CN104292217A - Preparation method and purification method of alpha crystal form eletriptan hydrobromide - Google Patents
Preparation method and purification method of alpha crystal form eletriptan hydrobromide Download PDFInfo
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- CN104292217A CN104292217A CN201310120085.2A CN201310120085A CN104292217A CN 104292217 A CN104292217 A CN 104292217A CN 201310120085 A CN201310120085 A CN 201310120085A CN 104292217 A CN104292217 A CN 104292217A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract
The invention discloses a preparation method and a purification method of alpha crystal form eletriptan hydrobromide. The preparation method is selected from any one of a method I and a method II. The method I comprises the following steps: dissolving beta crystal form eletriptan hydrobromide and/or an eletriptan hydrobromide monohydrate into an alcohol mixed solvent; performing heating reflux; and performing crystallization, wherein the alcohol mixed solvent is a mixed solvent of a solvent A and a solvent B; the solvent A is methanol and/or ethanol; and the solvent B is one or more of isopropanol, butanol, isobutanol, tertiary butanol and pentanol. The method II comprises the following steps: reacting hydrogen bromide with eletriptan in the alcohol solvent; and performing crystallization. The purification method comprises the following steps: performing heating reflux on a mixed solution of crude alpha crystal form eletriptan hydrobromide and the alcohol mixed solvent; and performing crystallization. The preparation method has the advantages of easiness and convenience in operation, stable process, high yield and the like. Through adoption of the purification method, impurities can be effectively removed. Moreover, the purification method is easy and convenient in operation, and high in yield.
Description
Technical field
The present invention relates to medicinal chemistry art, particularly relate to a kind of preparation method and purification process of alpha-crystal form Hydrogen bromide eletriptan.
Background technology
Hydrogen bromide eletriptan (Eletriptan Hydrobromide, trade(brand)name: Relpax), its chemistry (R)-3-[(1-methyl-2-pyrrolidyl) methyl]-5-[2-(benzene sulfonyl) ethyl]-1H-indole hydrobromide by name, molecular formula is C
22h
26n
2o
2s.HBr, structural formula is as follows:
US Patent No. 5545644, US5607951 disclose eletriptan and preparation method thereof, and international monopoly WO0250063 discloses the Refined preparation method of eletriptan.
International monopoly WO9606842 discloses Hydrogen bromide eletriptan, alpha-crystal form and preparation method thereof, and its alpha-crystal form is as the migrainous medicine listing for the treatment of.This disclosure of the invention preparation method of two kinds of alpha-crystal form Hydrogen bromide eletriptans, a kind of method: with the acetone soln of 48% Hydrogen bromide process eletriptan, concentration of reaction solution, obtains the crystallization of oily matter Virahol; Another kind method: with the acetone soln of 62% Hydrogen bromide process eletriptan, stirs pulping, cooling crystallization again after reflux.During extensive preparation, the yield of second method is only 73%.
International monopoly WO2005007649 discloses the Refined preparation method of alpha-crystal form Hydrogen bromide eletriptan, concrete steps are: with the 2-butanone solution of Hydrogen bromide process eletriptan, slurry dewaters (if desired through methylbenzene azeotropic) through component distillation, obtains alpha-crystal form product, and yield is 95%.
For better meeting global pharmacy needs, the method developing high yield and low cost has higher practical commercial value, is therefore necessary to seek easy and simple to handle, process stabilizing and the high alpha-crystal form Hydrogen bromide eletriptan preparation method of yield.
Summary of the invention
Technical problem solved by the invention is the defect such as existing alpha-crystal form Hydrogen bromide eletriptan preparation method yield is not high, complicated operation in order to overcome, and provides a kind of preparation method and purification process of alpha-crystal form Hydrogen bromide eletriptan.The preparation method of alpha-crystal form Hydrogen bromide eletriptan of the present invention is simple to operate, yield is high, process stabilizing, is applicable to suitability for industrialized production; Purification process of the present invention effectively can improve product purity, and yield is higher.
The present invention solves the problems of the technologies described above by the following technical programs:
The invention provides a kind of preparation method of alpha-crystal form Hydrogen bromide eletriptan, it adopts any one in following method:
Method one: by beta crystal Hydrogen bromide eletriptan and/or Hydrogen bromide eletriptan monohydrate, be dissolved in alcohols mixed solvent, reflux, crystallization; Described alcohols mixed solvent is the mixed solvent of solvent orange 2 A and solvent B, and solvent orange 2 A is methyl alcohol and/or ethanol, and solvent B is one or more in Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol;
Method two: in alcoholic solvent, reacts hydrogen bromide and eletriptan, crystallization.
In method one of the present invention, the volume ratio of described solvent orange 2 A and solvent B is preferably (1:5) ~ (1:15), is more preferably 1:10.
In method one of the present invention, the volume mass of described alcohols mixed solvent and beta crystal Hydrogen bromide eletriptan and/or Hydrogen bromide eletriptan monohydrate is 10 ~ 40mL/g than preferably, is more preferably 25mL/g.
In method one of the present invention, the temperature of described reflux is preferably 80 ~ 140 DEG C.The time of described reflux is preferably with till mixed solution clarification.
In method one of the present invention, described crystallization is preferably cooling crystallization.Described cooling crystallization can be naturally cooling crystallization.The temperature of described crystallization is preferably 10 ~ 30 DEG C, and the temperature of crystallization is herein envrionment temperature under normal circumstances.
In method one of the present invention, also can carry out conventional aftertreatment after described crystallization terminates, to obtain purer alpha-crystal form Hydrogen bromide eletriptan of the present invention.Described aftertreatment preferably includes the following step: filter, and washing is dry.Described washing is preferably for adopting solvent B to wash.
In method two of the present invention, described eletriptan can be the conventional eletriptan commodity in this area, and its HPLC purity is generally greater than 98%.
In method two of the present invention, described hydrogen bromide preferably exists with hydrogen bromide solution form, described hydrogen bromide solution is preferably aqueous solution of hydrogen bromide and/or hydrogen bromide acetic acid solution, more preferably for mass concentration be 34% ~ 62% aqueous solution of hydrogen bromide and/or mass concentration be the hydrogen bromide acetic acid solution of 34% ~ 48%.The mol ratio of the hydrogen bromide in described hydrogen bromide solution and described eletriptan is preferably (0.95:1) ~ (1.20:1), is more preferably 1.1:1.
Wherein, the feed postition of described hydrogen bromide solution is preferably for be added dropwise in the mixed solution of eletriptan and alcoholic solvent by hydrogen bromide solution, and drop rate preferably controls at 0.5 ~ 2 second/.The temperature of described eletriptan and the mixed solution of alcoholic solvent is preferably 0 ~ 35 DEG C, is more preferably 20 ~ 30 DEG C.
In method two of the present invention, described alcoholic solvent is preferably one or more in methyl alcohol, ethanol, Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol, is more preferably Virahol.
In method two of the present invention, the volume mass of described alcoholic solvent and eletriptan is 5 ~ 20mL/g than preferably, is more preferably 8mL/g.
In method two of the present invention, described crystallization is preferably crystallization under agitation, and time of described stirring is preferably with till at the end of crystallization, is generally 2 ~ 6 hours.
In method two of the present invention, also can carry out conventional aftertreatment after described crystallization terminates, to obtain alpha-crystal form Hydrogen bromide eletriptan of the present invention.Described aftertreatment preferably includes the following step: filter, and washing is dry.Described washing is preferably for adopting alcoholic solvent to wash.
Can also be further purified product after described crystallization terminates, it comprises the steps: to filter, the alpha-crystal form Hydrogen bromide eletriptan crude product above-mentioned preparation method obtained and the mixed solution reflux of alcohols mixed solvent, crystallization.
Wherein, described alcohols mixed solvent is preferably the mixed solvent of solvent orange 2 A and solvent B, and solvent orange 2 A is methyl alcohol and/or ethanol, and solvent B is one or more in Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol.The volume ratio of described solvent orange 2 A and solvent B is preferably (1:5) ~ (1:15), is more preferably 1:10.
Wherein, the volume mass of described alcohols mixed solvent and alpha-crystal form Hydrogen bromide eletriptan crude product is 10 ~ 40mL/g than preferably, is more preferably 25mL/g.
Wherein, the temperature of described reflux is preferably 80 ~ 140 DEG C.The time of described reflux is preferably with till mixed solution clarification.
In purification step of the present invention, described crystallization is preferably cooling crystallization.Described cooling crystallization can be naturally cooling crystallization.The temperature of described crystallization is preferably 10 ~ 30 DEG C, and the temperature of crystallization is herein envrionment temperature under normal circumstances.
Present invention also offers a kind of purification process of alpha-crystal form Hydrogen bromide eletriptan, it comprises the following steps: the mixed solution reflux by alpha-crystal form Hydrogen bromide eletriptan crude product and alcohols mixed solvent, crystallization; Described alcohols mixed solvent is the mixed solvent of solvent orange 2 A and solvent B, and solvent orange 2 A is methyl alcohol and/or ethanol, and solvent B is one or more in Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol.
Wherein, described alpha-crystal form Hydrogen bromide eletriptan crude product can be the alpha-crystal form Hydrogen bromide eletriptan crude product that this area common process prepares, and generally its HLPC purity is 95.0 ~ 98.0%; Described alpha-crystal form Hydrogen bromide eletriptan crude product obtains preferably by above-mentioned preparation method.
Wherein, the volume ratio of described solvent orange 2 A and solvent B is preferably (1:5) ~ (1:15), is more preferably 1:10.
Wherein, the volume mass of described alcohols mixed solvent and alpha-crystal form Hydrogen bromide eletriptan crude product is 10 ~ 40mL/g than preferably, is more preferably 25mL/g.
Wherein, the temperature of described reflux is preferably 80 ~ 140 DEG C.The time of described reflux is preferably with till mixed solution clarification.
In purification process of the present invention, described crystallization is preferably cooling crystallization.Described cooling crystallization can be naturally cooling crystallization.The temperature of described crystallization is preferably 10 ~ 30 DEG C, and the temperature of crystallization is herein envrionment temperature under normal circumstances.
In the present invention, also can carry out conventional aftertreatment after described crystallization terminates, to obtain purer alpha-crystal form Hydrogen bromide eletriptan of the present invention.Described aftertreatment preferably includes the following step: filter, and washing is dry.Described washing is preferably for adopting solvent B to wash.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can arbitrary combination, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material are all commercially.
Positive progressive effect of the present invention is:
(1) preparation method in the present invention achieves easy and simple to handle, process stabilizing and yield advantages of higher, before effectively prevent report method in change numerous and diverse operation steps such as solvent, repeatedly heating and cooling, component distillation etc.; Yield also reaches 99%, higher than report in WO2005007649 95%; Process stabilizing, reaction solution, can not variable color without the need to nitrogen protection, can obtain white solid product, and HPLC purity is greater than 99.5%.
(2) purification process of the present invention effectively can remove impurity, improves product purity, and easy and simple to handle, and yield is higher.
Accompanying drawing explanation
Fig. 1 is the powder X-ray RD figure of the alpha-crystal form Hydrogen bromide eletriptan of embodiment 1.
Fig. 2 is the infrared spectrogram of the alpha-crystal form Hydrogen bromide eletriptan of embodiment 1.
Embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
In following embodiment, by the route technique preparation that document (WO0250063) is reported in the preparation method of the eletriptan solid of embodiment 1 ~ 4, be white powder solid, its HPLC purity is 98.2%.
Beta crystal Hydrogen bromide eletriptan in embodiment 5 is the product of the commercially available routine in this area, and its HPLC purity is 97.8%.
Hydrogen bromide eletriptan monohydrate in embodiment 6 is the product of the commercially available routine in this area, and its HPLC purity is 97.7%.
Alpha-crystal form Hydrogen bromide eletriptan crude product in the purification process of embodiment 7 is the crude product of the commercially available routine in this area, and its HPLC purity is 98.0%.
The route technique preparation that in embodiment 8, the preparation method of eletriptan solid reports by document (WO0250063), its HPLC purity is 97.4%.
In following embodiment, X-ray powder diffraction (XRD) source of radiation is Cu-K α; Infrared spectra adopts KBr compressing tablet.
Embodiment 1
Eletriptan solid (20.0g) and Virahol (120mL) is added in the reaction flask of drying, under stirring at room temperature, slow dropping 48% aqueous solution of hydrogen bromide (9.7g) and Virahol (40mL) mixed solution, within 1.0 hours, add, gained slurry agitation 4.0h, filtering separation, wash with Virahol (16mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (24.1g), HPLC purity 99.6%, mp165-168 DEG C, its X-ray powder diffraction (XRD) as shown in figure 1 and table 1, infrared spectra (IR) as shown in Figure 2, XRD, IR characterization result is indicated as alpha-crystal form.In its Powder XRD pattern, in diffraction angle 2 θ=9.4, there is characteristic peak at 10.4,15.6,16.2,17.4,17.9,19.0,19.4,19.8,20.9,24.1,25.1,25.4,26.2,27.2,29.2 degree of places; 2 θ value limit of error are ± 0.2.
The XRD characteristic peak of table 1 alpha-crystal form Hydrogen bromide eletriptan
| Peak is numbered | 2 θ angles (°) |
| 1 | 9.4 |
| 2 | 10.4 |
| 6 | 15.6 |
| 8 | 16.2 |
| 10 | 17.4 |
| 11 | 17.9 |
| 12 | 19.0 |
| 13 | 19.4 |
| 14 | 19.8 |
| 16 | 20.9 |
| 22 | 24.1 |
| 23 | 25.1 |
| 24 | 25.4 |
| 25 | 26.2 |
| 27 | 27.2 |
| 29 | 29.2 |
Embodiment 2
Eletriptan solid (20.0g) and butanols (160mL) is added in the reaction flask of drying, under stirring at room temperature, slow dropping 34% hydrogen bromide acetic acid solution (12.5g) and butanols (40mL) mixed solution, within 1.0 hours, add, gained slurry agitation 6.0h, filtering separation, wash with butanols (16mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (24.2g), HPLC purity 99.5%, mp165-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 3
In the reaction flask of drying, add eletriptan solid (20.0g) and ethanol (80mL), under ice bath stirs, slowly drip 62% aqueous solution of hydrogen bromide (8.8g) and ethanol (20mL) mixed solution, within 0.5 hour, add, gained slurry agitation 5.0h, filtering separation, washs with ethanol (10mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (24.0g), HPLC purity 99.6%, mp165-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 4
Eletriptan solid (20.0g) and amylalcohol (320mL) is added in the reaction flask of drying, under 35 DEG C of stirrings, slow dropping 34% hydrogen bromide acetic acid solution (13.8g) and amylalcohol (80mL) mixed solution, within 2.0 hours, add, gained slurry agitation 2.0h, filtering separation, wash with amylalcohol (20mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (24.1g), HPLC purity 99.5%, mp165-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 5
To in the reaction flask of drying, add beta crystal Hydrogen bromide eletriptan solid (20.0g, HPLC purity is 97.8%), butanols (400mL) and methyl alcohol (30mL), reflux, be stirred to reaction solution clarification, slowly be down to room temperature, leave standstill 6.0 hours, filtering separation, washs with butanols (20mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (18.4g), HPLC purity 99.7%, mp166-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 6
To in the reaction flask of drying, add Hydrogen bromide eletriptan monohydrate (20.0g, HPLC purity is 97.7%), Virahol (500mL) and ethanol (65mL), reflux, be stirred to reaction solution clarification, slowly be down to room temperature, leave standstill 6.0 hours, filtering separation, washs with Virahol (20mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (18.5g), HPLC purity 99.7%, mp166-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 7
To in the reaction flask of drying, add alpha-crystal form Hydrogen bromide eletriptan crude solid (20.0g, HPLC purity is 98.0%), Virahol (500mL) and ethanol (65mL), reflux, be stirred to reaction solution clarification, slowly be down to room temperature, leave standstill 4.0 hours, filtering separation, washs with Virahol (20mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (18.2g), HPLC purity 99.8%, mp166-168 DEG C, XRD, IR characterization result, with embodiment 1, shows that it is alpha-crystal form.
Embodiment 8
Eletriptan solid (20.0g) and Virahol (120mL) is added in the reaction flask of drying, under stirring at room temperature, slow dropping 48% aqueous solution of hydrogen bromide (9.7g) and Virahol (40mL) mixed solution, within 1.0 hours, add, gained slurry agitation 4.0h, filtering separation, obtain alpha-crystal form Hydrogen bromide eletriptan crude product (24.2g), by this alpha-crystal form Hydrogen bromide eletriptan crude solid (24.2g), Virahol (600mL) and methyl alcohol (60mL) are added in dry reaction flask, reflux, be stirred to reaction solution clarification, slowly be down to room temperature, leave standstill 4.0 hours, filtering separation, wash with Virahol (20mL), vacuum-drying 8 hours at 60 DEG C, obtain alpha-crystal form Hydrogen bromide eletriptan (22.0g), HPLC purity 99.7%, mp166-168 DEG C, XRD, IR characterization result is with embodiment 1, show that it is alpha-crystal form.
Although accompanying drawing 1 is the X-ray powder diffraction of alpha-crystal form Hydrogen bromide eletriptan prepared by embodiment 1, but, the alpha-crystal form Hydrogen bromide eletriptan that embodiment 2 ~ 6 prepares, all as shown in Figure 1, the collection of illustrative plates of the application with accompanying drawing 1 exemplarily for its characteristic peak.
Claims (10)
1. a preparation method for alpha-crystal form Hydrogen bromide eletriptan, is characterized in that, it adopts any one in following method:
Method one: by beta crystal Hydrogen bromide eletriptan and/or Hydrogen bromide eletriptan monohydrate, be dissolved in alcohols mixed solvent, reflux, crystallization; Described alcohols mixed solvent is the mixed solvent of solvent orange 2 A and solvent B, and solvent orange 2 A is methyl alcohol and/or ethanol, and solvent B is one or more in Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol;
Method two: in alcoholic solvent, reacts hydrogen bromide and eletriptan, crystallization.
2. preparation method as claimed in claim 1, it is characterized in that, in method one, the volume ratio of described solvent orange 2 A and solvent B is (1:5) ~ (1:15), is preferably 1:10; And/or described alcohols mixed solvent is 10 ~ 40mL/g with the volume mass ratio of beta crystal Hydrogen bromide eletriptan and/or Hydrogen bromide eletriptan monohydrate, is preferably 25mL/g.
3. preparation method as claimed in claim 1, it is characterized in that, in method one, the temperature of described reflux is 80 ~ 140 DEG C, and the time of described reflux is with till mixed solution clarification; And/or described crystallization is cooling crystallization, the temperature of described crystallization is 10 ~ 30 DEG C.
4. preparation method as claimed in claim 1, it is characterized in that, in method two, described hydrogen bromide exists with hydrogen bromide solution form, described hydrogen bromide solution is aqueous solution of hydrogen bromide and/or hydrogen bromide acetic acid solution, preferably for mass concentration be 34% ~ 62% aqueous solution of hydrogen bromide and/or mass concentration be the hydrogen bromide acetic acid solution of 34% ~ 48%; The mol ratio of the hydrogen bromide in described hydrogen bromide solution and described eletriptan is (0.95:1) ~ (1.20:1), is preferably 1.1:1.
5. preparation method as claimed in claim 4, it is characterized in that, the feed postition of hydrogen bromide solution is be added dropwise to by hydrogen bromide solution in the mixed solution of eletriptan and alcoholic solvent, and drop rate controls at 0.5 ~ 2 second/; The temperature of described eletriptan and the mixed solution of alcoholic solvent is 0 ~ 35 DEG C.
6. preparation method as claimed in claim 1, is characterized in that, in method two, described alcoholic solvent is one or more in methyl alcohol, ethanol, Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol; And/or described alcoholic solvent is 5 ~ 20mL/g with the volume mass ratio of eletriptan; And/or described crystallization is crystallization under agitation.
