CN104530003A - Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds - Google Patents
Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds Download PDFInfo
- Publication number
- CN104530003A CN104530003A CN201410777796.1A CN201410777796A CN104530003A CN 104530003 A CN104530003 A CN 104530003A CN 201410777796 A CN201410777796 A CN 201410777796A CN 104530003 A CN104530003 A CN 104530003A
- Authority
- CN
- China
- Prior art keywords
- esomeprazole
- solvent
- hours
- single non
- crystallization
- 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.)
- Pending
Links
- DCZDANBSZVISQK-CJNGLKHVSA-N Cc(cnc([C@H](C1)[C@H]1S(c1nc2cc(OC)ccc2[nH]1)(=O)=O)c1C)c1OC Chemical compound Cc(cnc([C@H](C1)[C@H]1S(c1nc2cc(OC)ccc2[nH]1)(=O)=O)c1C)c1OC DCZDANBSZVISQK-CJNGLKHVSA-N 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
Abstract
The invention relates to a method for preparing (5-methoxyl-2-[(S)-[(4-methoxyl-3,5-dimethyl-2-pyridyl)methyl]sulfonyl]-1H-benzimidazole sodium salts; and the method comprises the steps of mixing and crystallizing esomeprazole and sodium hydroxide solids in single non-alcohol solvent. According to the preparation method provided by the invention, filtering and washing are only necessary in post-processing; the single non-alcohol solvent is adopted in the whole salt forming process; the solvent can be recycled; furthermore, the total yield in the two reaction steps including oxidization and salt forming is above 85%; the HPLC (High Performance Liquid Chromatography) purity (peak area) is above 99%; and the HPLC purity (peak area) of the content of the compound represented by an excessive oxidation impurity formula (II) is below 0.5%.
Description
Technical field
The present invention relates to medicinal chemistry art; be specifically related to prepare (the method for the Esomeprazole sodium of 5-methoxyl group-2-[(S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] alkylsulfonyl]-1H-benzoglyoxaline.
Background technology
Esomeprazole; its structure is such as formula shown in (I); its chemical name is 5-methoxyl group-2-[(S)-[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline; esomeprazole injection exists with the form of sodium salt, and the chemical structure of Ai Meila azoles sodium is such as formula shown in (Ia):
The embodiment 11 of PCT application WO 1996/025235, reacts by making Ai Meila azoles and sodium hydroxide and prepares Esomeprazole sodium in the mixture (by being wherein settled out Esomeprazole sodium) of methyl iso-butyl ketone (MIBK) (MIK)/acetonitrile.
The embodiment 41 of PCT application WO 2007/012650, reacts the Esomeprazole sodium preparing (deutered) methoxyl group with deuterate by making esomeprazole and sodium hydroxide in the mixture (by being wherein settled out Esomeprazole sodium) of methyl iso-butyl ketone (MIBK)/Virahol.
In the embodiment 1.1 to 1.3 of international patent application WO 2006/001753, in the mixture of toluene and methanol, toluene/ethanol and toluene/isopropanol, react by making esomeprazole and sodium hydroxide the Esomeprazole sodium preparing different solid form respectively.
The embodiment 15 of PCT application WO 2008/149204 describes prepares Esomeprazole sodium by the following method: be dissolved in by esomeprazole in aqueous sodium hydroxide solution, with dichloromethane extraction, distilling off solvent, then ethanol distillation is added, add ethyl acetate distillation, finally by crystallization in ethyl acetate.Embodiment 16 describes and uses sodium ethylate as alkali and use ethyl acetate to prepare Ai Meila azoles sodium as solvent.
Chinese patent application CN 201180008960 reviews the various shortcoming of other prior art with not enough, and the technical scheme of its technical solution problem comprises: a) mix Esso Suo Meila azoles and (C3-C8)-one or its mixture, sodium alkoxide and (C1-C5)-ol; Or mix Esomeprazole sodium and (C3-C8)-one or its mixture, and (C1-C5)-ol; And the Esomeprazole sodium that b) filtered and recycled is formed from reaction medium.The advantage of the method is superoxidized impurity sulfone, its structure is low such as formula the content of the compound shown in (II), but the method adopts two or more mixed solvents, productive rate is 51%-78% only, wherein productive rate 78% adopts the mixed solvent of four kinds of solvents, and the method crystallization time is long, need to spend the night
Term definition
Term " compound shown in (II) " refers to 5-methoxyl group-2-[(S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] alkylsulfonyl]-1H-benzoglyoxaline.
