Field of the Invention:

   The present invention relates to amorphous solid dispersion of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N^-2,4-pyrimidinediamine compound of formula-l5 represented by the following structural formula:

The present invention also relates to novel crystalline form of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl] -2,4-pyrimidinediamine compound of formula-1 and process for its preparation thereof. Background of the Invention:

Ceritinib is an anaplastic lymphoma kinase (ALK) inhibitor. ALK is a member of the insulin receptor superfamily of receptor tyrosine kinases. Genetic alterations of ALK have been implicated in oncogenesis in hematopoietic and non-hematopoietic tumours. The gene has been found to be rearranged, mutated, or amplified in a series of tumours, including non-small cell lung cancer.

Ceritinib has been approved by the US FDA as Zykadia® for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who has progressed on or are intolerant to crizotinib.

International PCT publication WO2008/073687 Al disclosed ceritinib (also named LDK378) as compound 66 in Example 7. Ceritinib is chemically described as 5-Chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine.

International PCT publication WO2012/082972 Al discloses crystalline form-A and form-B of ceritinib.

IPCOM00Q239900D  discloses  crystalline  form  of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidin^ having peaks 7.2, 8.0, 10.7, 13.4, 14.3, 16.8, 17.7, 18.4, 18.9, 21.0 ±0.2 degrees two theta.

CN105061397 A discloses crystalline form-C of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2?4-pyrimidinediamine.

CN105294650 A discloses crystalline form of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

IN201641006515 discloses amorphous form of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

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.

Polymorphic forms of a compound can be distinguished in a laboratory by X-ray diffraction spectroscopy and by other methods such as, infrared spectrometry. Additionally, polymorphic forms of the same drug substance or active pharmaceutical ingredient, can be administered by itself or formulated as a drug product (also known as the final or finished dosage form), and are well known in the pharmaceutical art to affect, for example, the solubility, stability, flowability, tractability and compressibility of drug substances and the safety and efficacy of drug products.

Crystalline solids normally require a significant amount of energy for dissolution due to their highly organized, lattice like structures. For example, the energy required for a drug molecule to escape from a crystal is more than from an amorphous or a non-crystalline form.

It is known that the amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to the crystalline form (Econno T., Chem. Pharm. Bull.,  1990; 38: 2003-2007). For some therapeutic indications, one bioavailability pattern may be favored over another. Brief description of the Invention:

The first aspect of the present invention is to provide novel crystalline form of 5-chloro«N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1, herein after designated as Form-M and its preparation thereof.

The second aspect of the present invention is to provide amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with one or more pharmaceutical acceptable carrier.

The third aspect of the present invention is to provide process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)  phenyl]-2,4-pyrimidinediamine  compound  of  formula-1  in combination with one or more pharmaceutical acceptable carrier. Brief description of the Drawings:

Figure 1: Illustrates the PXRD pattern of crystalline form-M of 5-chloro-N4-[2-[(l-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.

Figure 2: Illustrates the PXRD pattern of crystalline form-M of 5-chloro-N4-[2-[(l-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.

Figure 3: Illustrates the DSC thermogram of crystalline form-M of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.

Figure 4: Illustrates the PXRD pattern of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl] -2,4-pyrimidinediamine in combination with HPC.

Figure 5: Illustrates the PXRD pattern of amorphous solid dispersion of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2^-2,4-pyrimidinediamine in combination with PVP-K-30.

Figure 6: Illustrates the PXRD pattern of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)pheny]]-2,4-pyrimidinediamine in combination with HPMC.

Figure 7: Illustrates the PXRD pattern of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in combination with HPMC AS.

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 dichloro methane, 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, isobutanol, t-butanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, 2-methoxyethanol, 1, 2-ethoxyethanol, diethylene glycol, 1, 2, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, or glycerol and the like; "polar solvents" such as water or mixtures thereof.

The first aspect of the present invention provides novel crystalline form of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, herein after designated as form-M, characterized by its powder x-ray diffraction pattern having peaks at 6.8, 8.2, 9.6, 10.0, 12.4, 12.6, 13.2, 13.5, 14.5, 15.1, 16.5, 16.8, 17.5, 18.5, 19.1, 19.9, 20.2, 20.9, 21.1, 21.6, 22.6, 23.1, 23.6, 23.9, 25.0, 25.3, 25.8, 26.0, 27.4, 27.8, 28.5, 29.7, 30.6 and 32.2 ±0.2 degrees two theta.

The crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine further characterized by its powder x-ray diffraction pattern as depicted in figure-1.

The crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine further characterized by its differential scanning calorimetry (DSC) thermogram as depicted in figure-3.

In an embodiment of the present invention provides a process for the preparation of crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:

a) Adding a suitable solvent to 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of fomula-1,

b) heating the reaction mixture to a suitable temperature,

c) stirring the reaction mixture,

d) adding the reaction mixture to a pre-cooled solvent at a suitable temperature,

e) stirring the reaction mixture at a suitable temperature and filtering the precipitated solid to get the crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

Wherein,

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

in step-b) & e) the suitable temperature is ranging from 25°C to the reflux temperature of the solvent used in the reaction;

in step-d) the suitable solvent is selected from hydrocarbon solvent; preferably n-heptane and the suitable temperature is ranging from -70°C to 0°C.

The preferred embodiment of the present invention provides a process for the preparation of crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:

a) Adding ethyl acetate to 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of fomula-1,

b) heating the reaction mixture to 60-65°C,

c) stirring the reaction mixture,

d) adding the reaction mixture to a pre-cooled n-heptane at -50°C,

e) stirring the reaction mixture at 25-30°C and filtering the precipitated solid to get the crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl] -N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

The second aspect of the present invention provides amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl] -2,4-pyrimidinediamine compound of formula-1 in combination with one or more pharmaceutical acceptable carrier.

Wherein, the term pharmaceutical acceptable carrier is preferably a polymeric carrier, and more preferably at least one from the group consisting of starches, modified starches, cellulose, methyl cellulose (MC), Microcrystalline cellulose (MCC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydroxypropylmethyl acetate succinate (HPM AS), polycarbophil, polyethylene glycol (PEG), polyethylene oxides, polyoxyalkylene derivatives, polymethacrylates, polyvinyl pyrrolidone (PVP), PVP-K30, polyvinyl acetate (PVAc), PVP vinylacetate-copolymer (PVP-VA), Kollidon® VA 64 (a vinylpyrrolidone -vinyl acetate copolymer), lactose, sorbitol, mannitol, maltitol, saccharose, isomalt, cyclodextrins such as cc-cyclodextrins, P-cyclodextrins, y-cyclodextrins, hydroxyl-propyl-cyclodextrins, hydroxypropyl-cyclodextrin, sodium carboxymethyl cellulose cross -linked polyacrylic acid (carbipol), or a mixture thereof.

In general, the term "solid dispersion" refers to a system in a solid state comprising at least two components, wherein one component is dispersed throughout the other component or components.

The term "amorphous solid dispersion" as used herein, refers to solid dispersion which is substantially amorphous, that is, at least 80%, preferably at least 90%, most preferably at least 95%, is in amorphous form as determined by powder x-ray diffraction pattern.

The other embodiment of the present invention provides amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPC and the P-XRD pattern is depicted in figure-4.

The other embodiment of the present invention provides amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with PVP K-30 and the P-XRD pattern is depicted in figure-5.

The other embodiment of the present invention provides amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC and the P-XRD pattern is depicted in figure-6.

The other embodiment of the present invention provides amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl) phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC AS and the P-XRD pattern is depicted in figure-7.

The third aspect of the present invention provides a process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with one or more pharmaceutical acceptable carrier, comprising of:

a) Adding a suitable solvent to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and one or more pharmaceutical acceptable carrier,

b) stirring the reaction mixture,

c)  isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-254-pyrimidinediamine compound of formula-1 Wherein,

In step-a) the suitable solvent is selected from alcohol solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents and polar solvents like water or mixture thereof and suitable pharmaceutical acceptable carrier is same as defined in the second aspect of the present invention.

The preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPC, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and HPC,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPC.

Another preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and HPMC,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC.

Another preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with PVP-K-30, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and PVP-K-30,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with PVP-K-30.

Another preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC AS, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of S-chloro-ISR-p-isopropoxy-S-methyM-^-piperidiny^phenyll-W-^^^pyrimidinediamine and HPMC AS,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC AS.

The amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine obtained according to the present invention can be isolated using a rotational distillation device such as a Buchi Rotavapor, vacuum drying, spray drying, spray granulating, freeze drying and spray-freeze drying, agitated thin film drying (ATFD) or melt extrusion or freeze drying (lyophilization) or by any other suitable techniques.

In the present invention, the composition of the solid dispersion containing of a mole ratio of the amount of the ceritinib compound of formula-1 to the amount of the pharmaceutical acceptable carrier is ranging from about 1:0.5 to 1:10 by weight.

5-Chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 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. Milling or micronization may be performed before drying, or after the completion of drying of the product.

5-Chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 used in the present invention is prepared according to any of the process known in the art.

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 Ka radiation of wavelength 1.5406 A° and continuous scan speed of 0.03°/min. DSC Method of Analysis:

Differential scanning calorimetric (DSC) analysis was performed with Q2000 V24.ll Build 124 calorimeter. Samples of about 2 to 3 milligrams held in a closed pan were analyzed at a heating rate of 10°C per minute.

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 crystalline form-M of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl] - N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine

(Formula-1)

Ethyl acetate (150 ml) was added to 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (5.0 gms) at 25-30°C. Heated the reaction mixture to 60-65°C and stirred for 15 minutes at the same temperature. The reaction mixture was slowly added to a pre-cooled n-Heptane (300 ml) at -50°C. Slowly raised the temperature of the reaction mixture to 25-30°C and stirred for 30 minutes at the same temperature. Filtered the precipitated solid and dried to get the title compound. Yield: 4.2 gms.

The P-XRD pattern of the obtained compound was depicted in figure-1. Example-2:

Preparation of crystalline form-M of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl] -N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (Formula-1)

Ethyl acetate (150 ml) was added to 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-234-pyrimidinediamine (1.0 gms) at 25-30°C. Heated the reaction mixture to 60-65°C and stirred for 15 minutes at the same temperature. The reaction mixture was slowly added to a pre-cooled n-Heptane (300 ml) at -50°C. Slowly raised the temperature of the reaction mixture to 25-30°C and stirred for 30 minutes at the same temperature. Filtered the precipitated solid and dried to get the title compound. Yield: 0.75 gms.

The P-XRD pattern of the obtained compound was depicted in figure-2. Example-3:

Preparation of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl] phenyl]-N2-[5-methyl-2-(l-methyIethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine in combination with HPC: (1:1)

A mixture of dichloromethane (15 ml) and methanol (15 ml) was added to 5-chloro-N4-[2-[(l-methylethyl)sulfo^phenyl]-2,4-pyrimidinediamine (0.5 gms) and HPC (0.5 gms) at 25-30°C and stirred for 15 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture and dried to get amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-234-pyrimidine diamine in combination with HPC. Yield: 0.6 gms. The P-XRD pattern of the obtained compound was depicted in figure-4. Example-4:

Preparation of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyI)suIfonyl] phenyI]-N2-[5-methyI-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine in combination with PVP-K-30: (1:1)

A mixture of dichloromethane (12.5 ml) and methanol (12.5 ml) was added to 5-chloro-N4424(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine (0.5 gms) and PVP-K-30 (0.5 gms) at 25-30°C and stirred for 15 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture and dried to get amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in combination with PVP-K-30. Yield: 0.8 gms. The P-XRD pattern of the obtained compound was depicted in figure-5. Example-5:

Preparation of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl] phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine in combination with HPMC: (1:1)

A mixture of dichloromethane (15 ml) and methanol (15 ml) was added to 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]pte phenyl]-2,4-pyrimidinediamine (0.5 gms) and HPMC (0.5 gms) at 25-30°C and stirred for 15 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture and dried to get amorphous solid dispersion of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl] N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in combination with HPMC. Yield: 0.7 gms.

The P-XRJD pattern of the obtained compound was depicted in figure-6.

Example-6:

Preparation of amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in combination with HPMC AS: (1:1)

A mixture of dichloromethane (15 ml) and methanol (15 ml) was added to 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phen^phenyl]-2,4-pyrimidinediamine (0.5 gms) and HPMC AS (0.5 gms) at 25-30°C and stirred for 15 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture and dried to get amorphous solid dispersion of 5-chloro-N4-[2-[(l-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(l-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine in combination with HPMC AS. Yield: 0.6 gms. The P-XRD pattern of the obtained compound was depicted in figure-7.

