DESC:FIELD OF THE INVENTION
The present invention relates to an improved method of producing Rucaparib Camsylate and pharmaceutical compositions comprising the same. More particularly the invention relates to the preparation of compound of Formula-10, which is an intermediate in the preparation of Rucaparib S-Camsylate of Formula (I).

(10)
BACKGROUND OF THE INVENTION
Rucaparib Camsylate (Rubraca) chemically known as 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6one((1S, 4R) -7,7-dimethy l-2-oxobicyclo [2.2.1]hept-1-yl)methanesulfonic acid salt, represented by the Formula 1.

Rucaparib Camsylate is an inhibitor of the mammalian polyadenosine 5’-diphosphoribose polymerase (PARP) enzyme indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies.
US 6,495,541 disclose Rucaparib base and process of preparation thereof as shown below in Scheme 1. US’541 discloses reaction of methyl 6-fluoro-1H-indole-4-carboxylate with 1-acetoxy-2-nitroethane followed by cyclization to obtain 8-fluoro-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one.

Scheme –1
US 8,754,072 disclose crystalline form A, B and C of Rucaparib Camsylate and process of preparation thereof.
Organic process research & development, 16, 12, 1897-1904, 2012 discloses process of preparation of Rucaparib Camsylate as shown below in Scheme 2, which involve reaction of methyl 6-fluoro-1H-indole-4-carboxylate with phthalylacetaldehyde followed by cyclization to obtain 8-fluoro-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one. However, a significant level of phthalyl ethyl alcohol was observed due to direct reduction of the aldehyde, as well as multiple other by-products.
Scheme –2
It would be desirable to have an alternative convergent route for eventual commercial manufacturing with inexpensive, feasible reagents, solvents and intermediates and the process that can afford desired products with good yields and to prepare a substantially pure crystalline form.
SUMMARY OF THE INVENTION
First aspect of the present application relates to a process for the preparation of compound of Formula-10, comprising the step of:

(10)
I. reacting compound of Formula-6 and compound of Formula-7 to obtain compound of Formula-8; and

(6) (7) (8)

II. reducing compound of Formula-8 to obtain compound of Formula-9; and

(9)
III. reacting a compound of Formula-9 with methyl amine to obtain compound of Formula-10.
Second aspect of the present application relates to a process for the preparation of compound of Formula-10, comprising the step of:

(10)
I. reacting compound of Formula-6 and compound of Formula-7 to obtain compound of Formula-8; and

(6) (7) (8)

IV. reacting a compound of Formula-8 with methyl amine to obtain compound of Formula-16 ; and

(16)
V. reducing compound of Formula-16 to obtain compound of Formula-10.
Third aspect of the invention relates to compound of Formula-8 and compound of Formula-16.

(8) (16)
Fourth aspect of the invention provides converting compound of Formula-10 to Rucaparib Camsylate.
Fifth aspect of the invention provides an improved process for preparation of substantially pure Form A of Rucaparib Camsylate.

DETAILED DESCRIPTION OF THE INVENTION
Main aspect of the present invention relates to an improved process of preparation of compound of Formula-10, comprising the step of:

(10)
In an embodiment of the present invention, the step (I) reaction between Formula-6 and compound of Formula-7 to obtain compound of Formula-8 is carried out in an inert organic solvent including but not limited to solvent such as ethers such as diethyl ether, isopropyl ether, tetrahydrofuran (THF), dioxane, 2-methoxyethanol and 1,2-dimethoxyethane; nitriles such as acetonitrile (ACN) and propionitrile, halogenated hydrocarbons such as dichloromethane (DCM), chloroform, carbon tetrachloride (CCl4), 1,2-dichloroethane, trichloroethylene and tetrachloroethylene; aromatic compounds such as benzene, toluene, xylene, monochlorbenzene, nitrobenzene, indene, pyridine, quinoline, collidine and phenol; hydrocarbons such as pentane, cyclohexane, hexane, heptane, octane, isooctane, petroleum benzene and petroleum ether and the like or mixture thereof; more preferably dichloromethane. The reaction may be carried out in presence of suitable acid catalyst preferably in presence of lewis acid. Suitable lewis acid can be used is selected from the group of aluminiun chloride, trifluro acetic acid, boron trifluride ethrate, boron trifluoride, boron, aluminium hydride, trimethylaluminium, trimethylboron; more preferably aluminiun chloride. The reaction may be carried out at a temperature of about 0oC to about boiling point of the solvent used. Specifically, the reaction step (I) may be carried out at a temperature of about 50oC to 55oC.
In one embodiment, compound of Formula-8 may be isolated and purified if required from the reaction mixture by any known technique in the art OR the compound can be subjected to next reaction without isolation and/or purification. Optionally the compound of Formula-8 may be stirred with solvent or mixture thereof to remove impurities; suitable solvent may include diethyl ether, isopropyl ether, tetrahydrofuran (THF) or like.
In an embodiment of the present invention, the step (II) reduction of compound of Formula-8 to obtain compound of Formula-9 or step (V) reduction of compound of Formula-16 to obtain compound of Formula-10 is carried out in an inert organic solvent including but not limited to solvent such as lower alcohols such as methanol, ethanol, propanol and butanol; polyalcohols such as ethyleneglycol and glycerine; ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol and 1,2-dimethoxyethane; esters such as methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate and diethyl phthalate; aromatic compounds such as benzene, toluene, xylene, monochlorbenzene, nitrobenzene and the like or mixture thereof; more preferably tetrahydrofuran. The reaction may be carried out in presence of suitable reducing agent. Suitable reducing agent can be used is selected from the group of borane complexes; metals such as iron, tin, zinc; transition metals such as palladium-carbon, platinum oxide, Pd(dppf)Cl2, palladium acetate, palladium dichloride, Raney nickel in presence of hydrogen or hydrogen source selected from ammonium formate, sodium dihydrogen phosphate, hydrazine; for example, Fe-NH4Cl, Fe-HCl, Fe-CaCl2, Sn-HCl, NaHS, ZnAcOH, Pd/C-H2, hydrazine hydrate-Raney Ni, NaBH4-NiCl2.6H2O, Ni(OAc)2.4H2O, CoCl2 likes metals, NaBH4, NaBH3CN, triethylsilane, metal halides or metal salts; more preferably NaBH4. The reaction may be carried out in presence of suitable lewis acid. Suitable lewis acid can be used is selected from the group of aluminiun chloride, trifluro acetic acid, boron trifluride ethrate, boron trifluoride, boron, aluminium hydride, trimethylaluminium, trimethylboron; more preferably aluminiun chloride or boron trifluride ethrate or trifluro acetic acid. The reaction may be carried out at a temperature of about 0oC to about boiling point of the solvent used. Specifically, the reaction step (II) may be carried out at a temperature of about 0oC to 5oC.
