CN101921284A - The preparation method of cefathiamidine - Google Patents
The preparation method of cefathiamidine Download PDFInfo
- Publication number
- CN101921284A CN101921284A CN2009100859866A CN200910085986A CN101921284A CN 101921284 A CN101921284 A CN 101921284A CN 2009100859866 A CN2009100859866 A CN 2009100859866A CN 200910085986 A CN200910085986 A CN 200910085986A CN 101921284 A CN101921284 A CN 101921284A
- Authority
- CN
- China
- Prior art keywords
- cefathiamidine
- preparation
- slightly soluble
- crude product
- soluble solvent
- 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
- JYXACOFERDBGGQ-RHSMWYFYSA-N cefathiamidine Chemical compound S1CC(COC(C)=O)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CSC(NC(C)C)=NC(C)C)[C@H]21 JYXACOFERDBGGQ-RHSMWYFYSA-N 0.000 title claims abstract description 44
- 229950005040 cefathiamidine Drugs 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 22
- 239000012043 crude product Substances 0.000 claims abstract description 16
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 claims abstract description 15
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- KREOCUNMMFZOOS-UHFFFAOYSA-N 1,3-di(propan-2-yl)thiourea Chemical compound CC(C)NC(S)=NC(C)C KREOCUNMMFZOOS-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 238000002444 silanisation Methods 0.000 claims description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 239000002253 acid Substances 0.000 abstract description 14
- 238000000034 method Methods 0.000 abstract description 10
- 239000007787 solid Substances 0.000 abstract description 6
- 229930186147 Cephalosporin Natural products 0.000 abstract description 2
- 229940124587 cephalosporin Drugs 0.000 abstract description 2
- 150000001780 cephalosporins Chemical class 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- YKSNHLNTLVRITE-UHFFFAOYSA-N [Br].CC(Br)=O Chemical compound [Br].CC(Br)=O YKSNHLNTLVRITE-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 1
- SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241001312524 Streptococcus viridans Species 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 229960002682 cefoxitin Drugs 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical group O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- -1 sulphur amidine Chemical class 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
本发明涉及头孢硫脒的制备方法，该方法按如下步骤分三步进行：(1)制备头孢硫脒酸，7-ACA在室温下用BSA硅烷化，然后在0℃与溴乙酰溴反应，处理析出固体，抽滤，干燥，得到高纯度的头孢硫脒酸。(2)头孢硫脒酸加入碱性试剂后与N，N’-二异丙基硫脲反应，加入微溶溶剂，析出头孢硫脒粗品。(3)头孢硫脒粗品溶于适当溶剂，调节溶液pH为4-5.5，加入微溶溶剂至溶液出现浑浊，控制搅拌速度，继续缓慢滴加微溶溶剂，析出产品，分离，干燥，得头孢硫脒。该方法步骤少，工艺简单，纯度高，易于实现。The present invention relates to the preparation method of cefathiamidine, and this method is carried out in three steps as follows: (1) prepare cefathiame acid, 7-ACA is silanized with BSA at room temperature, then reacts with bromoacetyl bromide at 0 DEG C, Treat the precipitated solid, suction filter, and dry to obtain high-purity cefathiamic acid. (2) After adding an alkaline reagent, cefathiamidine reacts with N, N'-diisopropylthiourea, adds a slightly soluble solvent, and separates out the crude product of cefathiamidine. (3) The cefathiamidine crude product is dissolved in an appropriate solvent, the pH of the solution is adjusted to 4-5.5, a slightly soluble solvent is added until the solution becomes turbid, the stirring speed is controlled, and the slightly soluble solvent is continued to be slowly added dropwise to precipitate the product, separated and dried to obtain cephalosporin Thiamidine. The method has few steps, simple process, high purity and easy realization.
Description
Technical field
The present invention relates to the preparation method of medicinal chemicals cefathiamidine, belong to the synthetic field of chemicals.
Background technology
Cefathiamidine (Cefathiamidine) is a first generation cephalosporin, for China initiative and be used for clinical.
