide methanesulfonate compound of formula-lb, comprising of:

a) Dissolving the compound of formula-1 in tetrahydrofuran by heating to reflux temperature,

b) adding methane sulfonic acid to the above reaction mixture,

c) cooling the reaction mixture and stirring,

d) filtering the precipitated solid and drying to get the crystalline form-N of compound of formula-lb.

9. A process for the preparation of crystalline 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l- piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprising of,

a) adding dimethylformamide to ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride compound of formula-1 la,

b) cooling the reaction mixture and adding formamide to the reaction mixture at 0-10°C,

c) adding sodium methoxide and methanol to the reaction mixture,

d) stirring the reaction mixture,

e) raising the temperature of the reaction mixture to 25-30°C and stirring the reaction mixture at the same temperature,

f) filtering the precipitated solid and drying to get crystalline 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.

10. Use of crystalline form-S of the present invention in the preparation of highly pure 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-1 a.