Field of the Invention:
The present invention relates to acid addition salts of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine compound of formula-1, represented by the following structural formula:

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-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.
International PCT publication WO2012/082972 A1 discloses crystalline form-A and form-B of ceritinib.
IPCOM000239900D discloses crystalline form of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine 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-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine.
CN105294650 A discloses crystalline form of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine.
IN201641006515 discloses amorphous form of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine.
International PCT publication WO2016/081538 A1 discloses crystalline form-beta and
gamma of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl
ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine. The said publication also discloses crystalline Ceritinib dihydrochloride salt form-I, II, III, IV, V and crystalline Ceritinib sodium form-I and II.
Different salts and solid state forms of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts and solid state forms may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, improving the dissolution profile, or improving stability and shelf-life. These variations in the properties of different salts and solid state forms may also provide improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts and solid state forms of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess variations in the properties and characteristics of a solid active pharmaceutical ingredient.
Discovering new salts and solid state forms of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New salts and solid state forms of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials

that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, or improved shelf-life. For at least these reasons, there is a need for additional salts and solid state forms of Ceritinib; in particular there is a need for salts and solid state forms that have improved solubility.
Brief description of the Invention:
The first aspect of the present invention is to provide novel crystalline form of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a, herein after designated as form-S1 and process for it preparation.
The second aspect of the present invention is to provide novel crystalline form of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b, herein after designated as form-S2 and process for its preparation.
The third aspect of the present invention is to provide novel crystalline form of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c, herein after designated as form-S3 and process for its preparation.
The fourth aspect of the present invention is to provide novel crystalline form of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, herein after designated as form-N and process for its preparation.
The fifth aspect of the present invention is to provide a process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.
Brief description of the Drawings:
Figure 1: Illustrates the PXRD pattern of crystalline form-S1 of 5-chloro-N4-[2-[(1-methyl
ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-
pyrimidinediamine succinate salt compound of formula-1a.

Figure 2: Illustrates the DSC thermogram of crystalline form-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl] -2,4-pyrimidinediamine succinate salt compound of formula-1a.
Figure 3: Illustrates the PXRD pattern of crystalline form-S2 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b.
Figure 4: Illustrates the DSC thermogram of crystalline form-S2 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl] -2,4-pyrimidinediamine fumarate salt compound of formula-1b.
Figure 5: Illustrates the PXRD pattern of crystalline form-S3 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c.
Figure 6: Illustrates the DSC thermogram of crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl] -2,4-pyrimidinediamine oxalate salt compound of formula-1c.
Figure 7: Illustrates the PXRD pattern of crystalline form-N of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.
Figure 8: Illustrates the PXRD pattern of crystalline form-M of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.
Detailed description of the Invention:
The suitable solvent used in the present invention is selected from “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, l, 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-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a characterized by,
a) its powder x-ray diffraction pattern having peaks at 2.6, 5.3, 8.0, 9.6, 9.9, 10.6, 11.6, 12.4, 13.3, 14.3, 15.9, 17.6, 18.0, 18.5, 18.7, 19.2, 19.4, 19.6, 19.9, 20.8, 21.4, 22.0, 22.3, 22.7, 23.2, 23.5, 24.0, 24.2, 24.7, 25.1, 26.0, 26.9, 30.0, 32.6, 36.3, 38.9 and 41.1 ±0.2 degrees two theta as depicted in figure-1,
b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-2. Another embodiment of the present invention provides a process for the preparation of
crystalline form-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent,
b) optionally filtering the reaction mixture through hyflow bed,
c) adding succinic acid to the reaction mixture of step-a) or step-b),
d) stirring the reaction mixture,
e) distilling off the solvent from the reaction mixture to get crystalline form-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-

(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a.
Wherein, in step-a) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof.
The preferred embodiment of the present invention provides a process for the preparation of crystalline form-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in dichloromethane,
b) filtering the reaction mixture through hyflow bed,
c) adding succinic acid to the obtained filtrate,
d) stirring the reaction mixture,
e) distilling off the solvent from the reaction mixture to get crystalline form-S1 of 5-
chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-
(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a.
The second aspect of the present invention provides novel crystalline form-S2 of 5-
chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-
piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b
characterized by,
a) its powder x-ray diffraction pattern having peaks at 2.6, 5.2, 7.9, 9.7, 10.0, 11.7, 12.5, 13.2, 16.0, 17.5, 18.0, 18.6, 19.5, 19.8, 21.2, 21.8, 22.3, 23.9, 25.4, 26.3 and 26.7 ±0.2 degrees two theta as depicted in figure-3,
b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-4. Another embodiment of the present invention provides a process for the preparation of
crystalline form-S2 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-
methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent,

b) optionally filtering the reaction mixture through hyflow bed,
c) adding fumaric acid to the reaction mixture of step-a) or step-b),
d) stirring the reaction mixture,
e) filtering the precipitated solid to get crystalline form-S2 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b.
Wherein, in step-a) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof.
The preferred embodiment of the present invention provides a process for the preparation of crystalline form-S2 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in dichloromethane,
b) filtering the reaction mixture through hyflow bed,
c) adding fumaric acid to the obtained filtrate,
d) stirring the reaction mixture,
e) filtering the precipitated solid to get crystalline form-S2 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b.
The third aspect of the present invention provide novel crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c characterized by,
a) its powder x-ray diffraction pattern having peaks at 3.6, 4.6, 5.3, 6.4, 7.0, 10.7, 11.4, 11.7, 12.5, 13.2, 13.7, 14.3, 16.5, 17.7, 18.5, 19.6, 20.6, 22.7, 22.8, 23.4, 23.6, 24.4, 24.7, 25.2, 26.3, 28.5 and 29.0 ±0.2 degrees two theta as depicted in figure-5,
b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-6. Another embodiment of the present invention provides a process for the preparation of

crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent,
b) optionally, filtering the reaction mixture through hyflow bed,
c) adding oxalic acid to the reaction mixture of step-a) or step-b),
d) stirring the reaction mixture,
e) filtering the precipitated solid to get crystalline form-S3 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c.
Wherein, in step-a) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof.
The preferred embodiment of the present invention provides a process for the
preparation of crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-
methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt
compound of formula-1c, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in dichloromethane,
b) filtering the reaction mixture through hyflow bed,
c) adding oxalic acid to the obtained filtrate,
d) stirring the reaction mixture,
e) filtering the precipitated solid to get crystalline form-S3 of 5-chloro-N4-[2-[(1-methyl ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt compound of formula-1c.
The crystalline forms of acid addition salts of 5-chloro-N4-[2-[(1-methyl ethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine compound of formula-1a, 1b and 1c obtained from the present invention are useful in the preparation of pure 5-chloro-N4-[2-[(1-methyl ethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-

methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.
The crystalline forms of acid addition salts of Ceritinib can be converted into highly pure Ceritinib free base compound of formula-1, by treating the crystalline forms of acid addition salts of Ceritinib with a suitable base.
The fourth aspect of the present invention provides novel crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, characterized by: its powder x-ray diffraction pattern having peaks at 6.4, 8.4, 8.5, 9.0, 10.9, 12.0, 12.7, 12.9, 14.6, 15.6, 17.3, 17.8, 18.2, 18.9, 19.2, 19.5, 20.1, 20.7, 21.9, 23.0, 23.2, 24.1, 25.4, 26.2, 26.9, 28.4, 29.5, 30.2, 30.9, 31.7 and 37.0 ±0.2 degrees two theta as depicted in figure-7.
Another embodiment of the present invention provides a process for the preparation of crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent,
b) adding the reaction mixture to a pre-cooled suitable solvent at a suitable temperature,
c) raising the temperature of the reaction mixture to a suitable temperature,
d) stirring the reaction mixture and filtering the precipitated solid,
e) micronizing the obtained solid of step-(d) and drying to get crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl) phenyl] -2,4-pyrimidinediamine compound of formula-1.
Wherein, in step-a) and b) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof; in step-b) the suitable temperature is ranging from - 50°C to 0°C; in step-c) the suitable temperature is ranging from 20°C to 30°C.
Micronized 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-
methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 can be obtained for instance by single or multistage micronization in the dry state using dry mills,

such as cutting mills, pin/cage mills, hammer mills, jet mills, fluidized bed jet mills, ball mills and roller mills. Milling or micronization may be performed before drying, or after the completion of drying of compound of formula-1.
Drying 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1 may also be carried out for shorter or longer periods of time depending on the product specifications. Temperatures and pressures will be chosen based on the volatility of the solvent being used and the foregoing conditions should be considered as only a general guidance. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven, or using a fluidized bed drier, spin flash dryer, flash dryer, and the like. Drying equipment selection is well within the ordinary skill in the art.
The preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in ethyl acetate,
b) adding the reaction mixture to a pre-cooled n-heptane at -50°C,
c) raising the temperature of the reaction mixture to 25-30°C,
d) stirring the reaction mixture and filtering the precipitated solid,
e) optionally, micronizing the obtained solid of step-(d) and drying to get crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine compound of formula-1.
The fifth aspect of the present invention provides a process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Adding a suitable solvent to acid addition salts of chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-

pyrimidinediamine,
b) optionally heating the reaction mixture,
c) adding a suitable base to the reaction mixture and stirring the reaction mixture,
d) adding a suitable solvent to the reaction mixture,
e) distilling off the solvent from the reaction mixture,
f) adding a suitable solvent to the obtained solid and stirring the reaction mixture,
g) filtering the reaction mixture through hyflow bed,
h) adding the filtrate obtained in step-g) to a pre-cooled suitable solvent at a suitable temperature and stirring the reaction mixture at a suitable temperature,
i) filtering the precipitated solid,
j) adding a suitable solvent to the obtained solid at a suitable a suitable temperature,
k) optionally heating the reaction mixture,
l) stirring the reaction mixture, filtering, drying the solid and optionally micronizing to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine. Wherein, in step-a) the acid used in the present invention is selected from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric 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 step-b) and step-k) the suitable temperature is ranging from 35°C to the reflux temperature of the solvent used in the reaction; in step-c) the suitable base is selected from organic or inorganic base, wherein the base is used in the mole ratio ranging from 2.2 to 3.0 per mole of acid addition salts of compound of formula-1; in step-h) the suitable temperature is ranging from -30°C to 0°C; in step-a), d), f), h) and j) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof; in step-k) the drying temperature is ranging from 30°C to 100°C; in step-l) the micronization is same as

defined above.
The preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Adding a mixture of acetone and water to chloro-N4-[2-[(1-methylethyl) sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine dihydrochloride,
b) heating the reaction mixture to 45-50°C,
c) adding aqueous sodium hydroxide to the reaction mixture and stirring the reaction mixture,
d) adding water to the reaction mixture,
e) distilling off the solvent from the reaction mixture,
f) adding dichloromethane to the obtained solid and stirring the reaction mixture,
g) filtering the reaction mixture through hyflow bed,
h) adding the filtrate obtained in step-g) to a pre-cooled n-heptane at -20°C and stirring
the reaction mixture at -20°C, i) filtering the precipitated solid,
j) adding n-heptane to the obtained solid at 0-5°C,
k) stirring the reaction mixture, filtering the solid and drying at 90°C to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.
In another preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Adding a mixture of acetone and water to chloro-N4-[2-[(1-methylethyl) sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine dihydrochloride,
b) adding aqueous sodium hydroxide to the reaction mixture and stirring the reaction

mixture,
c) adding water to the reaction mixture,
d) distilling off the solvent from the reaction mixture,
e) adding dichloromethane to the obtained solid and stirring the reaction mixture,
f) filtering the reaction mixture through hyflow bed,
g) adding the filtrate obtained in step-f) to a pre-cooled n-heptane at -20°C and stirring the reaction mixture at -20°C,
h) filtering the precipitated solid, i) adding n-heptane to the obtained solid, j) heating the reaction mixture to 75-80°C,
k) stirring the reaction mixture, filtering the solid and drying at 75°C to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.
In another preferred embodiment of the present invention provides a process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:
a) Adding water to chloro-N4-[2-[(1-methylethyl) sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine dihydrochloride,
b) adding aqueous sodium hydroxide to the reaction mixture and stirring the reaction mixture,
c) adding dichloromethane and aqueous sodium hydroxide to the reaction mixture,
d) distilling off the solvent from the reaction mixture,
e) adding dichloromethane to the obtained solid and stirring the reaction mixture,
f) filtering the reaction mixture through hyflow bed,
g) adding the filtrate obtained in step-f) to a pre-cooled n-heptane at -20°C and stirring the reaction mixture at -20°C,
h) filtering the precipitated solid,
i) adding n-heptane to the obtained solid,
j) heating the reaction mixture to 75-80°C,

k) stirring the reaction mixture, filtering the solid and drying at 75°C to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.
The crystalline form-N of Ceritinib compound of formula-1 of the present invention can be prepared by using crystalline form-M of Ceritinib disclosed in our co-pending Indian patent application (or) amorphous/crystalline forms 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 Kα 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 Q10 V9.6 Build 290 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-S1 of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt: (Formula-1a)
Dichloromethane (16 ml) was added to 5-chloro-N4-[2-[(1-methylethyl)sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (4 gms) at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture through hyflow bed and washed the bed with dichloromethane. Succinic acid (0.93 gms) was added to the obtained filtrate at 25-30°C and stirred for 3 hours at the same

temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure to get the title compound. Yield: 4 gms; Succinic acid content: 21.26 % The P-XRD pattern of the obtained compound was depicted in figure-1.
Example-2: Preparation of crystalline form-S2 of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt: (Formula-1b)
Dichloromethane (16 ml) was added to 5-chloro-N4-[2-[(1-methylethyl)sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (4 gms) at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture through hyflow bed and washed the bed with dichloromethane. Fumaric acid (0.91 gms) was added to the obtained filtrate at 25-30°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound. Yield: 3.0 gms; Fumaric acid content: 20.15 %. The P-XRD pattern of the obtained compound was depicted in figure-3.
Example-3: Preparation of crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate salt: (Formula-1c)
Dichloromethane (16 ml) was added to 5-chloro-N4-[2-[(1-methylethyl)sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (4 gms) at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture through hyflow bed and washed the bed with dichloromethane. Oxalic acid (0.99 gms) was added to the obtained filtrate at 25-30°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid, washed with dichloromethane and dried to get the title compound. Yield: 3 gms; Oxalic acid content: 17.46 %. The P-XRD pattern of the obtained compound was depicted in figure-5.
Example-4: Preparation of crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine: (Formula-1)
Ethyl acetate (1.5 lts) was added to 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine (50 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 (3.0 lts) 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.
The P-XRD pattern of the obtained compound was depicted in figure-8.
The obtained compound was micronized and dried for 5 hours at 70°C to get the title
compound. Yield: 38.0 gms.
The P-XRD pattern of the obtained compound was depicted in figure-7.
Example-5: Preparation of crystalline form-N of 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidin-2,4-diamine:
Acetone (300 ml) and water (100 ml) were added to 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl) phenyl)-N4-(2-(isopropyl sulfonyl) phenyl) pyrimidin-2,4-diamine dihydrochloride (100 gms) at 25-30°C and stirred for 10 minutes at the same temperature. Heated the reaction mixture to 50-55°C. Aqueous sodium hydroxide solution (650 ml) was slowly added to the reaction mixture at 50-55°C and stirred for 20 minutes at the same temperature. Water (650 ml) was added to the reaction mixture at50-55°C and stirred for 20 minutes at the same temperature. Distilled off the solvent from the reaction mixture under reduced pressure. Dichloromethane (400 ml) was added the reaction mixture at 25-30°C. Both the aqueous and organic layers were separated and the organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure. Dichloromethane (300 ml) was added to the reaction mixture at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture to get clear solution. The reaction mixture was slowly added to a pre-cooled n-heptane (1.9 lts) at -15°C to -20°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid and washed with n-heptane. n-heptane (750 ml) was added to the obtained wet compound at 0-5°C and stirred for 90 minutes at the same temperature. Filtered the precipitated solid, washed with n-heptane and dried to get the title compound. Yield: 66 gms. The P-XRD pattern of the obtained compound was depicted in figure-7.
Example-6: Preparation of crystalline form-N of 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidin-2,4-diamine:

Acetone (300 ml) and water (100 ml) were added to 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl) phenyl)-N4-(2-(isopropyl sulfonyl) phenyl) pyrimidin-2,4-diamine dihydrochloride (100 gms) at 25-30°C and stirred for 10 minutes at the same temperature. Heated the reaction mixture to 50-55°C. Aqueous sodium hydroxide solution (140 ml) was slowly added to the reaction mixture at 50-55°C and stirred for 20 minutes at the same temperature. Water (650 ml) was added to the reaction mixture at50-55°C and stirred for 20 minutes at the same temperature. Distilled off the solvent from the reaction mixture under reduced pressure. Dichloromethane (400 ml) was added the reaction mixture at 25-30°C. Both the aqueous and organic layers were separated and the organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure. Dichloromethane (300 ml) was added to the reaction mixture at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture to get clear solution. The reaction mixture was slowly added to a pre-cooled n-heptane (1.9 lts) at -15°C to -20°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid and washed with n-heptane. n-heptane (750 ml) was added to the obtained wet compound at 25-30°C. Heated the reaction mixture to 75-80°C and stirred for 90 minutes at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 60 minutes at the same temperature. Filtered the precipitated solid, washed with n-heptane and dried to get the title compound. Yield: 66 gms; M.R: 166-171°C. The P-XRD pattern of the obtained compound was depicted in figure-7.
Example-7: Preparation of crystalline form-N of 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidin-2,4-diamine:
Acetone (300 ml) and water (100 ml) were added to 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidin-2,4-diamine dihydrochloride (100 gms) at 25-30°C and stirred for 10 minutes at the same temperature. Aqueous sodium hydroxide solution (140 ml) was slowly added to the reaction mixture at 25-30°C and stirred for 20 minutes at the same temperature. Water (650 ml) was added to the reaction mixture at50-55°C and stirred for 20 minutes at the same temperature. Distilled off the solvent from the reaction mixture under reduced pressure. Dichloromethane (400 ml) was added the reaction mixture at 25-30°C. Both the aqueous and organic layers were separated

and the organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure. Dichloromethane (300 ml) was added to the reaction mixture at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture to get clear solution. The reaction mixture was slowly added to a pre-cooled n-heptane (1.9 lts) at -15°C to -20°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid at -15°C to -20°C and washed with n-heptane. n-heptane (750 ml) was added to the obtained wet compound at 25-30°C. Heated the reaction mixture to 75-80°C and stirred for 90 minutes at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 60 minutes at the same temperature. Filtered the precipitated solid, washed with n-heptane and dried to get the title compound. Yield: 66 gms; M.R: 166-171°C. The P-XRD pattern of the obtained compound was depicted in figure-7.
Example-8: Preparation of crystalline form-N of 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidin-2,4-diamine:
Aqueous sodium hydroxide solution (300 ml) was slowly added lot wise to a mixture of 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropyl sulfonyl) phenyl) pyrimidin-2,4-diamine dihydrochloride (100 gms) and water (600 ml) at 25-30°C. Dichloromethane (400 ml) was added to the reaction mixture at 25-30°C and stirred for 10 minutes at the same temperature. Both the aqueous and organic layers were separated and the organic layer was washed with aqueous sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure. Dichloromethane (300 ml) was added to the reaction mixture at 25-30°C and stirred for 20 minutes at the same temperature. Filtered the reaction mixture to get clear solution. The reaction mixture was slowly added to n-heptane (1.9 lts) at -15°C to -20°C and stirred for 3 hours at the same temperature. Filtered the precipitated solid and washed with n-heptane. n-heptane (750 ml) was added to the obtained wet compound at 25-30°C. Heated the reaction mixture to 75-80°C and stirred for 90 minutes at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 60 minutes at the same temperature. Filtered the precipitated solid, washed with n-heptane and dried to get the title compound. Yield: 66 gms; M.R: 166-171°C. The P-XRD pattern of the obtained compound was depicted in figure-7.

We Claim:
1. Crystalline acid addition salts of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, which include:

i). Crystalline form-S1 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine succinate salt compound of formula-1a, characterized by,
a) its powder x-ray diffraction pattern having peaks at 2.6, 5.3, 8.0, 9.6, 9.9, 10.6, 11.6, 12.4, 13.3, 14.3, 15.9, 17.6, 18.0, 18.5, 18.7, 19.2, 19.4, 19.6, 19.9, 20.8, 21.4, 22.0, 22.3, 22.7, 23.2, 23.5, 24.0, 24.2, 24.7, 25.1, 26.0, 26.9, 30.0, 32.6, 36.3, 38.9 and 41.1 ±0.2 degrees two theta as depicted in figure-1,
b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-2.
ii). Crystalline form-S2 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine fumarate salt compound of formula-1b, characterized by,
a) its powder x-ray diffraction pattern having peaks at 2.6, 5.2, 7.9, 9.7, 10.0, 11.7, 12.5, 13.2, 16.0, 17.5, 18.0, 18.6, 19.5, 19.8, 21.2, 21.8, 22.3, 23.9, 25.4, 26.3 and 26.7 ±0.2 degrees two theta as depicted in figure-3,
b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-4.
iii). Crystalline form-S3 of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-
methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine oxalate
salt compound of formula-1c, characterized by,
a) its powder x-ray diffraction pattern having peaks at 3.6, 4.6, 5.3, 6.4, 7.0, 10.7,

11.4, 11.7, 12.5, 13.2, 13.7, 14.3, 16.5, 17.7, 18.5, 19.6, 20.6, 22.7, 22.8, 23.4, 23.6, 24.4, 24.7, 25.2, 26.3, 28.5 and 29.0 ±0.2 degrees two theta as depicted in figure-5, b) its differential scanning calorimetry (DSC) thermogram as depicted in figure-6.
2. Crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, characterized by: its powder x-ray diffraction pattern having peaks at 6.4, 8.4, 8.5, 9.0, 10.9, 12.0, 12.7, 12.9, 14.6, 15.6, 17.3, 17.8, 18.2, 18.9, 19.2, 19.5, 20.1, 20.7, 21.9, 23.0, 23.2, 24.1, 25.4, 26.2, 26.9, 28.4, 29.5, 30.2, 30.9, 31.7 and 37.0 ±0.2 degrees two theta as depicted in figure-7.
3. A process for the preparation of crystalline acid addition salts of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:

a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents,
b) optionally filtering the reaction mixture through hyflow bed,
c) adding a suitable acid selected from fumaric acid, oxalic acid, succinic acid to the reaction mixture of step-a) or step-b),
d) stirring the reaction mixture,
e) distilling off the solvent from the reaction mixture to provide crystalline acid addition salts of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1.
4. A process for the preparation of crystalline form-N of 5-chloro-N4-[2-[(1-methyl
ethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-
pyrimidinediamine compound of formula-1, comprising of:
a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-

methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in a suitable solvent,
b) adding the reaction mixture to a pre-cooled suitable solvent at a suitable temperature,
c) raising the temperature of the reaction mixture to a suitable temperature,
d) stirring the reaction mixture and filtering the precipitated solid,
e) optionally, micronizing the obtained solid of step-(d) and drying to get crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl) phenyl]-2,4-pyrimidinediamine compound of formula-1.

5. The process as claimed in claim-4, wherein, in step-a) and b) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof; in step-b) the suitable temperature is ranging from – 50°C to 0°C; in step-c) the suitable temperature is ranging from 20°C to 30°C; in step-e) micronizing the compound of formula-1 using dry mills, such as cutting mills, pin/cage mills, hammer mills, jet mills, fluidized bed jet mills, ball mills and roller mills; milling or micronization may be performed before drying, or after the completion of drying of compound of formula-1; drying the compound of formula-1 can be carried out in a tray dryer, vacuum oven, air oven, or using a fluidized bed drier, spin flash dryer, flash dryer.
6. The process as claimed in claim-4, wherein, a process for the preparation of crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1, comprising of:

a) Dissolving 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine in ethyl acetate,
b) adding the reaction mixture to a pre-cooled n-heptane at -50°C,
c) raising the temperature of the reaction mixture to 25-30°C,
d) stirring the reaction mixture and filtering the precipitated solid,
e) micronizing the obtained solid of step-(d) and drying to get crystalline form-N of 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-

(4-piperidinyl) phenyl]-2,4-pyrimidinediamine compound of formula-1.
7. A process for the preparation of crystalline form-N of chloro-N4-[2-[(1-methylethyl)
sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-
pyrimidinediamine compound of formula-1, comprising of:
a) Adding a suitable solvent to acid addition salts of chloro-N4-[2-[(1-methylethyl) sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine,
b) optionally heating the reaction mixture,
c) adding a suitable base to the reaction mixture and stirring the reaction mixture,
d) adding a suitable solvent to the reaction mixture,
e) distilling off the solvent from the reaction mixture,
f) adding a suitable solvent to the obtained solid and stirring the reaction mixture,
g) filtering the reaction mixture through hyflow bed,
h) adding the filtrate obtained in step-g) to a pre-cooled suitable solvent at a suitable temperature and stirring the reaction mixture at a suitable temperature,
i) filtering the precipitated solid,
j) adding a suitable solvent to the obtained solid at a suitable a suitable temperature,
k) optionally heating the reaction mixture,
l) stirring the reaction mixture, filtering, drying the solid and optionally micronizing to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.
8. The process as claimed in claim-7, wherein, in step-a) the acid used in the present
invention is selected from inorganic acids such as hydrochloric acid, hydrobromic acid,
sulfuric 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 step-b) and step-k) the

suitable temperature is ranging from 35°C to the reflux temperature of the solvent used in the reaction; in step-c) the suitable base is selected from organic or inorganic base, wherein the base is used in the mole ratio ranging from 2.2 to 3.0 per mole of acid addition salts of compound of formula-1; in step-h) the suitable temperature is ranging from -30°C to 0°C; in step-a), d), f), h) and j) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, hydrocarbon solvents, ketone solvents, polar aprotic solvents, nitrile solvents, ether solvents and polar solvents like water or mixture thereof; in step-k) the drying temperature is ranging from 30°C to 100°C;
9. The process as claimed in claim-7, wherein a process for the preparation of crystalline
form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl
ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1,
comprising of:
a) Adding a mixture of acetone and water to chloro-N4-[2-[(1-methylethyl) sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine dihydrochloride,
b) heating the reaction mixture to 45-50°C,
c) adding aqueous sodium hydroxide to the reaction mixture and stirring the reaction mixture,
d) adding water to the reaction mixture,
e) distilling off the solvent from the reaction mixture,
f) adding dichloromethane to the obtained solid and stirring the reaction mixture,
g) filtering the reaction mixture through hyflow bed,
h) adding the filtrate obtained in step-g) to a pre-cooled n-heptane at -20°C and stirring the reaction mixture at -20°C,
i) filtering the precipitated solid,
j) adding n-heptane to the obtained solid at 0-5°C,
k) stirring the reaction mixture, filtering the solid and drying at 90°C to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.

10. The process as claimed in claim-7, wherein a process for the preparation of crystalline
form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl
ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine compound of formula-1,
comprising of:
a) Adding a mixture of acetone and water to chloro-N4-[2-[(1-methylethyl) sulfonyl] phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidine diamine dihydrochloride,
b) adding aqueous sodium hydroxide to the reaction mixture and stirring the reaction mixture,
c) adding water to the reaction mixture,
d) distilling off the solvent from the reaction mixture,
e) adding dichloromethane to the obtained solid and stirring the reaction mixture,
f) filtering the reaction mixture through hyflow bed,
g) adding the filtrate obtained in step-f) to a pre-cooled n-heptane at -20°C and stirring the reaction mixture at -20°C,
h) filtering the precipitated solid,
i) adding n-heptane to the obtained solid,
j) heating the reaction mixture to 75-80°C,
k) stirring the reaction mixture, filtering the solid and drying at 75°C to provide crystalline form-N of chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methyl ethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.