We claim:

1. A novel crystalline form-M of 5-chloro-N4-[2-[(l-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(l -methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, characterized by its powder x-ray diffraction pattern having peaks 6.8, 8.2, 9.6, 10.0, 12.4, 12.6, 13.2, 13.5, 14.5, 15.1, 16.5, 16.8, 17.5, 18.5, 19.1, 19.9, 20.2, 20.9, 21.1, 21.6, 22.6, 23.1, 23.6, 23.9, 25.0, 25.3, 25.8, 26.0, 27.4, 27.8, 28.5, 29.7, 30.6 and 32.2 ±0.2 degrees two theta.

2. A process for the preparation of crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:

a) Adding a suitable solvent to 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of fomula-1,

b) heating the reaction mixture to a suitable temperature,

c) stirring the reaction mixture,

d) adding the reaction mixture to a pre-cooled solvent at a suitable temperature,

e) stirring the reaction mixture at a suitable temperature and filtering the precipitated solid to get the crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

3. The process according to claim-2, wherein,
in step-a) the suitable solvent is selected from alcohol solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents and polar solvents like water or mixture thereof;

in step-b) & e) the suitable temperature is ranging from ambient to the reflux temperature of the solvent used in the reaction;

in step-d) the suitable solvent is selected from hydrocarbon solvent; preferably n-heptane and the suitable temperature is ranging from -70°C to 0°C.

4. A process for the preparation of crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediaminecompound of formula-1, comprising of:

a) Adding ethyl acetate to 5-chloro-N2-[2-isopropoxy-5-methyM-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-234-pyrimidinediamine compound of fomula-1,

b) heating the reaction mixture to 60-65°C,

c) stirring the reaction mixture,

d) adding the reaction mixture to a pre-cooled n-heptane at -50°C,

e) stirring the reaction mixture at 25-30°C and filtering the precipitated solid to get the crystalline form-M of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine.

5. Amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl) phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with one or more pharmaceutical acceptable carrier, wherein, pharmaceutical acceptable carrier includes at least one from the group consisting of starches, modified starches, cellulose, methyl cellulose (MC), microcrystalline cellulose (MCC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydroxypropylmethyl acetate succinate (HPM AS), polycarbophil, polyethylene glycol (PEG), polyethylene oxides, polyoxyalkylene derivatives, polymethacrylates, polyvinyl pyrrolidone (PVP), PVP-K30, polyvinyl acetate (PVAc), PVP vinylacetate-copolymer (PVP-VA), Kollidon® VA 64 (a vinylpyrrolidone -vinyl acetate copolymer), lactose, sorbitol, mannitol, maltitol, saccharose, isomalt, cyclodextrins such as cc-cyclodextrins, p-cyclodextrins, y-cyclodextrins, hydroxyl-propyl-cyclodextrins, hydroxypropyl-cyclodextrin, sodium carboxymethyl cellulose cross-linked polyacrylic acid (carbipol), or a mixture thereof.

6. A process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine  compound  of formula-1  in  combination  with  one  or  more pharmaceutical acceptable carrier, comprising of:

a) Adding a suitable solvent to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and one or more pharmaceutical acceptable carrier,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1

Wherein,

In step-a) the suitable solvent is selected from alcohol solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, polar aprotic solvents, nitrile solvents and polar solvents like water or mixture thereof and suitable pharmaceutical acceptable carrier is selected from HPC, HPMC, PVPK-30 and HPMC AS.

7. A process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPC, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and HPC,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPC.

8. A process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and HPMC,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC.

9. A process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2J4-pyrimidinediamine compound of formula-1 in combination with PVP-K-30, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2"(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine and PVP-K-30,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with PVP-K-30.

10. A process for the preparation of amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC AS, comprising of:

a) Adding a mixture of dichloromethane and methanol to a mixture of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-254-pyrimidinediamine and HPMC AS,

b) stirring the reaction mixture,

c) isolating amorphous solid dispersion of 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 in combination with HPMC AS.