In one embodiment, compound of Formula-9 or compound of Formula-10 may be isolated and purified if required from the reaction mixture by any known technique in the art OR the compound can be subjected to next reaction without isolation and/or purification. Specifically, compound of Formula-9 or compound of Formula-10 may be crystallized from a suitable solvent or mixture thereof or may be stirred with suitable solvent to remove impurities.
In an embodiment of the present invention, in the step (III) a compound of Formula-9 or in step (IV) a compound of Formula-8 is reacted with methyl amine in an inert organic solvent to obtain compound of Formula-10 or compound of Formula-16 respectively, whereas in an inert organic solvent including but not limited to solvent such as lower alcohols such as methanol, ethanol, propanol and butanol; polyalcohols such as ethyleneglycol and glycerine; water and the like or mixture thereof; more preferably water. The reaction may be carried out at a temperature of about 0oC to about boiling point of the solvent used. Specifically, the reaction step (III) may be carried out at a temperature of about 25oC to 30oC.
In one embodiment, compound of Formula-10 or compound of Formula-16 may be isolated and purified if required from the reaction mixture by any known technique in the art OR the compound can be subjected to next reaction without isolation and/or purification. Specifically, compound of Formula-10 or compound of Formula-16 may be stirred with suitable solvent to remove impurities.
Another aspect of the invention relates to an improved process for preparation of substantially pure form A of Rucaparib Camsylate.
In an embodiment, process of preparing Form A of Rucaparib Camsylate involves;
1) providing solution of Rucaparib in suitable solvent or mixture thereof;
2) adding S-(+)-camphor sulfonic acid in reaction mixture;
3) isolating substantially pure form A of Rucaparib Camsylate.
In an embodiment, a suitable solvent or mixture thereof in step (1) is selected from N-methyl pyrollidine, dimethyl acetamide, methylene dichloride, methanol, isopropyl alcohol, benzyl alcohol, butanol, propanol, pentanol, sulfolane, tetramethylurea (TMU), propylene carbonate, anisole, butyl acetate, isopropyl acetate, methyl acetate, t-butyl acetate, acetone, THF, trifluro-ortho anilne, acetonitrile, acetic acid, ethyl acetate, methyl ethyl ketone, methyl isobutyl ketone, toluene, haptane, N-N-dimethyl formamide, dimethyl sulfoxide, cyclohexane, carbon tetrachloride, xylene, cumene, P-cymene, 1,4-dioxane, dimethoxy ethane, cyclopropyl methyl ether, diphenyl ether. Preferable solvent is mixture of methanol and acetonitrile.
Providing a solution of Rucaparib in suitable solvent or mixture thereof means the solution of Rucaparib may be obtained by dissolving Rucaparib in suitable solvent or mixture thereof, or such a solution may be obtained directly from a reaction mixture in which Rucaparib is formed. Providing a solution of Rucaparib optionally involves use of other suitable solvents capable of dissolving Rucaparib. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fibre, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Then finally, isolating form A of Rucaparib Camsylate. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature crystallization.
In an embodiment the present invention relates to a pharmaceutical composition comprising Rucaparib Camsylate and at least one pharmaceutically acceptable excipient.
Another aspect of the invention relates to pharmaceutical composition comprising Rucaparib Camsylate for the treatment in disease or injury where PARP activity is deleterious to a patient, the therapeutic methods comprising inhibiting PARP enzyme activity in the relevant tissue.
In an embodiment, the process for the preparation according to present invention is represented schematically in Scheme-3 and 4 as shown below.

Scheme-3
Scheme-4
Another aspect of the invention, wherein the compound of Formula-10 is converted in to Rucaparib Camsylate by any known technique in the art or by following the Scheme-5.

Scheme-5
The following examples are given for the purpose of illustrating the present invention and should not be considered as limitation on the scope of the invention.
1 H NMR spectra are recorded at 300 MHz on a Bruker Avance III instrument. Dimethyl sulfoxide (99.8% D) is used as solvent, and tetramethylsilane (TMS) is used as internal reference standard.

EXAMPLES
Example-1: Preparation of compound of Formula-8
To a solution of compound of Formula-5 (100.0 g) in dichloromethane (250 ml) and N, N-dimethyl formamide (20.0 ml), oxalyl chloride (68.14 g) was added at ambient temperature. The reaction mixture was stirred for 2 hours at ambient temperature. This reaction mass of compound of Formula-6 was preserved under nitrogen atmosphere.
Meanwhile, in another RBF was charged dichloromethane (250 mL) and anhydrous aluminium chloride (260.0 g) at ambient temperature. To the obtained reaction mass the preserved reaction mass of compound of Formula-6 was added at ambient temperature. The reaction mass was heated to 50-55°C and a solution of compound of Formula-7 (103.65 g) in dichloromethane (860 ml.) was added at 50-55°C. The reaction mixture was stirred at 50-55°C. After completion of reaction, reaction mixture was cooled to 0-5°C. THF was added into the reaction mass at 0-5°C and stirred at ambient temperature. The reaction mixture was filtered and the wet cake was washed with THF. Obtained wet cake was treated with sodium bicarbonate solution and filtered. The material was dried in ATD at 50-55°C to get 120 g of compound of Formula-8.
1HNMR: dH: (300 MHz, DMSO-d6) 3.62 (s,3H), 5.07 (s, 2H), 7.19-7.15 (dd, 1H), 7.49-7.53 (dd, 1H), 7.89-8.03 (m, 4H), 8.76 (s, 1H), 12.52 (s, 1H)1CNMR:dC: (75 MHz, DMSO-d6) 44.72, 52.08, 101.34-101.68, 110.11-110.45, 114.32, 118.26, 123.79, 128.33, 132.09, 135.19, 136.75, 137.95-138.12, 157.25, 160.42, 168.11-168.35, 186.16 Mass: 382.61 (M+H) Melting point: 288.16°C
Example-2: Preparation of compound of Formula -9
Sodium borohydride (0.98 g) was charged to cooled solution of compound of Formula -8 (5.0 g) in THF (50 mL) at 0-5°C. Boron trifluoride etherate (5.53 g) was added into the reaction mass at 0-5°C. The temperature was raised of reaction mixture to ambient temperature and stirred overnight at ambient temperature. After completion of reaction, the reaction mass was cooled to 0-5°C and water was added at 0-5°C. The reaction mixture was extracted with ethyl acetate; organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 3.88 g of compound of Formula-9.
Example-3: Preparation of the compound of Formula -9
Sodium borohydride (0.40 g) was charged to cooled solution of compound of Formula 8 (2.0 g) in THF (20 mL) at 0-5°C. Anhydrous Aluminium chloride (2.67 g) was charged into the reaction mass at 0-5°C. The reaction mixture temperature was raised to ambient temperature and stirred overnight at ambient temperature. After completion of reaction, the reaction mass was cooled to 0-5°C and quenched in water at 0-5°C. The reaction mixture was extracted with ethyl acetate; organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 1.38 g of compound of Formula-9.
Example-4: Preparation of compound of Formula 9
Triethyl silane (2.29 g) was charged to cooled solution of compound of Formula -8 (5.0 g) in THF (50 mL) at 0-5°C. Trifluoro acetic acid (4.45 g) was added into the reaction mass at 0-5°C. The reaction mixture was heated to 60-65°C and stirred overnight at 60-65°C. After completion of reaction, the reaction mass was cooled to ambient temperature and water was added into the reaction mass at ambient temperature. The reaction mixture was extracted with ethyl acetate, organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 3.78 g of the compound of Formula -9.
Example-5: Preparation of compound of Formula -9
Sodium borohydride (0.98 g) was charged to cooled solution of compound of Formula -8 (5.0 g) in THF (50 mL) at 0-5°C. Trifluoro acetic acid (5.53 g) was charged into the reaction mass at 0-5°C. The reaction mixture was heated to 50-55°C and stirred overnight at 50-55°C. After completion of reaction, the reaction mass was cooled to 0-5°C and quenched in water at 0-5°C. The reaction mixture was extracted with ethyl acetate, organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 3.33 g of compound of Formula -9.
Example-6: Preparation of compound of Formula -10
A solution of compound of Formula -9 (5.0 g) in 40 % aqueous methyl amine solution (30 mL) was stirred overnight at 25-30°C. Water (10 mL) was added into the reaction mixture at 25-30°C. The reaction mass was then filtered and the wet cake was washed with water. The material was dried under vacuum at 50-55°C to get 2.50 g of compound of Formula -10.
Example-7: Preparation of compound of Formula-16
To a stirred solution of compound of Formula -8 (100.0 g) in methanol (200 mL), 23 % solution of methyl amine in methanol (300 mL) was added. The reaction mixture was stirred at ambient temperature. After completion of reaction, the reaction mixture was filtered and wet cake was washed with methanol. The wet cake was dried in ATD at 50-55°C to get 43 g of compound of Formula-16.
1HNMR: dH: (300 MHz, DMSO-d6) 3.94-3.96 (d, 2H), 7.57-7.67 (m, 2H), 8.23-8.25 (s, 2H), 1CNMR: dC: (75 MHz, DMSO-d6) 52.62, 103.40-103.75, 112.13-112.47, 116.47, 122.01, 126.49-126.60, 133.72, 137.30-137.46, 157.76, 160.90, 168.32, 189.46 Mass: 216.95 (M-H)
Example-8: Preparation of compound of Formula -10
Sodium borohydride (34.70 g) was charged into cooled solution of compound of Formula -16 (100.0 g) in THF (1000 mL) at 0-5°C. Boron trifluoride etherate (9.76 g) was added into the reaction mass at 0-5°C. The reaction mixture temperature was raised to ambient temperature and stirred for 12 hours at ambient temperature. After completion of reaction, methanol was added, stirred and distilled. Obtained distilled residue was extracted with ethyl acetate; organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 56 g of compound of Formula -10.
Example-9: Preparation of compound of Formula -10
Sodium borohydride (0.69 g) was charged into cooled solution of compound of Formula -16 (2.0 g) in THF (20 mL) at 0-5°C. Anhydrous Aluminium chloride (3.66 g) was charged into the reaction mass at 0-5°C. The reaction mixture temperature was raised to RT and stirred overnight at ambient temperature. After completion of reaction, the reaction mass was cooled to 0-5°C and quenched in water at 0-5°C. The reaction mass temperature was raised to ambient temperature. The reaction mixture was extracted with ethyl acetate, organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 4.05 g of compound of Formula -10.
Example-10: Preparation of compound of Formula -10
Triethyl silane (5.35 g) was charged into cooled solution of compound of Formula -16 (5.0 g) in THF (50 mL) at 0-5°C. Trifluoro acetic acid (7.87 g) was added into the reaction mass at 0-5°C. The reaction mixture was heated to 60-65°C and stirred overnight at 60-65°C. After completion of reaction, the reaction mass was cooled to ambient temperature and water (100 mL) was added into the reaction mass at RT. The reaction mixture was extracted with ethyl acetate (100 mL), organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C for 8 hours to get 3.90 g of compound of Formula -10.
Example-11: Preparation of compound of Formula -10
Sodium borohydride (0.347 g) was charged into cooled solution of compound of Formula-16 (1.0 g) in THF (10 mL) at 0-5°C. Trifluoro acetic acid (1.56 g) was charged into the reaction mass at 0-5°C. The reaction mixture was heated to 50-55°C and stirred overnight at 50-55°C. After completion of reaction, the reaction mass was cooled to 0-5°C and quenched in water (100 mL) at 0-5°C. The reaction mass temperature was raised to ambient temperature. The reaction mixture was extracted with ethyl acetate, organic layer was separated, concentrated. The residue was crystallized in MDC and filtered. The wet cake was dried under vacuum below 50°C to get 4.10 g of compound of Formula -10.
Reference Example-1: Preparation of compound of Formula-5
To solution of phthalic anhydride (100.0 g) and glycine (50.67 g) in toluene (300 mL), triethyl amine (6.83 g) was charged at ambient temperature. The reaction mixture was heated to refluxing temperature and stirred to remove water azeotropically by using dean-stark apparatus. After completion of reaction, reaction mixture was cooled to ambient temperature and stirred for 12 hours and filtered. The wet material was washed with toluene. The wet cake was slurried in water and filtered again. The wet cake was dried in ATD at 50-55°C to get 110 g of compound of Formula-5.
Reference Example-2: Preparation of compound of Formula -5
To solution of phthalic acid (250.0 g) and glycine (126.68 g) in toluene (750 mL), triethyl amine (17.09 g) was charged at ambient temperature. The reaction mixture was heated to refluxing temperature and stirred to remove water azeotropically by using dean-stark apparatus. After completion of reaction, reaction mixture was cooled to ambient temperature and stirred for 6 hours and filtered. The wet material was washed with toluene). The wet cake was slurried in water and filtered again. The wet cake was dried in ATD at 50-55°C to get 293 g of compound of Formula -5.
Reference Example-3: Preparation of compound of Formula -11
A solution of Pyridinium perbromide (172.28 g) in THF (500 mL) was added to stir solution of compound of Formula-10 (50.0 g, 0.245) in DCM (500 mL) at 0-5°C. The reaction mixture was stirred for 1 hour at 0-5°C. Water was added into the reaction mixture at 0-5°C. The pH of the reaction mixture was adjusted to 7-8 by aq. Sodium carbonate solution. Organic solvents was removed under vacuum below 65°C from the reaction mixture. The reaction mixture was cooled to 25-30°C and further stirred for 2 hours. The reaction mixture was filtered and the wet cake was crystallized with 1, 4-dioxane. After drying the material at 40-50°C to get 115 g of compound of Formula -11.
Reference Example-4: Preparation of compound of Formula -13
Compound of Formula -11 (100.0 g) was charged into a THF (500 mL) at 25-30°C. 4-Formylphenyl boronic acid (58.21 g) was then charged into the reaction mass at 25-30°C Sodium bicarbonate (44.48 g), water (200 ml) and 1, 1’-Bis (diphenylphosphino) ferrocene] palladium (II) dichloride (6.45 g) was charged into the reaction mixture at 25-30°C. Nitrogen was purged into the reaction mixture for 30 minutes. The reaction mixture was heated to 65-70°C and maintained for 1 hour. N-Acetyl cysteine (20.0 g) was charged into the reaction mixture and stirred for 1 hour at 65-70°C. The reaction mixture was cooled to 25-30°C and stirred for 2 hours. The reaction mixture was filtered. THF was added to obtained wet cake and heated up to 65-70°C followed by addition of water. Obtained reaction mixture was stirred for 1 hour at 65-70°C and cooled to 25-30°C and further stirred for 2 hours. The reaction mixture was filtered and the wet cake was washed with water. The wet material was dried under reduced pressure at 50-55°C to get 80 g of compound of Formula -13.
Reference Example-5: Preparation of Rucaparib
Compound of Formula -13 (50.0 g) and 23 % solution of methyl amine in methanol (65 mL) were charged in 1:1 mixture of THF and methanol (500 mL) in autoclave. The reaction mixture was heated to 55°C under pressure and maintained for 4 hours. The reaction mixture was cooled to 25-30°C. 10 % palladium on carbon (2.5 g) was charged into the reaction mixture. Under 4 Kg/cm2 hydrogen pressure the reaction mixture was heated to 55°C and stirred for 3 hours at 55°C. The reaction mixture was cooled to 25-30°C and the catalyst was filtered. Organic solvents were removed under reduced pressure below 50°C from the reaction mixture. To the residue was charged acetonitrile (750 mL) and water (250 mL) and the reaction mixture was heated to 75°C. The reaction mixture was stirred for 1 hour at 75°C. The reaction mixture was cooled to RT and filtered. The wet cake was washed with water. The material was dried at 55°C under vacuum to get 45.62 g of Rucaparib.
Reference Example-6: Preparation of Rucaparib
Compound of Formula -13 (100.0 g) and 23 % solution of methyl amine in methanol (65 mL) were charged in mixture of THF (500 mL) and methanol (1000 mL). The reaction mixture was heated to 52-55°C and stirred for 2 hours. The reaction mixture was cooled to 25-30°C and stirred for 2 hours. The reaction mixture was filtered and washed with methanol. To the wet cake THF (500 mL) and methanol (1000 mL) was charged at ambient temperature and cooled to 3-5°C. To the reaction mass sodium borohydride (30.68 g) was charged and stirred for 2 hours at ambient temperature. To the reaction mass water (1000mL) was charged and pH was adjusted 1-2 with hydrochloric acid at to 3-5°C. after completion of reaction solvent was distilled and stirred for 2 hours at ambient temperature. Obtained reaction mass was filtered and wash with water. THF (300mL) and water (700mL) was added to wet cake and heated up to 62-65°C. Aodium hydroxide solution was added to reaction mass to adjust the pH 11-12 and stirred. Reaction mass was filtered at ambient temperature. The wet material was dried under reduced pressure at 70-75°C to get 80 g of Rucaparib.
Reference Example-7: Preparation of Rucaparib Camsylate form A
A solution of Rucaparib (20.0 g) in isopropanol (300 mL) was heated to 75°C. S-(+)-Camphor sulfonic acid (17.24 g) was charged into the reaction mass at 75°C. The reaction mixture was stirred for 1 hour at 75°C. The reaction mixture was cooled to ambient temperature and then stirred for 6 hours. The reaction mixture was filtered and washed with isopropanol. The material was dried at 50-55°C under vacuum to get 30.32 g of Rucaparib Camsylate form A.
Example-12: Preparation of Rucaparib Camsylate form A
A solution of Rucaparib (100.0 g) in acetonitrile (650 mL) and methanol (650mL) was heated to 62-65°C. S-(+)-Camphor sulfonic acid (79 g) was charged into the reaction mass. The reaction mixture was stirred for 1 hour at 62-65°C. The reaction mixture was cooled to ambient temperature and then stirred for 2 hours. The reaction mixture was filtered and washed with acetonitrile and methanol. The material was dried at 50-55°C under vacuum to get 140 g of Rucaparib Camsylate form A.
,CLAIMS:We claim:
1. A process for the preparation of 8-fluoro-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, a compound of Formula-10, which comprises;

(10)
I. reacting compound of Formula-6 and compound of Formula-7 to obtain compound of Formula-8;

(6) (7) (8)

II. reducing compound of Formula-8 in presence of a reducing agent to obtain compound of Formula-9; and

(9)
III. reacting a compound of Formula-9 with methyl amine to obtain compound of Formula-10.
2. A process for the preparation of 8-fluoro-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one a compound of Formula-10, which comprises;

(10)

IV. reacting a compound of Formula-8 with methyl amine to obtain compound of Formula-16; and

(16)
V. reducing compound of Formula-16 in presence of a reducing agent to obtain compound of Formula-10.
3. The process as claim in claim 1, wherein step I is carried out in presence of suitable lewis acid selected from the group comprising of aluminiun chloride, trifluro acetic acid, boron trifluride ethrate, boron trifluoride, boron, aluminium hydride, trimethylaluminium and trimethylboron.
4. The process as claim in any of the proceeding claim wherein the reducing agent selected from the group comprising of Fe-NH4Cl, Fe-HCl, Fe-CaCl2, Sn-HCl, NaHS, ZnAcOH, Pd/C-H2, hydrazine hydrate-Raney Ni, NaBH4-NiCl2.6H2O, Ni(OAc)2.4H2O, CoCl2 NaBH4, NaBH3CN, triethylsilane, and more preferably NaBH4; wherein reduction is optionally carried out in presence of lewis acid selected from the group comprising of aluminiun chloride, trifluro acetic acid, boron trifluride ethrate, boron trifluoride, boron, aluminium hydride, trimethylaluminium and trimethylboron.
5. The process according to claim 1 and 2, further comprising the converting the compound of Formula 10 in to Rucaparib.
6. Methyl-3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]-6-fluoro-1H-indole-4-carboxylate, a compound of Formula-8.

(8)
7. 8-Fluoro-4,5-dihydro-1H-azepino[5,4,3-cd]indole-3,6-dione, a compound of Formula-16.

(16)
8. A process of the preparation of Form A of Rucaparib Camsylate comprises;
1) providing solution of Rucaparib in acetonitrile and methanol;
2) adding S-(+)-camphor sulfonic acid in reaction mixture;
3) isolating substantially pure form A of Rucaparib Camsylate.