Term " esomeprazole " refers to 5-methoxyl group-2-[(S)-[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline; esomeprazole of the present invention can be prepared by the method disclosed in known prior art, also can be prepared by the embodiment of the present invention 2.
In content below, no matter whether use the wording such as " approximately " or " about ", all numerals disclosed at this are approximation.The numerical value of each numeral likely there will be the difference such as 1%, 2%, 5%, 7%, 8%, 10%, 15% or 20%.
Summary of the invention
Here provide a kind of preparation method of Esomeprazole sodium salt, the high and over oxidation impurity sulfone of described method yield, its structure such as formula shown in (II), content low, postprocessing working procedures is simple, and the crystallization time is short,
A preparation method for Esomeprazole sodium, it comprises: esomeprazole mixes in single non-alcoholic solvent with sodium hydrate solid, crystallization.
In certain embodiments, described single non-alcoholic solvent is selected from the one of ketones solvent, esters solvent, halogenated hydrocarbon solvent or aromatic hydrocarbon solvent, described ketones solvent is selected from such as acetone, 2-butanone or 4-methyl-2 pentanone, described esters solvent is selected from such as ethyl acetate, isopropyl acetate, n-butyl acetate or tert.-butyl acetate, described halogenated hydrocarbon solvent is selected from such as methylene dichloride (DCM), chloroform, tetracol phenixin, and described aromatic hydrocarbon solvent is selected from such as benzene,toluene,xylene; In one embodiment, described single non-alcoholic solvent is acetone; In another embodiment, described single non-alcoholic solvent is ethyl acetate; In certain embodiments, described single non-alcoholic solvent is methylene dichloride; In a certain embodiment, described single non-alcoholic solvent is toluene.
In one embodiment, the preparation method of described Esomeprazole sodium salt, it comprises: added by esomeprazole in acetone, stir, add sodium hydrate solid, be warming up to backflow, insulated and stirred is cooled to about 25 DEG C after about 4.0 hours, crystallization, filter, washing with acetone, dry.
In some embodiments, joined by esomeprazole in toluene, add sodium hydrate solid after stirring, be warming up to about 65 DEG C, about 6.0 hours of insulated and stirred, is cooled to about 30 DEG C, about 4.0 hours of crystallization, filters, toluene wash, dry.
In some embodiments, be added to by esomeprazole in methylene dichloride, add sodium hydrate solid after stirring, be warming up to backflow, about 4.0 hours of insulated and stirred, is cooled to about 25 DEG C, about 4.0 hours of crystallization, filters, washed with dichloromethane, dry.
In some embodiments, esomeprazole is joined in ethyl acetate, after stirring, add sodium hydrate solid, be warming up to about 65 DEG C, about 6.0 hours of insulated and stirred, is cooled to about 30 DEG C, and crystallization is after about 4.0 hours, filter, ethyl acetate is washed, dry.
In certain embodiments, the preparation method of described Esomeprazole sodium salt, it comprises: esomeprazole and sodium hydrate solid be selected from acetone, toluene, methylene dichloride, ethyl acetate single non-alcoholic solvent mix, the mixture obtained is heated to 40 DEG C to 70 DEG C, insulated and stirred is after 30 minutes to 12 hours, cool the temperature to about 35 DEG C to-5 DEG C, crystallization, filtration.
In the above-described embodiments, the esomeprazole of every gram, described single non-alcoholic solvent consumption is about 6ml to about 10ml, is 8ml/g in certain embodiments.
In the above-described embodiments, described sodium hydrate solid is 1.0 equivalent to 2.0 equivalents relative to esomeprazole, is 1.2 equivalents in certain embodiments.
In the above-described embodiment, the time needed for described crystallization within 12 hours, preferably within 6 hours, more preferably within 4 hours.