Be commonly called as: Cefathiamidine, C-18.Antimicrobial spectrum is similar to cefoxitin, to golden Portugal bacterium, Streptococcus viridans, pneumococcal effect is stronger, faecalis there is unique anti-microbial activity, is mainly used in infection such as respiratory tract infection due to golden Portugal bacterium, streptococcus pneumoniae and the suis, biliary tract infection, urinary tract infections, gynecological infection, septicemia, pneumonia, meningitis.USP 3,646, and 025 and " Chinese pharmaceutical chemistry magazine ", 2001,10, o. 11th, P293-294, and application number 200410102519.7 provides the synthetic method of cefathiamidine crude product.
Wherein preceding two kinds of more complicated are difficult for realizing.In U.S. Pat 3499893, preparation cefathiamidine acid two steps of experience.At first, with 7-ACA, NaCO3 is water-soluble, and in the acetone mixed solvent, 0 ℃ adds bromoacetyl bromide fast, behind the room temperature reaction 1h, concentrates then, and adding diethyl ether extracts and discard organic layer.Water layer adds ethyl acetate, transfers PH=2 with phosphoric acid under the low temperature, filters, and tells organic layer and washes with water.Add 2 ethyl hexanoic acid after the drying, friction bottle wall makes oily liquid separate out solid, filters.Obtain the sodium salt of cefathiamidine acid.Again that sodium salt is water-soluble, in the acetone mixed solvent, transfer PH=2 with phosphoric acid, separate out solid with glass rod friction bottle wall.Filter, get the acid of free cefathiamidine.It is too loaded down with trivial details that this method prepares cefathiamidine acid, and do not provide yield.
" Chinese pharmaceutical chemistry magazine ", 2001,10, o. 11th, the described method for preparing cefathiamidine of P293-294, experience 3 step reaction.The starting raw material 1 that the first step is used, 3-di-isopropyl amidino groups-2-sulfo--acetic acid hydrochloride just is difficult to obtain, and prepare the reagent that active ester uses is phosphorus oxychloride in addition, and very big pungency is arranged, and meets water and fiercely decomposes, and certain danger is arranged.Should avoid using as far as possible.The second, three step was the active ester reaction of the 7-ACA silanization is later and the first step, transferred PH, separated out crystal.After the recrystallization, yield 56%.
Chinese patent 200410102519.7 is simplified and has been improved United States Patent (USP) and prepares the method for cefathiamidine acid, and two steps were merged, and directly prepares cefathiamidine acid.But in the acid of mass production cefathiamidine, the solvent for use system is water-acetone, and the large percentage of water (2: 1) can make the bromoacetyl bromide hydrolysis, makes its consumption increase (1.3eq).Can produce a large amount of foams during with sodium bicarbonate dissolving 7-ACA, jar phenomenon of overflowing is arranged, could continue slowly to add sodium bicarbonate after must waiting lather collapse, make the operating time prolongation.And 7-ACA is unstable in basic solution, and time lengthening can influence quality product, and is particularly serious in the production.From the dripping bromine acetyl bromide, to regulating pH value, reaction all must be carried out at low temperature, and energy consumption is higher.And the cefathiamidine acid that dissociates out solubleness in ethyl acetate and acetone is all bad, must add the solvent extraction of a large amount of volumes, causes operational inconvenience.And the yield of this method 42% is unsatisfactory.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of new method for preparing cefathiamidine.
Used following raw material is conventional commercially available prod among the present invention.
7-amino-cephalosporanic acid (being called for short 7-ACA), molecular formula is C
10H
12N
2O
5S, molecular weight are 272.28, and chemical name is 3-acetyl-o-methyl-5-sulphur-7-amino-8-oxygen-1-azabicyclic oct-2-ene-2 carboxylic acid.
N, two (trimethyl silicon based) ethanamides of O-, common name: BSA, molecular formula: C
8H
21NOSi
2, molecular weight: 203.43, CAS No.:10416-59-8
Bromoacetyl bromide, molecular formula: C
2H
2Br
2O; Molecular weight: 201.84; CASNo.:598-21-0.
For solving technical problem of the present invention, the present invention adopts following technical scheme:
(a) with 7-amino-cephalosporanic acid N, two (trimethyl silicon based) ethanamides of O-carry out silanization, react with bromoacetyl bromide again;
(b) again in alkaline reagents with N, N '-di-isopropyl thiourea prepared in reaction cefathiamidine.
Preferred organic is a methylene dichloride in the step (a).
