CN101050220A - Method for preparing Cefquinome sulfate of antibiotics of animal - Google Patents
Method for preparing Cefquinome sulfate of antibiotics of animal Download PDFInfo
- Publication number
- CN101050220A CN101050220A CN 200710022451 CN200710022451A CN101050220A CN 101050220 A CN101050220 A CN 101050220A CN 200710022451 CN200710022451 CN 200710022451 CN 200710022451 A CN200710022451 A CN 200710022451A CN 101050220 A CN101050220 A CN 101050220A
- Authority
- CN
- China
- Prior art keywords
- cefquinome
- antibiotics
- preparation
- amino
- cefquinome sulfate
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
This invention discloses a method for preparing cefquinome sulfate as an animal antibiotic. The method comprises: synthesizing 1-[[(6R,7R)-7-[[(2Z)-(2-amino-4-thiazole)(methoxyimino)acetyl]amino]-2-carboxyl-8-O-5-S-1-diazabicyclo[4.2.0]-2-octene-3-yl]methyl]-5,6,7,8-tetrahydroquinoline hydroiodate cefquinome dihydroiodate, and then preparing cefquinome sulfate.
Description
Technical field
The present invention relates to a kind of preparation method of raw material sulphuric acid cefquinome of antibiotics of animal.
Background technology
Along with the continuous popularization of intensive culture and the people demand to livestock product, the breeding stock of domestic animals such as China pig, ox constantly rises, and the difficulty of epidemic prevention and control also increases thereupon.Domestic animal respiratory system infection and mammitis of cow are that sickness rate is the highest in the big livestock culturing, the maximum and two the most serious class diseases of financial loss of treatment difficulty.Control for this two classes disease, except that good feeding and management, antibiotic therapy is an important measures, yet because the unreasonable use of medicine, cause the resistance of pathogenic bacteria progressively to increase, the breed personnel have to strengthen dosage and medication number of times, thereby be absorbed among antibiotic " vicious cycle ", not only result of treatment worse and worse, and increased the residual quantity of microbiotic in meat, milk, finally bring serious threat, so development is the most important thing that current veterinary drug is researched and developed with exploitation low toxicity animal specific microbiotic efficient, low residue to human health.
Summary of the invention:
The invention provides a kind of preparation method who is used to make the raw material sulphuric acid cefquinome of antibiotics of animal, not only result of treatment is good for it, and toxic effect is low, and can avoid the problem that increases of the incident cross resistance of the shared microbiotic of people and animals, drug residue and zoonosis.
The present invention has adopted following technical scheme: 1, a kind of preparation method of Cefquinome sulfate of antibiotics of animal, it may further comprise the steps: step 1,1-[[(6R, 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates synthetic: it is raw material with the cefotaxime: cefotaxime and methylene dichloride are stirred under ice bath carry out the first time and cool off, slowly add 5 then, 6,7, the 8-tetrahydroquinoline, add Iodotrimethylsilane again, add back temperature rising reflux reaction, carry out the cooling second time again, begin to drip hydroiodic acid HI then, the mixed solution that distilled water and ethanol are formed, separate out and leach precipitation after two hydriodates precipitation leaves standstill, use washed with dichloromethane and washing with acetone at last, air drying obtains 1-[[(6R, 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates; Step 2, the preparation of Cefquinome sulfate: with the 1-[[(6R that makes in the step 1,7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates, the diamine liquid resin, distilled water and ethyl acetate be stirring and dissolving at room temperature, layering, water layer toluene wash wherein, activated carbon decolorizing stirs under the room temperature, the elimination gac, and filtrate is carried out sterile filtration, filtrate is used sulfuric acid acidation under aseptic condition, add dehydrated alcohol then and carry out crystallization, suction filtration, absolute ethanol washing, vacuum-drying obtains Cefquinome sulfate; Its reaction formula is
Slowly add 5,6,7 after for the first time being cooled to 5 ℃ in the step 1 of the present invention, the 8-tetrahydroquinoline need remain on 5 ℃.Temperature rising reflux reacted 3 hours after dripping Iodotrimethylsilane in the step 1.For the second time be cooled to 5 ℃ in the step 1.Hydroiodic acid HI in the step 1 mixed solution is 45% hydroiodic acid HI, 45% hydroiodic acid HI: distilled water: ethanol=1: 1: 3.Separating out the temperature that two hydriodates precipitations leaves standstill in the step 1 is 0 ℃, and time of repose is 4 hours.
1-[[(6R in the step 2 of the present invention; 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5; 6; 7, at room temperature the time of stirring and dissolving is 30 minutes for 8-tetrahydroquinoline hydriodate cefquinome two hydriodates, diamine liquid resin, distilled water and ethyl acetate.The time that activated carbon decolorizing stirs under the room temperature in the step 2 is 30 minutes.Step 2 filtrate is carried out sterile filtration by the polymeric amide filter membrane.