Raw material esomeprazole for the preparation of Esomeprazole sodium can adopt method preparation disclosed in prior art, as WO 2006040635, CN95194956 etc., also method of the present invention can be adopted to prepare, usually used as the over oxidation impurity of the esomeprazole of raw material, shown in formula (II), its HPLC purity (peak area) of content of compound is more than 0.5%.
Preparation method provided by the present invention, aftertreatment only needs to filter, wash, whole salification process adopts single non-alcoholic solvent, and solvent can be recycled, and this two-step reaction total recovery of oxidation salify is brought up to more than 85%, the HPLC purity (peak area) of product more than 99%, over oxidation impurity, its HPLC purity (peak area) of content of compound shown in formula (II) is below 0.3%, preferably less than 0.15%, more preferably less than 0.1%.
Embodiment
In order to make those skilled in the art understand technical scheme of the present invention better, below disclose further some non-limiting embodiments the present invention is described in further detail.
Reagent used in the present invention all can be buied from the market or can be obtained by method described in the invention preparation.
In the present invention, mmol represents mmole, and h represents hour, and g represents gram, and ml represents milliliter.
Embodiment 1 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl } preparation of-1H-benzoglyoxaline
To in reaction flask, add water (36ml), NaOH solid (15g), be cooled to about about 30 DEG C, after solution clarification, add methyl alcohol (70.0ml) and 2-sulfydryl-5-methoxybenzimidazol (30g), by 2-chloromethyl-3, 5-dimethyl-4-methoxypyridine hydrochloride (36.2g) is dissolved in methyl alcohol (18.0ml) and water (55.0ml), be warming up to about 35 DEG C, 2-chloromethyl-3, the methanol-water solution of 5-dimethyl-4-methoxypyridine hydrochloride slowly drops in the methanol-water solution of 2-sulfydryl-5-methoxybenzimidazol, after 2 hours, HPLC detection reaction, after reacting completely, cooling, stirring and crystallizing 2h, suction filtration, filter cake is extremely neutral with tap water, vacuum-drying, until moisture content lower than 0.2% time, terminate dry, obtain intermediate 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3, 5-dimethyl-2-pyridyl)-methyl }-1H-benzoglyoxaline (52.2g), yield 95.1%
Embodiment 2 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation of-1H-benzoglyoxaline
In four-hole bottle, 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3 is added under room temperature, 5-dimethyl-2-pyridyl)-methyl }-1H-benzoglyoxaline (60g), toluene (210ml), D-diethyl tartrate (22.5g), titanium isopropylate (15.54g) is added after stirring, be warming up to 60 DEG C, insulated and stirred half an hour, add water, continue insulated and stirred half an hour, cooling room temperature, add diisopropyl ethyl amine (7.05g) again, slowly drip the toluene solution of hydrogen phosphide cumene (33.24g) again, control time for adding 1 hours, after dropwising, temperature control stirring reacts, react complete after, system adds NaOH solution cancellation reaction, remove organic phase, aqueous phase acetic acid is adjusted to pH and is about 7.5, extraction into ethyl acetate three times, underpressure distillation obtains oily matter 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3, 5-dimethyl-2-pyridyl)-methyl-sulfoxide }-1H-benzoglyoxaline (esomeprazole), 60g, the HPLC purity of gained oily matter is 95.113%, shown in formula (II), the content of compound is 0.513%, the oily matter of gained is directly used in next step salify.
Embodiment 3 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation of-1H-benzoglyoxaline sodium
In four-hole bottle, 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3 is added under room temperature, 5-dimethyl-2-pyridyl)-methyl }-1H-benzoglyoxaline (60g), toluene (210ml), D-diethyl tartrate (22.5g), stir, add titanium isopropylate (15.54g), be warming up to 65 DEG C, insulated and stirred half an hour, add water, continue insulated and stirred half an hour, be cooled to room temperature, add diisopropyl ethyl amine (7.05g) again, stir 10 minutes, system is cooled to 0 DEG C, the toluene solution of slow dropping hydrogen phosphide cumene (33.24g), control time for adding 1 hours, drip completely, temperature control stirring reacts, react complete after, NaOH solution cancellation reaction is added toward system, remove organic phase, aqueous phase acetic acid is adjusted to pH and is about 7.5, ethyl acetate (160ml x 3) extracts, merge organic phase, organic phase is directly used in next step reaction.
To in above-mentioned solution, add NaOH solid (8.0g), be warming up to 55 DEG C, insulated and stirred 6.0 hours, a large amount of solid occurs, is cooled to 30 DEG C, crystallization 4.0 hours, filter, ethyl acetate is washed, vacuum-drying at 45 DEG C, obtain Esomeprazole sodium salt (57.38g), yield 85.0%, HPLC purity 99.589%, the compounds content (peak area) 0.06% shown in formula (II).
Embodiment 4 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation of-1H-benzoglyoxaline sodium (Esomeprazole sodium)
The product (60g) prepared by step according to embodiment 2 is added in toluene (480ml), NaOH solid (8.0g) is added after stirring, be warming up to 65 DEG C, insulated and stirred 6.0 hours, a large amount of solid occurs, be cooled to 30 DEG C, crystallization 4.0 hours, filter, toluene wash, vacuum-drying at 45 DEG C, obtain title compound (55.4g), yield 82.69%, HPLC purity 99.849%, the compounds content (peak area) 0.017% shown in formula (II).
Embodiment 5 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation of-1H-benzoglyoxaline sodium
The product 60g prepared by method according to embodiment 2 is added in methylene dichloride (480ml), NaOH solid (8.0g) is added after stirring, be warming up to backflow, insulated and stirred 4.0 hours, a large amount of solid occurs, be cooled to 25 DEG C, crystallization 4.0 hours, filter, DCM washs, vacuum-drying at 45 DEG C, obtain title compound (55.4g), yield 82.68%, HPLC purity is 99.628%, the content 0.106% of compound shown in formula (II).
Embodiment 6 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation of-1H-benzoglyoxaline sodium
5-methoxyl group-2-{ (S)-[(4-methoxyl group-3 that method according to embodiment 2 is prepared, 5-dimethyl-2-pyridyl)-methyl-sulfoxide } oily matter (esomeprazole) (60g) of-1H-benzoglyoxaline add in acetone (480ml), stir, add NaOH solid (8.0g), temperature rising reflux, insulated and stirred 4.0 hours, a large amount of solid occurs, be cooled to 25 DEG C, crystallization, filter, washing with acetone, vacuum-drying at 45 DEG C, obtain 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3, 5-dimethyl-2-pyridyl)-methyl-sulfoxide }-1H-benzoglyoxaline sodium (58.17g), yield 86.7%, HPLC purity (peak area) 99.368%, compounds content (peak area) 0.018% shown in formula (II).
Embodiment 7 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation (comparative example 1) of-1H-benzoglyoxaline sodium
The product (60g) prepared by method according to embodiment 2 is added in methylene dichloride (480ml), the methanol solution (200mmol) of the sodium methylate of 30% is added after stirring, be warming up to backflow, after reacting completely, be cooled to about 25 DEG C, separate out without solid, after underpressure distillation is extremely dry, what obtain is oily matter, yield 66.2%, HPLC purity (peak area) 89.3%.
Embodiment 8 5-methoxyl group-2-{ (S)-[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl-sulfoxide } preparation (comparative example 2) of-1H-benzoglyoxaline sodium
The product (60g) prepared by method according to embodiment 2 is added in methylene dichloride (480ml), the aqueous sodium hydroxide solution (200mmol) of 50% is added after stirring, be warming up to backflow, after reacting completely, after underpressure distillation band water, more centrifugal; Obtain faint yellow solid, yield 65%.
Embodiment 9 HPLC testing conditions
Liquid phase chromatogram condition
Phosphate buffered saline buffer: measure SODIUM PHOSPHATE, MONOBASIC two water thing 70ml (10.92g) of 1mol/L and Sodium phosphate dibasic (1.42g) 20ml of 0.5mol/L, be diluted with water to 1000ml.Get above-mentioned solution 250ml, be diluted with water to 1000ml, filter, degassed, to obtain final product;
A phase: phosphate buffered saline buffer: methyl alcohol (92.5:7.5); B phase: acetonitrile;
Chromatographic column: Agilent Poroshell 120EC-C18 (50mm × 4.6mm, 2.7 μm);
Flow velocity: 1.0mlmin
-1;
Column temperature: 30 DEG C;
Wavelength: 280nm
Gradient elution program:
Method of the present invention is described by preferred embodiment, and related personnel obviously can change methods and applications as herein described or suitably change and combination in content of the present invention, spirit and scope, realizes and applies the technology of the present invention.Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.
Claims (10)
1. a preparation method for Esomeprazole sodium, it comprises: esomeprazole mixes in single non-alcoholic solvent with sodium hydrate solid, crystallization.
2. the method for claim 1, described single non-alcoholic solvent is selected from the one in ketones solvent, esters solvent, halogenated hydrocarbon solvent or aromatic hydrocarbon solvent, described ketones solvent is selected from such as acetone, 2-butanone or 4-methyl-2 pentanone, described esters solvent is selected from such as ethyl acetate, isopropyl acetate, n-butyl acetate or tert.-butyl acetate, described halogenated hydrocarbon solvent is selected from such as methylene dichloride, chloroform or tetracol phenixin, and described aromatic hydrocarbon solvent is selected from such as benzene, toluene or dimethylbenzene.
3. method as claimed in claim 2, described single non-alcoholic solvent is acetone, ethyl acetate, methylene dichloride or toluene.
4. the method for claim 1, it comprises further: esomeprazole and sodium hydrate solid be selected from acetone, toluene, methylene dichloride, ethyl acetate single non-alcoholic solvent mix, the mixture obtained is heated to 40 DEG C to 70 DEG C, insulated and stirred is after 30 minutes to 12 hours, cool the temperature to about 35 DEG C to-5 DEG C, crystallization, filtration.
5. the method for claim 1, the esomeprazole of every gram, required single non-alcoholic solvent consumption is about 6ml to about 10ml.
6. method as claimed in claim 5, the esomeprazole of every gram, required single non-alcoholic solvent consumption is about 8ml/g.
7. the method for claim 1, described sodium hydrate solid is 1.0 equivalent to 2.0 equivalents relative to esomeprazole, or is 1.2 equivalents.
8. the method as described in as arbitrary in claim 1-7, the time needed for described crystallization within 12 hours, preferably within 6 hours, more preferably within 4 hours.
9. the method for claim 1, it comprises: by esomeprazole, ((60g) adds in toluene (480ml), add NaOH solid (8.0g) after stirring, be warming up to 65 DEG C, insulated and stirred 6.0 hours, a large amount of solid occurs, be cooled to 30 DEG C, crystallization 4.0 hours, filter, toluene wash, vacuum-drying at 45 DEG C.
10. the method for claim 1, it comprises: by esomeprazole, ((60g) adds in acetone (480ml), stirs, and adds NaOH solid (8.0g), temperature rising reflux, insulated and stirred 4.0 hours, a large amount of solid occurs, is cooled to 25 DEG C, crystallization, filter, washing with acetone, vacuum-drying at 45 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410777796.1A CN104530003A (en) | 2014-06-10 | 2014-12-15 | Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410256374 | 2014-06-10 | ||
| CN201410256374X | 2014-06-10 | ||
| CN201410777796.1A CN104530003A (en) | 2014-06-10 | 2014-12-15 | Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104530003A true CN104530003A (en) | 2015-04-22 |
Family
ID=52845674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410777796.1A Pending CN104530003A (en) | 2014-06-10 | 2014-12-15 | Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104530003A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113582973A (en) * | 2021-09-28 | 2021-11-02 | 丽珠医药集团股份有限公司 | Preparation method of thioether |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1110477A (en) * | 1993-05-28 | 1995-10-18 | 阿斯特拉公司 | Optically pure salts of pyridinylmethyl sulfinyl-1H-benzimidazole compounds |
| CN1665805A (en) * | 2002-06-27 | 2005-09-07 | 雷迪实验室有限公司 | Method for preparing optical purity or optically concentrated sulfoxide compounds comprising amorphous esomeprazole and its salts |
| CN101268051A (en) * | 2005-07-26 | 2008-09-17 | 尼科梅德有限责任公司 | Isotopically substituted proton pump inhibitors |
