DESC:FIELD OF THE INVENTION
The present invention relates to a process for the preparation of Ribociclib of Formula (I) and salts thereof. The present invention also relates to the process of the preparation of Ribociclib Succinate of formula (II) with purity greater than 99%.

BACKGROUND OF THE INVENTION
Ribociclib is a pyrrolopyrimidine compound represented by Formula (I), known as inhibitors of cyclin dependent kinases (CDK). Chemically it is known as 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. It is highly specific cell cycle-dependent kinase that can significantly inhibit the growth of a variety of neuroblastomas for advanced treatment of breast cancer. Ribociclib, as the succinic acid salt of the Formula (II), has been approved for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancers.

US patent no. 8,415,355 discloses in Example 74 a manufacturing process for Ribociclib from 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide of Formula (III) and 5-piperazin-1-yl-pyridin-2-ylamine of Formula (IV).

The manufacturing processes, known in the prior art produce the product of low yield and inferior quality. The prior art methods also use toxic reagents. The prior art processes are inconvenient to scale up.

SUMMARY OF THE INVENTION
The present invention provides novel process for the preparation of Ribociclib succinate having purity greater than 99% that comprises following steps:
1) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Va) in the presence of haloalkane and base to give methyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V);

2) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V) with tert-butyl 4-(6-aminopyridie-3-yl)piperazine-1-carboxylate (VI) in the presence of catalyst and base to give methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII);

3) hydrolysis of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) to 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) in the presence of base;

4) condensation of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) with dimethyl amine in the presence of a base and a condensing agent to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX);

5) conversion of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) to ribociclib by deprotection using a deprotecting agent;

6) conversion of ribociclib to ribociclib succinate and

7) purification of ribociclib succinate by crystallization from a suitable solvent or mixture of solvents thereof.

The present invention thus provides compounds of Formula (VII) and Formula (VIII) which are useful for the preparation of Ribociclib of Formula (I).

DESCRIPTION OF THE DRAWINGS:
Figure 1: X-ray powder diffractogram (XRPD) for crystalline form of ribociclib succinate obtained by the process of the present invention.
Figure 2: IR spectrum for crystalline form of ribociclib succinate obtained by the process of the present invention.
Figure 3: DSC for crystalline form of ribociclib succinate obtained by the process of the present invention.

DETAILED DESCRIPTION OF THE INVENTION
The present invention is related to a novel process for the preparation of Ribociclib succinate (II) as described in scheme (I), having purity > 99.8% that comprises the following steps:

1) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Va) in the presence of haloalkane and base to give methyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V);

2) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V) with tert-butyl 4-(6-aminopyridie-3-yl)piperazine-1-carboxylate (VI) in the presence of catalyst and base to give methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII);

3) conversion of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) to 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) in the presence of base;

4) condensation of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) with dimethyl amine in the presence of a base and a condensing agent to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX);

5) conversion of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) to ribociclib by deprotection using a deprotecting agent;

6) conversion of ribociclib to ribociclib succinate and

7) purification of ribociclib succinate by crystallization from a suitable solvent or mixture of solvents thereof.
The synthetic scheme of the process of present invention is shown in scheme I
(Scheme I)
In one embodiment of the present invention, the compound 2-chloro-7-cyclopentyl-7H-pyrrolo [2,3-d]pyrimidine-6-carboxylic acid (Va) is treated with halo alkyl in the presence of inorganic base and suitable solvent to give 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V) in step-1. The base is selected from a group of inorganic bases such as hydroxides like sodium hydroxide, potassium hydroxide, carbonates like sodium carbonate, potassium carbonate, bicarbonates like sodium bicarbonate, potassium bicarbonate etc. The preferred base being potassium carbonate. The halo alkane is selected from a group of methyl iodide, methyl bromide.

The process of step 1 of the present invention can be carried out in organic solvent that include methanol, ethanol, tetrahydrofuran, 1,4-dioxane, dimethylforamide, acetonitrile, propionitrile, acetone, ethylmethyl ketone, water and mixtures thereof. The most preferred solvent is dimethyl formamide.

In another embodiment of the present invention, the compound 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V) is reacted with tert-butyl 4-(6-aminopyridie-3-yl)piperazine-1-carboxylate (VI) in the presence of catalyst and base to give methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) in step-2.

The base used in step-2 is selected from the group comprising of potassium carbonate, sodium carbonate, potassium phosphate, cesium carbonate, potassium t-butoxide, sodium t- butoxide, lithium hexamethyl disilazide or hexamethyldisiloxane, sodium amide. The preferred base is cesium carbonate. The catalyst is selected from the group comprising of palladium salts or palladium complexes such as palladium acetate, palladium chloride, tetrakistriphenylphosphine palladium, ditriphenylphosphine palladium dichloride, Ruthenium complexes, BINAP. The reaction solvent is selected from the group comprising of toluene, dimethylforfamide, dimethyl acetamide, dichloromethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, acetone. The reaction temperature is 20-120°C.

In yet another embodiment, 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) is converted to 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) in the presence of base in step 3. The base used for hydrolysis in step-3 is selected from the group comprising of sodium hydroxide, potassium hydroxide or lithium hydroxide and the reaction solvent is selected from the group comprising of dimethyl formamide, dimethyl acetamide, tetrahydrofuran, 1-4 dioxane, methanol, ethanol, isopropanol, acetonitrile, acetone or water or a mixture of solvents thereof. The acid used for acidification is selected from a group comprising of hydrochloric acid, sulphuric acid, acetic acid, tartaric acid or citric acid. The reaction is carried at a temperature of 0 to 80°C.

In further embodiment of the present invention, 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) is condensed with dimethyl amine in the presence of a base and a condensing agent to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) in step-4. The base used in condensation reaction is selected from a group comprising of organic bases such as diisopropyl ethyl amine, triethyl amine, DBU, triethylenediamine, or inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, potassium hydrogen carbonate. The condensing agent is selected from DCC, DIC, EDCI, HATU, HBTU or BOP. The reaction solvent in step-4 is selected from group comprising of dimethylformamide, dimethyl acetamide, dichloromethane, tetrahydrofuran, 1-4-dioxane, acetonitrile or acetone. The reaction temperature is -10 to 80°C.

The compound 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) can be directly converted to tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) by treating compound of formula (VII) with dimethyl amine and methanol.

Another embodiment of the present invention is conversion of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) to ribociclib in step-5 by deprotection using a deprotecting agent. The deprotecting agent is selected from acid comprising of sulphuric acid, hydrochloric acid, phosphoric acid, trifluoro acetic acid, trifluoromethane sulphonic acid. The reaction solvent is selected from the group comprising of methanol, ethanol, isopropanol, tetrahydrofuran, toluene 2-methyltetrahydrofuran, dichloromethane. The reaction temperature is -15 to 80°C.

Ribociclib is converted to ribociclib succinate by the conventional methods known in the prior art.

In another embodiment of the present invention, the step 7 involves purification of crude ribociclib succinate. The purification method involves crystallization of crude ribociclib succinate from the suitable solvents. The organic solvents are selected from the group comprising of hydrocarbons such as cyclohexane, cycloheptane, cyclopentane, benzene toluene xylene, esters such as ethyl acetate, isopropyl acetate, alcohols such as ethanol, butanol, isopropanol and methanol, ketones such as acetone, propanone, 2-butanone, methyl ethyl ketone or mixtures thereof. The most preferred solvent is mixture of methanol and butanone.

The purity of ribociclib succinate (II) obtained by the process of the present invention is 99.46 %.

The crystalline form of ribociclib succinate (II) obtained by the process of the present invention is characterized by XRPD pattern as shown in figure 1. The characteristic peaks in XRPD of ribociclib succinate (II) are as shown in table 1.

