CN1054127C - Process for preparing monohydrate of sulfamonomethoxine - Google Patents
Process for preparing monohydrate of sulfamonomethoxine Download PDFInfo
- Publication number
- CN1054127C CN1054127C CN96106799A CN96106799A CN1054127C CN 1054127 C CN1054127 C CN 1054127C CN 96106799 A CN96106799 A CN 96106799A CN 96106799 A CN96106799 A CN 96106799A CN 1054127 C CN1054127 C CN 1054127C
- Authority
- CN
- China
- Prior art keywords
- sulfamonomethoxine
- water
- alkali
- acetone
- monohydrate
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a method for preparing sulfa-6-methoxypyrimidine-hydrate, which is characterized in that sulfa-6-methoxypyrimidine-anhydrous substance is recrystallized with water / a water-solubility solvent system, and thereby, the sulfa-6-methoxypyrimidine-hydrate can be prepared.
Description
The present invention relates to prepare the novel method of sulfamonomethoxine monohydrate (Sulfamonomethoxine hydrate, i.e. formula I compound).
Sulfa drugs is used for clinical existing more than 60 year, is the chemical synthetic drug of at first treating the general infectation of bacteria.Though microbiotic constantly develops in recent years, but sulfonamides has has a broad antifungal spectrum because of it, determined curative effect, and proterties is stable, be convenient to store and transportation, can be oral, easy to use, do not consume grain during production, advantage such as cheap, in worldwide, still be widely used in clinically, be a focus of medical worker research always.
Sulfamonomethoxine is a long-acting sulfonamides, is used for Hemolytic streptococcus, and its anhydride is used in the infection of streptococcus pneumoniae and meningococcus etc. for a long time clinically always.In recent years, Japanese scholar Takayama, the research of Kozo etc. (see Chem.Pharm.Bull.1978,26 (1), 96-100; 1969,17,499:1977,25,3125) show that the sulfamonomethoxine monohydrate has better crystal formation, solvability and hypotoxicity than its anhydride, therefore the medicament made from its monohydrate has higher bioavailability.In Japan, it is clinical to replace its anhydride to be used for its monohydrate.(see Pharmacopeia of Japan, the 12 corrects version)
About the preparation method of sulfamonomethoxine monohydrate, only at Chem.Pharm.Bull.1978,26 (1), report is with acetone solvent systems recrystallization among the 96-100, does not but describe concrete crystallization condition and solvent ratio.
The purpose of this invention is to provide the new preparation method of sulfamonomethoxine monohydrate, present method solvent for use is cheap and easy to get, and the crystallization condition gentleness is suitable for industrial production.Products obtained therefrom purity height, crystal formation is good.
The present invention is to be raw material with the sulfamonomethoxine anhydride, and water/water-soluble solvent system dissolves raw material is transferred pH to 7-11 with dilute alkaline aqueous solution when needing, crystallization then, the crystal of separating out in the filtering solution, drying, the sulfamonomethoxine monohydrate.Sulfamonomethoxine wherein: water: the weight of water-soluble solvent (g)/volume (ml) is than being 1: 2-1 2: 1-5, preferred 1: 6-9: 2.5-4.5.
Water-soluble solvent is meant alcohols, as methyl alcohol, and ethanol, n-propyl alcohol, Virahol etc.; Ketone, as acetone, preferred acetone.
During dissolving sulphur-6-Sulfamonomethoxine, can at room temperature carry out, also can heat, Heating temperature is room temperature-reflux temperature, and decide on the dissolving situation heat-up time, with molten being as the criterion entirely, is generally 10 minutes-2 hours.
For Cu Jin Rong is separated, can in dissolution process, add a certain amount of dilute alkaline aqueous solution, so that raw material dissolves fast, and draw crystallization preferably.
Used alkali is meant alkali-metal oxyhydroxide, as NaOH, and KOH etc.; Alkali-metal carbonate is as yellow soda ash; Alkali-metal supercarbonate is as sodium bicarbonate; Amine, as ammoniacal liquor, preferred weak ammonia, weak ammonia is meant the ammonia soln of 1-6 times of gained of strong aqua thin up.
The consumption of alkali lye is looked the pH value of solution and the concentration of alkali lye is decided, and adds lye pH adjustment to 7-11, preferably transfers pH to 8-9.As so that the weak ammonia of 4 times of strong aqua dilutions is transferred the pH value of solution, consumption is 1 with the ratio (w/v) of sulfamonomethoxine generally: 0.5-5.
During cooling crystallization, solution can be left standstill crystallization in room temperature, also can be at but crystallization of refrigerator and cooled.