| WO2008149204A1 (en) * | 2007-06-07 | 2008-12-11 | Aurobindo Pharma Limited | An improved process for preparing an optically active proton pump inhibitor |
| WO2010148314A2 (en) * | 2009-06-19 | 2010-12-23 | Dr. Reddy's Laboratories Ltd. | Preparation of esomeprazole and its pharmaceutically acceptable salts |
| CN102770423A (en) * | 2010-02-12 | 2012-11-07 | 埃斯特维化学股份有限公司 | Preparation process of the sodium salt of esomeprazole |
-
2014
- 2014-12-15 CN CN201410777796.1A patent/CN104530003A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1110477A (en) * | 1993-05-28 | 1995-10-18 | 阿斯特拉公司 | Optically pure salts of pyridinylmethyl sulfinyl-1H-benzimidazole compounds |
| CN1665805A (en) * | 2002-06-27 | 2005-09-07 | 雷迪实验室有限公司 | Method for preparing optical purity or optically concentrated sulfoxide compounds comprising amorphous esomeprazole and its salts |
| CN101268051A (en) * | 2005-07-26 | 2008-09-17 | 尼科梅德有限责任公司 | Isotopically substituted proton pump inhibitors |
| WO2008149204A1 (en) * | 2007-06-07 | 2008-12-11 | Aurobindo Pharma Limited | An improved process for preparing an optically active proton pump inhibitor |
| WO2010148314A2 (en) * | 2009-06-19 | 2010-12-23 | Dr. Reddy's Laboratories Ltd. | Preparation of esomeprazole and its pharmaceutically acceptable salts |
| CN102770423A (en) * | 2010-02-12 | 2012-11-07 | 埃斯特维化学股份有限公司 | Preparation process of the sodium salt of esomeprazole |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113582973A (en) * | 2021-09-28 | 2021-11-02 | 丽珠医药集团股份有限公司 | Preparation method of thioether |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102731605B (en) | A kind of purification process of Abiraterone acetate | |
| CN108947949B (en) | Anxiolytic deuterated compounds and medical application thereof | |
| CN102351847B (en) | Industrial method for refining esomeprazole sodium salt | |
| CN102775387B (en) | Method for refining fasudil hydrochloride | |
| CN110590767B (en) | Method for synthesizing AMG837 | |
| CN105949118B (en) | A kind of preparation method of 2- aryl quinoline derivatives | |
| CN110684024B (en) | Synthetic method of moxifloxacin degradation impurities | |
| CN104530003A (en) | Preparation method of salts of pyridylmethyl sulfinyl-1H-benzimidazole compounds | |
| CN103664887B (en) | The preparation method of Esomeprazole sodium | |
| CN111848517A (en) | Preparation method of edaravone | |
| CN102212060A (en) | Method for preparing lafutidine by virtue of aminolysis | |
| CN113248396B (en) | Preparation method of chlorobenzene para-aminated compound mediated by high-valence iodine reagent | |
| CN102827161B (en) | A kind of method of purifying Moxifloxacin | |
| CN104803978A (en) | Preparation method of esomeprazole magnesium | |
| CN101808960A (en) | Process for the production of tertiary alcohols | |
| CN105272918B (en) | Halogenation -1- alkyl -3- vinyl -2,4,5- triarylimidazoles and preparation method and purposes | |
| CN103664990A (en) | Preparation method of Vicagrel | |
| CN106588786A (en) | Preparation method of high purity favipiravir impurity | |
| CN103497145B (en) | A kind of preparation technology of optical purity E2020 | |
| CN102827229A (en) | Method for purifying halometasone carboxylate | |
| CN112920033A (en) | Preparation method of o-alkynyl phenylcyclobutanone and preparation method of naphthalenone | |
| CN107235837B (en) | Preparation method of fenofibric acid | |
| CN105272965A (en) | Esomeprazole sodium purification method | |
| CN110627771B (en) | Preparation method of esomeprazole thioether | |
| CN105061398B (en) | A kind of refining methd of Esomeprazole sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150422 |
|
| RJ01 | Rejection of invention patent application after publication |