Process for the preparation of 2-(E)-N-hydroxy-3-[4-([[2-(2-mefhyl-1 H- indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide 2-hydroxypropanoic acid (1 : 1 ) and its polymorphs thereof

Related Applications:

This application claims the benefit of priority of our Indian patent application numbers 201641039595 filed on 2 1 ^st November 2016 and 201 741013736 filed on 1 8 ^th April 201 7 which are incorporated herein by reference.

Field of the Invention:

The present invention relates to novel crystalline and amorphous forms of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-y l)ethyl]amino]methyl]phenyl]-2-propenamide 2- hydroxypropanoic acid ( 1 : 1 ) and its process for the preparation.

Formula- l a

Further the present invention also relates to solid dispersions of 2-(E)-N-hydroxy-3-(4- ([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide 2-hydroxypropano ic acid ( 1 : 1 ) and its preparation thereof.

Further the present invention also relates to improved process for the preparation of 2- (E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl)-2-propen amide 2-hydroxypropanoic acid ( 1 : 1 ) .

Background of the Invention:

2-(E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2- propenamide 2-hydroxypropanoic acid is commonly known as Panobinostat lactate.

Panobinostat lactate is marketed in US by Novartis under the brand name of "Farydak" for the treatment of various cancers. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). US6552065 B2 (hereinafter referred as US'065) first discloses the Panobinostat and its process for the preparation thereof.

US201 101 12308 A l discloses formation of amorphous form of calcium, zinc, potassium, hemi fumarate, oxalate, hemi maleate, mesylate and phosphate salts of Panobinostat.

US7989494 B2 relates to crystalline forms of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide and its salts. In particular, it discloses calcium, potassium, zinc, phosphate, tartrate, mesylate, acetate, benzoate, hemi malate and lactate salts of Panobinostat.

However, there is a significant need in the art to develop novel polymorphic forms of compound of formula- l a which are stable and having advantageous physical properties such as free flowability, greater stability and greater bioavailability.

Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore, a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as different solubility profiles, different melting point temperatures and/or different x-ray diffraction peaks. Since the solubility of each polymorph may vary, identifying the existence of pharmaceutical polymorphs is essential for providing pharmaceuticals with predicable solubility profiles. It is desirable to investigate all solid state forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form.

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, ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms.

For at least these reasons, there is a need for additional solid state forms or polymorphs of compound of formula- 1 a.

Brief description of the Invention:

The first aspect of the present invention is to provide amorphous form of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indolO-yl)ethyl]amino]methyl]phenyl]-2-propenam lactate compound of formula- l a and process for its preparation.

The second aspect of the present invention is to provide amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-y l)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- l a and at least one pharmaceutically acceptable excipient and process for its preparation.

The third aspect of the present invention is to provide novel crystalline form of 2-(E)- N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide of compound formula- 1 and process for its preparation.

The fourth aspect of the present invention is to provide amorphous form of 2-(E)-N- hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide of compound formula- 1 and process for its preparation.

The fifth aspect of the present invention is to provide novel crystalline form of 2-(E)- N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- 1 a and process for its preparation.

The sixth aspect of the present invention is to provide an improved process for the preparation of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-y l)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- l a.

The seventh aspect of the present invention is to provide novel acid addition salts of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate compound of formula-5 and its process for the preparation.

The eighth aspect of the present invention is to provide novel crystalline form of 2- (E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide hydrobromide salt compound of formula- l b, herein after designated as crystalline Form-M3.

Brief description of the Drawings:

Figure-1 : Illustrates the PXRD pattern of amorphous form of 2-(E)-N-hydroxy-3-[4- [[[2-(2- methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- 1 a obtained according to example- 1 .

Figure-2: Illustrates the PXRD pattern of amorphous form of 2-(E)-N-hydroxy-3-[4- [[[2-(2- methyl- 1 H-indol-3-yi)ethyl]amino]methyl)phenyl]-2-propenamide lactate compound of formula- l a obtained according to example-2.

Figure-3: Illustrates the PXRD pattern of amorphous solid dispersion comprising 2-(E)-N- hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a and PVP-K-30.

Figure-4: Illustrates the PXRD pattern of amorphous solid dispersion comprising 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a and HPMC.

Figure-5: Illustrates the PXRD pattern of amorphous solid dispersion comprising 2-(E)-N- hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino)methyl]phenyl)-2-propenamide compound of formula- l a and HPC.

Figure-6: Illustrates the PXRD pattern of amorphous solid dispersion comprising 2-(E)-N- hydroxy-3-[4-[((2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- 1 a and HPMC-AS( 1 : 1 ).

Figure-7: Illustrates the PXRD pattern of novel crystalline Form-M of 2-(E)-N-hydroxy-3-(4- [[[2-(2-methyl- 1 H-ihdol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide of compound formula- 1 obtained according to example-7.

Figure-8: Illustrates the PXRD pattern of novel crystalline Form-S of 2-(E)-N-hydroxy-3-(4- [[[2-(2-methyl- 1 H-indo!-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide of compound formula- 1 obtained according to example-8.

Figure-9: Illustrates the PXRD pattern of amorphous form of 2-(E)-N-hydroxy-3-[4- (((2-(2- methyl- 1 H-indol-3-yl)ethyl)amino]methyl]phenyl]-2-propenamide of compound formula- 1 obtained according to example-9.

Figure-10: Illustrates the PXRD pattern of crystalline Form-M of 2-(E)-N-hydroxy-3-[4-[((2- (2-methyl- 1 H-indol-3-yl)ethyl]amino]methy)]phenyl]-2-propenamide lactate compound of formula- l a.

Figure-11 : Illustrates the PXRD pattern of crystalline Form-S of 2-(E)-N-hydroxy-3-[4-[[[2- (2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a.

Figure-12: Illustrates the PXRD pattern of novel crystalline Form-N of 2-(E)-N-hydroxy-3- [4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]pheny l]-2-propenamide lactate.

Figure-13: Illustrates the PXRD pattern of crystalline Form-L of 2-(E)-N-hydroxy-3-[4- (([2- (2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a.

Figure-14: Illustrates the PXRD pattern of crystalline Form-M I of (E)-methyl 3-(4-(((2-(2- methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate hydrobromide compound of formula-5a.

Figure-15: Illustrates the PXRD pattern of crystalline Form-M2 of (E)-methyl 3-(4-(((2-(2- methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate oxalate compound of formula-5b. Figure-16: Illustrates the PXRD pattern of crystalline Form-M3 of 2-(E)-N-hydroxy-3-[4- [[[2-(2-methyl - 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide hydrobromide. Detailed description of the Invention:

As used herein the term "suitable solvent" used in the present invention refers to "hydrocarbon solvents" such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane, cycloheptane, methylcyclohexane, m-, o-, or p-xylene, and the like; "ether solvents" such as dimethoxy methane, tetrahydrofuran, 1 ,3-dioxane, 1 ,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, 1 ,2-dimethoxy ethane and the like; "ester solvents" such as methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate and the like; "polar-aprotic solvents such as dimethylacetamide (DMA), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N- methylpyrrolidone (NMP) and the like, "chloro solvents" such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like; "ketone solvents" such as acetone, methyl ethyl ketone, methyl isobutylketone and the like; "nitrile solvents" such as acetonitrile, propionitrile, isobutyronitrile and the like; "alcoholic solvents" such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutano), t-butanol, 2-nitroethano), 2- fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, propylene glycol, 2-methoxyethanol, I, 2-ethoxyethanol, diethylene glycol, I , 2, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monoethyl ether, cyclohexanol, anisole, benzyl alcohol, phenol, or glycerol and the like; "polar solvents" such as water or mixtures thereof. The term "suitable base" used herein the present invention until unless specified is selected from inorganic bases like "alkali metal hydroxides" such as lithium hydroxide, sodium hydroxide, potassium hydroxide and the like; "alkali metal carbonates" such as sodium carbonate, potassium carbonate, lithium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate, lithium bicarbonate and the like; "alkali metal hydrides" such as potassium hydride, lithium hydride and the like; "organic base" such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide and the like; ammonia; and organic bases such as triethyl amine, methyl amine, ethyl amine, 1 ,8-diazabicyclo [5.4.0] undec-7-ene (DBU), ! ,5-diazabicyclo(4.3.0)non-5-ene (DBN), lithium dioisopropyl amide (LDA), n-butyl lithium, tribenzylamine, isopropylamine, diisopropylamine, diisopropylethyl amine, N- methylmorpholine, N-ethylmorpholine, piperidine, dimethylaminopyridine, morpholine, pyridine, 2,6-lutidine, 2,4,6-collidine, imidazole, 1 -methylimidazole, 1 ,2,4-triazole, 1 ,4- diazabicyclo[2.2.2]octane (DABCO) or mixtures thereof.

The "suitable acid" used in the present invention can be selected from but not l imited to hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid, formic acid, acetic acid, propionic acid, palmitic acid, stearic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, malic acid, tartaric acid, citric acid, aspartic acid, ascorbic acid, glucuronic acid, 2-oxopropionic acid (pyruvic acid), furan-2-carboxylic acid (mucic acid), benzoic acid, 4-hydroxybenzoic acid, salicyclic acid, vanillic acid, 4-hydroxycinammic acid, gallic acid, hippuric acid, aceturic acid, phloretinic acid, phthalic acid, methane sulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, orotic acid and the like.

The first aspect of the present invention provides an amorphous form of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl-1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- 1 a.

In an embodiment of the present invention the amorphous form of compound of formula- l a is characterized by its PXRD pattern as illustrated in figures 1 and 2.

In an embodiment of the present invention provides a process for the preparation of amorphous form of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- 1 a, comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl] -2-propenamide lactate compound of formula- l a in a suitable solvent or mixture of solvents,

b) optionally filtering the reaction mixture,

c) removing the solvent from the reaction mixture provides amorphous form of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino]methyl]phenyl]-2-propen amide lactate compound of formula-l a.

Wherein, in step-a) the suitable solvent is selected from chloro solvents, ketone solvents, C i-C ₆ alcohol solvents, ester solvents, hydrocarbon solvents, nitrile solvents, ether solvents or their mixtures; and the dissolution of compound of formula- 1 in a suitable solvent or mixture of solvents can be carried out at 25-30° C or by heating the reaction mixture to a temperature ranging from 30°C to reflux temperature of the solvents employed;

in step-c) suitable techniques which may be used for the removal of solvent from the reaction mixture includes but not limited to evaporation, evaporation under reduced pressure, flash evaporation, vacuum drying, filtering, concentrating the reaction mixture, atmospheric distillation, vacuum distillation, distillation by using a rotational distillation device such as a Buchi Rotavapor, agitated thin film drying (ATFD), melt extrusion, spray drying, freeze drying (lyophilization), spray-freeze drying, addition of suitable anti-solvent to the reaction mixture followed by filtration of the precipitated solid, cooling the clear solution to lower temperatures such as below 20° C to precipitate the solid followed by filtration or by any other suitable techniques.

The solvent may be removed at temperatures ranging from 25°C to 100°C, optionally under reduced pressures.

The preferred embodiment of the present invention provides a process for the preparation of amorphous form of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a, comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino) methyl]phenyl]-2-propenamide lactate compound of formula- l a in methanol, b) filtering the reaction mixture,

c) distilling off the solvent from the filtrate obtained in step-b) provides amorphous form of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyJ]amino]methyl]phenyl] -2- propenamide lactate compound of formula- 1 a.

In another preferred embodiment of the present invention provides a process for the preparation of amorphous form of 2-(E)-N-hydroxy-3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl)-2-propenamide lactate compound of formula- l a, comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a in methanol, b) filtering the reaction mixture,

c) spray drying the filtrate obtained in step-b) provides amorphous form of 2-(E)-N- hydroxy-3 -[4-(([2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide lactate compound of formula- l a.

The second aspect of the present invention provides amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- l a and at least one pharmaceutically acceptable excipient.

Wherein, the excipient is selected from but not limited to polyvinylpyrrolidone (povidone or PVP), polyvinylpolypyrrolidone, polysorbate, cross linked polyvinyl pyrrolidone (crospovidone), polyethylene glycol (macrogol or PEG), polyvinyl alcohol, polyvinyl chloride, polyvinyl acetate, propylene glycol, cellulose, cel lulose acetate phthalate (CAP), methyl cellulose, carboxymethyl cellulose (CMC, its sodium and calcium salts), carboxymethylethyl cellulose (CMEC), ethyl cellulose, hydroxymethyl cellulose, ethyl hydroxyethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose (HPC), hydroxypropyl cellulose acetate succinate (HPCAS), hydroxypropyl methyl cellulose (hypromellose or HPMC), hydroxypropyl methylceilulose acetate succinate (HPMC-AS), hydroxyethyl methyl cellulose succinate (HEMCS), hydroxypropyl methylceilulose phthalate (HPMC-P), hydroxypropyl methylceilulose acetate phthalate, microcrystalline cellulose (MCC), cross linked sodium carboxymethyl cellulose (croscarmellose sodium), cross linked calcium carboxymethyl cellulose, magnesium stearate, aluminium stearate, calcium stearate, magnesium carbonate, talc, iron oxide (red, yellow, black), stearic acid, dextrates, dextrin, dextrose, sucrose, glucose, xylitol, lactitol, sorbitol, mannitol, maltitol, maltose, raffinose, fructose, maltodextrin, anhydrous lactose, lactose monohydrate, starches such as maize starch or corn starch, sodium starch glycolate, sodium carboxymethyl starch, pregelatinized starch, gelatin, sodium dodecyl sulfate, edetate disodium, sodium phosphate, sodium lauryl sulfate, triacetin, sucralose, calcium phosphate, polydextrose, α-, β-, γ-cyclodextrins, su!fobutylether beta-cyclodextrin, sodium stearyl fumarate, fumaric acid, alginic acid, sodium alginate, propylene glycol alginate, citric acid, succinic acid, carbomer, docusate sodium, glyceryl behenate, glyceryl stearate, meglumine, arginine, polyethylene oxide, polyvinyl acetate phthalates and the like

The another embodiment of the present invention provides amorphous solid dispersion of 2-(E)-N-hydroxy-3-[4-[([2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide lactate compound of formula- l a in combination with PVP-K-30 and the P-XRD pattern is depicted in figure-3.

