WO2014033758A1 - 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium - Google Patents
4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium Download PDFInfo
- Publication number
- WO2014033758A1 WO2014033758A1 PCT/IN2013/000529 IN2013000529W WO2014033758A1 WO 2014033758 A1 WO2014033758 A1 WO 2014033758A1 IN 2013000529 W IN2013000529 W IN 2013000529W WO 2014033758 A1 WO2014033758 A1 WO 2014033758A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- bosentan sodium
- bosentan
- sodium
- mixture obtained
- theta
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 0 CC(C)(C)c(cc1)ccc1S(*c(nc(-c1ncccn1)nc1OCCO)c1Oc1ccccc1OC)(=O)=O Chemical compound CC(C)(C)c(cc1)ccc1S(*c(nc(-c1ncccn1)nc1OCCO)c1Oc1ccccc1OC)(=O)=O 0.000 description 1
- FAOHCINTLFVHEJ-UHFFFAOYSA-O CC(C)(C)c(cc1)ccc1S(Nc(nc(-c1ncccn1)nc1C)c1Oc1ccccc1OC)([OH2+])=O Chemical compound CC(C)(C)c(cc1)ccc1S(Nc(nc(-c1ncccn1)nc1C)c1Oc1ccccc1OC)([OH2+])=O FAOHCINTLFVHEJ-UHFFFAOYSA-O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Definitions
- the present invention provides a purification method of 4-tert-butyl-n-[6- (2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-pyrimidine-4-yl]- benzenesulfonamide sodium and a novel polymorphic form of the Bosentan sodium.
- Bosentan is first disclosed in, the patent US5292740 and used in the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with grade III functional status.
- the patent US5292740 (hereinafter referred as US'740) discloses a method for the preparation of Bosentan sodium (formula III) involving the reaction of chloropyrimidin benzenesulfonamide (formula II) with sodium metal in ethylene glycol.
- Bosentan sodium (formula III) is employed for the preparation of Bosentan Formula I)
- the PCT publication WO 2011/058524 discloses form C and form D of Bosentan sodium salt characterized by XPRD values and the process for preparing the same thereof.
- the PCT publication WO2012056468 discloses the crystalline Bosentan Lithium salt and the process for preparing the same thereof.
- the primary aspect of the present invention is to provide a novel crystalline form of substantially pure Bosentan sodium.
- a further aspect of the present invention provides the process for the preparation of the novel crystalline form B of Bosentan sodium salt, characterized by an X-ray powder diffraction pattern having peaks expressed as 2-theta which include 5.5, 7.5, 11.1, 18.9, 22.7 ⁇ 2-theta.
- Another aspect of the invention provides a process for the purification of Bosentah sodium comprising the steps of:
- step (a) optionally refluxing the mixture obtained in step (a);
- step (c) treating the mixture obtained in step (c) with activated charcoal;
- Yet another aspect of the invention provides bosentan sodium having less than about 0.5 % of dimer impurity, preferably 0.2 % of dimer impurity
- Figure 1 depicts X-Ray Powder Diffraction (XRPD) pattern of Form A of Bosentan sodium.
- Figure 2 depicts X-Ray Powder Diffraction (XRPD) pattern of Form B of Bosentan sodium.
- FIG. 3 depicts Differential Scanning Calorimetry (DSC) pattern of Form B of Bosentan sodium.
- FIG. 4 depicts Thermal Gravimetric Analysis (TGA) of Form B of Bosentan sodium. Description of the invention
- the present invention provides a process for preparing the highly pure Bosentan sodium having less than about 0.2 % of dimer impurity.
- step (a) optionally refluxing the mixture obtained in step (a);
- step (c) treating the mixture obtained in step (c) with activated charcoal;
- the bosentan sodium used as starting material may be prepared according to the any known prior art methods.
- the organic solvent used in the step (a) is selected from the group comprising of polar solvents such as dimethylformamide, acetonitrile and acetone; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol, tert- butanol and i-amylalcohol; fluorinated alcohols such as trifluorOethanol or the mixtures thereof, preferably acetonitrile.