Table 1:
2 theta D spacing Relative intensity (%)
4.59 19.23 21.24
8.87 9.95 19.63
10.60 8.33 38.69
10.68 8.27 34.85
12.89 6.86 74.05
12.96 6.82 80.76
16.00 5.53 31.25
16.1 5.49 34.64
17.74 4.99 47.30
18.19 4.87 100.00
19.93 4.45 54.65
21.51 4.12 75.17
21.94 4.04 85.99
23.36 3.80 16.63
25.34 3.51 15.61
26.12 3.40 21.57

The crystalline ribociclib succinate (II) described herein is further identified by IR spectrum as shown in figure 2. The IR spectrum of crystalline ranolazine free base described herein has characteristic bands at 2868, 2961, 2483, 2175, 1711, 1631, 1561, 1597, 1534, 1473, 1427, 1388, 1246, 1137, 1031, 1015, 788, 718 cm-1.

The melting point of the obtained ranolazine free base by DSC shows a peak at 181.30°C which is shown in the DSC in Figure 3.

The aforementioned process for the preparation of Ribociclib succinate (II) has the following advantages:
i) purity of Ribociclib succinate is > %,
ii) simple and quick process,
iii) easy to scale up,
iv) economical process,
v) avoids toxic reagents and
vi) avoids chromatographic techniques,

Hereinafter, the present invention is illustrated by the following non-limiting examples without restraining the scope of the same.

Examples
Example-1: Preparation of methyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (Formula V)
To a solution of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Va) (1.0 g, 1.88 mmol) in DMF (10 mL) K2CO3 (0.39 g, 2.82 mmol) and methyl iodide (0.51 g, 3.7 mmol) was added and stirred at ambient temperature. After consumption of starting acid compound, it was poured in water and extracted with EtOAc (2X20 mL). Organic layer was concentrated under reduced pressure to give methyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate.
Yield 0.9 g.

Example-2: Preparation of methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (Formula VII)
To a nitrogen-flushed solution of 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (V) (3.0 g, 10.7 mmol) in MIBK (60 mL), tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (3.33 g, 11.8 mmol) of the Formula (VI), palladium (II) acetate (50 mg, 0.21 mmol), (±) 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (0.26 g, 0.42 mmol) and cesium carbonate (5.24 g, 16 mmol) were added. The resulting suspension was heated to 95 °C and stirred for 3 h. The sample was cooled, diluted with EtOAc(30 mL) and then washed with water. Organic layer was concentrated under reduced pressure, residue obtained was stirred in ethyl acetate; hexane mixture to give solid material. It was filtered and dried at 60 °C to afford methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate.
Yield 5.7 g.

Example-3: Preparation of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Formula VIII)
To a solution of methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) (5.0 g, 9.6 mmol) in THF (50 mL), methanol (20 mL) aqueous NaOH (1.15 g in 20 mL) was added. Reaction mixture was stirred for 4 h at ambient temperature. Organic solvents were removed and was diluted with water (50 mL). Reaction mixture was acidified with 1 N HCl to give solid material and was filtered and then dried at 50 °C to provide 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid.
Yield 4.7 g.

Example-4: Preparation of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (Formula IX)
Method A: From 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Formula VIII)
To a solution of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) (4.5 g, 8.86 mmol) in DMF (30 mL), HATU (4.04, 10.6 mmol), and DIPEA (3.19 g, 26.5 mmol) were added and stirred for 10 mins at ambient temperature. Dimethyl amine (2N) solution (13.9 mmol) was added and stirred at ambient temperature for 2 h. Reaction mixture was poured in ice-cooled water and then extracted with EtOAc (2 X 50 mL). Organic layer was concentrated to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate.
Yield 4.4 g.
Method B: From methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (Formula VII)
To a solution of methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) (1.0 g, 1.91 mmol) in methanol, dimethyl amine was added and stirred for 10 h at ambient temperature. After completion it was concentrated to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate.
Yield 1.0 g.

Example-5: Preparation of 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (Formula I)
To a cooled solution of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (4.0 g, 7.48 mmol) in toluene (20 mL), 6N aqueous hydrochloric acid (6 mL) was added over 10 min maintaining a batch temperature 15±3 °C. The resulting 2-phase solution was warmed to 25±3°C and stirred at this temperature for 1 h until the remaining starting material consumed. Toluene was separated and aqueous layer was diluted with water (30 mL). It was basified with NaOH solution (2N) to give solid material. The solid was filtered and then dried to give 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide.
Yield 3.2 g.

Example-6: Preparation of Ribociclib succinate (Formula II)
To a solution of 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (3.5g, 8.05 mmol) in IPA (150 mL) at 70 °C succinic acid (1.0 g, 8.46 mmol) was added portion wise. It was stirred for 1 h and then cooled to ambient temperature. Solid obtained was filtered and dried at 60 °C to give Ribociclib succinate.
Yield 3.8 g.

Example-7: Crystallization of Ribociclib succinate
Ribociclib succinate 3.0 g was dissolved in Methanol:2-butanone (200 mL) at ambient temperature. It was stirred for 10 min and then cooled. Solid obtained was filtered and dried at 60 °C in vacuum oven to give crystalline Ribociclib succinate.
Yield 2.4 g.
Purity: 99.46%
,CLAIMS:1) A process for the preparation of Ribociclib succinate (II) comprising the steps of :
1) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (Va) in the presence of haloalkane and base to give methyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V);

2) reaction of 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (V) with tert-butyl 4-(6-aminopyridie-3-yl)piperazine-1-carboxylate (VI) in the presence of catalyst and base to give methyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII);

3) conversion of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (VII) to 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) in the presence of base;

4) condensation of 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridine-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (VIII) with dimethyl amine in the presence of a base and a condensing agent to give tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX);

5) conversion of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (IX) to ribociclib by deprotection using a deprotecting agent;

6) conversion of ribociclib to ribociclib succinate and

7) purification of ribociclib succinate by crystallization from a suitable solvent or mixture of solvents thereof.

2) A process of claim 1, wherein the base used in step-1 is selected from group comprising of inorganic bases such as hydroxides like sodium hydroxide, potassium hydroxide, carbonates like sodium carbonate, potassium carbonate, bicarbonates like sodium bicarbonate, potassium bicarbonate.
3) A process of claim 1, wherein the base used in step-2 is selected from group comprising of potassium carbonate, sodium carbonate, potassium phosphate, cesium carbonate, potassium t-butoxide, sodium t- butoxide, lithium hexamethyl disilazide or hexamethyldisiloxane, sodium amide.
4) A process of claim 1, wherein the catalyst used in step-2 is selected from the group comprising of palladium salts or palladium complexes such as palladium acetate, palladium chloride, tetrakistriphenylphosphine palladium, ditriphenylphosphine palladium dichloride, Ruthenium complexes, BINAP.
5) The process of claim 1, wherein the base used in step-3 is selected from the group comprising of sodium hydroxide, potassium hydroxide or lithium hydroxide.
6) The process of claim 1, wherein the base used in step-4 is selected from a group comprising of organic bases such as diisopropyl ethyl amine, triethyl amine, DBU, triethylenediamine, or inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, potassium hydrogen carbonate.
7) The process of claim 1, wherein the condensing agent used in step-4 is selected from DCC, DIC, EDCI, HATU, HBTU or BOP.
8) The process of claim 1, wherein the deprotecting agent used in step-5 is selected from acid comprising of sulphuric acid, hydrochloric acid, phosphoric acid, trifluoro acetic acid, trifluoromethane sulphonic acid.
9) The process of claim 1, wherein the solvent used for crystallization is selected from group comprising of are selected from the group comprising of hydrocarbons such as cyclohexane, cycloheptane, cyclopentane, benzene toluene xylene, esters such as ethyl acetate, isopropyl acetate, alcohols such as ethanol, butanol, isopropanol and methanol, ketones such as acetone, propanone, 2-butanone, methyl ethyl ketone or mixtures thereof.
10) The process of claim 1, wherein the most preferred solvent used for crystallization is a mixture of methanol and butanone.