Preferred step (a) 7-amino-cephalosporanic acid and N, the Silanization reaction of two (trimethyl silicon based) ethanamides of O-is at room temperature to carry out; Behind step (b) the 7-amino-cephalosporanic acid silanization again with bromoacetyl bromide 0 ℃ of reaction, dropwise the afterreaction temperature and can slowly rise to room temperature, continue reaction 1-3 hour.
Alkaline reagents described in the step (b) is preferably triethylamine.Preferred solvent is a methylene dichloride.Preferred reaction is at room temperature carried out, and the time of reaction is 2-4 hour.
Step (b) reaction finishes the back and adds the slightly soluble solvent, and the cefathiamidine crude product is separated out.Preferred slightly soluble solvent is selected from acetone.
The invention also discloses the process for purification of cefathiamidine crude product.The purification step of spore sulphur amidine crude product is: the cefathiamidine crude product is dissolved in appropriate solvent, and regulator solution PH is 4-5.5, adds slightly soluble solvent to solution and occurs muddy, the control stirring velocity continues slowly to drip the slightly soluble solvent, separates out product, separate, drying obtains cefathiamidine.Preferred appropriate solvent is selected from water; Preferred slightly soluble solvent is selected from acetone.
Useful technique effect of the present invention:
This patent focuses on the synthetic method of the key intermediate cefathiamidine acid of preparation cefathiamidine is improved; Simple to operate, the yield height, purity is good.
Use methylene dichloride to be solvent, the operation inconvenience that has brought when having solved sodium bicarbonate dissolving in the production with the BSA silanization, promptly avoid 7-ACA for a long time in the unstable of basic solvent, avoided the hydrolysis of bromoacetyl bromide again, reduced the charging capacity (leq gets final product) of bromoacetyl bromide;
After dripping bromoacetyl bromide, can room temperature reaction, reduced energy consumption.
Aftertreatment is simple, need not low temperature and transfers pH value, adds water treatment solid is separated out.Purity is good, and yield can reach about 90%.
Embodiment
The following examples are used for further specifying the present invention, but this and do not mean that any limitation of the invention.
Synthesizing of embodiment 1 cefathiamidine acid
Add methylene dichloride 50ml in the 250ml round-bottomed flask, 7-ACA 12g (0.044mol), BSA 11.2g, stirring at room 2h is to dissolving.At 0 ℃ of slow dripping bromine acetyl bromide 8.82g (0.044mol), dropwise the afterreaction temperature and can slowly rise to room temperature then, reaction 2h.In reaction solution, add distilled water 100ml, have a large amount of solids to separate out, continue to stir half an hour, suction filtration, filter cake washes with water, and vacuum-drying gets cefathiamidine acid 15.56g.Yield 90.2%.
Synthesizing of embodiment 2 cefathiamidine crude products
In the 150ml round-bottomed flask, add the acid of 3.93g cefathiamidine, the 40ml methylene dichloride, the 1.3ml triethylamine, the solution becomes clarification adds 1.6g N, N '-di-isopropyl thiourea, stirring at room 3 hours, the TLC detection reaction is complete.Slowly Dropwise 5 0ml acetone has solid to separate out, and continues to stir 2h, leaves standstill half an hour.Suction filtration, washing with acetone.Vacuum-drying gets cefathiamidine crude product 4.45g.Yield 94.1%.
Embodiment 3 refining cefathiamidine crude products
Add 5g cefathiamidine crude product in the 100ml round-bottomed flask, use the 5ml dissolved in distilled water, hydrochloric acid is regulated PH 5.5, adds a certain amount of acetone to solution and occurs muddy, the control stirring velocity continues slowly to drip acetone 50ml, crystallization 3h, suction filtration, washing with acetone, vacuum-drying gets cefathiamidine 4.6g.Purity 98.48%.
Claims (10)
1. the preparation method of cefathiamidine is characterized in that, comprises the steps:
(a) with 7-amino-cephalosporanic acid N, two (trimethyl silicon based) ethanamides of O-carry out silanization, react with bromoacetyl bromide again;
(b) again in alkaline reagents with N, N '-di-isopropyl thiourea prepared in reaction cefathiamidine.
2. according to the preparation method of claim 1, it is characterized in that, step (a) 7-amino-cephalosporanic acid and N, the Silanization reaction of two (trimethyl silicon based) ethanamides of O-is at room temperature to carry out.
3. according to the preparation method of claim 1, it is characterized in that, behind step (b) the 7-amino-cephalosporanic acid silanization again with bromoacetyl bromide 0 ℃ of reaction.
4. according to the preparation method of claim 1, it is characterized in that the alkaline reagents described in the step (b) is a triethylamine.
5. according to the preparation method of claim 1, it is characterized in that step (b) reaction finishes the back and adds the slightly soluble solvent, and the cefathiamidine crude product is separated out.
6. according to the preparation method of claim 5, it is characterized in that described slightly soluble solvent is an acetone.
7. according to the preparation method of claim 1, it is characterized in that, also comprise the purification step of cefathiamidine crude product.
8. according to the preparation method of claim 7, it is characterized in that, the purification step of described cefathiamidine crude product is: the cefathiamidine crude product is dissolved in appropriate solvent, and regulator solution PH is 4-5.5, adds slightly soluble solvent to solution and occurs muddy, the control stirring velocity, continue slowly to drip the slightly soluble solvent, separate out product, separate, drying obtains cefathiamidine.
9. preparation method according to Claim 8 is characterized in that, the appropriate solvent of described dissolving cefathiamidine crude product is a water.
10. preparation method according to Claim 8 is characterized in that, described slightly soluble solvent is an acetone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100859866A CN101921284A (en) | 2009-06-10 | 2009-06-10 | The preparation method of cefathiamidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100859866A CN101921284A (en) | 2009-06-10 | 2009-06-10 | The preparation method of cefathiamidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101921284A true CN101921284A (en) | 2010-12-22 |
Family
ID=43336518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100859866A Pending CN101921284A (en) | 2009-06-10 | 2009-06-10 | The preparation method of cefathiamidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101921284A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070654A (en) * | 2011-01-24 | 2011-05-25 | 广东省石油化工研究院 | Preparation method of cefathiamidine |
| CN102285999A (en) * | 2011-09-07 | 2011-12-21 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for preparing cefathiamidine in one-step process |
| CN102491986A (en) * | 2011-12-22 | 2012-06-13 | 苏州致君万庆药业有限公司 | Method for preparing antibiotic cefathiamidine |
| CN102863461A (en) * | 2011-07-08 | 2013-01-09 | 广州白云山制药股份有限公司广州白云山化学制药厂 | (6R, 7R)-3-hydroxymethyl-7-[alpha-(N, N'-diisopropylamidino thio)-acetamido]-8-oxo-5-thia-1-azabicycle [4, 2, 0]-oct-2-ene-2-carboxylic acid |
| CN103102358A (en) * | 2011-11-10 | 2013-05-15 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Cephalosporin compound, crystal thereof, and preparation method and application thereof |
| CN104059088A (en) * | 2014-07-07 | 2014-09-24 | 江苏汉斯通药业有限公司 | Preparation technology for cefathiamidine |
| CN104072517A (en) * | 2014-07-07 | 2014-10-01 | 江苏汉斯通药业有限公司 | Production process for bromoacetyl aminodesa ce-toxycephalosporanicacid |
| CN110407857A (en) * | 2019-07-22 | 2019-11-05 | 山东罗欣药业集团股份有限公司 | A kind of preparation process of cefathiamidine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646025A (en) * | 1969-10-30 | 1972-02-29 | Bristol Myers Co | 7-(alpha-(1 3-substituted amidino-2-thio)acetamido)cephalosporanic acids |
| CN85102130A (en) * | 1985-04-01 | 1987-01-31 | 生化企业 | The novel method of preparation penicillin and cephalosporins derivatives |
| CN1640878A (en) * | 2004-12-27 | 2005-07-20 | 托新权 | Method for preparing cefathiamidide |
| CN101302226A (en) * | 2008-06-12 | 2008-11-12 | 齐鲁安替制药有限公司 | Preparation of cephamycine intermediate compound |
-
2009
- 2009-06-10 CN CN2009100859866A patent/CN101921284A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646025A (en) * | 1969-10-30 | 1972-02-29 | Bristol Myers Co | 7-(alpha-(1 3-substituted amidino-2-thio)acetamido)cephalosporanic acids |
| CN85102130A (en) * | 1985-04-01 | 1987-01-31 | 生化企业 | The novel method of preparation penicillin and cephalosporins derivatives |
| CN1640878A (en) * | 2004-12-27 | 2005-07-20 | 托新权 | Method for preparing cefathiamidide |
| CN101302226A (en) * | 2008-06-12 | 2008-11-12 | 齐鲁安替制药有限公司 | Preparation of cephamycine intermediate compound |
Non-Patent Citations (1)
| Title |
|---|
| 刘丹青，等: "头孢硫脒的合成方法改进", 《中国药物化学杂志》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070654A (en) * | 2011-01-24 | 2011-05-25 | 广东省石油化工研究院 | Preparation method of cefathiamidine |
| CN102070654B (en) * | 2011-01-24 | 2013-02-27 | 广东省石油化工研究院 | Preparation method of cefathiamidine |
| CN102863461A (en) * | 2011-07-08 | 2013-01-09 | 广州白云山制药股份有限公司广州白云山化学制药厂 | (6R, 7R)-3-hydroxymethyl-7-[alpha-(N, N'-diisopropylamidino thio)-acetamido]-8-oxo-5-thia-1-azabicycle [4, 2, 0]-oct-2-ene-2-carboxylic acid |
| CN102285999A (en) * | 2011-09-07 | 2011-12-21 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for preparing cefathiamidine in one-step process |
| CN102285999B (en) * | 2011-09-07 | 2014-04-02 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for preparing cefathiamidine in one-step process |
| CN103102358A (en) * | 2011-11-10 | 2013-05-15 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Cephalosporin compound, crystal thereof, and preparation method and application thereof |
| CN103102358B (en) * | 2011-11-10 | 2015-09-02 | 广州白云山制药股份有限公司广州白云山化学制药厂 | A kind of cephalosporin compound, its crystal and its production and use |
| CN102491986A (en) * | 2011-12-22 | 2012-06-13 | 苏州致君万庆药业有限公司 | Method for preparing antibiotic cefathiamidine |
| CN104059088A (en) * | 2014-07-07 | 2014-09-24 | 江苏汉斯通药业有限公司 | Preparation technology for cefathiamidine |
| CN104072517A (en) * | 2014-07-07 | 2014-10-01 | 江苏汉斯通药业有限公司 | Production process for bromoacetyl aminodesa ce-toxycephalosporanicacid |
| CN110407857A (en) * | 2019-07-22 | 2019-11-05 | 山东罗欣药业集团股份有限公司 | A kind of preparation process of cefathiamidine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101921284A (en) | The preparation method of cefathiamidine | |
| CN102391289B (en) | Synthetic methods of ceftazidime intermediate and ceftazidime | |
| CN103539803B (en) | A kind of method preparing ceftriaxone sodium | |
| CN102603841B (en) | Preparation method of dehydroisoandrosterone | |
| CN102219795B (en) | Method for preparing ceftezole sodium | |
| CN102134252B (en) | Preparation method of high-purity cefuroxime acid | |
| CN104356146B (en) | A kind of preparation method of cefotiam chloride | |
| CN101220040A (en) | Preparation of cefixime cephalosporin and fine purification method | |
| CN101704827B (en) | Synthesis method of cefathiamidine compound | |
| CN102702230A (en) | Method for preparing cefotaxime acid | |
| CN104844625A (en) | Cefamandole nafate new crystal form and crystallization preparing method thereof | |
| CN101817835B (en) | Cefdinir compound and new preparation method thereof | |
| CN103319503A (en) | Preparation method of cefdinir | |
| CN101830912A (en) | Cefetamet pivoxil hydrochloride compound and new preparation method thereof | |
| CN102295653A (en) | One-step recovery and preparation method of cefuroxime sodium | |
| CN102911186B (en) | Ceftizoxime sodium preparation and refining method | |
| CN110407857B (en) | Preparation process of cefathiamidine | |
| CN102351861A (en) | Industrial preparation method of ertapenem | |
| CN103172530B (en) | Preparation method of tolfenamic acid | |
| CN105440054A (en) | Process for preparing high-purity cefathiamidine | |
| CN1431211A (en) | Amine salt of cefathiamiding, its preparing method and application | |
| CN105017285A (en) | Synthetic process of novel cephalosporin anti-infective drug | |
| CN102070654B (en) | Preparation method of cefathiamidine | |
| CN104478811B (en) | Fimasartan intermediate preparation method | |
| CN102942575A (en) | Method for preparing cefodizime sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20101222 |