CN100503596C - Process for purifying 6-methoxy omeprazole - Google Patents
Process for purifying 6-methoxy omeprazole Download PDFInfo
- Publication number
- CN100503596C CN100503596C CNB028084594A CN02808459A CN100503596C CN 100503596 C CN100503596 C CN 100503596C CN B028084594 A CNB028084594 A CN B028084594A CN 02808459 A CN02808459 A CN 02808459A CN 100503596 C CN100503596 C CN 100503596C
- Authority
- CN
- China
- Prior art keywords
- methoxyl group
- methyl
- sulfinyl
- benzoglyoxaline
- pyridyl
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 229960000381 omeprazole Drugs 0.000 title abstract description 41
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 239000002904 solvent Substances 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 abstract description 2
- 210000004211 gastric acid Anatomy 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 15
- 239000000463 material Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 8
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000009736 wetting Methods 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 238000002288 cocrystallisation Methods 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 244000287680 Garcinia dulcis Species 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention provides processes for purifying 6-methoxy omeprazole, products using such processes, pharmaceutical formulations using such products, and methods of using such products for gastric acid inhibition.
Description
Background technology
Up to date, omeprazole is with trade mark
Activeconstituents in the AstraZeneca proton pump inhibitor that american commerce is sold; its chemical structure is considered to 5-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-the 1H-benzoglyoxaline, it is solid-state, is represented by general formula (1b):
1b.5-methoxy omeprazole
Yet; Whittle; R.R. wait and in PCT patent application WO 01/14367, disclose such content: omeprazole; as free alkali or salt, hydrate or its mixture; be actually two kinds of positional isomerss of cocrystallization in single lattice; promptly by the above-mentioned 5-methoxy omeprazole of general formula (1b) expression; with its preferential 6-methoxyl group isomer: by the 6-methoxyl group-2-[[(4-methoxyl group-3 of general formula (1a) expression, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-the 1H-benzoglyoxaline:
1a.6-methoxy omeprazole
The stability that Whittle etc. further disclose omeprazole is subjected to the influence of the ratio of 6-methoxy omeprazole and 5-methoxy omeprazole, and when the percentage ratio of 6-methoxy omeprazole improved, omeprazole was more advantageously stable.Yet, can be used to prepare isomer more preferably, the 6-methoxy omeprazole of higher percentages at present and reduce the method for less preferential 5-methoxy omeprazole percentage ratio, need solvent and other environmental factorss of control recrystallization speed, use.Therefore, be used for substituting expensive and time-consuming be used for raising from the replacement scheme of the method for the lattice 6-methoxy omeprazole percentage ratio of a certain amount of 5 (6)-methoxy omeprazoles technically with commercial be favourable.
Summary of the invention
Therefore; the invention provides and be used for from a certain amount of 5 (6)-methoxyl groups-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-improve 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl in 1H-benzoglyoxaline or its medicinal acceptable salt, hydrate or the mixture) methyl] sulfinyl]-the solid-state percentage ratio of 1H-benzoglyoxaline or its medicinal acceptable salt, hydrate or mixture and therefore reduce simultaneously the method for 5-methoxy omeprazole percentage ratio pro rata.
Detailed description of preferred embodiments
Describe the present invention in detail below with reference to embodiment preferred.Yet proposing these embodiments and be for the present invention being described, should not be construed as is restriction of the present invention to being defined by the claims.
Reported and further confirmed that the omeprazole API that has higher 6-methoxy omeprazole compound percentage ratio with respect to corresponding 5 (6)-methoxy omeprazole parent materials provides advantages of higher stability usually, causes commercial viability preferably.Improved stability can also provide improved safety performance by minimizing the degradation product that produces in time.
Therefore, one aspect of the present invention be provided in solid-state improving with (1a) of cocrystallization and (1b) parent material (also claim omeprazole active pharmaceutical ingredient or " API "; Be also referred to as 5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 at this; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline, perhaps 5 (6)-methoxy omeprazoles or its medicinal acceptable salt, hydrate or mixture) in this compounds compare the method for general formula (1a) compound percentage ratio.At this, be also referred to as the 6-methoxy omeprazole and be also referred to as the 5-methoxy omeprazole by the compound of general formula (1b) expression by the compound of general formula (1a) expression.
Therefore, the parent material that is used for the inventive method is 5 (6)-methoxyl groups-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline, perhaps its medicinal acceptable salt, hydrate or mixture.5 (6) methoxy omeprazoles prepare by various known method, for example the method for describing in PCT publication WO 01/14367 and United States Patent (USP) 4,255,431.
In one embodiment, a certain amount of 5 (6)-methoxy omeprazoles are placed suitable container, perhaps preferably in the B, to the short carbon chain (C that wherein adds aliquots containig
1-C
4) alcoholic solvent, comprise for example methyl alcohol, ethanol and Virahol, perhaps furyl solvent tetrahydrofuran (THF) (" THF ") for example.THF has the solvent nature that is similar to this class short carbon chain alcohol solvent.Under gentle and abundant the stirring, add enough solvents to cover basically and wetting described parent material.By means known in the art, preferably under vacuum, remove and desolvate then.At this, this method is called as " rinsing " 5 (6)-methoxy omeprazole API.
The time that this class rinsing needs, size common and the parent material sample was proportional.In addition, stir the time length of wetting material, and the percentage ratio of 5-methoxy omeprazole in parent material, can influence ultimate yield, long wetting/churning time obtains lower productive rate potentially.Therefore, be preferably minimize this class wetting/churning time, the vacuum removal solvent uses identical program rinsing parent material one or many again then, up to the 6-methoxy omeprazole that to need and the ratio of 5-methoxy omeprazole.
Usually, this rinsing is handled and is carried out at ambient temperature.
Unexpectedly, find in the organic solvent of test, only be useful on the in fact optionally 5-methoxy omeprazole in the solubilising parent material of THF in the inventive method and short carbon chain alcohol solvent, in the product that obtains, stay the 6-methoxy omeprazole of higher percentages.The solvent of other experiments comprises for example ethyl acetate, isopropyl ether, acetone, acetonitrile and water.In addition, finding that the validity of rinse method is directly relevant with the carbon chain lengths of this kind solvent, is preferred than the short chain alcohol solvent, and methyl alcohol is particularly preferred.
Therefore, the rinsing part of the inventive method for little pilot batch, can continue about 5 seconds to about 30 seconds, is more typically about 10 seconds to about 20 seconds, when increasing in batches, needs the obviously long time.
Second step of the inventive method is dry product from rinse step.Usually, drying can be finished by the known method of numerous those of ordinary skills, and condition is if use heating, the heating of use should be not enough to degrade or modification from the product of first step.
Usually, product is placed suitable inert containers, place vacuum drying oven then.Preferably, baking oven is arranged on about 0mmHg and envrionment temperature (about 25 ℃), is dried up to product, although other conditions may be operable.For the small-scale test sample, about 24 hours of product drying for relatively large product, should prolong time of drying.
Preferably, the inventive method provides the 5-methoxyl group percentage ratio with respect to the total percentage of 5-methoxy omeprazole and 6-methoxy omeprazole to be not more than 5 (6)-methoxy omeprazoles (the 6-methoxy omeprazole of perhaps essentially no 5-methoxy omeprazole) of about 10%.Yet the bigger reduction of comparing 5-methoxy omeprazole amount with corresponding parent material can provide improved stability characteristic usually.Therefore, when 5-methoxy omeprazole % descended, for example from about 30% to about 25% to about 20% to about 15% to about 10% to about 5% to about 0%, and the relative stability of the inventive method the finished product improves.Usually, the inventive method is the most effective 5-methoxy omeprazole percentage ratio being reduced to about 6% during to about 9% scope.Therefore, when the percentage ratio of this class 5-methoxy omeprazole in parent material greater than about 9% the time, the inventive method is the most effective for the 5-methoxy omeprazole level that is reduced in a certain amount of 5 (6)-methoxy omeprazoles.
The ratio of 5-methoxy omeprazole and 6-methoxy omeprazole of measuring in the given sample is preferably utilized fourier transformation (FT) raman spectrum to use to carry out as PCT publication W0 01/13919 and the described method of WO01/14367.This class FT Raman method can be simplified to be used for procedure inspection by the number that duplicates and scan that reduces per sample (p.s.), still can not obtain the optimum resolution that the preferred embodiment in these PCT publications proposes like this.Therefore, simplified method only should be as the estimation in process development or the procedure inspection, and under these circumstances, best resolving power is not requirement.
Another aspect of the present invention provides 5 (6)-methoxy omeprazoles by method preparation of the present invention, perhaps its medicinal acceptable salt, hydrate or mixture.Preferably, this compounds comprises and is no more than about 9% 5-methoxy omeprazole.
The present invention further provides pharmaceutical preparation, be preferably unit dosage form, it comprises at least a compound and at least a medicinal acceptable carrier, thinner, vehicle or its mixture by the inventive method preparation.Preferably, at least a compound of this class is pressed into tablet or encapsulated, is used for oral.Especially preferably this class oral dosage form is applied with casing.The method and the preferred dosage intensity that are used to prepare oral dosage form have description at for example PCT publication WO01/14367.
In addition, compound of the present invention preferably is mixed with above-mentioned oral dosage form, is effectively for suppressing the secretion of Mammals hydrochloric acid in gastric juice, and is therefore helpful to treatment, prevention or the inhibition illness relevant with gastric acid secretion.Therefore, the invention provides the method for the gastric acid secretion that suppresses Mammals, preferred people, it comprises the pharmaceutical preparation of the present invention to the Mammals drug treatment significant quantity of needs treatment.
Following examples limit the scope of the present invention and should not be construed as in order to explanation the present invention.At this; phrase " 5 (6)-methoxyl groups-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl-1H-benzoglyoxaline; perhaps its medicinal acceptable salt; hydrate or its mixture " refer to the 5-methoxyl group-2-[[(4-methoxyl group-3 of cocrystallization respectively; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-the 1H-benzoglyoxaline; perhaps its medicinal acceptable salt; hydrate or its mixture; with 6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline and its medicinal acceptable salt, hydrate or its mixture.
Embodiment 1
6-methoxyl group-2-[[(4-methoxyl group-3 with increasing amount; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 of 1H-benzoglyoxaline, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-preparation of 1H-benzoglyoxaline
5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 that in 50mL pottery B, adds about 1.8g; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-sample of 1H-benzoglyoxaline; it has 5-methoxyl group-2-[[(4-methoxyl group-3 of about 33%, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-the 1H-benzoglyoxaline.Add 20ml methyl alcohol in sample, stirred sample is up to the covering and wetting fully of sample quilt.Mixture was placed about 15 seconds, removed at ambient temperature in a vacuum and desolvate.The aliquots containig that adds additional 10mL methyl alcohol in the product that obtains with about 15 seconds of sample restir, is covered and wetting fully up to sample.Remove additional solvent again in a vacuum at ambient temperature.The product that obtains is assigned in the 25mL beaker fully, places to be arranged on 0mmHg and about 25 ℃ vacuum drying oven.With product drying 24 hours.The productive rate of title product is 49%, 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-percentage ratio of 1H-benzoglyoxaline brings up to about 91% from about 67%.
Embodiment 2
6-methoxyl group-2-[[(4-methoxyl group-3 with increasing amount; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 of 1H-benzoglyoxaline, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-preparation of 1H-benzoglyoxaline
Use the method among the embodiment 1, only be to use ethanol to replace second ethanol that the solvent aliquots containig is 20mL of methyl alcohol and adding.The productive rate of title product is 65%, 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-percentage ratio of 1H-benzoglyoxaline brings up to about 76% from about 67%.
Embodiment 3
6-methoxyl group-2-[[(4-methoxyl group-3 with increasing amount; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 of 1H-benzoglyoxaline, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-preparation of 1H-benzoglyoxaline
Use the method among the embodiment 1, just replace methyl alcohol with Virahol, second solvent aliquots containig of adding is the 20ml Virahol, and uses the parent material of 2.0g.The productive rate of title product is 85%, 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-percentage ratio of 1H-benzoglyoxaline brings up to about 69% from about 67%.