The preparation method of sulfamonomethoxine monohydrate provided by the invention, agents useful for same is common being easy to get, and inexpensive solvent is easy and simple to handle, is suitable for industrial production.Products obtained therefrom is a needle crystal, the purity height, and crystal formation is good, meets the Pharmacopeia of Japan standard fully, and product is suitable for outlet at present, and in the future is used for the clinical favourable condition that provides in China for the sulfamonomethoxine monohydrate.
The present invention can be further specified by the following example, but should not be construed as limitation of the present invention.Embodiment 1.
The 10g sulfamonomethoxine is added in the solvent systems of being made up of 80ml water and 40ml acetone, reflux, and add the 15ml dilute ammonia solution, the pH value that makes solution is 8.Continued reflux 1 hour, and stopped heating, naturally cooling is separated out needle crystal, filters, and the crystallization seasoning is spent the night, and gets the colourless needle of 8.8g.Identify: m.p.204-206 ℃.IR(KBr)ν/cm
-1?3560，3400，3350，3150，1615，1600，1500，1490，1200，1150。Compare with the infrared spectra of sulfamonomethoxine, have more 3560 water absorption peak.Weight loss on drying: (105 ℃, dry 4 hours) 6.40% embodiment 2.
Get the 13g sulfamonomethoxine and place round-bottomed flask, add 60ml water, add 20ml acetone again, be heated to backflow, slowly adding weak ammonia (being got by 4 times of strong aqua dilutions) 24ml to pH is 9.Continue reflux and dissolve fully, be cooled to room temperature, place refrigerator overnight then until solid.Filter,, weigh, be 10.05g the colourless needle of gained air-dry ten days.m.p.204-206℃。Weight loss on drying: 6.45% embodiment 3.
Get the 27g sulfamonomethoxine and place round-bottomed flask, add 80ml water, add 20ml acetone under the stirring at room, slowly add 67ml weak ammonia (being got by 4 times of strong aqua dilutions), stir after 2 hours, solid is molten entirely, examination pH value of solution value is 10, placement is spent the night, and separates out small amount of crystalline, filters, merge the gained crystallization, air-dry, weigh 13.75g.m.p.204-206℃。Weight loss on drying: 6.50% embodiment 4.
Get the 10g sulfamonomethoxine and place round-bottomed flask, add water 100ml, add acetone 30ml, be heated to backflow, not molten entirely yet after 2 hours, continue to add acetone 10ml, reflux 2 hours, solid is molten entirely, slowly cools to room temperature, leaves standstill crystallization, the colourless needle of separating out in the flask is filtered, air-dry, weigh 3.88g.m.p.：204-206℃。Weight loss on drying: 6.30% embodiment 5.
Get the 7.2g sulfamonomethoxine and place round-bottomed flask, add 20ml water, reflux adds dehydrated alcohol 40ml, continues reflux, adds 8% the NaOH aqueous solution (adding 8.7g NaOH preparation by 100ml water) 20ml, to the pH value be 11, solid is molten entirely.Cooling crystallization filters, and crystal washes with water three times, and 70 ℃ of dryings 0.5 hour are weighed 0.55g.m.p.204-206℃。Weight loss on drying: 6.40%
Claims (9)
1. method for preparing the sulfamonomethoxine monohydrate, comprise the sulfamonomethoxine anhydride is dissolved in the solvent systems of being made up of ethanol or acetone and water, adding alkali aqueous solution transfers the pH value of solution to be 7-11, cooling crystallization then, the proportioning of raw material and each solvent is: sulfamonomethoxine anhydride: water: ethanol or acetone=1: 2-12: 0.5-5.
2. according to the method for claim 1, it is characterized in that solvent systems wherein is made up of acetone and water.
3. according to the method for claim 1, it is characterized in that alkali aqueous solution is selected from alkali-metal oxyhydroxide, alkali-metal carbonate, supercarbonate, and acetate or organic bases.
4. according to the method for claim 3, it is characterized in that used alkali is ammoniacal liquor.
5. according to the method for claim 1, the ratio of components that it is characterized in that raw material sulfamonomethoxine and alkali aqueous solution is 1: 0.25-5.0.
6. according to the method for claim 1, it is characterized in that sulfamonomethoxine: water: the ratio of components of water-soluble solvent is 1: 3.6-9: 2.0-4.5.
7. according to the method for claim 1, it is characterized in that in solution, adding adjusting PH with base to 8-9.
8. according to the method for claim 1, need heat when it is characterized in that dissolving, Heating temperature is room temperature-reflux temperature.
9. according to the method for claim 1, the temperature that it is characterized in that cooling crystallization is 0 a ℃-room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96106799A CN1054127C (en) | 1996-07-16 | 1996-07-16 | Process for preparing monohydrate of sulfamonomethoxine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96106799A CN1054127C (en) | 1996-07-16 | 1996-07-16 | Process for preparing monohydrate of sulfamonomethoxine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1150149A CN1150149A (en) | 1997-05-21 |
| CN1054127C true CN1054127C (en) | 2000-07-05 |
Family
ID=5119401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96106799A Expired - Fee Related CN1054127C (en) | 1996-07-16 | 1996-07-16 | Process for preparing monohydrate of sulfamonomethoxine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1054127C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294576B (en) * | 2015-11-23 | 2018-04-13 | 和夏化学(太仓)有限公司 | A kind of preparation method of 6 methoxy pyrimidine sodium of sulfanilamide (SN) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56139414A (en) * | 1980-04-01 | 1981-10-30 | Dai Ichi Seiyaku Co Ltd | Stabilizing method of aqueous solution |
| CN1078464A (en) * | 1993-02-19 | 1993-11-17 | 河南省南阳地区益民制药厂 | Synthesizing method for bacteriostatic sulphur |
-
1996
- 1996-07-16 CN CN96106799A patent/CN1054127C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56139414A (en) * | 1980-04-01 | 1981-10-30 | Dai Ichi Seiyaku Co Ltd | Stabilizing method of aqueous solution |
| CN1078464A (en) * | 1993-02-19 | 1993-11-17 | 河南省南阳地区益民制药厂 | Synthesizing method for bacteriostatic sulphur |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1150149A (en) | 1997-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102020617B (en) | The polymorphs body and preparation method thereof of 2- (3- cyano-4-isobutoxy phenyl) -4- methyl-5-thiazole formic acid | |
| US20080085903A1 (en) | Novel crystalline forms of aripiprazole | |
| FI82189C (en) | Process for producing a stable modification of torasemide | |
| JP2001508077A (en) | Novel modification of 2-amino-4- (4-fluorobenzylamino) -1-ethoxycarbonyl-aminobenzene and process for producing the same | |
| JP2002509919A (en) | Pyridazinone compound hydrochloride and method for producing the same | |
| CN103664881A (en) | Dabigatran etexilate of crystallized variant form B as well as preparation method thereof and application | |
| CN1054127C (en) | Process for preparing monohydrate of sulfamonomethoxine | |
| AU2005284331B2 (en) | Method for manufacturing imidazole compounds and salts and pseudopolymorphs thereof | |
| CN111471057A (en) | Process for preparing mezlocillin sodium by solvent crystallization | |
| CA1077502A (en) | Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) compositions thereof methods of making and using | |
| Wilson | 229. Some 2: 4-diamino-5-acylamido-6-hydroxypyrimidines | |
| WO2023122868A1 (en) | Posaconazole impurity reference substance and preparation method therefor | |
| CN101823980B (en) | Preparation method of large-grain occrycetin | |
| Fargher | LXX.—Orientation of the nitro-and arylazoglyoxalines. Fission of the glyoxalone nucleus | |
| US5442051A (en) | Anhydrous crystal of 4-carbamoyl-1-β-D-ribofuranosyl imidazolium-5-oleate | |
| CN107325013A (en) | A kind of method for synthesizing glycine propionyl levo-carnitine hydrochloride | |
| WO2010108417A1 (en) | Method for preparing acyclovir 2/3 hydrate | |
| EP1363882A1 (en) | 3-(3-amidinophenyl)-5- ( 1-(1-(-iminoethyl)-4-piperidyl amino)methyl]benzoic acid dihydrochloride and process for preparing the same | |
| Wolfrom et al. | The Free Aldehyde Form of Fucose Tetraacetate | |
| CN114195761B (en) | Preparation method of high-purity sitafloxacin hydrate 3/2 | |
| CN111100121B (en) | Purification method of berberine or hydrochloride thereof | |
| US20050014739A1 (en) | Aztreonam beta polymorph with very low residual solvent content | |
| CN117209454A (en) | Novel levocetirizine sodium crystal form and preparation method thereof | |
| CZ298424B6 (en) | Crystallization process of rosiglitazone and derivatives thereof from mixed solutions | |
| CN101768136A (en) | New crystal form of febuxostat and preparation method thereof |
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 | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: China Medicine Research and Development Centre Document name: Notification of Termination of Patent Right |
|
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |