DESC:
FIELD OF THE INVENTION
The present invention relates to a field of pharmaceuticals, in particular to an improved process for the preparation of a crystalline form of deucravacitinib.

BACKGROUND OF THE INVENTION
Deucravacitinib (BMS-986165) is a selective tyrosine kinase 2 (TYK2) inhibitor approved by USFDA and marketed in the United States under the brand name SOTYKTU®. Deucravacitinib is structurally represented as a compound of Formula I as shown below:
.
International (PCT) Publication No. WO 2014/074661 A1 (WO ‘661) discloses deucravacitinib and process for preparation thereof.

International (PCT) Publication No. WO 2018/183649 A1 (WO ‘649) discloses a process for the preparation deucravacitinib.

International (PCT) Publication No. WO 2018/183656 A1 (WO ‘656) discloses process for the preparation deucravacitinib and a crystalline form thereof.

The journal article: Org. Process Res. Dev. 2022, 26, 4, 1202–1222 also discloses process for the preparation of deucravacitinib.

The solid form of a compound plays a pivotal role in the formulation of pharmaceutical compositions. For example, different forms of a compound can have different physical properties (e.g., stability, dissolution rate, density, etc.) relating to their suitability for use in pharmaceutical compositions. Different polymorphic forms can also show different behavior with respect to their dissolution properties, flow properties, particle size distribution and chemical stability. Thus, having a suitable polymorphic form with desired properties is an important prerequisite during drug development.

The present invention provides an improved process for the preparation of a crystalline form of deucravacitinib as herein described. The process is robust and can produce the specified crystalline form of deucravacitinib with high purity and substantially free of the impurities as herein described.

SUMMARY OF THE INVENTION
In one general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction (XRPD) pattern peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
crystallizing the deucravacitinib from a mixture of dimethyl sulfoxide (DMSO) and ethanol.

In another general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction pattern peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) dissolving deucravacitinib in dimethylsulfoxide to obtain a solution; and
(b) adding ethanol to the obtained solution at step (a) to obtain the crystalline form of deucravacitinib.

In another general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction pattern peaks expressed in degree 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) heating a mixture of deucravacitinib and dimethyl sulfoxide to a temperature of about 50° C to about 80° C to obtain a solution;
(b) adding ethanol to the obtained solution of the step (a) to obtain a reaction mixture; and
(c) cooling to obtain the crystalline form of deucravacitinib.

The process of the present invention is economically viable and industrially scalable for preparing the specified crystalline form of deucravacitinib with high purity on consistent basis.

BRIEF DESCRIPTION OF DRAWING
Figure 1. X-ray powder diffraction pattern of crystalline deucravacitinib as prepared in example 1.
Figure 2. X-ray powder diffraction pattern of crystalline deucravacitinib as prepared in example 2.

DETAILED DESCRIPTION OF THE INVENTION
The invention can further be understood in light of the description of the embodiments provided herein after. It is to be understood that the description, in no way, is intended to limit the scope of the invention to the expressly specified embodiments only. The equivalents and variants thereof or trivial modifications thereof which are apparently obvious to those skilled in the art, are also intended to be included within the scope of the present invention.

Detailed description of routine and conventional unit operations, which are easily understood by the skilled artisan, are not included herein. Such routine unit operations are to be construed as ordinarily understood and as routinely practiced by the person skilled in the field of the invention, unless otherwise specifically described.

Optionally, the solution, prior to any solid formation, can be filtered to remove any undissolved solids, solid impurities prior to removal of the solvent. Any filtration system and filtration techniques known in the art can be used.

The following definitions are used in connection with present application, unless it is indicated otherwise.

All ranges recited herein include the endpoints, including those that recite a range “between” two values. Terms such as “about”, “generally”, “substantially,” and the like are to be construed as modifying a term or value such that it is not an absolute. This includes, at very least, the degree of expected experimental error, technique error and instrument error for a given technique used to measure a value.