In another embodiment of the present invention provides amorphous solid dispersion of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methy|]phenyl]-2-propen amide lactate compound of formula- l a in combination with HPMC and the P-XRD pattern is depicted in figure-4.

In another embodiment of the present invention provides amorphous solid dispersion of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino]methyl]phenyl]-2-propen amide lactate compound of formula- l a in combination with HPC and the P-XRD pattern is depicted in figure-5.

In another embodiment of the present invention provides amorphous solid dispersion of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl}-2-propen amide lactate compound of formula- l a in combination with HPMC AS and the P-XRD pattern is depicted in figure-6. In an embodiment of the present invention provides a process for the preparation of amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-(4-([[2-(2-methyl- 1 H-indol-3- yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a and at least one pharmaceutically acceptable excipient. The said process comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a and at least one excipient in a suitable solvent or mixture of solvents at a suitable temperature, b) removing the solvent from the reaction mixture to provide amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a and an excipient.

Wherein, in step-a) the suitable excipient is same as defined above; the suitable solvent is same as defined in step-a) of the first aspect of the present invention; the suitable temperature ranges from 25°C to reflux temperature of the solvent used,

After dissolving the compound of formula- 1 and excipient in the solvent system, the solution may optionally be treated with charcoal or any other suitable material to remove color and/or to clarify the solution;

in step-b) the suitable techniques which may be used for the removal of solvent from the reaction mixture are same as defined in step-c) of the first aspect of the present invention;

The solvent may be removed at temperatures ranging from 25°C to 1 00°C optionally under reduced pressures.

(n the present invention, the ratio of the amount of weight of 2-(E)-N-hydroxy-3-(4- [[[2-(2-methyl-1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a within the solid dispersion to the amount by weight of the excipient therein ranges from about 1 :0.05 to about 1 : 5.

The preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-(4-[[(2-(2- methyl-1 H-indol-3-yl)ethyl]amino]methyl]phenyl)-2-propenamide lactate compound of formula- l a and hydroxypropyl methylcellulose (HPMC). The said process comprising of: a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[(2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a and hydroxypropyl methylcellu!ose (HPMC) in methanol at 55-60°C,

b) distilling off the solvent from the reaction mixture to provide amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino)methyl]phenyl]-2-propenamide lactate compound of formula- l a and HPMC.

Using the same procedure described above, amorphous solid dispersion comprising of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide lactate compound of formula- l a with PVP-K-30, HPC and HPMC AS can be prepared.

The third aspect of the present invention provides novel crystalline forms of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- 1 , which includes:

a) Crystalline form-M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide compound of formula- 1 is further characterized by its PXRD 2 theta values as illustrated in figure-7.

b) Crystal line form-S of 2-(E)-N-hydroxy-3-[4-[([2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide compound of formula- 1 is further characterized by its PXRD 2 theta values as illustrated in figure-8.

In an embodiment of the present invention provides a process for the preparation of crystalline Form-M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino) methylJphenyl]-2-propenamide compound of formula- 1 , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide compound of formula- 1 in a suitable solvent or mixture of solvents at a suitable temperature,

b) optionally filtering the reaction mixture,

c) cooling the reaction mixture to a suitable temperature,

d) filtering the precipitated solid to provide crystalline form-M of 2-(E)-N-hydroxy-3-[4- ([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- 1 . Wherein, in step-a) the suitable solvent is same as defined in step-a) of first aspect of the present invention; and the dissolution of compound of formula- 1 in a suitable solvent or mixture of solvents can be carried out at 25-30°C or by heating the reaction mixture to a temperature ranging from 30°C to reflux temperature of the solvents employed; in step-c) the suitable temperature is ranging from -20°C to 25°C.

The preferred embodiment of the present invention provides a process for the preparation of crystalline Form-M of 2-(E)-N-hydroxy-3-(4-(((2-(2-methvl- 1 H-indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- 1 , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino] methy!]phenyl]-2-propenamide compound of formula- 1 in dimethyl formamide at 75- 80°C,

b) cooling the reaction mixture to 25-30 ⁶ C,

c) filtering precipitated solid from the reaction mixture to provide crystalline form-M of 2-(E)-N-hydroxy-3- [4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2- propenamide compound of formula-1 .

In another embodiment of the present invention provides a process for the preparation of crystalline Form-S of 2-(E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methylJphenyl]-2-propenamide compound of formula- 1 , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3 -[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide compound of formula- 1 in a suitable solvent or mixture of solvents at a suitable temperature,

b) cooling the reaction mixture to a suitable temperature,

c) adding a suitable anti-solvent to the reaction mixture,

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

Wherein, in step-a) the suitable solvent is selected from chloro solvents, ketone solvents, ether solvents, C |-C ₆ alcohol solvents, ester solvents, nitrile solvents or their mixtures and suitable temperature is ranging from 30°C to reflux temperature of the solvent used in the reaction; in step-b) the suitable temperature is ranging from -20°C to 20°C;

in step-c) the suitable anti-solvent is ether solvents.

The preferred embodiment of the present invention provides a process for the preparation of crystalline Form-S of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- ! , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[([2-(2-methyl- | H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide compound of formula- 1 in a mixture of tetrahydrofuran and methanol at 65-70°C,

b) cooling the reaction mixture to 0-5°C,

c) adding methyl tert-butyl ether to the reaction mixture,

d) filtering the precipitated solid and drying to provide crystalline form-S of 2-(E)-N- hydroxy-3-[4- [[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide compound of formula- 1 .

The fourth aspect of the present invention provides an amorphous form of 2-(E)-N- hydroxy-3-[4-([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide of compound formula- 1 .

In an embodiment of the present invention the amorphous form of compound of formula- 1 is further characterized by its PXRD pattern as illustrated in figure-9.

In another embodiment of the present invention provides a process for the preparation of amorphous form . of 2-(E)-N-hydroxy-3-[4-{[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl)phenyl]-2-propenamide compound formula- 1 , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino) methyl]phenyl]-2-propenamide compound of formula- 1 in a suitable solvent or mixture of solvents at a suitable temperature,

b) stirring the reaction mixture,

c) distilling off the solvent from the reaction mixture to provide amorphous form of 2- (E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2- propenamide compound of formula- 1 . Wherein, in step-a) the suitable solvent is same defined in step-a) of the first aspect of the present invention. '

The preferred embodiment of the present provides a process for the preparation of amorphous form of 2-(E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propen amide compound formula- 1 , comprising of:

a) Dissolving the 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide compound of formula- 1 in a mixture of methanol and tetrahydroruran at 55-60°C,

b) stirring the reaction mixture,

c) distilling off the solvent from the reaction mixture to provide amorphous form of 2- (E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino]methyl]phenyl]-2- propenamide compound of formula- 1 .

The fifth aspect of the present invention provides a novel crystalline forms of 2-(E)-N- hydroxy-3-[4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a, which includes:

a) Crystalline form-M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl) amino]methy|]phenyl)-2-propenamide lactate compound of formula- 1 a is further characterized by its PXRD 2-theta values as illustrated in figure- 10.

b) Crystalline form-S of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a is further characterized by its PXRD 2 theta values as illustrated in figure- 1 1 .

c) Crystalline form-N of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a is further characterized by its PXRD 2 theta values as illustrated in figure- 1 2.

d) Crystalline form-L of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a is further characterized by its PXRD 2 theta values as illustrated in figure- 1 3.

In an embodiment of the present invention provides a process for the preparation of crystalline form-M of 2-(E)-N-hydroxy-3-[4-[([2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound formula- 1 a, comprising of: a) Adding a suitable solvent to 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl) ethyl]amino)methyl]phenyl]-2-propenamide lactate compound of formula- 1 a, b) stirring the reaction mixture,

c) heating the reaction mixture to a suitable temperature,

d) adding the reaction mixture obtained to suitable second solvent,

e) stirring the reaction mixture and filtering the precipitated solid to get crystalline form- M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- l a.

Wherein, in step-a) the suitable solvent is selected from alcohol solvents, in step-c) the temperature is ranging from 25°C to reflux temperature of the solvent; and in step-d) the suitable second solvent is selected from nitrile solvents.

The preferred embodiment of the present provides a process for the preparation of crystalline form-M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino] methyl]phenyl]-2-propenamide lactate compound formula- 1 a, comprising of:

a) Adding methanol to the 2-(E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl] amino]methyl)phenyl]-2-propenamide lactate compound of formula- l a,

b) stirring the reaction mixture,

c) heating the reaction mixture to 50-60°C,

d) adding the reaction mixture obtained in step-c) to acetonitrile,

e) stirring the reaction mixture and filtering the precipitated solid to get crystall ine form- M of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- l a.

In an embodiment of the present invention provides a process for the preparation of crystalline form-S of 2-(E)-N-hydroxy-3-(4-(([2-(2-methyl- | H-indol-3-yl)ethyl]amino] methyl]phenyl)-2-propenamide lactate compound formula- l a, comprising of:

a) Adding a suitable solvent to 2-(E)-N-hydroxy-3-[4-([[2-(2-methyl- 1 H-indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a, b) stirring the reaction mixture, c) filtering the solid and drying to get crystalline form-S of 2-(E)-N-hydroxy-3-[4-(((2- (2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a.

Wherein, in step-a) the suitable solvent is selected from polar aprotic solvents, chloro solvents, ketone solvents, C|-C ₆ alcohol solvents, ester solvents, nitrile solvents, ether solvents or their mixtures.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-S of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide lactate compound formula- l a, comprising of: a) Adding dimethyl formamide to 2-(E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl) ethylJamino]methylJphenylJ-2-propenamide lactate compound of formula- 1 a, b) stirring the reaction mixture,

c) filtering the solid and drying to get crystalline form-S of 2-(E)-N-hydroxy-3-[4-[[(2- (2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl)-2-propenamide lactate compound of formula- l a

In an embodiment of the present invention provides a process for the preparation of crystalline form-N of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound formula- 1 a, comprising of:

a) Adding 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl)-2-propenamide lactate compound of formula- 1 a to a suitable solvent or mixture of solvents,

b) optionally filtering the reaction mixture, , .

c) cooling the reaction mixture to a suitable temperature,

d) filtering the solid to provide crystalline form-N of 2-(E)-N-hydroxy-3-[4-[[[2-(2- methyl- 1 H-indol-3-yl)ethyl)amino]methyl)phenyl]-2-propenamide lactate compound of formula- l a.

Wherein, in step-a) the suitable solvent is same as defined in step-a) of the first aspect of the present invention; in step-c) the suitable temperature is ranging from -20°C to 10°C. The preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of 2-(E)-N-hydroxy-3-[4-[([2-(2-methyl- 1 H-indol-3-yl) ethyljamino] methyl]pheny!]-2-propenamide lactate compound formula- 1 a, comprising of: a) Adding 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyt] phenyl]-2-propenamide lactate compound of formula- l a to n-heptane,

b) cooling the reaction mixture to 0-5°C and stirring the reaction mixture,

c) filtering the solid to provide crystalline form-N of 2-(E)-N-hydroxy-3-(4-[[[2-(2- methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a.

In an embodiment of the present invention provides a process for the preparation of crystalline form-L of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino] methyl]phenyl]-2-propenamide lactate compound formula- l a, comprising of:

a) Adding a suitable solvent to 2-(E)-N-hydroxy-3-[4-[[(2-(2-methyl- 1 H-indol-3-yl) ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- 1 a, b) heating the reaction mixture to a suitable temperature and stirring the reaction mixture, c) filtering the solid and drying to get the crystalline Form-L of 2-(E)-N-hydroxy-3-[4- [([2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate compound of formula- 1 a.

Wherein, in step-a) the suitable solvent is selected from chloro solvents, ketone solvents, C 1 -C6 alcohol solvents, ester solvents, nitrile solvents, ether solvents or their mixtures; in step-b) the suitable temperature is ranging from 30°C to reflux temperature of the solvent used.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-L of 2-(E)-N-hydroxy-3-[4-[[(2-(2-methyl- 1 H-indol-3-yl) ethyl]amino)methyl]phenyl]-2-propenamide lactate compound formula- l a, comprising of: a) Adding isopropanol to 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl) amino]methyl]phenyl]-2-propenamide lactate compound of formula- l a,

b) heating the reaction mixture to 60-70°C and stirring the reaction mixture, c) filtering the precipitated solid and drying to get the crystalline form-L of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl)amino]methyl]phenyl]-2-propen amide lactate compound of formula- 1 a.

The sixth aspect of the present invention provides an improved process for the preparation of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- ] H-indol-3-yl)ethyl]amino)methyl] phenyl]-2-propenamide lactate compound of formula- l a, comprising of:

a) Reacting 2-(2-methyl- 1 H-indol-3-yl)ethanamine compound of formula-2 with (E)- methyl 3-(4-formylphenyl)acrylate compound of formula-3 in a suitable solvent to provide imine compound, which is on reduction with a suitable reducing agent to provide (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-y l)ethyl)amino)methy l)phenyl) acrylate compound of formula-4,

b) optionally treating the compound of formula-4 with a suitable acid in a suitable solvent to provide corresponding acid addition salt of compound of general formula-5, c) optionally purifying the compound of general formula-5 from a suitable solvent to provide pure compound of general formula-5,

d) treating the compound of formula-4 obtained in step-b) or compound of formula-5 obtained in step-c) with a suitable base in a suitable solvent followed by treating the obtained compound with aqueous hydroxylamine to provide 2-(E)-N-hydroxy-3 -[4- ([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide compound of formula- 1 ,

e) treating the compound of formula- 1 with a suitable acid in a suitable solvent lo provide corresponding acid addition salt of 2-(E)-N-hydroxy-3-[4-[[(2-(2-methyl- 1 H- indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide compound of general formula-

1 ,

f) optionally purifying the compound obtained in step-(e) from a suitable solvent to provide pure compound of general formula- 1 ,

g) treating the compound of general formula- 1 with a suitable base in a suitable solvent followed by treating the obtained compound with DL-lactic acid in a suitable solvent to provide 2-(E)-N-hydroxy-3-[4- [[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl] -2 -propenamide lactate compound of formula- l a. Wherein, in step-(a) the suitable reducing agent is selected from Pd/C, NaB H4, Fe- acetic acid and Fe-hydrochloric acid;

in step-d) & g) the suitable base used is selected from organic or inorganic base;

in step-b) & e) the suitable acid is same as defined as above;

in step-a) to step-g) the suitable solvent is selected from alcohol solvents, chloro solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents, polar solvents like water or mixture thereof.

