FORM 2
THE PATENTS ACT. 1970
(39 OF 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention - A Novel Process For The Preparation of Sorafenib Tosylate Form III
2. Applicani(s)
(a) NAME: Intas Pharmaceuticals Limited
(b) NATIONALITY: An Indian Company.
(c) ADDRESS: 2nd Floor. Chinubhai Centre.
Ashram Road. Ahmedabad 380009 Gujarat. India
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention relates to a novel process for the preparation of Sorafenib Tosylate Form III.
BACKGROUND OF THE INVENTION
Sorafenib tosylate is a well-known antineoplastic agent, and is useful for the treatment of primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer (hepatocellular carcinoma). The generic name sorafenib tosylate is marketed by Bayer Healthcare under the brand name NEXAVAR®.
Sorafenib and its salts, such' as the tosylate salt and a process for preparation thereof are disclosed in WO 00/41698 At.
WO 2006/034796 Al discloses processes for preparing Sorafenib base and its tosylate salt. It further discloses the preparation of ethanol solvate at higher temperature about 74°C followed by seeding and then dried under reduced pressure results to obtain form I.
WO 2006/034797 At depicts crystalline forms of Sorafenib tosylate, forms 1, II, and 111. methanol solvate, ethanol solvate and preparation thereof. Crystalline Sorafenib tosylate form III is characterized by a PXRD pattern having peaks selected from a list consisting of: 7.7. 8.5. 9.8. 10.6. 12.0. 12.3. 12.9. 13.4. 13.5, 15.4 and 16.0, 16.5, 16.9. 17.3. 1 7.8, 18.7, 18.8. 19.3, 19.9.20.3.20.8.21.2.21.6. 22.5, 23.0, 23.4, 24.2. 24.5, 24.8, 25.2. 25.9, 26.9, 27.5. 27.7. 28.2. 29.2. 29.4, 29.8. 30.3, 31.4. 32.2, 33.5. 34.0. 35.2. 36.1. 37.2. and 37.7+-0.2 degrees 2theta.

Crystalline Sorafenib tosylate methanoi solvate is characterized by a PXRD pattern having peaks selected from a list consisting of : 8.0, 8.4, 9.3, 11.2. 5 2,2. 13.0; 13.4, 15.8, 16.3. 16.9, 17.7, 18.3. 18.7. 19.0, 19.4. 20.2. 20.5. 20.9. 21.4, 21.7, 22.3, 22.4. 23.8. 24.0. 24.4, 24.7. 24.9. 25.2. 25.7. 26.0, 26.1. 26.4. 26,9, 27.0. 27.5, 27.7. 28.1, 28.3. 28.8, 29.1, 29.7. 30.2. 30.4. 30.7. 30.8: 31.4. 31.6. 31.9, 32.3, 32.6. 32.9, 33.4. 33.8. 34.0. 34.2, 34.5. 34.9. 36.2. 36.6, 37.2. and 37.7+-0.2 degrees 2theta. Crystalline Sorafenib tosylate ethanol solvate is characterized by a PXRD pattern having peaks selected from a list consisting of: 7.9.8.4.9.3.9.5. 11.2, 12.0. 12.2. 12.8, 13.4. 15.9. 16.1. 16.8. 17,4. 17.7. 18.1. 18.3. 18.6. 18.8. 19.4. 20.0. 20.4, 21.0. 21.2. 21.5, 21.7. 22.3. 22.4. 22.8. 23.3. 23.6. 23.8, 24.3: 24.7. 25.3, 25.8. 25.9. 26.4. 26.9. 27.3. 27.6, 28.3, 28.8. 29.1. 29.5, 29.7, 30.2, 30.4, 30.9. 31.4, 32.0, 32.6, 32.9, 33.2, 33.7, 33.9. 34.5, 35.5, 36.0. 36.3, 36.6. 37.1. and 37.7+-0.2 degrees 2lheta. It further discloses Sorafenib tosylate form III can be prepared from Sorafenib tosylate form II but as disclosed that form II is a meta stable form there is a need for developing simple, efficient and industrially feasible process for the preparation of Sorafenib Tosylate form III,
WO 2009/092070 describes Sorafenib tosylate form III preparation from Sorafenib tosylate methanol solvate.
The present inventors have directed their research towards a process which is devoid of such drawbacks and have developed a process for the preparation of Sorafenib tosylate form III.

OBJECTS OF THE INVENTION
The main object of the present invention is to provide a novel process for the preparation of Sorafenib tosylate form III.
Another object of the present invention is to provide a simple, efficient and industrially feasible process for the preparation of Sorafenib tosylate form III.
Yet another object of the present invention is to provide a process for the preparation of Sorafenib tosylate form III. which comprises steps of:
a) suspending sorafenib base in ethanol;
b) adding ethanolic solution of para toluene sulfonic acid in step (a):
c) isolating sorafenib tosylate ethanoi solvate and;
d) drying the solid of step (c) to obtain sorafenib tosylate form III.
SUMMARY OF THE INVENTION
The present aspect discloses a novel process for the preparation of Sorafenib tosylate form III from Sorafenib base through the formation Sorafenib tosylate ethanol solvate.
Yet another aspect of the present invention is to provide a process for the preparation of sorafenib tosylate form III, which comprises steps of:
a) suspending sorafenib base in ethanol;
b) adding ethanolic solution of para toluene sulfonic acid in step (a):
c) isolating sorafenib tosylate ethanol solvate and:
d) drying the soiid of step (c) to obtain sorafenib tosylate form TIL

BREIF DESCRIPTION OF THE DRAWINGS
FIG I is a FTIR of sorafenib tosylate ethanol solvate
FIG 2 is a powder X-ray diffractogram patterns of sorafenib tosylate form III
DETAILED DESCRIPTION
The present embodiment discloses a novel process for the preparation of Sorafenib tosylate form III from Sorafenib base through the formation Sorafenib tosylate ethanol solvate.
Another embodiment of the present invention is to provide a process for the preparation of sorafenib tosylate form III, which comprises steps of::
a) suspending sorafenib base in ethanol:
b) adding ethanolic solution of para toluene sulfonic acid in step (a);
c) isolating sorafenib tosylate ethanol solvate and;
d) drying the solid of step (c) to obtain sorafenib tosylate form III.
Advantageously, according to the process of the present invention, substantially pure end product is obtained and there is no requirement of any additional purification of final API to remove impurities so as to bring the final API in compliance with stipulated regulatory requirement.
The present invention also provides the process for the preparation of sorafenib tosylate form III by using lower alcohol i.e C1-C4 or their mixtures instead the use of ethanol solvent.

Another embodiment of the present invention also provides the purification oi' sorafenib base by using the solvent or their mixtures selected from the group comprising alcohols, esters, ethers, ketones, chlorinated solvents, nitrile solvents. The alcoholic solvent is selected from methanol, ethanol. isopropanol. n-propanol or butanol; the ester solvent is selected from ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl aeetalc or isopropyl acetate: the ether solvent selected from tetrahydrofuran. methyl icrt-butyl ether or diisopropyi ether; the ketone solvent is selected from acetone, methylelhylketone or methylisobutylketone; the nitrile solvent is acetonilrile. Most preferred solvent for the purification of Sorafenib base is acetone.
Another embodiment of the present invention also provides the process for the preparation of sorafenib base comprising a step of purifying crude sorafenib base with acetone to obtain pure Sorafenib base.
The term pure Sorafenib base has HPLC purity greater than 99%. In one embodiment, the HPLC purity is greater than 99.4%. In another embodiment, the HPLC purity is greater than 99.8%.
The invention will now be further described by the following examples, which are illustrative rather than limiting.
EXAMPLES Example 1:
Step-I: Preparation of Sorafenib Ethanol solvate

5 gin of Sorafenib base was suspended in 25 ml of Ethanol al 25-30 °C. 2.5 gm of Para toluene sulfonic'acid monohydrate was dissolved in 25 ml of Ethanol and added drop wise in 10 minutes at 25-30 °C. Reaction mass was stirred for 7 days at 25-30 °C. Solid was filtered and washed with 10 ml of Ethanol.
Slep-fl: Preparation of Sorafenib tosylate form 111
Solid was dried at 80-85oC under vacuum for 20-22 11rs.
Example 2:
Step-I: Preparation of Sorafenib Ethanol solvate
Sorafenib base (15 gm) was suspended in ethanol (75 ml) al 25-30 °C, Para toluene sulfonic acid monohydrate (7.5 gm) was dissolved in ethanol (75 ml) and added drop wise in 10 min al 25-30 °C Reaction mass was stirred for 72 hrs at 25-30 °C. Solid was filtered and washed with 30 ml of ethanol. Solid was dried at 25-30 °C for 24 hrs.
Step-11: Preparation of Sorafenib tosylate form HI
Obtained sorafenib ethanol solvate was dried under vacuum at 80-85°C,

WE CLAIM,
1. A process for the preparation of sorafenib tosyiate form III. which comprises
steps of:
a) suspending sorafenib base in ethanol;
b) adding elhanolic solution of para toluene sulfonic acid in step fa):
c) isolating sorafenib tosyiate ethanol solvate and
d) drying the solid of step (c) to obtain sorafenib tosyiate form ill.
2. A process for the preparation of sorafenib tosyiate form ill. which comprises
steps of:
a) suspending sorafenib base in ethanol at 25-30°C
b) adding elhanolic solution of para toluene sulfonic acid in step fa) at 25-30°C:
c) isolating sorafenib tosyiate ethanol solvate at 25-30°C and
d) drying the solid of step (c) at 80-85°C under vacuum to obtain sorafenib tosyiate form 111.
3. A process for the preparation of sorafenib tosylate form III. which comprises
steps of:
a) purifying crude sorafenib base with acetone to obtain pure sorafenib base
b) suspending pure sorafenib base in ethanol at 25-30°C
c) adding elhanolic solution oi" para toluene sulfonic acid in step (a) at 25-30°C;
d) isolating sorafenib tosyiate ethanol solvate at 25-30°C and
e) drying the solid of step (c) to obtain sorafenib tosyiate form III.

4. A process for the preparation of pure Sorafcnib base according to claim 3 having HPLC purity greater than 99.0%,