- polar solvents such as dimethylformamide, acetonitrile and acetone
- ethers such as tetrahydrofuran and dioxane
- alcohols such as methanol, tert- butanol and i-amylalcohol
- fluorinated alcohols such as trifluorOethanol or the mixtures thereof, preferably acetonitrile.
- the present invention provides a crystalline Form B of Bosentan sodium.
- the XRPD of crystalline Form B of Bosentan sodium characterized by an X-ray powder diffraction pattern having peaks expressed in 2-theta which includes 5.5, 7.5, 1 1.1, 18.9, 22.7 ⁇ 2-theta and further peaks at 9.77, 10.24, 1 1.60, 12.21 , 12.56, 12.89, 14.06, 14.59, 15.1 1, 16.71 , 17.40, 18.1 1 , 19.20, 19.60.
- the DSC has substantially the same pattern as depicted in Figure 3.
- DSC exhibits one melting endotherm between about 204 ⁇ 3°C.
- a weight loss of about 3.0 % to about 3.7 % at a temperature of about 50°C to about 200°C is observed as measured by TGA( Figure 4)
- the present invention provides a process for preparing novel crystalline Form B of Bosentan sodium salt, characterized by an X-ray powder diffraction pattern having peaks expressed as 2-theta which includes 5.5, 7.5, 1 1.1, 18.9, 22.7 ⁇ 2-theta comprising the steps of:
- step (a) optionally refluxing the mixture obtained in step (a);
- step (c) treating the mixture obtained in step (c) with activated charcoal;
- the organic solvent used in the step (a) is selected from the group comprising of polar solvents such as dimethylformamide, acetonitrile and acetone; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol, tert-butanol and i-amylalcohol; fluorinated alcohols such as trifluoroethanol or the mixtures thereof, preferably acetonitrile.
- polar solvents such as dimethylformamide, acetonitrile and acetone
- ethers such as tetrahydrofuran and dioxane
- alcohols such as methanol, tert-butanol and i-amylalcohol
- fluorinated alcohols such as trifluoroethanol or the mixtures thereof, preferably acetonitrile.
- Crystalline Bosentan Sodium prepared in the present process has less than about 0.2 % of dimer impurity
- Crystalline Bosentan Sodium prepared in the present process may be employed in the preparation of Bosentan monohydrate.
- Bosentan sodium Form B [0032] A mixture of Bosentan sodium (lOOgm) and acetonitrile (450 ml) was heated up to reflux temperature for 15 min, and then purified water was added drop wise up to hazy solution at the reflux temperature. The reaction mixture was stirred for 15 min and added activated charcoal. The reaction mixture was stirred for 30 min, filtered and washed with acetonitrile. The filtrate was slowly cooled to 25-30°C for 3 hours and maintained for 1 hour at the same temperature. The resultant solid was filtered and dried at vacuum.
- the wet material (168 gm) was suspended in acetonitrile (360 ml) at 30°C, heated to 85°C and maintained for 15 minutes at the same temperature. Purified water was slowly added to the contents at 85 °C till formation of clear solution and maintained for 30 minutes at the same temperature. The contents were cooled to 30°C for 3 hours and maintained at the same temperature for 1 hour. The resultant solid was filtered, washed with acetonitrile (100 ml) and dried at 65°C for 10 hours.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
-TERT-BUTYL-N-[6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)-2(2-PY RIMIDINYL)-PYRIMIDINE-4-YL)-BENZEN ESULFONAMIDE SODIUM
SPECIFICATION
Title of the invention
Process for the purification of 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxy phenoxy) -2-(2-pyrimidinyl)-pyrimidine-4-yl]-benzen esulfonamide sodium.
Cross reference to related application
[0001] This application claims priority from the provisional specification No. 3618/CHE/2012 filed on 31.08 2012.
Field of the invention
[0002] The present invention provides a purification method of 4-tert-butyl-n-[6- (2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-pyrimidine-4-yl]- benzenesulfonamide sodium and a novel polymorphic form of the Bosentan sodium.
Background of the invention
[0003] 4-Tert-butyl-n-[6- (2-hydroxyethoxy)- 5- (2-methoxyphenoxy)- 2- (2- pyrimidinyl)-pyrimidine-4-yl] -benzenesulfonamide, monohydrate also known as Bosentan monohydrate is represented by structural formula (I).