The preferred embodiment of the present invention provides an improved process for the preparation of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl] phenyl]-2-propenamide lactate compound of formula- 1 a, comprising of:

a) Reacting 2-(2-methyl- 1 H-indol-3-yl)ethanamine compound of formula-2 with (E)- methyl 3-(4-formylphenyl)acrylate compound of formula-3 in methanol to provide imine compound, which is on reduction with sodium borohydride to provide (E)- methyl 3 -(4-(((2-(2-methyl- 1 H-indoN3-y])ethyl)amino)methyl)phenyl)acrylate compound of formula-4,

b) treating the compound of formula-4 with hydrobromic acid in water to provide (E)- methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate hydro bromide salt compound of formula-5a,

c) purifying the compound obtained in step-(b) from methanol to provide pure compound of formula-5a,

d) treating the compound of formula-5a with sodium hydroxide in methanol followed by treating the obtained compound with aqueous hydroxylamine to provide 2-(E)-N- hydroxy-3-[4-([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide compound of formula- 1 ,

e) treating the compound of formula- 1 with hydrobromic acid in water to provide 2-(E)- N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propen amide hydrobromide salt compound of formula- l b,

f) purifying the compound obtained in step-(e) from methanol to provide pure compound of formula- l b, g) treating the compound of formula- l b with aqueous ammonia in dimethylsulfoxide followed by treating the obtained compound with DL-lactic acid in water to provide 2- (E)-N-hydroxy-3-(4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]ainino]methyl]phenyl]-2- propenamide lactate compound of formula- l a.

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl)-2- propenamide lactate compound of formula- l a obtained according to the present invention having the following impurities less than 0.05% as measured by HPLC.

The seventh aspect of the present invention provides novel acid addition salts of (E)- methy] 3-(4-(((2-(2-methyl- 1 H-indol-3-y])ethyJ)amino)methyl)phenyl)acrylate compound of general formula-5.

Wherein, the acid is selected from inorganic acids, such as hydro bromic acid, sul furic acid, nitric acid or phosphoric acid; and organic acids, such as oxalic acid, maleic acid, malonic acid, tartaric acid, fumaric acid, citric acid, malic acid, succinic acid, mandelic acid, lactic acid, acetic acid, propionic acid, 2-chloromandelate, p-toluene sulfonic acid, ethane- 1 ,2- disulfonic acid, camphor sulfonic acid, ethane sulfonic acid, methane sulfonic acid, naphthalene-2-sulfonic acid, benzene sulfonic acid, adipic acid, glutaric acid, glutamic acid, palmitic acid or aspartic acid.

In an embodiment of the present invention provides (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate hydrobromide salt compound of formula- 5a and (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate oxalate salt compound of formula-5b.

In another embodiment of the present invention provides crystalline acid addition salts of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate, which includes:

a) Crystalline form-M i of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino) methyl)phenyl)acrylate hydrobromide salt compound of formula-5a is further characterized by its PXRD 2-theta values as illustrated in figure- 14.

b) Crystalline form-M2 of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino) methyl)phenyl)acrylate oxalate salt compound of formula-5b is further characterized by its PXRD 2-theta values as illustrated in figure- 1 5.

Further, in another embodiment of the present invention also provides a process for the preparation of novel acid addition salts of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl) ethyl)amino)methyl)phenyl) acrylate compound of general formula-5, comprising of:

a) Reacting 2-(2-methyl- 1 H-ind0l-3-yl)ethanamine compound of formula-2 with (E)- methyl 3-(4-formylphenyl)acrylate compound of formula-3 in a suitable solvent to provide imine compound, which is on reduction with a suitable reducing agent to provide (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl) acrylate compound of formuIa-4,

b) treating the compound of formula-4 with a suitable acid in a suitable solvent provides acid addition salts of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino) methyl)phenyl)acrylate compound of general formula-5.

Wherein, in step-a) the suitable reducing agent is same as defined in step-a) of the sixth aspect of the present invention; in step-b) the suitable acid is same as defined above; in step-a) and b) the suitable solvent is selected from alcohol solvents, chloro solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents, polar solvents like water or mixture thereof.

The preferred embodiment of the present invention provides a process for the preparation of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl) acrylate hydrobromide salt compound of formula-5a, comprising of:

a) Reacting 2-(2-methyl- 1 H-indol-3-yl)ethanamine compound of formula-2 with (E)- methyl 3-(4-formylpheny!)acrylate compound of formula-3 in methanol to provide imine compound, which on in-situ reduction with sodium borohydride to provide (E)- methyl 3-(4-(((2-(2-methyl- 1 H-ind61-3-yl)ethyl)amino)methyl)phenyl)acrylate compound of formula-4,

b) treating the compound of formula-4 with hydrobromic acid in water provides hydrobromide salt of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino) methyl)phenyl)acrylate compound of formula-5a.

In another preferred embodiment of the present invention provides a process for the preparation of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amtno)methyl)phenyl) acrylate oxalate salt compound of formula-5b, comprising of:

a) Reacting 2-(2-methyl- 1 H-indol-3-yl)ethanamine compound of formula-2 with (E)- methyl 3-(4-formylphenyl)acrylate compound of formula-3 in methanol to provide imine compound, which on in-situ reduction with sodium borohydride to provide (E)- methyl 3 -(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylate compound of formula-4,

b) treating the compound of formula-4 with oxalic acid in ethylacetate provides oxalate salt of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl)phenyl) acrylate compound of formula-5b.

The eighth aspect of the present invention provides crystalline form-M3 of 2-(E)-N- hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl)phenyl]-2-propenamide hydrobromide salt compound of formula- l b is further characterized by its PXRD pattern as illustrated in figure- 16.

The starting materials compound of formula-2 and compound of formula-3 can be prepared by using any of the prior known process.

The 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl] 2-propenamide lactate salt compound of formula- l a utilized as starting material for the preparation of novel crystalline forms of the present invention can be prepared by the process described in the present invention (or), any of the processes known in the art.

The intermediate compounds and their crystalline Form-M i and M2 of the present invention are useful for the preparation of pure compound of formula- l a.

The solid state forms of compound of formula- l a of the present invention are useful for the preparation of various pharmaceutical compositions formulated in a manner suitable for the route of administration to be used where at least a portion of compound of formula- l a is present in the composition in particular polymorphic form mentioned.

In a further aspect, the solid state forms of compound of formula- l a of the present invention can be micronized to achieve the desired better particle size distribution in order to make suitable formulation.

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2- propenamide lactate compound of formula- 1 a obtained according to the present invention is having purity greater than 99.96% as measured by HPLC.

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2- propenamide lactate compound of formula- l a obtained according to the present invention is having particle size distribution D90 < 200 μιη; preferably < 1 00 μm.

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino)methyl)phenyl]-2- propenamide lactate compound of formula- l a produced by the present invention can be further micronized or milled in a conventional techniques 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. MiUing or micronization may be performed before drying, or after the completion of drying of the product.

The invention also encompasses pharmaceutical compositions comprising compound of formula- 1 or salts thereof of the present invention. As used herein, the term "pharmaceutical compositions" or "pharmaceutical formulations" include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.

P-XRD Method of Analysis:

PXRD analysis of compounds produced by the present invention were carried out using BRUKER D8 ADVANCE/AXS X-Ray diffractometer using Cu Kα radiation of wavelength 1 .5406 A ⁰ and continuous scan speed of 0.03°/min.

PSD method of Analysis:

Particle size distribution (PSD) analysis was performed using Malvern Mastersizer 2000 instrument

The process of the present invention can be represented schematically as follows.

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 amorphous form of 2-(E)-N-hydroxy-3-[4- [{[2-(2-methyl- 1 H- indol-3-yl)ethyl]amino]methyl]phenyl)-2-propenamide lactate: (Formula-l a)

A mixture of 2-(E)-N-hydroxy-3-[4-([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a (0.5 gm) and methanol (8 ml) were stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 15 minutes at the same temperature. Filtered the reaction mixture and distilled off the solvent completely from the filtrate under reduced pressure and dried to get the title compound. Yield: 0.36 gms.

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

Examp!e-2: Preparation of amorphous form of 2-(E)-N-hydroxy-3-|4- [|[2-(2-methyl-1 H- indol-3-yl)ethyl|aminolmethyl]phenyl|-2-propenamide lactate: (Formula-l a)

A mixture of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- 1 a (5 gm) and methanol ( 100 ml) were stirred for 10 minutes at 25-30°C. Heated the reaction mixture 55-60°C and stirred for 1 5 minutes at the same temperature. Filtered the reaction mixture at 25-30°C and the obtained filtrate was spray dried under following conditions.

Inlet temperature: 60°C

Feed rate: 5 ml/ min

Aspirator flow rate: 70%

Nitrogen pressure: 2.0 kg

The obtained solid was collected from the spray dryer and dried at 40-45°C under reduced pressure to get the title compound. Yield: 2.8 gms

The PXRD pattern of the obtained compound is shown in Figure-2.

Example-3: Preparation of amorphous solid dispersion of 2-(E)-N-hydroxy-3-|4-| | |2-(2- methyl-lH-indol-3-yl)ethyllamino]methyl|phenyl)-2-propenamid e lactate in combination with polyvinyl pyrrolidine-K-30: 2-(E)-N-hydroxy-3-(4-[([2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]rnethyl)phenyl]-2- propenamide lactate compound of formula- l a (0.5 gms) was added to methanol (5 ml) and stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 10- 15 minutes at the same temperature. A solution of polyvinyl pyrrolidine-K-30 (0.5 gms) in methanol (5 ml) was added to the reaction mixture at 25-30°C and distilled off the solvent completely from the reaction mixture under reduced pressure and then dried the material to get the title compound. Yield: 0.86 gms.

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

Example-4: Preparation of amorphous solid dispersion of 2-(E)-N-hydroxy-3-|4-|| |2-(2- meihyl-1 H- indol-3-yl)ethylJaminoJmeihylJphenyl]-2-propenamide lactate in combination with hydroxypropyl methylcellulose (HPMC):

2-(E)-N-hydroxy-3-[4-[[(2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl)-2- propenamide lactate compound of formula- l a (0.5 gms) was added to methanol ( 10 ml) and stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 1 5 minutes at the same temperature. A solution of Hydroxypropyl methylcellulose (0.5 gms) in methanol ( 10 ml) was added to reaction mixture at 25-30°C and distilled off the solvent completely from the reaction mixture under reduced pressure and then dried the material to get the title compound. Yield: 0.8 gms.

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

Example-5: Preparation of amorphous solid dispersion of (2-(E)-N-hydroxy-3-|4-| ||2-(2- methyl-1 H- indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate in combination with hydroxypropyl cellulose (HPC):

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino)methyl]phenyl]-2- propenamide lactate compound of formula- 1 a (0.5 gms) was added to methanol ( 10 ml) and stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 1 5 minutes at the same temperature. A solution of Hydroxypropyl cellulose (0.5 gms) in methanol ( 10 ml) was added to the reaction mixture at 25-30°C and distilled off the solvent completely from the reaction mixture under reduced pressure and then dried the material to get the title compound. Yield: 0.73 gms.

The PXRD pattern of the obtained compound is shown in Figure-5. Example-6: Preparation of amorphous solid dispersion of 2-(E)-N-hydroxy-3-[4-[([2-(2- methyl-lH-indol-3-yl)ethyl]aminol methyl]phenyl)-2-propenamide lactate in combination with hydroxypropyl methyl cellulose-acetate succinate (HPMC-AS):

2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyi]-2- propenamide lactate compound of formula- l a (0.5 gms) was added to methanol ( 10 ml) and stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 1 5 minutes at the same temperature. A solution of Hydroxypropyl methylcellulose-acetate succinate (0.5 gms) in methanol ( 10 ml) was added to the reaction mixture and distilled off the solvent completely from the reaction mixture under reduced pressure and then dried the material to get the title compound. Yield: 0.70 gms.

The PXRD pattern of the obtained compound is shown in Figure-6.

Example-7: Preparation of crystalline form-M of 2-(E)-N-hydroxy-3-(4-[((2-(2-methyl- 1 H- indol-3-yl)ethyl]amino]methyl] phenyl|-2-propenamide: (Formula-1)

Dimethylformamide (5 ml) was added to the compound of formula- 1 (0.5 gms) at 25- 30° C and stirred for 10 minutes at the same temperature. Heated the reaction mixture to 75- 80° C and stirred for 1 5 minutes at the same temperature. Cooled the reaction mixture to 25- 30° C. Filtered the solid and dried to get the title compound. Yield: 0.25 gms.

The PXRD pattern of the obtained compound is shown in figure-7.

Example-8: Preparation of crystalline form-S of 2-(E)-N-hydroxy-3-|4-| | |2-(2-methyl- 1 H- indol-3-yl)ethy!]amino]methyI) phenyl)-2-propenamide: (Formula-1)

A mixture of tetrahydrofuran ( 1 5 ml) and methanol ( 1 5 ml) was added to the compound of formula- 1 (0.5 gms) at 25-30°C and stirred for 10 minutes at the same temperature. Heated the reaction mixture to 65-70°C and stirred for 1 5 minutes at the same temperature. Cooled the reaction mixture to 0-5°C and stirred for 10 minutes at same temperature. Methyl tertiary butyl ether (5 ml) was added to reaction mixture at 0-5°C and stirred for 1 0 minutes at same temperature. Filtered the precipitated solid and dried to get the title compound. Yield: 0.3 gms.

The PXRD pattern of the obtained compound is shown in figure-8.

Example-9: Preparation of amorphous form of 2-(E)-N-hydroxy-3-(4-| |l2-(2-methyI-1 H- indol-3-yl)ethyl|aminojmethyl)phenyl|-2-propenamide: (Formula-1) A mixture of tetrahydrofuran ( 1 5 ml) and methanol was added to 2-(E)-N-hydroxy-3- [ ^4_ ([[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (0.5 gm) and stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 55-60°C and stirred for 1 5 minutes at the same temperature to get a clear solution. Filtered the resulting solution and distilled off the solvent completely from the filtrate under reduced pressure and dried to get the title compound. Yield: 0.38 gms.

The PXRD pattern of the obtained compound is shown in figure-9.

Example-10: Preparation of crystalline form-N of 2-(E)-N-hydroxy-3-|4- | ||2-(2-methyl- 1 H- indol-3-yl)ethyl]amino)methyl|phenyl]-2-propenarnide lactate: (Formula-l a)

n-Heptane ( 1 0 ml) was added to the compound of formula- l a (0.3 gms) at 25-30°C and stirred for 1 0 minutes at the same temperature. Cooled the reaction mixture to 0-5°C and stirred for 2 hours at the same temperature. Filtered the solid and dried to get the title compound. Yield : 0.2 gms.

The PXRD pattern of the obtained compound is shown in figure- 12.

Example-1 1 : Preparation of 2-(2-methyl- 1 H- indol-3-yl)ethanamine: (Formula-2)

A mixture of phenyl hydrazine (1 00 gm), 5-chloropentan-2-one ( 1 1 7.07 gm) and water (500 ml) were stirred for 10 minutes at 25-30° C. Heated the reaction mixture to 65-75°C and stirred for 2 hours at the same temperature. Cooled the reaction mixture to 25-30°C. Toluene (500 ml) was added to the reaction mixture and stirred for 1 5 minutes. Separated both the organic and aqueous layers and washed the aqueous layers with toluene. Toluene (800 ml) was added to the obtained aqueous layer followed by aqueous sodium hydroxide solution (44.3 gm of sodium hydroxide dissolved in 500 ml of water) to the reaction mixture and stirred for 1 5 minutes at 25-30°C. Heated the reaction mixture to 65-75°C and stirred for 1 5 minutes. Filtered the reaction mixture through hyflow bed at 65-70°C and washed the hyflow bed with toluene. Separated both the aqueous and organic layers and organic layers was charged into RBF and cooled the reaction mixture to 0-5°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid, washed with chilled toluene and drying to get the title compound. Yield: 105 gm.

Example-12: Preparation of (E)-methyl 3-(4-(((2-(2-methyl-1 H- indol-3-yl)ethyl)amino) methyl)phenyl)acrylate hydrobromide: (Formula-5a) A mixture of 2-(2-methyl- 1 H-indol-3-yl)ethanamine (50 gm), (E)-methyl 3-(4- formylphenyl)acryiate (54.57 gm) and methanol (300 ml) were stirred for I ½ hour at 25-30° C. Cooled the reaction mixture to 0-5°C. Sodium borohydride (5.42 gm) was added lot wise to the reaction mixture for four times at the same temperature. Raised the temperature of the reaction mixture to 25-30°C and stirred for 2 hours at the same temperature. Acidified the reaction mixture with hydrobromic acid (70 ml) at 25-30°C. Water (300 ml) was added to the reaction mixture and stirred for 1 hour. Filtered the solid and washed with methanol and suck dried the compound for 2 hours under reduced pressure. Methanol (225 ml) was added to the obtained wet compound and stirred for 45 minutes at 25-30°C. Filtered the compound, dried and washed with methanol and further drying to get the title compound. Yield: 87 gm.

The P-XRD of the obtained compound was depicted in Figure- 14.

Example-13: Preparation of (E)-methyl 3-(4-(((2-(2-methyl-1 H- indol-3-yl)ethyl)amino) methyl)phenyl)acrylate hydrobromide: (Formula-5a)

A mixture of 2-(2-methyl- 1 H-indol-3-yl)ethanamine (30 gm), (E)-methyl 3-(4-formyl phenyl)acrylate (32.74 gm) and methanol (360 ml) were stirred for 1 ½ hour at 25-30° C. Cooled the reaction mixture to 0-5° C. Sodium borohydride (3.25 gm) was added lot wise to the reaction mixture for four times at the same temperature. Raised the temperature of the reaction mixture to 25-30° C and stirred for 2 hours at the same temperature. Acidified the reaction mixture with hydrobromic acid (42 ml) at 25-30°C. Water ( 1 80 ml) was added to the reaction mixture at 25-30°C and stirred for 1 hour at the same temperature. Filtered the solid and washed with methanol. Methanol ( 1 35 ml) was added to the obtained wet compound and stirred for 45 minutes at 25-30°C. Filtered the compound, dried and washed with methanol and further drying to get the title compound.

Yield: 54.3 gm; M R: 225.4-226.8°C; bromide content: 1 8.9 %.

Purity by HPLC: 98.99%; Alcohol ester impurity: 0.07%; indole amine impurity: 0. 10%; Aldehyde ester impurity: 0.01 %, indole acid impurity: 0 06%; bromo acid impurity: Not detected; hydrazine ester impurity: Not detected.

Example-14: Preparation of (E)-methyl 3-(4-(((2-(2-methyl- 1 H- indol-3-yl)ethyl)amino) methyl)phenyl)acrylate oxalate: (Formula-5b)

A mixture of 2-(2-methyl- 1 H-indol-3-yl)ethanamine (50 gm), (E)-methyl 3-(4- formylphenyl)acrylate (54.57 gm) and methanol (600 ml) were stirred for 1 ½ hour at 25-30° C. Cooled the reaction mixture to 0-5°C. Sodium borohydride (5.42 gm) was added lot wise to the reaction mixture for four times at the same temperature. Raised the temperature of the reaction mixture to 25-30°C and stirred for 2 hours at the same temperature. Water (225 ml) and dichloromethane (300 ml) were added to the reaction mixture and stirred for 10 minutes. Separated both the organic and aqueous layers and organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure. Ethylacetate ( 100 ml) and oxalic acid solution (60.83 gm of oxalic acid dissolved in 100 ml of water & 600 ml of acetonitrile) were added to the reaction mixture and stirred for 45 minutes at 25-30°C. Filtered the compound and washed with acetonitrile. Ethyi acetate (500 ml) was added to the obtained wet compound and stirred for 45 minutes. Filtered the compound, washed with ethyl acetate and drying to get the title compound.

Yield: 74.66 gm.

The P-XRD of the obtained compound was depicted in Figure- 1 5.

Example-15: Preparation of 2-(E)-N-hydroxy-3-(4-[([2-(2-methyl-1 H- indol-3-yl)ethyl) amino|methylJphenyl]-2-propenamide hydrobromide salt: (Formula-l b)

A mixture of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3 -yl)ethyl)amtno)methyl) phenyl)acrylate hydrobromide ( 100 gm) and methanol (600 ml) were stirred for 10 minutes at 25-30°C. Cooled the reaction mixture to -20 to - 10°C. A solution of sodium hydroxide (27.84 gm of sodium hydroxide dissolved in 600 of methanol) was added to the reaction mixture and stirred for 1 5 minutes at the same temperature. 50% aqueous hydroxy! amine solution was added to the reaction mixture and stirred for 6 hours at -20 to - 10°C. Raised the temperature of the reaction mixture to 25-30°C. Water (400 ml) was added to the reaction mixture at the same temperature. Acidified the reaction mixture with aqueous hydrobromic acid (600 ml) at 25-30°C and stirred for 2 hours. Filtered the solid and washed with water and suck dried the compound under reduced pressure to get the wet compound. Methanol (600 ml) was added to the obtained wet compound at 25-30°C. Heated the reaction mixture to 60-70°C and stirred for 2 hours at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 2 hours at the same temperature. Filtered the solid and washed with methanol and drying to get the title compound. Yield: 70 gms; M R: 192.2- 195.6°C; bromide content: 19.1 1 %. Purity by HPLC: 99:71 %; Amide impurity: 0.07 %; Indole acid impurity: 0.07 %; Indole ester impurity: 0.01 %; hydroxyl amine alcohol impurity: Not detected; Indole amine impurity: Not detected; bromo impurity: Not detected.