Embodiment 4
6-methoxyl group-2-[[(4-methoxyl group-3 with increasing amount; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-5 (6)-methoxyl groups-2-[[(4-methoxyl group-3 of 1H-benzoglyoxaline, 5-dimethyl-2-pyridyl) methyl] sulfinyl]-preparation of 1H-benzoglyoxaline
Use the method among the embodiment 1, only be to use tetrahydrofuran (THF) to replace second tetrahydrofuran (THF) that the solvent aliquots containig is 20mL of methyl alcohol and adding.The productive rate of title product is 53%, 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-percentage ratio of 1H-benzoglyoxaline brings up to about 73% from about 67%.
Claims (6)
1. be used for from a certain amount of 5-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-1H-benzoglyoxaline and 6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-mixture of 1H-benzoglyoxaline or its medicinal acceptable salt, hydrate or mixture improve 6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-method of the solid-state percentage ratio of 1H-benzoglyoxaline or its medicinal acceptable salt, hydrate or mixture, it comprises:
(a) with being selected from the 5-methoxyl group-2-[[(4-methoxyl group-3 of the solvent of short carbon chain alcohol solvent and tetrahydrofuran (THF) with described amount, 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-1H-benzoglyoxaline and 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl] sulfinyl]-the mixture rinsing one or many of 1H-benzoglyoxaline; Wherein said short carbon chain alcohol solvent is selected from methyl alcohol, ethanol and Virahol;
(b) dry product from step (a).
2. the process of claim 1 wherein that described short carbon chain alcohol solvent is a methyl alcohol.
3. the process of claim 1 wherein that described solvent is a tetrahydrofuran (THF).
4.6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline or its medicinal acceptable salt; hydrate or mixture are used for from a certain amount of 5-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-1H-benzoglyoxaline and 6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-mixture or its medicinal acceptable salt of 1H-benzoglyoxaline; improve the purposes of solid-state percentage ratio in hydrate or the mixture; wherein said 5-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-1H-benzoglyoxaline and 6-methoxyl group-2-[[(4-methoxyl group-3; 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-5-methoxyl group-2-[[(4-methoxyl group-3 that the mixture of 1H-benzoglyoxaline has; 5-dimethyl-2-pyridyl) methyl] sulfinyl]-percentage ratio of 1H-benzoglyoxaline comprises greater than 9%:
(a) with being selected from the 5-methoxyl group-2-[[(4-methoxyl group-3 of the solvent of short carbon chain alcohol solvent and tetrahydrofuran (THF) with described amount, 5-dimethyl-2-pyridyl)-and methyl] sulfinyl]-1H-benzoglyoxaline and 6-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl)-methyl] sulfinyl]-the mixture rinsing one or many of 1H-benzoglyoxaline; Wherein said short carbon chain alcohol solvent is selected from methyl alcohol, ethanol and Virahol;
(b) dry product from step (a).
5. the purposes of claim 4, wherein said short carbon chain alcohol solvent is a methyl alcohol.
6. the purposes of claim 4, wherein said solvent is a tetrahydrofuran (THF).
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/839,449 US6608091B2 (en) | 2001-04-20 | 2001-04-20 | Process for purifying 6-methoxy omeprazole |
| US09/839,449 | 2001-04-20 | ||
| US09/839,395 | 2001-04-20 | ||
| US09/839,395 US6673936B2 (en) | 2001-04-20 | 2001-04-20 | Process for purifying 6-methoxy omeprazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1503791A CN1503791A (en) | 2004-06-09 |
| CN100503596C true CN100503596C (en) | 2009-06-24 |
Family
ID=27126104
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB028084594A Expired - Fee Related CN100503596C (en) | 2001-04-20 | 2002-04-17 | Process for purifying 6-methoxy omeprazole |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1379518A2 (en) |
| JP (1) | JP2004528331A (en) |
| KR (1) | KR20030088506A (en) |
| CN (1) | CN100503596C (en) |
| CA (1) | CA2443605A1 (en) |
| HU (1) | HUP0304004A2 (en) |
| NO (1) | NO20034679L (en) |
| WO (1) | WO2002085312A2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001013919A1 (en) * | 1999-08-26 | 2001-03-01 | Applied Analytical Industries, Inc. | Ft-raman spectroscopic measurement of omeprazole isomer ratio in a composition |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0204215B1 (en) * | 1985-05-24 | 1993-08-11 | G.D. Searle & Co. | 2-[(1H-benzimidazol-2-ylsulfinyl)methyl]-benzenamines |
-
2002
- 2002-04-17 EP EP02736828A patent/EP1379518A2/en not_active Withdrawn
- 2002-04-17 WO PCT/US2002/015254 patent/WO2002085312A2/en not_active Application Discontinuation
- 2002-04-17 CN CNB028084594A patent/CN100503596C/en not_active Expired - Fee Related
- 2002-04-17 JP JP2002582888A patent/JP2004528331A/en active Pending
- 2002-04-17 CA CA002443605A patent/CA2443605A1/en not_active Abandoned
- 2002-04-17 HU HU0304004A patent/HUP0304004A2/en unknown
- 2002-04-17 KR KR10-2003-7013544A patent/KR20030088506A/en not_active Application Discontinuation
-
2003
- 2003-10-20 NO NO20034679A patent/NO20034679L/en not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001013919A1 (en) * | 1999-08-26 | 2001-03-01 | Applied Analytical Industries, Inc. | Ft-raman spectroscopic measurement of omeprazole isomer ratio in a composition |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004528331A (en) | 2004-09-16 |
| HUP0304004A2 (en) | 2004-04-28 |
| WO2002085312A3 (en) | 2003-04-03 |
| EP1379518A2 (en) | 2004-01-14 |
| CA2443605A1 (en) | 2002-10-31 |
| WO2002085312A2 (en) | 2002-10-31 |
| NO20034679D0 (en) | 2003-10-20 |
| NO20034679L (en) | 2003-10-20 |
| CN1503791A (en) | 2004-06-09 |
| KR20030088506A (en) | 2003-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2431359B1 (en) | Process for preparing diaminophenothiazinium compounds | |
| CN1141097C (en) | Stabilized compositions containing benzimidzole-type compounds | |
| CN1212833C (en) | Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same | |
| Xu et al. | Asymmetric synthesis of a potent, aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV inhibitor | |
| CN1090582A (en) | New erythromycin derivatives and preparation method thereof and as the purposes of medicine | |
| TW200621310A (en) | A process for preparing formulations of lypophilic active substances by spray freeze drying | |
| NZ242191A (en) | Crystalline tiagabine hydrochloride monohydrate, preparation and pharmaceutical compositions thereof | |
| CZ20013800A3 (en) | Polymorph of salt of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]-benzyl]thiazolidine-2,4-dione with maleic acid | |
| US6673936B2 (en) | Process for purifying 6-methoxy omeprazole | |
| CN100503596C (en) | Process for purifying 6-methoxy omeprazole | |
| EP2874628B1 (en) | Salts and hydrates of antipsychotics | |
| WO2004089948A1 (en) | Novel crystalline forms of ziprasidone hydrochloride | |
| US6608091B2 (en) | Process for purifying 6-methoxy omeprazole | |
| JP6694029B2 (en) | Pharmaceutical preparation containing 3-formylrifamycin SV and 3- (4-cinnamyl-1-piperazinyl) amino derivative of 3-formylrifamycin S, and methods for producing the same | |
| EP1726591B1 (en) | Process for manufacturing paroxetine hydrochloride hemihydrate | |
| CN1427721A (en) | Peptide deformylase inhibitors | |
| KR101733387B1 (en) | Method for preparation of organic acid ester | |
| CN114773294A (en) | Preparation method of ebselen compounds | |
| US7544801B2 (en) | Method of manufacturing of 7-ethyl-10-hydroxycamptothecin | |
| CN103710406A (en) | Method for preparing main intermediate of dabigatran etexilate through enzymatic reaction | |
| AU2002309805A1 (en) | Process for purifying 6-methoxy omeprazole | |
| CN107954998B (en) | Preparation method of fosaprepitant intermediate | |
| Dai et al. | Eu (fod) 3-Catalyzed rearrangement of allylic esters possessing a chelating site. Application to enediyne synthesis | |
| EP1615902B1 (en) | Method for production of 4,10 beta-diacetoxy-2 alpha-benzoyloxy-5 beta,20-epoxy-1,13 alpha-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene | |
| WO2006128688B1 (en) | Process for the preparation of pramipexole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090624 Termination date: 20100417 |