[0004] Bosentan is first disclosed in, the patent US5292740 and used in the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with grade III functional status.
[0005] The patent US5292740 (hereinafter referred as US'740) discloses a method for the preparation of Bosentan sodium (formula III) involving the reaction of chloropyrimidin benzenesulfonamide (formula II) with sodium metal in ethylene glycol. Bosentan sodium (formula III) is employed for the preparation of Bosentan Formula I)
chloro bipyrimidine benzene sulfonamide Bosentan sodium salt
Formula II Formula III
[0006] The process according to the patent US'740 leads to the formation of undesired ethylene glycol bisulfonamide along with Bosentan which show negative impact on yield of Bosentan. This ethylene glycol bisulfonamide is also known as dimer impurity. Hence Bosentan. prepared according to the patent
US'740 requires repeated purification to get desired purity.
[0007] The patent US'740 discloses crystalline Bosentan sodium salt having characteristic peaks of XPRD shown in Figure 1 and melting point of 195 to 198°C.
[0008] The PCT publication WO 2011/058524 discloses form C and form D of Bosentan sodium salt characterized by XPRD values and the process for preparing the same thereof. The PCT publication WO2012056468 discloses the crystalline Bosentan Lithium salt and the process for preparing the same thereof.
Summary of the invention
[0009] The primary aspect of the present invention is to provide a novel crystalline form of substantially pure Bosentan sodium.
[0010] A further aspect of the present invention provides the process for the preparation of the novel crystalline form B of Bosentan sodium salt, characterized by an X-ray powder diffraction pattern having peaks expressed as 2-theta which include 5.5, 7.5, 11.1, 18.9, 22.7 ± 2-theta.
[0011] Another aspect of the invention provides a process for the purification of Bosentah sodium comprising the steps of:
a) adding an organic solvent to Bosentan sodium;
b) optionally refluxing the mixture obtained in step (a);
c) adding water to the mixture obtained in step (a) or (b);
d) treating the mixture obtained in step (c) with activated charcoal;
e) filtering the reaction mass, optionally washing the filter bed;
f) optionally heating the filtrate;
g) cooling the reaction mass; and
h) filtering the Bosentan sodium.
[0012] Yet another aspect of the invention provides bosentan sodium having less than about 0.5 % of dimer impurity, preferably 0.2 % of dimer impurity
Brief Description of the Drawings
[0013] Figure 1 depicts X-Ray Powder Diffraction (XRPD) pattern of Form A of Bosentan sodium.
[0014] Figure 2 depicts X-Ray Powder Diffraction (XRPD) pattern of Form B of Bosentan sodium.
[0015] Figure 3 depicts Differential Scanning Calorimetry (DSC) pattern of Form B of Bosentan sodium.
[0016] Figure 4 depicts Thermal Gravimetric Analysis (TGA) of Form B of Bosentan sodium.
Description of the invention
[0017] The present invention provides a process for preparing the highly pure Bosentan sodium having less than about 0.2 % of dimer impurity.
[0018] The process for preparing the. highly pure Bosentan sodium with less than about 0.2 % of dimer impurity comprising the steps of :
a) adding an organic solvent to Bosentan sodium;
b) optionally refluxing the mixture obtained in step (a);
c) adding water to the mixture obtained in step (a) or (b);
d) treating the mixture obtained in step (c) with activated charcoal;
e) filtering the reaction mass, optionally washing the filter bed;
fj. optionally heating the filtrate;
g) cooling the reaction mass; and
h) filtering the Bosentan sodium.
[0019] The bosentan sodium used as starting material may be prepared according to the any known prior art methods.
[0020] The organic solvent used in the step (a) is selected from the group comprising of polar solvents such as dimethylformamide, acetonitrile and acetone; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol, tert- butanol and i-amylalcohol; fluorinated alcohols such as trifluorOethanol or the mixtures thereof, preferably acetonitrile.
[0021] The present invention provides a crystalline Form B of Bosentan sodium.