The term “substantially free” herein means impurity content within the permissible ICH limits suitable for pharmaceutical preparations. In particular, the impurity content for each of the impurities of compound of Formulae A, B, C, D, E, F, G and H by weight percentage of high-performance liquid chromatography (HPLC) is about 0.15% or less, particularly about 0.10% or less, more particularly about 0.05% or less, or more particularly not in detectable amount by HPLC method of analysis.

As used herein, the phrase “not in detectable amount” abbreviated as ND, refers to the level of impurity in the product, which is below the level of detection limit of the HPLC method.
The term “optionally” is taken to mean that the event or circumstance described in the specification may or may not occur, and that the description includes instances where the event occurs and instances where it does not.

The product(s) obtained may further be subjected to physical processing which includes, but not limited to, pressing, crushing, triturating, milling or grinding to adjust the particle size of the product(s) to desired levels.

In general, deucravacitinib to be used as the starting material may be prepared by the known methods reported in the prior art, for example, by using the process as disclosed in the International (PCT) Publication No(s). WO 2014/074661 A1 or WO 2018/183649 A1.

Particularly, deucravacitinib to be used as the starting material in the process of the present invention can be prepared by a process comprising: reacting the compound of Formula III,

with a compound of Formula II or a salt thereof,

to obtain deucravacitinib.

In general, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction (XRPD) peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°.

In one embodiment, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by x-ray powder diffraction (XRPD) peaks expressed in 2? at 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°.

In another embodiment, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by x-ray powder diffraction pattern substantially as same as depicted in Figure 1, or Figure 2.

Thus, in one general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) dissolving deucravacitinib in dimethylsulfoxide to obtain a solution; and
(b) adding ethanol to the obtained solution at step (a) to obtain the crystalline form of deucravacitinib.

In general, deucravacitinib may be dissolved in dimethylsulfoxide by heating the mixture of deucravacitinib and dimethylsulfoxide to a temperature of about 40 °C to about 90 °C, particularly to a temperature of about 50 °C to about 80 °C, or more particularly, to a temperature of about 65 °C to about 75 °C. The reaction mixture can be then be stirred at this temperature for a time sufficient to obtain the solution of deucravacitinib in dimethylsulfoxide. Optionally it can be filtered to obtain the solution of deucravacitinib in dimethylsulfoxide.

In general, dimethylsulfoxide at step a, is used in an amount which is 4 to 6 times the quantity of deucravacitinib in volumes.

In general, ethanol is added to the solution of deucravacitinib at a temperature of about 40 °C to about 90 °C, particularly at a temperature of about 50 °C to about 80 °C, or more particularly, at a temperature of about 65 °C to about 75 °C.

In general, ethanol at step b, is used in an amount which is 7 to 10 times the quantity of deucravacitinib in volumes.

In general, after the addition of ethanol, the resultant reaction mixture is cooled, wherein the cooling comprises cooling the reaction mixture obtained at step (b) to a temperature of about 25 °C to 35 °C with stirring, and optionally, further cooling to a temperature of about -10 °C to about 5 °C with stirring.

In general, the obtained crystalline form of deucravacitinib may be isolated by the methods known to skilled artisan such as filtration, centrifugation, etc.

In another general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) heating a mixture of deucravacitinib and dimethyl sulfoxide to a temperature of about 50° C to about 80° C to obtain a solution;
(b) adding ethanol to the obtained solution at step (a) to obtain a reaction mixture; and
(c) cooling to obtain the crystalline form of deucravacitinib.

In general, step (a) of the above process is carried out by heating the mixture of deucravacitinib and dimethylsulfoxide to a temperature of about 50 °C to about 80 °C, or more particularly, to a temperature of about 65 °C to about 75 °C. The reaction mixture then can be stirred at this temperature for a time sufficient to obtain the solution of deucravacitinib in dimethylsulfoxide. Optionally, after stirring the reaction mixture, it can be filtered to obtain the solution of deucravacitinib in dimethylsulfoxide.

