Field of the invention:

The present invention provides novel crystalline forms of antidepressant drug i.e., 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 represented by the following structural formula-1.

Further the present invention also relates to novel acid addition salt compounds of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2.

Background of the Invention:

US 5,532,241 (hereafter referred to as "241") first disclosed 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide and its hydrochloride salt compound of formula-2a 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-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide and its hydrochloride salt compound of formula-2a by reacting 5-(4-(4-(5-cyano-lH-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-2a.

US7834020 describes several crystalline forms of vilazodone hydrochloride, such as Form-I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XIII, XIV, XV and XVI and process for their preparation.

CN102219783 A discloses crystalline form of vilazodone dihydrochloride and process for its preparation.

Discovering new polymorphic forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New polymorphic forms and solvates of a pharmaceutically useful compound or salts thereof can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation, optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile or improved shelf-life.

The present invention involves the novel crystalline forms of vilazodone free base as well as novel acid addition salts of vilazodone.

The present invention also provides novel acid addition salts of vilazodone in solid state form. The novel salts of vilazodone of the present invention can be used to prepare vilazodone free base in pure form, which in turn useful in the preparation of highly pure vilazodone hydrochloride.

Brief description of the invention:

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

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

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

The fourth aspect of the present invention is to provide a novel crystalline form herein after designated as form-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a The fifth aspect of the present invention is to provide a process for the preparation of crystalline form-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a.

The sixth aspect of the present invention is to provide a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.
The seventh aspect of the present invention is to provide acid addition salt of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2.

The eighth aspect of the present invention is to provide a process for the preparation of acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2.

Brief description of the drawings:

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

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

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

Detailed description of the invention:
As used herein the term "suitable solvent" is selected from "alcoholic solvent" such as methanol, ethanol, isopropanol, n-propanol, 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, diisopropyl ether, di-tert-butyl ether, ethyl tert-butyl ether, dimethoxy ethane and the like; "hydrocarbon solvents" such as benzene, toluene, xylene, cyclohexane, hexane, heptane, pentane and the like; "chloro solvents" such as methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like; "polar aprotic solvents" such as dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like; "polar solvent" such as water and the like; "nitrile solvents" such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile and the like; "ketone solvents" such as acetone, methyl isobutyl ketone, ethyl methyl ketone, diethyl ketone, methyl tert-butyl ketone, isopropyl ketone and the like; and/or their- mixtures thereof.

As used herein the present invention the term "suitable base" refers to "alkali metal carbonates" such as sodium carbonate, potassium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate and the like; "alkali metal hydroxides" such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; "alkali metal alkoxides" such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium tert.butoxide and the like; "alkali metal phosphates" such as disodium hydrogen phosphate, dipotassium hydrogen phosphate and "organic bases" like diisopropyl amine, diisopropylethylamine, diisobutylamine, triethylamine, pyridine, 4-pyrrolidino pyridine, 4-dimethylaminopyridine (DMAP) and the like.

The first aspect of the present invention provides novel crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 characterized by its X-ray powder diffraction pattern having peaks at about 5.8, 7.4, 11.0, 13.4, 13.8, 16.1, 17.2, 18.5, 19.1, 20.0, 20.8, 21.4, 21.9, 24.3, 25.3, 26.8, 27.2, 28.0 and 27.5 ± 0.2 degrees of two-theta as illustrated in figure-1.
The second aspect of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, which comprises of;

a) Taking the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in a suitable solvent,

b) heating the reaction mixture,

c) filtering the reaction mixture,

d) distilling off the solvent from filtrate,

e) slurrying the compound obtained in step d) in a suitable solvent,

f) optionally heating the reaction mixture,

g) filtering the precipitated solid and drying the compound to provide crystalline form-M of compound of formula-I.

Wherein in step-a) & e) the suitable solvent is selected from nitrile solvents, ketone solvents, alcohol solvents, hydrocarbon solvents, ether solvents, ester solvents, polar solvents like water and/or their mixture thereof.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, which comprises of;

a) Dissolving the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in acetonitrile,

b) heating the reaction mixture to 80-85°C and stirring for 1 hour at same temperature,

c) filtering the reaction mixture,

d) distilling off the solvent from filtrate,

e) slurrying the compound obtained in step d) in acetonitrile,

f) filtering the solid and drying the compound to provide crystalline form-M of compound of formula-I.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, which comprises of;

a) Dissolving the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in acetonitrile,

b) heating the reaction mixture to 80-85°C and stirring for 1 hour at same temperature,

c) filtering the reaction mixture,

d) distilling off the solvent from filtrate,

e) slurrying the compound obtained in step d) in water,

f) heating the reaction mixture to 90-95 °C and stirring for 30 minutes at same temperature,

g) cooling the reaction mixture to 25-3 0°C,

h) filtering the solid and drying the compound to provide crystalline form-M of compound of formula-I.

The third aspect of the present invention provides a novel crystalline form-N of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 characterized by its X-ray powder diffraction pattern having peaks at about 6.0, 7.6, 11.3, 14.0, 16.3, 17.5, 18.8, 20.3, 21.1, 21.8, 22.2, 24.6, 25.6, 28.2, 29.9 and 36.2 ± 0.2 degrees of two-theta as illustrated in figure-2.

The fourth aspect of the present invention provides a novel crystalline form-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a characterized by its X-ray powder diffraction pattern having peaks at about 4.9, 9.0, 10.6, 12.6, 12.8, 13.8, 14.4, 15.2, 16.2, 17.7, 18.8, 19.9, 20.7, 21.4, 22.3, 22.6, 23.9, 24.5, 25.8, 27.0, 27.4, 28.1, 28.6 and 30.0 ± 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-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a, which comprises of;

a) Dissolving the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a in formic acid,

b) slowly adding a suitable solvent to the reaction mixture,

c) stirring the reaction mixture,

d) 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 hydrochloride compound of formula-2a.

Wherein, in step-b) the suitable solvent is selected from chloro solvents, ketone solvents, ester solvents, alcohol solvents, hydrocarbon solvents, ether solvents, polar aprotic and polar solvents like water and/or their mixtures thereof.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a, which comprises of;

a) Dissolving the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride compound of formula-2a in formic acid,

b) adding ethyl acetate to the reaction mixture,

c) stirring the reaction mixture for 2 hours at 25-30°C.

d) 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 hydrochloride compound offormula-2a.

The sixth aspect of the present invention provides a process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide compound of formula-1, comprises of,

a) Taking the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in a suitable solvent,

b) heating the reaction mixture,

c) cooling the reaction mixture,

d) filtering the precipitated solid and drying to provide crystalline form-M of compound of formula-1.

Wherein, in step-a) the suitable solvent is selected from ketone solvents, hydrocarbon solvents, ester solvents, ether solvents and chloro solvents, alcohol solvents, polar aprotic solvents, polar solvents and/or their mixture thereof.

The seventh aspect of the present invention provides acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2.

Formula-2 Wherein, the term "Acid" represents inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid; and organic acids such as formic acid, acetic acid, propionic acid, pyruvic acid, hexanoic acid, methane sulfonic acid, ethane sulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxy ethanesulfonic acid, benzene sulfonic acid, para toluene sulfonic acid, 4-methylbenzene sulfonic acid, naphthalene-1,5-disulfonic acid, oxalic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 4-amino benzoic acid, 4-hydroxybenzoic acid, 2-acetoxybenzoic acid, 2,4,6-trimethyl benzoic acid, succinic acid, mandelic acid, acetyl mandelic acid, lactic acid, stearic acid, carbonic acid, glutamic acid, gluconic acid, glycolic acid, malonic acid, aspartic acid, phthalic acid, cinnamic acid, 4-hydroxy cinnamic acid, salicylic acid, acetyl salicylic acid, orotic acid, oleic acid, nicotinic acid and their hydrates or solvates thereof.

The preferred embodiment of the present invention provides acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2 in crystalline solid form, wherein the suitable acid is selected from hydrobromic acid, phosphoric acid, nitric acid, benzene sulfonic acid, para toluene sulfonic acid.

Further the acid-addition salt compound of general formula-2 can be converted into pure 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 by treating the compound of formula-2 with a suitable base in a suitable solvent.

Wherein the suitable base is selected form alkali metal hydroxides, alkali metal alkoxides, alkali metal carbonates and alkali metal bicarbonates; and the suitable solvent is selected from chloro solvents, alcoholic solvents, ketone solvents, ether solvents, ester solvents, hydrocarbon solvents, polar solvents and/or their mixtures thereof.

The eighth aspect of the present invention provides a process for the preparation of acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2, comprises of, reacting the compound of formula-1 with a suitable acid in a suitable solvent provides corresponding acid addition salt compound of general formula-2.

Wherein, the suitable acid is same as defined in seventh aspect of the present invention; and the suitable solvent is selected from ketone solvents, hydrocarbon solvents, ester solvents, ether solvents and chloro solvents, alcohol solvents, polar solvents and/or their mixtures thereof.

HPLC method of analysis for 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 and its hydrochloric acid compound of formula-2a can be done by using the following conditions:

Apparatus: A liquid chromatographic system equipped with variable wavelength UV-detector; Column: Symmetry C18, 150 x 4.6mm, 3.5 urn (or) equivalent; Flow rate: 1.0 ml/min; Wavelength: 242 nm; Column Temperature: 40°C; Injection volume: 5 uL; Run time: 35 min; Diluent: 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.

The PXRD analysis of the crystalline compounds of formula-1 and its hydrochloride salt compound of formula -2a were carried out using BRUKER/AXS X-Ray diffractometer using Cu Ka radiation of wavelength 1.5406 A° and continuous scan speed of 0.03°/min.

5- [4- [4-(5-cyano-1 H-indol-3 -yl)butyl] -1 -piperazinyl] -2-benzofuran carboxamide
compound of formula-1 and its hydrochloric acid compound of formula-2a 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 mills, roller and hammer mills and jet mills. Milling or micronization may be performed before drying or after completion of drying of the product.

The best mode of carrying out the present invention is illustrated by the below mentioned examples. These examples are provided as illustration only and hence should not be construed as limitation to the scope of the invention.

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

Mixture of dimethylformamide (450 ml) and ethyl 5-(4-(4-(5-cyano-lH-indol-3-yl)butyl)piperazin-l-yl)benzofuran-2-carboxylate hydrochloride (30.0 g) was cooled to 0-10°C and stirred for 20 minutes at the same temperature. Formamide (48.7 g) and followed by sodium methoxide in methanol (51.6 g) was added to reaction mixture at 0-10°C and stirred the reaction mixture for 45 minutes at same temperature. After completion of the reaction, water (900 ml) was added to the reaction mixture and stirred for 1 hour at 25-3 0°C. Filtered the precipitated solid and washed with water to get the title compound.

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

Acetonitrile (300 ml) was added to the wet compound obtained in example-1 and heated to 80-85°C and stirred for 1 hour. Filtered the reaction mixture and washed with acetonitrile at the same temperature.

Distilled off the solvent completely from the filtrate to obtain the crude compound. Acetonitrile (30 ml) was added to the crude compound and stirred for 2 hours at 25-30°C. Filtered the solid and washed with acetonitrile. Water (300 ml) was added to the wet compound and was heated to 90-95°C. Stirred the reaction mixture for 30 minutes at 90-95°C. Cooled the reaction mixture to 30-35°C and stirred for 45 minutes at the same temperature. Filtered the precipitated solid, washed with water and dried to get the crystalline form-M. The PXRD of the crystalline form-M is shown in figure-1.

Example-3: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride (Formula-2a) 20% hydrochloric acid (5 ml) was added to a mixture of 5-[4-[4-(5-cyano-lH-indol-3- yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (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 25-3 0°C and stirred for 15 minutes. Filtered the precipitated solid and washed with water and then dried to get the title compound. Yield: 1 g; MR: 272-275°C; Purity by HPLC: 99.0%.

Example-4: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrochloride (Formula-2a)

5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofbran carboxamide
hydrochloride obtained from example-3 (2.0 g) was dissolved in formic acid (2.0 ml) at 25-30°C. Slowly ethyl acetate (4.0 ml) was added to the reaction mixture and stirred for 45 minutes at 25-30°C. Filtered the precipitated solid, washed with ethyl acetate to get the title compound. Yield: 1.6 g; The PXRD of the obtained compound is shown in figure-3.

Example-5: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yi)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydro bromide (formula-2b)
5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide (3.0 g) was dissolved in acetone (225 ml) at 55-60°C. Aqueous hydrobromic acid (0.81 g) was added to the reaction mixture at 55-60°C and stirred for 20 minutes at the same temperature. Cooled the reaction mixture to 25-30°C and filtered the precipitated solid, washed with acetone and dried to get the title compound. Yield: 2.90 g; MR: 264-269°C; Purity by HPLC: 98.76%.

Example-6: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydro bromide (formula-2b)
5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide (3.0 g) was dissolved in acetone (225 ml) at 55-60°C. Slowly added hydrogen bromide in glacial acetic acid (0.54 g) to the reaction mixture at 55-60°C. Reaction mixture was cooled to 25-30°C and stirred for 30 minutes at the same temperature. Filtered the precipitated solid, washed with acetone and dried to get the title compound. Yield: 3. 0 g; MR: 264-269°C;

Example-7: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide phosphate (formula-2c) 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (1.0 g) was dissolved in tetrahydrofuran (10 ml) at 47-52°C. Slowly added ortho phosphoric acid (0.266 g) to the reaction mixture at 47-52°C and stirred for 15 minutes at the same temperature. Reaction mixture was cooled to 25-30°C and stirred for 1 hour at the same temperature. Filtered the precipitated solid, washed with tetrahydrofuran and dried to get the title compound. Yield: 1.1 g; MR: 208-212°C.

Example-8: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide benzene sulfonate (formula-2d)

5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (1.0 g) was dissolved in tetrahydrofuran at 47-52°C. Slowly added benzene sulfonic acid (0.42 g) to the reaction mixture at 47-52°C and stirred for 20 minutes at the same temperature. Reaction mixture was cooled to 25-30°C and stirred for 1 hour at the same temperature. Filtered the precipitated solid, washed with tetrahydrofuran and dried to get the title compound. Yield: 1.0 gm. MR: 205-209°C.

Example-9: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide nitrate (formula-2e)
5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (1.0 g) was dissolved in tetrahydrofuran (10 ml) at 47-52°C. Slowly added nitric acid (0.17 g) to the reaction mixture at 47-52°C. Reaction mixture was cooled to 25-30°C and stirred for 2 hour at the same temperature. Filtered the precipitated solid, washed with tetrahydrofuran and dried to get the title compound. Yield: 1.0 g. MR: 212-217°C.

Example-10: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide para toluene sulfonate (formula-2f)
5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide (1.0 g) was dissolved in tetrahydrofuran (12 ml) at 60-65°C and stirred for 10 minutes. Slowly added para toluene sulfonic acid (0.4 g) to the reaction mixture at 60-65°C and stirred for 1 hour at the same temperature. Reaction mixture was cooled to 25-30°C and stirred for 45 minutes at the same temperature. Filtered the precipitated solid, washed with tetrahydrofuran and dried to get the title compound.

Yield: 0.8 g. MR: 204-207°C.

Example-11: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from isopropanol (Formula-1) 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (2.0 g) was dissolved in isopropanol (100 ml) at 80-85°C. Slowly cooled the reaction mixture to 25-3 0°C and then further cooled to 5-10°C. Stirred the reaction mixture for 2 hours at 5-10°C. Filtered the precipitated solid, washed with chilled isopropanol and dried to get the title compound. Yield: 1.7 g. The PXRD of the crystalline form-M is shown in figure-1.

Example-12: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from tetrahydrofuran (Formula-1) 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (10 g) was dissolved in tetrahydrofuran (50 ml) at 50-55°C. Slowly cooled the reaction mixture to 25-30°C and then further cooled the reaction mixture to 5-10°C. Stirred the reaction mixture for 2 hours at 5-10°C. Filtered the precipitated solid, washed with chilled tetrahydrofuran and dried to get the title compound. Yield: 5.2 gm; MR: 185-190°C.

Example-13: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from ethyl acetate (Formula-1)

Mixture of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide obtained from example-1 (2.0 g) and ethyl acetate (50 ml) was heated to 75-80°C and stirred for 1 hour. Cooled the reaction mixture to 25-3 0°C and stirred the reaction mixture for 2 hours at the same temperature. Filtered the precipitated solid, washed with ethyl acetate and dried to get the title compound. Yield: 1.2 gm.

Example-14: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (Formula-1)

Mixture of 5-[4-[4-(5-cyano-1 H-indol-3-yl)butyl]-1 -piperazinyl]-2-benzofuran carboxamide obtained from example-1 (33 g) and acetone (1950 ml) was heated to 50-55°C and stirred for 1 hour. Filtered the reaction mixture and washed with acetone (66 ml).

Distilled off the 70% solvent from the reaction mixture and cooled the reaction mixture to 25-30°C and stirred the reaction mixture for 2 hours at the same temperature. Filtered the precipitated solid and washed with acetone (66 ml). To the obtained wet compound water (300 ml) was added and heated to 85-95°C. Stirred the reaction mixture for 30 minutes at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid, washed with water and dried to get the title compound. Yield: 27.5 gm.

Example-15: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide by anti solvent addition (Formula-1)
5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide
obtained from example-1 (2.0 g) was dissolved in tetrahydrofuran (14.0 ml) at 40-45°C. Filtered the reaction mixture and washed with tetrahydrofuran (2.0 ml). Distilled off the filtrate at to obtain residue. Cyclohexane (11.0 ml) was added to the residue. Stirred the reaction mixture for 45 minutes at 25-3 0°C. Filtered the precipitated solid and dried to get the title compound. Yield: 1.6 gm.

Example-16: Preparation of crystalline form-N of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (Formula-1)

5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (1.0 g) was dissolved in methylene dichloride (5.0 ml) at 35-40°C and stirred for 20 minutes. Cooled the reaction mixture to 25-3 0°C and stirred for 45 minutes. Filtered the precipitated solid, washed with methylene chloride and dried to get the title compound. Yield: 0.7 g; The PXRD of crystalline form-N is shown in figure-2.

Example-17: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (Formula-1).

5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide hydrobromide (5 gm) and methanol (30 ml) were charged into a clean and dry RBF at 25-30°C. Basifying the reaction mixture with aqueous sodium hydroxide solution. Filtered the precipitated solid, washed with methanol and then dried to get the title compound. Yield: 4.3 gm; Purity by HPLC: 99.9%.

Example-18: Preparation of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide (Formula-1).

5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide Para toluene sulfonate (5 gm) and acetone (30 ml) were charged into a clean and dry RBF at 25-30°C. Basifying the reaction mixture with aqueous sodium carbonate solution. Filtered the precipitated solid, washed with acetone and then dried to get the title compound. Yield: 4.2 gm; Purity by HPLC: 99.9%.

Example-19: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from acetone (Formula-1).

A mixture of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (2 gm) and acetone (200 ml) was heated to 50-55°C and stirred for 10 min at the same temperature. Filtered the reaction mixture through hyflow bed and washed with acetone. Distilled off 90% of the solvent from the reaction mixture. The reaction mixture was cooled to 25-30°C and stirred for 45 min at the same temperature. Filtered the precipitated solid, washed with acetone and dried to get the title compound.

Yield: 1.3 gm.

Example-20: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from tetrahydrofuran (Formula-1).

A mixture of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (2 gm) and tetrahydrofuran (18 ml) was heated to 40-45°C and stirred for 10 min at the same temperature. Distilled off 50% of the solvent from the reaction mixture. The reaction mixture was cooled to 25-30°C and stirred for 30 min at the same temperature. Filtered the precipitated solid, washed with tetrahydrofuran and dried to get the title compound.
Yield: 1.4 gm.

Example-21: Preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide from water (Formula-1).

A mixture of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide obtained from example-1 (2 gm) and water (100 ml) was heated to reflux and stirred for 40 min at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 45 min at the same temperature. Filtered the solid, washed with water and dried to get the title compound.
Yield: 1.1 gm.

We Claim:

1. Crystalline acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2.

2. Acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2 according to claim-1, wherein the acid is selected from hydrobromic acid, phosphoric acid, benzene sulfonic acid, nitric acid, para toluene sulfonic acid.

3. Crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 characterized by its X-ray powder diffraction pattern having peaks at about 5.7, 7.2, 10.9, 13.4, 13.7, 16.0, 17.1, 17.4, 18.6, 19.0, 19.9, 20.7, 21.4, 21.8, 24.2 and 27.9 ± 0.2 degrees of two-theta as illustrated in figure-1.

4. Process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, which comprises of;

a) Taking the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in a suitable solvent,

b) heating the reaction mixture,

c) filtering the reaction mixture,

d) distilling off the solvent from filtrate,

e) slurrying the compound obtained in step d) in a suitable solvent,

f) optionally heating the reaction mixture,

g) filtering the precipitated solid and drying the compound to provide crystalline form-M of compound of formula-I.

5. Crystalline form-N of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran
carboxamide compound of formula-1 characterized by its X-ray powder diffraction
pattern having peaks at about 6.0, 7.6, 11.3, 14.0, 16.3, 17.5, 18.8, 20.3, 21.1, 21.8, 22.2,
24.6, 25.6, 28.2, 29.9 and 36.2 ± 0.2 degrees of two-theta as illustrated in figure-2.

6. Crystalline form-S of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran
carboxamide hydrochloride compound of formula-2a characterized by its X-ray powder
diffraction pattern having peaks at about 4.9, 9.0, 10.6, 12.6, 12.8, 13.8, 14.4, 15.2, 16.2,
17.7, 18.8, 19.9, 20.7, 21.4, 22.3, 22.6, 23.9, 24.5, 25.8, 27.0, 27.4, 28.1, 28.6 and 30.0 ±
0.2 degrees of two-theta as illustrated in figure-3.

7. Process for the preparation of crystalline form-M of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1, which comprises of,

a) Taking the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 in a suitable solvent selected from chloro solvents, ketone solvents, ester solvents, alcohol solvents, hydrocarbon solvents and polar solvents like water and/or their mixture thereof,

b) heating the reaction mixture,

c) cooling the reaction mixture,

d) filtering the precipitated solid and drying to provide crystalline form-M of compound of formula-1.

8. Process for the preparation of acid addition salts of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of general formula-2, comprises of treating the compound of formula-1 with a suitable acid in a suitable solvent selected from chloro solvents, ketone solvents, ester solvents, alcohol solvents, hydrocarbon solvents and polar solvents like water and/or their mixtures thereof; provides corresponding acid addition salt compound of general formula-2.

9. Use of acid addition salts claimed in claim-1, in the preparation of highly pure 5-[4-[4-(5-cyano-1 H-indol-3 -yl)butyl] -1 -piperazinyl] -2-benzofurancarboxamide compound of formula-1 as well as it's hydrochloride salt compound of formula-2a.

10. A process for the purification of 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofurancarboxamide compound of formula-1, comprising of;

a) Converting the 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1 into its acid-addition salt compound of general formula-2 by treating it with a suitable acid in a suitable solvent selected from chloro solvents, alcoholic solvents, ketone solvents, ether solvents, polar solvents and/or their mixtures thereof,

b) treating the acid-addition salt compound of general formula-2 obtained in step-a) with a suitable base selected from alkali metal hydroxides, alkali metal alkoxides, alkali metal carbonates and alkali metal bicarbonates in a suitable solvent selected from chloro solvents, alcoholic solvents, ketone solvents, ether solvents, polar solvents and/or their mixtures thereof to provide pure 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l-piperazinyl]-2-benzofuran carboxamide compound of formula-1.