The P-XRD of the obtained compound was depicted in Figure- 16.

Example-16: Preparation of 2-(E)-N-hydroxy-3-I4-H(2-(2-methy!-1 H- indol-3-yl)ethyl| amino) rnethyl)phenyl]-2-propenamide ethanesulfonate: (Formula-l c)

A mixture of (E)-methyl 3-(4-(((2-(2-methyl- 1 H-indol-3-yl)ethyl)amino)methyl) phenyl)acrylate ( 100 gm) and methanol (600 ml) were stirred for 10 minutes at 25-30°C. Cooled the reaction mixture to -20 to - 10°C. A solution of sodium hydroxide (34.4 gm of NaOH dissolved in 600 of methanol) was added to the reaction mixture and stirred for 1 5 minutes at the same temperature. 50% aqueous hydroxyl amine solution was added to the reaction mixture and stirred for 6 hours at -20 to - 10°C. Raised the temperature of the reaction mixture to 25-30°C. A solution of ethane sulfonic acid (63.2 gm of ethane sulfonic acid dissolved in 500 ml of water) was added to the reaction mixture at 25-30°C and stirred for 2 hours. Filtered the solid and washed with water and suck dried the compound under reduced pressure to get the title compound. Yield: 82 gm

Example-17: Preparation of 2-(E)-N-hydroxy-3-(4-|(|2-(2-methyl- lH-indol-3-yl)ethylj amino]methyl)phenyl]-2-propenamide lactate: (Formula-l a)

A mixture of DL-Lactic acid (3.4 gm) and water (28.8 ml) were stirred for 10 minutes at 25-30°C. Heated the reaction mixture to 90°C and stirred for 1 5 hours at the same temperature and kept a side. A mixture of (E)-N-hydroxy-3-(4-(((2-(2-methyl- 1 H-indol-3- yl)ethyl)amino)methyl)phenyl)acrylamide hydrobromide ( 1 5 gm) and dimethyl sul foxide (60 ml) were taken into another RBF. A solution of potassium hydroxide (2.9 gm of potassium hydroxide in 15 ml of methanol) was added to the reaction mixture and stirred for 10 minutes at 25-30°C. Water ( 1 80 ml) was added to the reaction mixture and stirred for 45 minutes at the same temperature. Filtered the compound and washed with water. Water ( 132 ml) was added to the reaction mixture and raised the temperature of the reaction mixture to 60-70°C. The above prepared DL-Lactic acid solution was Slowly added to the reaction mixture. Cooled the reaction mixture to 30-35°C and stirred for 32 hours at the same temperature. Filtered the solid and washed with water and drying to get the title compound. Yield : 8.0 gm Example-18: Preparation of 2-(E)-N-hydroxy-3-(4-|[ [2-(2-methyl-1 H- indol-3-yI)ethyl| amino]methyl)phenyl]-2-propenamide lactate: (Formula- la)

A mixture of DL-Lactic acid (30.27 gm) and water (216 ml) were stirred for 10 minutes at 25-30° C. Heated the reaction mixture to 90° C and stirred for 1 5 hours at the same temperature and kept a side. A mixture of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3- yl)ethyl]amino]methyl]phenyl)-2-propenarnide hydrobromide (80 gms), tetrahydrofuran ( 1 .2 Itrs) and methanol ( 1 .2 Itrs) was stirred for 10 minutes at 25-30°C. Cooled the reaction mixture to 0-5°C. The reaction mixture was basified using aqueous ammonia solution (40 ml) at 0-5°C and stirred for 60 minutes at the same temperature. Filtered the reaction mixture and washed with a mixture of THF and methanol. Water was added to the obtained wet compound at 25-30°C and stirred for 45 minutes at the same temperature. Filtered the solid and washed with water. The above DL-Lactic acid solution was slowly added to a mixture of water and obtained wet compound within 45 minutes at 25-30°C. Filtered the reaction mixture and stirred the obtained filtrate for 35 hours at 25-30°C. Filtered the precipitated solid, washed with water and dried to get the title compound.

Yield: 49 gms; M.R: 130- 1 35°C; Purity by HPLC . 99.75 %; Amide impurity: 0.02 %, Indole amine impurity: Not detected; Indole acid impurity: 0.07 %; Indole ester impurity: 0.01 %. Particle Size Distribution (PSD): D(0.1 ) is 5.7 μm, D(0.5) is 69.0 μπι, D(0.9) is 408.6 μm; D[4.3] is 1 53.0 μm ;

Example-19: Preparation of crystalline form-M of 2-(E)-N-hyd roxy-3-|4-|||2-(2-rnethyl- 1 H- indol-3-yl)ethyl)amino] methyl]phenyl]-2-propenamide lactate: (Formula-l a)

A mixture of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino) methyl]phenyl]-2-propenamide lactate compound of formula- l a (5 gm) and methanol (25 ml) were stirred for 10 minutes at 25-30° C. Heated the reaction mixture to 55-60° C and stirred for 10 minutes at the same temperature. The resulting solution was added to acetonitrile (50 ml) and stirred the reaction mixture for 8 hours at 25-30° C. Filtered the solid and drying to get the title compound. Yield: 3.7 gms.

The PXRJD pattern of the obtained compound is shown in Figure- 10.

Example-20: Preparation of crystalline form-S of 2-(E)-N-hydroxy-3-[4-| |(2-(2-methyl- 1 H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide lactate: (Formula- l a) A mixture of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyI]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a (5 gm) and dimethylformamide (30 ml) were stirred for 10 minutes at 25-30°C. Further, stirred the reaction mixture for 30 minutes at the same temperature. Filtered the solid and drying to get the title compound. Yield: 3.6 gms.

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

Example-19: Preparation of crystalline form-L of 2-(E)-N-hydroxy-3-|4- |||2-(2-methyl- 1 H- indol-3-yl)ethylJaminoJ methyl)phenyl]-2-propenamide lactate: (Formula-l a)

A mixture of 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl- 1 H-indol-3-yl)ethyl]amino] methyl]phenyl]-2-propenamide lactate compound of formula- l a (5 gm) and isopropanol ( 1 50 ml) were stirred for 1 0 minutes at 25-30°C. Heated the reaction mixture to 65-70°C and stirred for 30 minutes at the same temperature. The resulting solution was filtered to make it particle free. Further, the obtained filtrate was stirred for 48 hours at 25-30°C Filtered the solid and drying to get the title compound. Yield: 3.0 gms.

The PXRD pattern of the obtained compound is shown in Figure- 1 3.