[0022] The crystalline form B of Bosentan sodium has substantially the same
XRPD pattern as depicted in Figure 2.
[0023] The XRPD of crystalline Form B of Bosentan sodium characterized by an X-ray powder diffraction pattern having peaks expressed in 2-theta which includes 5.5, 7.5, 1 1.1, 18.9, 22.7 ± 2-theta and further peaks at 9.77, 10.24, 1 1.60, 12.21 , 12.56, 12.89, 14.06, 14.59, 15.1 1, 16.71 , 17.40, 18.1 1 , 19.20, 19.60. 19.96, 21.12, 21.99, 22.24, 23.41 , 24.59, 25.80, 26.10 ,26.86, 27.96, 30.16, 31.48, 32.26, 35.18, 37.37 ± 2-theta.
[0024] The DSC has substantially the same pattern as depicted in Figure 3. The
DSC exhibits one melting endotherm between about 204 ± 3°C.
[0025] A weight loss of about 3.0 % to about 3.7 % at a temperature of about 50°C to about 200°C is observed as measured by TGA(Figure 4)
[0026] The present invention provides a process for preparing novel crystalline Form B of Bosentan sodium salt, characterized by an X-ray powder diffraction pattern having peaks expressed as 2-theta which includes 5.5, 7.5, 1 1.1, 18.9, 22.7 ± 2-theta comprising the steps of:
a) adding an organic solvent to Bosentan sodium;
b) optionally refluxing the mixture obtained in step (a);
c) adding water to the mixture obtained in step (a) or (b);
d) treating the mixture obtained in step (c) with activated charcoal;
e) filtering the reaction mass, optionally washing the filter bed;
f) optionally heating the filtrate;
g) cooling the reaction mass; and
h) filtering the Bosentan sodium.
[0027] The organic solvent used in the step (a) is selected from the group comprising of polar solvents such as dimethylformamide, acetonitrile and
acetone; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol, tert-butanol and i-amylalcohol; fluorinated alcohols such as trifluoroethanol or the mixtures thereof, preferably acetonitrile.
[0028] Crystalline Bosentan Sodium prepared in the present process has less than about 0.2 % of dimer impurity
[0029] Crystalline Bosentan Sodium prepared in the present process may be employed in the preparation of Bosentan monohydrate.
[0030] The following example provided in the disclosure is given for the purpose of illustrating the present invention and are not intended to limit the scope on the scope of the invention in any manner.
Examples
Example 1: Method for preparing Bosentan sodium:
[0031] Sodium hydroxide (19 g) was suspended in Ethylene glycol (300ml) and heated to 55 °C, and maintained for 30 min at the same temperature. Chloro- pyrimidine benzenesulfonamide (100 g) was added into the reaction mixture at 55 °C and slowly the temperature was raised up to 93 °C. The reaction mixture was maintained at 93 °C for 5 hours. After cooling the reaction mixture to 55 °C, water (1000 ml) was slowly added into the reaction mixture. The reaction was then cooled to room temperature and maintained for one hour at the same temperature. The resultant solid was filtered, washed with water (100 ml) and dried.
Yield = 95 %; Dimmer impurity: more than 2.5 %.
Method for preparing Bosentan sodium Form B:
[0032] A mixture of Bosentan sodium (lOOgm) and acetonitrile (450 ml) was heated up to reflux temperature for 15 min, and then purified water was added drop wise up to hazy solution at the reflux temperature. The reaction mixture was stirred for 15 min and added activated charcoal. The reaction mixture was stirred for 30 min, filtered and washed with acetonitrile. The filtrate was slowly cooled to 25-30°C for 3 hours and maintained for 1 hour at the same temperature. The resultant solid was filtered and dried at vacuum.
The wet material (168 gm) was suspended in acetonitrile (360 ml) at 30°C, heated to 85°C and maintained for 15 minutes at the same temperature. Purified water was slowly added to the contents at 85 °C till formation of clear solution and maintained for 30 minutes at the same temperature. The contents were cooled to 30°C for 3 hours and maintained at the same temperature for 1 hour. The resultant solid was filtered, washed with acetonitrile (100 ml) and dried at 65°C for 10 hours.
Yield = 65.7 %; HPLC purity: 99.7 %; Dimmer impurity: less than 0.2 %.
Claims
1. A novel crystalline form B of bosentan sodium salt, characterized by a x-ray powder diffraction pattern having peaks expressed in 2-theta which includes 5.5,
7.5, 11.1, 18.9, 22.7 ± 2-theta.
2. A process for the purification of Bosentan sodium comprising the steps of: a) adding an organic solvent to Bosentan sodium;
b) optionally refluxing the mixture obtained in step (a);
c) adding water to the mixture obtained in step (a) or (b);
d) treating the mixture obtained in step (c) with activated charcoal;
e) filtering the reaction mass, optionally washing the filter bed;
f) optionally heating the filtrate;
g) cooling the reaction mass; and
h) filtering the bosentan sodium.
3. The process according to the claim-2, wherein said organic solvent used in the step (a) is selected from the group comprising of polar solvents, ethers, alcohols, fluorinated alcohols or the mixtures thereof.
4. The process according to the claim-2, wherein said bosentan sodium have less than about 0.2 % of dimer impurity
5. A process for preparing novel crystalline form B of bosentan sodium salt, characterized by an x-ray powder diffraction pattern having peaks expressed in 2- theta which includes 5.5, 7.5, 1 1.1, 18.9, 22.7 ± 2-theta comprising the steps of: a) adding an organic solvent to bosentan sodium;
b) optionally refluxing the mixture obtained in step (a);
c) adding water to the mixture obtained in step (a) or (b);
d) treating the mixture obtained in step (c) with activated charcoal;
e) filtering the reaction mass, optionally washing the filter bed;
f) optionally heating the filtrate;
g) cooling the reaction mass; and
h) filtering the bosentan sodium.
6. The process according to the claim-5, wherein said organic solvent used in the step (a) is selected from the group comprising of polar solvents,ethers, alcohols, fluorinated alcohols or the mixtures thereof.
7. The process according to the claim-5, wherein said crystalline form B of bosentan sodium salt have less than about 0.2 % of dimer impurity.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13833890.0A EP2890694A4 (en) | 2012-08-31 | 2013-08-29 | 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium |
| US14/425,108 US9296705B2 (en) | 2012-08-31 | 2013-08-29 | 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN3618CH2012 | 2012-08-31 | ||
| IN3618/CHE/2012 | 2012-08-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2014033758A1 true WO2014033758A1 (en) | 2014-03-06 |
Family
ID=50182619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2013/000529 Ceased WO2014033758A1 (en) | 2012-08-31 | 2013-08-29 | 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US9296705B2 (en) |
| EP (1) | EP2890694A4 (en) |
| WO (1) | WO2014033758A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292740A (en) | 1991-06-13 | 1994-03-08 | Hoffmann-La Roche Inc. | Sulfonamides |
| WO2009083739A1 (en) * | 2008-01-01 | 2009-07-09 | Cipla Limited | Method of synthesis of bosentan, its polymorphic forms and its salts |
| US20110014291A1 (en) * | 2007-10-11 | 2011-01-20 | Actavis Group Ptc Ehf | Novel Polymorphs of Bosentan |
| WO2011058524A2 (en) | 2009-11-12 | 2011-05-19 | Ranbaxy Laboratories Limited | Crystalline forms of bosentan salt and processes for their preparation |
| WO2012056468A1 (en) | 2010-10-13 | 2012-05-03 | Matrix Laboratories Ltd | A process for the preparation of bosentan |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2621909B1 (en) * | 2010-10-01 | 2018-12-19 | ZaCh System S.p.A. | Process for preparing bosentan monohydrate and its intermediates |
| ITMI20120701A1 (en) * | 2012-04-27 | 2013-10-28 | Dipharma Francis Srl | PROCEDURE FOR THE PURIFICATION OF A BENZENSOLPHONAMID COMPOUND |
-
2013
- 2013-08-29 WO PCT/IN2013/000529 patent/WO2014033758A1/en not_active Ceased
- 2013-08-29 US US14/425,108 patent/US9296705B2/en not_active Expired - Fee Related
- 2013-08-29 EP EP13833890.0A patent/EP2890694A4/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292740A (en) | 1991-06-13 | 1994-03-08 | Hoffmann-La Roche Inc. | Sulfonamides |
| US20110014291A1 (en) * | 2007-10-11 | 2011-01-20 | Actavis Group Ptc Ehf | Novel Polymorphs of Bosentan |
| WO2009083739A1 (en) * | 2008-01-01 | 2009-07-09 | Cipla Limited | Method of synthesis of bosentan, its polymorphic forms and its salts |
| WO2011058524A2 (en) | 2009-11-12 | 2011-05-19 | Ranbaxy Laboratories Limited | Crystalline forms of bosentan salt and processes for their preparation |
| WO2012056468A1 (en) | 2010-10-13 | 2012-05-03 | Matrix Laboratories Ltd | A process for the preparation of bosentan |
Non-Patent Citations (1)
| Title |
|---|
| See also references of EP2890694A4 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US9296705B2 (en) | 2016-03-29 |
| EP2890694A4 (en) | 2015-12-30 |
| EP2890694A1 (en) | 2015-07-08 |
| US20150232430A1 (en) | 2015-08-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016515570A (en) | Production of pyrimidine intermediates useful for the production of masitentan | |
| WO2016092478A1 (en) | Process for preparation of luliconazole | |
| US20160362385A1 (en) | Method for producing 1,4-benzoxazine compound | |
| US9150547B2 (en) | Process for the preparation of pazopanib using novel intermediate | |
| US20140187569A1 (en) | Crystalline forms of bosentan salts and processes for their preparation | |
| EP2809665A1 (en) | Process for the preparation of vilazodone or its pharmaceutically acceptable salts | |
| WO2015049698A2 (en) | Process for regorafenib | |
| WO2015014984A1 (en) | A process for preparing rifaximin k | |
| US9695124B2 (en) | Method of producing 2-aminonicotinic acid benzyl ester derivatives | |
| US9296705B2 (en) | 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium | |
| US8575344B2 (en) | Process for preparing voriconazole by using new intermediates | |
| EP2603497B1 (en) | A novel process for preparation of bosentan | |
| WO2012011129A2 (en) | Novel polymorph of bis[(e)-7-[4-(4-fluorophenyl)-6-iso-propyl-2-[methyl (methylsulfonyl)amino]pyrimidin-5-yl](3r,5s)-3,5-dihydroxyhept-6-enoic acid] calcium salt | |
| JP6375374B2 (en) | Method for producing pyrimidine intermediate | |
| KR101471047B1 (en) | Improved process for preparation of highly pure bosentan | |
| EP3374349A1 (en) | Process for the preparation of eltrombopag olamine | |
| WO2013186706A1 (en) | Process for the preparation of bosentan | |
| CA2677204C (en) | Process for the preparation of (r) -5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione | |
| TW202019885A (en) | Preparation method of azoxystrobin performing first reduced-pressure distillation on the reacted alkaline mixture under the conditions of 70-80 DEG C and 80-120 torr to obtain azoxystrobin | |
| WO2009069014A1 (en) | Amorphous lamivudine and its preparation | |
| CN110105354A (en) | A method of preparing tetrabenazine | |
| WO2014108806A2 (en) | A novel process for the preparation of n-(4-nitro-2-sulfamoly-phenyl)-malonamic acid methyl ester and n-(4-amino-2-sulfamoyl-phenyl)-malonamic acid methyl ester | |
| KR20070065653A (en) | Preparation of 6- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -3-pyridin-4-yl-pyrazolo [1,5-a] pyrimidine | |
| WO2011121597A1 (en) | A PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED 3-(5-NITRO-4-THIOCYANATOPYRIMIDIN-2-YL)-3H-BENZO [d]-IMIDAZOLE | |
| HK1213239B (en) | A novel process for the preparation of n-(4-nitro-2-sulfamoyl-phenyl)-malonamic acid methyl ester and n-(4-amino-2-sulfamoyl-phenyl)-malonamic acid methyl ester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13833890 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 14425108 Country of ref document: US |