CN103613579A - Bilastine purifying method - Google Patents
Bilastine purifying method Download PDFInfo
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- CN103613579A CN103613579A CN201310566799.6A CN201310566799A CN103613579A CN 103613579 A CN103613579 A CN 103613579A CN 201310566799 A CN201310566799 A CN 201310566799A CN 103613579 A CN103613579 A CN 103613579A
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- Prior art keywords
- bilastine
- alpha
- compound
- mixed solvent
- ethyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention provides a method for refining and purifying 4-[2-[4-[1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]-1-piperidine]ethyl]-alpha, alpha-dimethyl phenylacetic acid (Bilastine). Bilastine is used for treating allergic rhinitis and chronic idiopathic urticaria, has good safety and does not have the sedative effect and cardiac toxicity of common antihistamine drugs. In most of Bilastine preparation processes, the impurity content is high, and stubborn impurities are difficult to remove. The method for refining and purifying Bilastine, provided by the invention, comprises the steps of dissolving a crude product of Bilastine into a hot mixed solvent, cooling, precipitating, filtering, washing and drying to obtain high-purity Bilastine, wherein the impurity content meets the requirements.
Description
Technical field
The invention belongs to pharmaceutical chemistry field, a kind of 4-[2-[4-[1-(2-ethoxyethyl group)-1 is provided
h-benzimidazolyl-2 radicals-yl]-1-piperidines] ethyl] the refining purification process of-alpha-alpha-dimethyl phenyl acetic acid (being below called Bilastine).
Background technology
Bilastine is the 2nd generation histamine H of Spain FAES drugmaker exploitation
1receptor antagonist, European Union in 2010 ratifies it and is used for the treatment of rhinallergosis and chronic idiopathic urticaria; In the U.S., carry out the clinical study of II phase, investigate its curative effect to seasonal allergy nose-conjunctivitis simultaneously.The research of carrying out in health volunteer and rhinitis patient shows: this product security is good, variable sedative effect and the cardiac toxic existing by antihistamine drug.
This product chemical structural formula:
As a rule, a kind of impurity of the drug total content should be less than 0.3 %, and single foreign matter content is less than 0.1 %; But prepare in the process of Bilastine in laboratory, according to the prepared product of the method for patent US5322850A, foreign matter content is too high, contain the less desirable impurity more than 0.3 %, wherein some intractable impurity can not effectively be removed by literature method.So, be necessary to study the method for refining Bilastine a kind of, make its foreign matter content reach requirement.Method provided by the present invention can effectively be removed above impurity.
Summary of the invention
The present invention relates to the method for purifying Bilastine a kind of, make its foreign matter content reach the requirement of qualified medicine, step comprises:
A) Bilastine is joined in mixed solvent, form suspension;
B) stir and heat described suspension, solid is all dissolved;
C) the described solution of cooling step (b), the cooling solid of separating out;
D) suction filtration, washing and dry after obtain highly purified Bilastine.
Wherein said solvent is methyl acetate, ethyl acetate, propyl acetate; Acetone, butanone, benzophenone; Methyl alcohol, ethanol, Virahol, propyl carbinol, ethylene glycol; Methylene dichloride, trichloromethane, tetracol phenixin; Acetonitrile, propionitrile; The solvent of two or more in ether, isopropyl ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF).
embodiment
The following examples are in order to describe the specific embodiment of the present invention in detail, and these descriptions are not that content of the present invention is further limited.
embodiment 1
Bilastine crude product 20.0 g are dissolved in 250 mL ethyl acetate and acetone, after being heated to reflux, solid all dissolves, filter, filtrate stirring at normal temperature approximately 3 hours, separates out white solid, filter, ethyl acetate washing twice for filter cake, then drains, finally at vacuum drying oven inner drying, obtain white solid 17.8 g, purity 99.7 %.
embodiment 2
Bilastine crude product 20.0 g are dissolved in the mixed solvent of 250 mL acetone and ethylene glycol (volume ratio 1 to 1), after being heated to reflux, solid all dissolves, filter, filtrate stirring at normal temperature approximately 3 hours, separates out white solid, filter, washing with acetone twice for filter cake, then drains, finally at vacuum drying oven inner drying, obtain white solid 18.9 g, purity 99.8 %.
Claims (4)
1. a refining purifying 4-[2-[4-[1-(2-ethoxyethyl group)-1
h-benzimidazolyl-2 radicals-yl]-1-piperidines] ethyl] method of-alpha-alpha-dimethyl phenyl acetic acid, it is characterized in that: by 4-[2-[4-[1-(2-ethoxyethyl group)-1
h-benzimidazolyl-2 radicals-yl]-1-piperidines] ethyl]-alpha-alpha-dimethyl phenyl acetic acid (Bilastine) crude product adds in mixed solvent, heating for dissolving, crystallisation by cooling, suction filtration, the dry bilastine highly finished product that obtain.
2. according to the method for claim 1, it is characterized in that described mixed solvent is ester compound, ketone compounds, alcohol compound, nitrile compounds, halogenated hydrocarbon compound, ether compound.
3. according to the method for claim 2, it is characterized in that the ester compound in described mixed solvent is methyl acetate, ethyl acetate, propyl acetate; Ketone compounds is acetone, butanone, benzophenone; Alcohol compound is methyl alcohol, ethanol, Virahol, propyl carbinol, ethylene glycol; Nitrile compounds is acetonitrile, propionitrile; Halogenated hydrocarbon compound is methylene dichloride, trichloromethane, tetracol phenixin; Ether compound is ether, isopropyl ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF).
4. according to the method for claim 2 and 3, it is characterized in that mixed solvent is described two classes or the mixing of several kind solvents.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310566799.6A CN103613579A (en) | 2013-11-13 | 2013-11-13 | Bilastine purifying method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310566799.6A CN103613579A (en) | 2013-11-13 | 2013-11-13 | Bilastine purifying method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103613579A true CN103613579A (en) | 2014-03-05 |
Family
ID=50164309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310566799.6A Pending CN103613579A (en) | 2013-11-13 | 2013-11-13 | Bilastine purifying method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103613579A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104530002A (en) * | 2015-01-29 | 2015-04-22 | 天津梅花生物医药科技有限公司 | Bilastine compound and preparation method thereof |
| CN105319288A (en) * | 2014-07-31 | 2016-02-10 | 重庆华邦制药有限公司 | Method for separating and measuring bilastine and technical impurities in preparation of bilastine |
| WO2017167949A1 (en) | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| WO2019175722A1 (en) * | 2018-03-12 | 2019-09-19 | Symed Labs Limited | Process for the preparation of stable and highly pure crystalline form 2 of bilastine |
-
2013
- 2013-11-13 CN CN201310566799.6A patent/CN103613579A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105319288A (en) * | 2014-07-31 | 2016-02-10 | 重庆华邦制药有限公司 | Method for separating and measuring bilastine and technical impurities in preparation of bilastine |
| CN105319288B (en) * | 2014-07-31 | 2019-04-16 | 重庆华邦制药有限公司 | A kind of method of process impurity in separation determination bilastine and its preparation |
| CN104530002A (en) * | 2015-01-29 | 2015-04-22 | 天津梅花生物医药科技有限公司 | Bilastine compound and preparation method thereof |
| WO2017167949A1 (en) | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| WO2019175722A1 (en) * | 2018-03-12 | 2019-09-19 | Symed Labs Limited | Process for the preparation of stable and highly pure crystalline form 2 of bilastine |
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Legal Events
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| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140305 |