7. a purification process for alpha-crystal form Hydrogen bromide eletriptan, is characterized in that, it comprises the following steps: the mixed solution reflux by alpha-crystal form Hydrogen bromide eletriptan crude product and alcohols mixed solvent, crystallization; Described alcohols mixed solvent is the mixed solvent of solvent orange 2 A and solvent B, and solvent orange 2 A is methyl alcohol and/or ethanol, and solvent B is one or more in Virahol, butanols, isopropylcarbinol, the trimethyl carbinol and amylalcohol.
8. purification process as claimed in claim 7, it is characterized in that, the HLPC purity of described alpha-crystal form Hydrogen bromide eletriptan crude product is 95.0 ~ 98.0%; And/or described alpha-crystal form Hydrogen bromide eletriptan crude product is obtained by the preparation method according to any one of claim 1 ~ 6.
9. purification process as claimed in claim 7, it is characterized in that, the volume ratio of described solvent orange 2 A and solvent B is (1:5) ~ (1:15), is preferably 1:10; And/or described alcohols mixed solvent is 10 ~ 40mL/g with the volume mass ratio of alpha-crystal form Hydrogen bromide eletriptan crude product, is preferably 25mL/g.
10. purification process as claimed in claim 7, it is characterized in that, the temperature of described reflux is 80 ~ 140 DEG C, and the time of described reflux is with till mixed solution clarification; And/or described crystallization is cooling crystallization, the temperature of described crystallization is 10 ~ 30 DEG C.
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| CN201310120085.2A CN104292217A (en) | 2013-04-08 | 2013-04-08 | Preparation method and purification method of alpha crystal form eletriptan hydrobromide |
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| CN201310120085.2A CN104292217A (en) | 2013-04-08 | 2013-04-08 | Preparation method and purification method of alpha crystal form eletriptan hydrobromide |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008137134A2 (en) * | 2007-05-01 | 2008-11-13 | Teva Pharmaceuticals Usa, Inc. | Amorphous eletriptan hydrobromide and process for preparing it and other forms of eletriptan hydrobromide |
| WO2010097703A1 (en) * | 2009-02-25 | 2010-09-02 | Actavis Group Ptc Ehf | Highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan n-oxide impurity |
| WO2011004391A2 (en) * | 2009-06-25 | 2011-01-13 | Matrix Laboratories Ltd | An improved process for the preparation of eletriptan and its salt thereof |
| WO2011089614A1 (en) * | 2010-01-19 | 2011-07-28 | Sms Pharmaceuticals Limited | PROCESS FOR PREPARING ELETRIPTAN HYDROBROMIDE HAVING α-FORM |
| WO2012004811A1 (en) * | 2010-07-06 | 2012-01-12 | Ind-Swift Laboratories Limited | Process for the preparation of 5-substsituted indole derivative |
-
2013
- 2013-04-08 CN CN201310120085.2A patent/CN104292217A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008137134A2 (en) * | 2007-05-01 | 2008-11-13 | Teva Pharmaceuticals Usa, Inc. | Amorphous eletriptan hydrobromide and process for preparing it and other forms of eletriptan hydrobromide |
| WO2010097703A1 (en) * | 2009-02-25 | 2010-09-02 | Actavis Group Ptc Ehf | Highly pure eletriptan or a pharmaceutically acceptable salt thereof substantially free of eletriptan n-oxide impurity |
| WO2011004391A2 (en) * | 2009-06-25 | 2011-01-13 | Matrix Laboratories Ltd | An improved process for the preparation of eletriptan and its salt thereof |
| WO2011089614A1 (en) * | 2010-01-19 | 2011-07-28 | Sms Pharmaceuticals Limited | PROCESS FOR PREPARING ELETRIPTAN HYDROBROMIDE HAVING α-FORM |
| WO2012004811A1 (en) * | 2010-07-06 | 2012-01-12 | Ind-Swift Laboratories Limited | Process for the preparation of 5-substsituted indole derivative |
Non-Patent Citations (1)
| Title |
|---|
| U. SAMPATH KUMAR，ET AL.: "nvestigational Study into the Formation of Methoxy Derivative and Other Impurities during the Optimization of Eletriptan Hydrobromide", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
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