The microbiotic that the present invention makes has good therapeutic action for domestic animal respiratory system such as treatment pig, ox and mammitis of cow, and toxicity is little, not influence of resistance for the people, can avoid the problem that increases of the incident cross resistance zoonosis of the shared microbiotic of people and animals, in meat, not have drug residue.
Embodiment
The present invention is a kind of to be used to make the preparation method of the raw material sulphuric acid cefquinome of antibiotics of animal, and embodiment specifies below adopting.
Embodiment one: step 1; 1-[[(6R; 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5; 6; 7; synthesizing of 8-tetrahydroquinoline hydriodate (cefquinome two hydriodates); concrete grammar is as follows: add 98 gram (0.2mol) cefotaxime and 1800ml methylene dichloride in reaction flask; ice bath stirs down and is cooled to below 5 ℃, slowly adds 5,6 then; 7; the 8-tetrahydroquinoline remains on below 5 ℃, drips the 200ml Iodotrimethylsilane; after adding; temperature rising reflux reaction 3 hours is cooled to below 5 ℃, begins to drip the 400ml mixed solution (by 45% hydroiodic acid HI: distilled water: ethanol=form at 1: 1: 3).Separate out lurid two hydriodates precipitation, under 0 ℃, left standstill 4 hours, leach precipitation.With 100ml * 2 washed with dichloromethane and 100ml washing with acetone; air drying obtains the 1-[[(6R of 103g; 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5; 6; 7; 8-tetrahydroquinoline hydriodate (cefquinome two hydriodates), yield 65%, fusing point: 173 ℃-175 ℃.
Step 2, the preparation of Cefquinome sulfate is with cefquinome two hydriodate 85g (purity 93%, 0.1mol), 150ml diamine liquid resin, 300ml distilled water and 500ml ethyl acetate be stirring and dissolving (about 30 minutes) at room temperature, layering, water layer 400ml toluene wash.Activated carbon decolorizing stirred 30 minutes under the room temperature, the elimination gac, and filtrate is with 0.3 micron polymeric amide filter membrane sterile filtration, and filtrate is used the 6N sulfuric acid acidation under aseptic condition, add dehydrated alcohol 1000ml crystallization then, suction filtration, absolute ethanol washing, vacuum-drying obtains the 48g product, yield 74.7%.
Claims (9)
1, a kind of preparation method of Cefquinome sulfate of antibiotics of animal, it may further comprise the steps:
Step 1,1-[[(6R, 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates synthetic: it is raw material with the cefotaxime: cefotaxime and methylene dichloride are stirred under ice bath carry out the first time and cool off, slowly add 5 then, 6,7, the 8-tetrahydroquinoline, add Iodotrimethylsilane again, add back temperature rising reflux reaction, carry out the cooling second time again, begin to drip hydroiodic acid HI then, the mixed solution that distilled water and ethanol are formed, separate out and leach precipitation after two hydriodates precipitation leaves standstill, use washed with dichloromethane and washing with acetone at last, air drying obtains 1-[[(6R, 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates;
Step 2, the preparation of Cefquinome sulfate: with the 1-[[(6R that makes in the step 1,7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5,6,7,8-tetrahydroquinoline hydriodate cefquinome two hydriodates, the diamine liquid resin, distilled water and ethyl acetate be stirring and dissolving at room temperature, layering, water layer toluene wash wherein, activated carbon decolorizing stirs under the room temperature, the elimination gac, and filtrate is carried out sterile filtration, filtrate is used sulfuric acid acidation under aseptic condition, add dehydrated alcohol then and carry out crystallization, suction filtration, absolute ethanol washing, vacuum-drying obtains Cefquinome sulfate;
Its reaction formula is
2, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1 slowly adds 5,6,7 after it is characterized in that being cooled to 5 ℃ for the first time in the step 1, and the 8-tetrahydroquinoline need remain on 5 ℃.
3, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1, temperature rising reflux reacted 3 hours after it is characterized in that dripping Iodotrimethylsilane in the step 1.
4, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1 is characterized in that being cooled to 5 ℃ for the second time in the step 1.
5, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1 is characterized in that the hydroiodic acid HI in the step 1 mixed solution is 45% hydroiodic acid HI, 45% hydroiodic acid HI: distilled water: ethanol=1: 1: 3.
6, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1, it is characterized in that separating out in the step 1 temperature that two hydriodates precipitation leaves standstill is 0 ℃, time of repose is 4 hours.
7, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1; it is characterized in that 1-[[(6R in the step 2; 7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (methoxyimino) ethanoyl] amino]-2-carboxyl-8-oxygen-5-sulphur-1-azabicyclo [4.2.0] oct-2-ene-3-yl] methyl]-5; 6; 7, at room temperature the time of stirring and dissolving is 30 minutes for 8-tetrahydroquinoline hydriodate cefquinome two hydriodates, diamine liquid resin, distilled water and ethyl acetate.
8, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1 is characterized in that the time that activated carbon decolorizing stirs under the room temperature in the step 2 is 30 minutes.
9, the preparation method of Cefquinome sulfate of antibiotics of animal according to claim 1 is characterized in that step 2 filtrate carries out sterile filtration by the polymeric amide filter membrane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710022451 CN101050220A (en) | 2007-05-21 | 2007-05-21 | Method for preparing Cefquinome sulfate of antibiotics of animal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710022451 CN101050220A (en) | 2007-05-21 | 2007-05-21 | Method for preparing Cefquinome sulfate of antibiotics of animal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101050220A true CN101050220A (en) | 2007-10-10 |
Family
ID=38781842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710022451 Pending CN101050220A (en) | 2007-05-21 | 2007-05-21 | Method for preparing Cefquinome sulfate of antibiotics of animal |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101050220A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102002058A (en) * | 2010-11-05 | 2011-04-06 | 山东鲁抗立科药物化学有限公司 | Synthetic method of cefquinome sulfate |
| JP2012533596A (en) * | 2009-07-20 | 2012-12-27 | インターベツト・インターナシヨナル・ベー・ベー | Method for producing cefquinome particles |
| CN101787038B (en) * | 2010-01-22 | 2013-04-10 | 普莱柯生物工程股份有限公司 | Preparation method of cefquinome sulfate |
| CN103275103A (en) * | 2013-06-14 | 2013-09-04 | 河北科技大学 | Method for preparing cefquinome sulfate |
-
2007
- 2007-05-21 CN CN 200710022451 patent/CN101050220A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012533596A (en) * | 2009-07-20 | 2012-12-27 | インターベツト・インターナシヨナル・ベー・ベー | Method for producing cefquinome particles |
| JP2016047827A (en) * | 2009-07-20 | 2016-04-07 | インターベット インターナショナル ベー． フェー． | Method of producing cefquinome particles |
| CN101787038B (en) * | 2010-01-22 | 2013-04-10 | 普莱柯生物工程股份有限公司 | Preparation method of cefquinome sulfate |
| CN102002058A (en) * | 2010-11-05 | 2011-04-06 | 山东鲁抗立科药物化学有限公司 | Synthetic method of cefquinome sulfate |
| CN102002058B (en) * | 2010-11-05 | 2012-04-04 | 山东鲁抗立科药物化学有限公司 | Synthetic method of cefquinome sulfate |
| CN103275103A (en) * | 2013-06-14 | 2013-09-04 | 河北科技大学 | Method for preparing cefquinome sulfate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102093349B (en) | Method for performing industrialized production on moxifloxacin hydrochloride | |
| CN101050220A (en) | Method for preparing Cefquinome sulfate of antibiotics of animal | |
| CN112280720B (en) | Bacteroides thetaiotaomicron GL-02 and complex microbial inoculum compounded with bile acid and application thereof | |
| CN102516262A (en) | Method for crystallizing cefixime trihydrate | |
| CN101967156B (en) | Method for recrystallizing cefuroxime sodium | |
| CN86102363A (en) | The preparation method of Carbostyril carboxylic acid derivatives and application thereof | |
| CN101597248B (en) | Preparation method of valnemulin and hydrochloride thereof | |
| CN101654458B (en) | Preparation method of hydrochloric acid ceftiofur | |
| CN104341435B (en) | The process for purification of ceftriaxone sodium | |
| CN111620893B (en) | C-3 tetrahydrofuran substituted cephalosporin-siderophore coupling compound and preparation method and application thereof | |
| CN102898509B (en) | Method for preparing enramycin crude product | |
| US8871927B2 (en) | Method for purifying Ceftizoxime sodium | |
| CN114586897B (en) | Composition, application thereof and sterile-like mouse model constructed by using composition | |
| CN104860841B (en) | 4-chlorocinnamaldehyde aminobutyric acid Schiff base, 4-chlorocinnamaldehyde aminobutyric acid Schiff base salt, and preparation method thereof | |
| CN113143971B (en) | Application of bile acid complex microbial inoculum in preparation of preparation for preventing and treating pet tear stains | |
| CN102617327B (en) | Dexibuprofen compound and preparation method thereof | |
| CN109432092A (en) | A kind of lactation period compounded antibiotic preparation and the preparation method and application thereof | |
| CN112401071B (en) | Application of bile acid composite microbial inoculum in preparation of mutton sheep feed additive | |
| CN104031069A (en) | Method for preparing cefquinome sulfate | |
| CN102464642B (en) | Compound, preparation method thereof and application thereof as feed additive | |
| CN101143871B (en) | Cephalosporin derivative | |
| CN110156737B (en) | Pyrone compounds and application thereof in resisting pseudomonas aeruginosa biomembrane | |
| CN104892507B (en) | Water-soluble methanesulfonic acid sarafloxacin and preparation method thereof | |
| CN102550837B (en) | Feed additive and preparation method thereof | |
| CN102875433A (en) | Preparation method of cilastatin acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |