WO2014118807A1 - A novel process for the preparation of sorafenib tosylate form iii - Google Patents

A novel process for the preparation of sorafenib tosylate form iii Download PDF

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Publication number
WO2014118807A1
WO2014118807A1 PCT/IN2014/000078 IN2014000078W WO2014118807A1 WO 2014118807 A1 WO2014118807 A1 WO 2014118807A1 IN 2014000078 W IN2014000078 W IN 2014000078W WO 2014118807 A1 WO2014118807 A1 WO 2014118807A1
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WO
WIPO (PCT)
Prior art keywords
sorafenib
preparation
ethanol
sorafenib tosylate
tosylate form
Prior art date
Application number
PCT/IN2014/000078
Other languages
French (fr)
Inventor
Sandipan Prabhurao Bondge
Mahesh Purushottam EKBOTE
Mithun Narandas PAREKH
Brijesh Nitinkumar Kapadia
Sanjay Jagdish Desai
Original Assignee
Intas Pharmaceuticals Limited
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Publication date
Application filed by Intas Pharmaceuticals Limited filed Critical Intas Pharmaceuticals Limited
Publication of WO2014118807A1 publication Critical patent/WO2014118807A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a novel process for the preparation of Sorafenib Tosylate Form 111.
  • 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 A 1.
  • 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 Al depicts crystalline forms of Sorafenib tosylate, forms I, II, and III, 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, 17.3.17.8, 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 methanol solvate is characterized by a PXRD pattern having peaks selected from a list consisting of: 8.0, 8.4, 9.3, 11.2. 12.2, 13.0, 13.4, 15.8, 16.3, 16.9, 17.7, 18.3.
  • 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, 1.6.1, 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.
  • Sorafenib tosylate form.111 can be prepared from Sorafenib tosylate form li 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 HI preparation from Sorafenib tosylate methanol solvate.
  • 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 o f:
  • step (a) adding ethanol ic solution of para toluene sulfonic acid in step (a);
  • step (c) drying the solid of step (c) to obtain sorafeni b tosylate form I I I .
  • 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:
  • step (a) adding ethanolic solution of para toluene sulfonic acid in step (a);
  • step (c) drying the solid of step (c) to obtain sorafenib tosylate form III.
  • FIG 1 is a FYIR of sorafenib tosylate ethanol solvate
  • FIG 2 is a powder X-ray diffractogram pattei ' ns 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 Soralenib tosylate ethanol solvate.
  • Another embodiment o f the present invention is to provide a process for the preparation of sorafenib tosylate form III, which comprises steps of:
  • step (a) adding ethanolic solution of para toluene sulfonic acid in step (a);
  • step (c) drying the solid of step (c) to obtain sorafenib tosylate form I II .
  • 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 C 1 -C4 or their mixtures instead the use of ethanol solvent.
  • Another embodiment o f the present invention also provides the puri fication of sorafenib base by using the solvent or their mixtures selected from the group comprising alcohols, esters, ethers, ketones, chlorinated solvents, nitri le 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 acetate or isopropyl acetate; the ether solvent selected from tetrahydrofuran, methyl tert-butyl ether or diisopropyl ether; the ketone solvent is selected from acetone, methylethylketone or methylisobutylketone; the nitrile solvent is acetonitri le. Most preferred sol vent for the puri fication 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 puri fying 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 embodi ment, the HPLC purity is greater than 99.8%.
  • the invention will now be further described by the fol lowing examples, which are i llustrative rather than limiting.
  • Step-I Preparation of Sorafenib Ethanol solvate 5 gm of Sorafenib base was suspended in 25 ml of Ethanol at 25-30 °C, 2.5 gm of Para toluene sulfonic acid monohydrate was dissolved in 25 ml of Ethanol and added drop wise in 1 0 minutes at 25-30 °C. Reaction mass was stirred for 7 days at 25-30 °C. Solid was filtered and washed with 1 0 ml of Ethanol .
  • Step-II Preparation of Sorafenib tosylate form III Solid was dried at 80-85°C under vacuum for 20-22 Hrs. ' .
  • Example 2
  • Sorafenib base 15 gm was suspended in ethanol (75 ml) at 25-30 °C.
  • Para toluene sulfonic acid monohydrate 7.5 gm was dissolved in ethanol (75 ml) and. added drop wise in 10 min at 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.

Abstract

The present invention relates to a novel process for the preparation of Sorafenib Tosylate Form I II from Sorafenib Tosylate Ethanol Solvate.

Description

FIELD OF THE INVENTION
The present invention relates to a novel process for the preparation of Sorafenib Tosylate Form 111.
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 A 1.
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 Al depicts crystalline forms of Sorafenib tosylate, forms I, II, and III, 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, 17.3.17.8, 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 methanol solvate is characterized by a PXRD pattern having peaks selected from a list consisting of: 8.0, 8.4, 9.3, 11.2. 12.2, 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, 1.6.1, 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 2theta. It further discloses Sorafenib tosylate form.111 can be prepared from Sorafenib tosylate form li 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 HI 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 111. 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 o f:
a.) suspending sorafenib base in ethanol ;
b) adding ethanol ic 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 sorafeni b tosylate form I I I .
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 solid of step (c) to obtain sorafenib tosylate form III. BREIF DESCRIPTION OF THE DRAWINGS
FIG 1 is a FYIR of sorafenib tosylate ethanol solvate FIG 2 is a powder X-ray diffractogram pattei'ns 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 Soralenib tosylate ethanol solvate.
Another embodiment o f 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 I II . 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 C 1 -C4 or their mixtures instead the use of ethanol solvent. Another embodiment o f the present invention also provides the puri fication of sorafenib base by using the solvent or their mixtures selected from the group comprising alcohols, esters, ethers, ketones, chlorinated solvents, nitri le 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 acetate or isopropyl acetate; the ether solvent selected from tetrahydrofuran, methyl tert-butyl ether or diisopropyl ether; the ketone solvent is selected from acetone, methylethylketone or methylisobutylketone; the nitrile solvent is acetonitri le. Most preferred sol vent for the puri fication 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 puri fying 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 embodi ment, the HPLC purity is greater than 99.8%. The invention will now be further described by the fol lowing examples, which are i llustrative rather than limiting.
EXAMPLES Example 1 :
Step-I: Preparation of Sorafenib Ethanol solvate 5 gm of Sorafenib base was suspended in 25 ml of Ethanol at 25-30 °C, 2.5 gm of Para toluene sulfonic acid monohydrate was dissolved in 25 ml of Ethanol and added drop wise in 1 0 minutes at 25-30 °C. Reaction mass was stirred for 7 days at 25-30 °C. Solid was filtered and washed with 1 0 ml of Ethanol .
Step-II: Preparation of Sorafenib tosylate form III Solid was dried at 80-85°C under vacuum for 20-22 Hrs. ' . Example 2:
Step-I: Preparation of Sorafenib Ethanol solvate
Sorafenib base ( 15 gm) was suspended in ethanol (75 ml) at 25-30 °C. Para toluene sulfonic acid monohydrate (7.5 gm) was dissolved in ethanol (75 ml) and. added drop wise in 10 min at 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-H: Preparation of Sorafenib tosylate form III
Obtained sorafenib ethanol solvate was dried under vacuum at 80-85°C.

Claims

WE CLAIM,
1 . A process for the preparation of sorafeni b tosylate form III. which comprises steps of:
a) suspending sorafenib base in ethanol ;
b) adding ethanolic solution of para toluene sul fonic acid in step (a);
c) isolating sorafenib tosylate ethanol solvate and
d) drying the solid of step (c) to obtain sorafenib tosylate form II I.
2. A process for the preparation of sorafenib tosylate form ill, which comprises steps of:
a) suspending sorafenib base in ethanol at 25-30°C
b) adding ethanol ic solution of para toluene sul fonic acid in step (a) at 25- 30°C;
c) isolating sorafenib tosylate ethanol solvate at 25-30°C and
d) drying the solid of step (c) at 80-85°C under vacuum to obtain sorafenib tosylate form III.
3. A process for the preparation of sorafenib tosylate form lit, which comprises steps of:
a) purifying crude sorafenib base with acetone to obtain pure sorafenib base b) suspending pure sorafenib base i n ethanol at 25-30°C
c) adding ethanol ic solution of para tol uene sul fonic acid in step (a) at 25- 30°C;
d) isolating sorafenib tosylate ethanol solvate at 25-30°C and
e) drying the solid of step (c) to obtain sorafenib tosylate form I II.
4. A process for the preparation of pure Sorafenib base accordi ng to claim 3 having HPLC purity greater than 99.0%.
PCT/IN2014/000078 2013-02-04 2014-01-31 A novel process for the preparation of sorafenib tosylate form iii WO2014118807A1 (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104177292A (en) * 2014-08-08 2014-12-03 亿腾药业（泰州）有限公司 Method for industrial production of sorafenib tosylate polymorphic form I
CN105503715A (en) * 2015-12-03 2016-04-20 神威药业集团有限公司 Sorafenib semi-tosylate polymorphism and preparing method thereof
EP3109236A1 (en) 2015-06-23 2016-12-28 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Scalable process for the preparation of sorafenib tosylate ethanol solvate and sorafenib tosylate form iii
CN107840823A (en) * 2016-09-20 2018-03-27 意大利合成制造有限公司 For the method for the scalable for preparing Sorafenib Tosylate alcohol solvent compound and III type Sorafenib Tosylates
CN111704574A (en) * 2019-03-17 2020-09-25 齐鲁制药有限公司 Preparation method of high-purity sorafenib tosylate crystal form III

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006034796A1 (en) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide
WO2006034797A1 (en) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Thermodynamically stable form of bay 43-9006 tosylate
WO2009092070A1 (en) * 2008-01-17 2009-07-23 Sicor Inc. Polymorph form iii of sorafenib tosylate, sorafenib tosylate methanol solvate and sorafenib tosylate ethanol solvate, and processes for preparation thereof
WO2011036647A1 (en) * 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Process for the preparation of sorafenib tosylate

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006034796A1 (en) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Process for the preparation of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide
WO2006034797A1 (en) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Thermodynamically stable form of bay 43-9006 tosylate
WO2009092070A1 (en) * 2008-01-17 2009-07-23 Sicor Inc. Polymorph form iii of sorafenib tosylate, sorafenib tosylate methanol solvate and sorafenib tosylate ethanol solvate, and processes for preparation thereof
WO2011036647A1 (en) * 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Process for the preparation of sorafenib tosylate

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104177292A (en) * 2014-08-08 2014-12-03 亿腾药业（泰州）有限公司 Method for industrial production of sorafenib tosylate polymorphic form I
EP3109236A1 (en) 2015-06-23 2016-12-28 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Scalable process for the preparation of sorafenib tosylate ethanol solvate and sorafenib tosylate form iii
US9738607B2 (en) 2015-06-23 2017-08-22 F.I.S.—Fabbrica Italiana Sintetici S.p.A. Scalable process for the preparation of Sorafenib tosylate ethanol solvate and Sorafenib tosylate form III
CN105503715A (en) * 2015-12-03 2016-04-20 神威药业集团有限公司 Sorafenib semi-tosylate polymorphism and preparing method thereof
CN107840823A (en) * 2016-09-20 2018-03-27 意大利合成制造有限公司 For the method for the scalable for preparing Sorafenib Tosylate alcohol solvent compound and III type Sorafenib Tosylates
CN107840823B (en) * 2016-09-20 2021-08-17 意大利合成制造有限公司 Variable-scale process for preparing sorafenib tosylate ethanol solvate and sorafenib tosylate form III
CN111704574A (en) * 2019-03-17 2020-09-25 齐鲁制药有限公司 Preparation method of high-purity sorafenib tosylate crystal form III

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