In an embodiment, the process as described above, further comprises optional seeding with the crystalline form of the deucravacitinib as herein described, during the addition of ethanol in step (b). The crystalline form of the deucravacitinib which is used for seeding is characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°.

In general, dimethylsulfoxide at step (a), is used in an amount which is 4 to 6 times the quantity of deucravacitinib in volumes.

In general, ethanol is added to the solution of deucravacitinib at a temperature of about 50 °C to about 80 °C, particularly, at a temperature of about 65 °C to about 75 °C.

In general, ethanol at step b, is used in an amount which is 7 to 10 times the quantity of deucravacitinib in volumes.

In general, the cooling at step (c) comprises cooling the reaction mixture obtained at step (b) to a temperature of about 25 °C to 35 °C with stirring, and optionally, further cooling to a temperature of about -10 °C to about 5 °C with stirring.

In another general aspect, the present invention provides a process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) heating a mixture of deucravacitinib and dimethyl sulfoxide to a temperature of about 50 °C to about 80 °C to obtain a solution;
(b) adding ethanol to the obtained solution;
(c) seeding the obtained solution at step (b) with the crystalline form of the deucravacitinib to obtain a reaction mixture;
(d) adding ethanol to the reaction mixture; and
(e) cooling to obtain the crystalline form of deucravacitinib.

In general, step (a) of the above process is carried out by heating the mixture of deucravacitinib and dimethylsulfoxide to a temperature of about 50 °C to about 80 °C, more particularly, to a temperature of about 65 °C to about 75 °C. The reaction mixture then can be stirred at this temperature for a time sufficient to obtain the solution of deucravacitinib in dimethylsulfoxide. Optionally, after stirring the reaction mixture, it can be filtered to obtain the solution of deucravacitinib in dimethylsulfoxide.

In general, dimethylsulfoxide at step (a), is used in an amount which is 4 to 6 times the quantity of deucravacitinib in volumes.

In general, ethanol is added to the solution of deucravacitinib at a temperature of about 50 °C to about 80 °C, particularly, at a temperature of about 65 °C to about 75 °C.

In general, ethanol is used in an amount which is 7 to 10 times the quantity of deucravacitinib in volumes.

In another embodiment, the ethanol at step (b) of the above process is added in an amount which is 30% to 40% of the total amount of the ethanol at step (b) and step (d).
In general, the seed of the crystalline form can be added in a quantity ranging from 0.5% to 1.5 % w/w, particularly 0.5% to 1% w/w with respect to the starting material. The crystalline form of the deucravacitinib which is used for seeding is characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°.

In general, the cooling at step (e) comprises cooling the reaction mixture obtained at step (d) to a temperature of about 25 °C to 35 °C with stirring, and optionally, further cooling to a temperature of about -10 °C to about 5 °C with stirring.

In another aspect, the crystalline form of deucravacitinib prepared by the process of present invention is having a purity of about 99% or more, by weight percentage of HPLC.

In another embodiment, the crystalline form of deucravacitinib prepared by the process of present invention is having a purity of about 99.5% or more, by weight percentage of HPLC.

In another embodiment, the crystalline form of deucravacitinib prepared by the process of present invention is having a purity of about 99% or more, by weight percentage of HPLC and is substantially free of impurities of compounds of Formulae A, B, C, D, E, F, G, and H,
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In another embodiment, the crystalline form of deucravacitinib prepared by the process of present invention is having a purity of about 99.5% or more, by weight percentage of HPLC and is substantially free of impurities of compounds of Formulae A, B, C, D, E, F, G, and H.

The present invention is further illustrated by the following examples which is provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modification and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The examples are set forth to aid in understanding the invention but are not intended to, and should not be construed to limit its scope in any way. The examples do not include detailed descriptions of conventional methods. Such methods are well known to those of ordinary skill in the art and are described in various publications.
EXAMPLES:
Characterization by X-Ray Powder Diffraction
The X-ray powder diffraction spectrum was measured under the following experimental conditions:
Instrument: X-Ray Diffractometer, PW3050/60, Make: PANalytical.
X-Ray : Cu K alpha radiation
Tension : 45KV
Current : 40mA
Divergence slit : Automatic
Incident beam side
Off set : 0.000
Anti-scatter slit: ½°
Receiving slit : None
Detector : PIXcel1D-Medipix3
Mode : Scanning line detector (1D)
Method parameter
Start position : 2°2?
End position : 40°2?
Step size : 0.02° rad
Time per step : 67.575s
Scan mode : Continuous

HPLC method of analysis:
Method A:
Chromatographic conditions:
Equipment : HPLC equipped with UV/PDA detector
Column : C8 (250 x 4.6) mm, 5µm
Flow rate : 1.0 mL/minute
Column oven temp. : 40°C
Wavelength : 210 nm
Injection volume : 20 µL
Buffer solution-A: Mixture of 10 mM monobasic potassium phosphate and 0.1 % v/v of Triethyl amine solution adjusted pH 2.5 + 0.05 with orthophosphoric acid
Buffer solution-B: Mixture of 10 mM monobasic potassium phosphate and 0.1 % v/v of Triethyl amine solution adjusted pH 6 + 0.05 with orthophosphoric acid
Mobile phase-A: Mixture of Buffer-A and Acetonitrile in the ratio of 95:05 % v/v.
Mobile phase-B: Mixture of Acetonitrile and Buffer-B in the ratio of 70:30 % v/v
Diluent: Mixture of Acetonitrile, water and Trifluoroactic acid in the ratio of 50:50:0.5 %v/v/v.
Sample conc: 500 µg/mL of Deucravacitinib
Gradient Program:
Time (min) % Mobile Phase-B
0 0
10 0
50 65
60 65
61 70
70 0

Impurity/compound Relative retention time (RRT)
Impurity-D 0.88
Impurity-F 0.90
Impurity-C 0.98
Deucravacitinib 1.00
Impurity-A 1.14
Impurity-E 1.19
Impurity-B 1.28

Method B:
Chromatographic conditions:
Equipment : HPLC equipped with UV/PDA detector
Column : Two columns in series C8 (250 x 4.6) mm, 5µm and C8 (150 x 4.6) mm, 3.5µm
Flow rate : 1.0 mL/minute
Column oven temp. : 35°C
Wavelength : 230 nm
Injection volume : 15 µL

Dilute Potassium Hydroxide solution: 1.0 g potassium hydroxide dissolved in 100 mL of water and mixed.
Buffer: About 1.36 g of potassium dihydrogen phosphate was transferred in 1000 mL of water and sonicated to dissolve, pH of the solution was adjusted to 5.0 ± 0.05 with dilute Potassium Hydroxide solution, then it was filtered through 0.45 µm PVDF filter.
Mobile phase-A: Mixture of Water, Acetonitrile and Orthophosphoric acid in the ratio of 95:5:0.1 % v/v/v.
Mobile phase-B: Mixture of Acetonitrile and Buffer in the ratio of 50:50 % v/v
Diluent: Mixture of Water, Acetonitrile and Trifluoro acetic acid in the ratio of 50:50:0.5 %v/v/v.
Sample conc: 500 µg/mL of Deucravacitinib
Gradient Program:
Time (min) % Mobile Phase-A % Mobile Phase-B
0 85 15
30 32 68
50 20 80
60 20 80
62 85 15
80 85 15

Impurity/compound Relative retention time (RRT)
Impurity-D 0.83
Impurity-F 0.81
Impurity-C 1.08
Deucravacitinib 1.00
Impurity-A 1.28
Impurity-E 1.45
Impurity-B 1.75
Impurity-G 0.74
Impurity-H 0.49

Example 1: Preparation of crystalline form of deucravacitinib
N-methyl imidazole (122.84 g, 1.496 mol) was charged into a solution of acetonitrile (2.2 L), N-methyl pyrrolidone (2.75 L). Deuterated methyl amine hydrochloride (211.09 g, 2.992 mol) and zinc(II) 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)pyridazine-3-carboxylate (1.1 kg, 2.49 mol) were added into reaction mixture at temperature 20 °C to 30 °C. The resultant slurry was heated to 60 °C to 70 °C. Hydroxybenzotriazole monohydrate (190.95 g, 1.246 mol) was charged followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl (669.28 g, 3.49 mol) and flushed with acetonitrile (1.1 L). The resultant reaction mass was stirred for 1 hour. After completion of reaction, water (1.1 L) and acetonitrile (6.6 L) were charged into the reaction mixture. The reaction mixture was cooled at -10 °C to 0 °C and stirred for 4 hours. The solid was filtered and washed with 1:2 acetonitrile: water mixture (3.3 L), followed by washing with acetonitrile (3.3 L). The wet cake was unloaded. The wet cake and DMSO (4.4 L) were charged in 10 L reactor, the reaction mass was heated at 65 °C to 75 °C and stirred it for 30 min. 2.53 L Ethanol was charged into the reaction mass and seeded with deucravacitinib (8.8 g) at 65 °C to 75 °C. The reaction mass was stirred for 30 min at 65 °C to 75 °C. Then ethanol (5.17L) was further charged at 55 °C to 75 °C. The reaction mass was cooled up to -10 °C to 0 °C and stirred for 4 hours. The solid was filtered and washed with ethanol (5.06 L). The product was dried at 60 °C to 70 °C to obtain the crystalline form of deucravacitinib (0. 726 kg, 68.7%).
X-ray powder diffraction pattern is as set forth in Figure 1.
HPLC Purity: 99.54% (Method A).
Content of Compound of Formula A: 0.09 % by weight,
Content of Compound of Formula B: 0.01 % by weight,
Content of Compound of Formula C: Not detected,
Content of Compound of Formula D: Not detected,
Content of Compound of Formula E: 0.08 % by weight,
Content of Compound of Formula F: 0.01 % by weight.

Example 2: Preparation of crystalline form of deucravacitinib
Deucravacitinib (2.5 g) and DMSO (12.5ml) were charged in 3N-RBF, the reaction mass was heated at 65 °C to 75 °C and stirred it for 30 min. Ethanol (7.5 mL) was charged into the reaction mass at 65 °C to 75 °C and the reaction mass was stirred for 30 min at 65 °C to 75 °C. Ethanol (15 ml) was further charged at 55 °C to 75 °C. The reaction mass was cooled up to -10 °C to 0 °C and stirred for 4 hours. The solid was filtered and washed with ethanol (2 X 5 mL). The product was dried at 60 °C to 70 °C to obtain the crystalline form of deucravacitinib (2.20 g, 88 %).
X-ray powder diffraction pattern is as set forth in Figure 2.

Example 3: Preparation of crystalline form of Deucravacitinib
N-methyl imidazole (128.43 g, 1.564 mol) was charged into a solution of acetonitrile (1.15 L), N-methyl pyrrolidone (2.875 L). Deuterated methyl amine hydrochloride (220.69 g, 3.129 mol) and zinc(II) 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)pyridazine-3-carboxylate (1.15 kg, 1.304 mol) were added into reaction mixture at temperature 25 °C to 35 °C. The resultant slurry was heated to 60 °C to 70 °C. Hydroxybenzotriazole monohydrate (199.63 g, 1.304 mol) was charged followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl (699.71 g, 3.650 mol) and flushed with acetonitrile (1.15 L). The resultant reaction mass was stirred for 1 hour. After completion of reaction, water (1.15 L) and acetonitrile (6.9 L) were charged into the reaction mixture. The reaction mixture was cooled at -5 °C to 5 °C and stirred for 4 hours. The solid was filtered and washed with 1:2 acetonitrile: water mixture (3.45 L), followed by washing with acetonitrile (3.45 L). The wet cake was unloaded. The wet cake and DMSO (4.6 L) were charged in 10 L reactor, the reaction mass was heated at 65 °C to 75 °C and stirred it for 30 min. 2.645 L Ethanol was charged into the reaction mass and seeded with deucravacitinib (9.2 g) at 65 °C to 75 °C. The reaction mass was stirred for 30 min at 65 °C to 75 °C. Then ethanol (5.405 L) was further charged at 55 °C to 75 °C. The reaction mass was cooled up to -5 °C to 5 °C and stirred for 4 hours. The solid was filtered and washed with ethanol (6.9 L). The product was dried at 60 °C to 70 °C to obtain the crystalline form of Deucravacitinib (0. 810 kg, 73.36 %).
X-ray powder diffraction pattern is substantially same as set forth in Figure 2.
HPLC Purity: 99.54% (Method B)
Content of Compound of Formula A: 0.06 % by weight,
Content of Compound of Formula B: 0.02 % by weight,
Content of Compound of Formula C: Not detected,
Content of Compound of Formula D: Not detected,
Content of Compound of Formula E: 0.02 % by weight,
Content of Compound of Formula F: 0.01 % by weight,
Content of Compound of Formula G: 0.01 % by weight,
Content of Compound of Formula H: 0.02% by weight.

While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

,CLAIMS:We Claim:

1. A process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
crystallizing the deucravacitinib from a mixture of dimethyl sulfoxide and ethanol.

2. The process as claimed in claim 1, wherein the process comprising:
(a) dissolving deucravacitinib in dimethylsulfoxide to obtain a solution; and
(b) adding ethanol to the obtained solution at step (a) to obtain the crystalline form of deucravacitinib.

3. A process for the preparation of a crystalline form of deucravacitinib characterized by at least six x-ray powder diffraction peaks expressed in 2? selected from 10.1°, 12.3°, 13.0°, 14.4°, 15.7°, 18.8°, 19.3°, 20.3°, 23.6°, and 25.2° ± 0.2°, the process comprising:
(a) heating a mixture of deucravacitinib and dimethyl sulfoxide to a temperature of about 50 °C to about 80 °C to obtain a solution;
(b) adding ethanol to the obtained solution at step (a) to obtain a reaction mixture; and
(c) cooling to obtain the crystalline form of deucravacitinib.

4. The process as claimed in claim 3, wherein the process further comprises optional seeding with the crystalline form of the deucravacitinib during step (b).

5. The process as claimed in claim 3, wherein the cooling comprises cooling the reaction mixture obtained at step (b) to a temperature of about 25 °C to 35 °C with stirring, and optionally, further cooling to a temperature of about -10 °C to about 5 °C with stirring.

6. The process as claimed in claim 3, wherein the process further comprising:
(a) heating a mixture of deucravacitinib and dimethyl sulfoxide to a temperature of about 50 °C to about 80 °C to obtain a solution;
(b) adding ethanol to the obtained solution;
(c) seeding the obtained solution at step (b) with the crystalline form of deucravacitinib to obtain a reaction mixture;
(d) adding ethanol to the reaction mixture; and
(e) cooling to obtain the crystalline form of deucravacitinib.

7. The process as claimed in claim 6, wherein dimethylsulfoxide is used in an amount which is 4 to 6 times the quantity of deucravacitinib in volumes.

8. The process as claimed in claim 6, wherein ethanol is used in an amount which is 7 to 10 times the quantity of deucravacitinib in volumes.

9. The process as claimed in claim 6, wherein the ethanol at step (b) is added in an amount which is 30% to 40% of the total amount of the ethanol at step (b) and step (d).

10. The process as claimed in any preceding claims, wherein the obtained crystalline form of the deucravacitinib is substantially free of compounds of Formulae A, B, C, D, E, F, G, and H,
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Dated this 25th day of June 2024

(HARIHARAN SUBRAMANIAM)
IN/PA-93
Of SUBRAMANIAM & ASSOCIATES
ATTORNEYS FOR THE APPLICANTS