CN111039958B - Preparation method of cefdinir - Google Patents
Preparation method of cefdinir Download PDFInfo
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- CN111039958B CN111039958B CN201911331229.2A CN201911331229A CN111039958B CN 111039958 B CN111039958 B CN 111039958B CN 201911331229 A CN201911331229 A CN 201911331229A CN 111039958 B CN111039958 B CN 111039958B
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- cefdinir
- condensation reaction
- dicyclohexylamine
- amino
- ester
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Links
- 229960003719 cefdinir Drugs 0.000 title claims abstract description 19
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 27
- 150000002148 esters Chemical class 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 150000001780 cephalosporins Chemical group 0.000 claims abstract description 7
- UXRCOVLPEITJJU-IOJJLOCKSA-N 2,2,2-trichloroethyl (6R)-7-amino-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound ClC(COC(=O)C1=C(CS[C@H]2N1C(C2N)=O)C=C)(Cl)Cl UXRCOVLPEITJJU-IOJJLOCKSA-N 0.000 claims abstract description 6
- XBQSBXZWISUNBO-BOPFTXTBSA-N benzotriazol-1-yl (2z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound N1=NC2=CC=CC=C2N1OC(=O)\C(=N/OC(=O)C)C1=CSC(N)=N1 XBQSBXZWISUNBO-BOPFTXTBSA-N 0.000 claims abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- -1 cefdinir dicyclohexylamine salt Chemical class 0.000 claims description 12
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 10
- 238000006482 condensation reaction Methods 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 239000003495 polar organic solvent Substances 0.000 claims description 2
- 229930186147 Cephalosporin Natural products 0.000 claims 1
- 229940124587 cephalosporin Drugs 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 8
- GQLGFBRMCCVQLU-SVGQVSJJSA-N (6r,7r)-7-azaniumyl-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(C=C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@H]21 GQLGFBRMCCVQLU-SVGQVSJJSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 150000007970 thio esters Chemical class 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 241000588655 Moraxella catarrhalis Species 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 229940124588 oral cephalosporin Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- KFCMZNUGNLCSJQ-NFBKMPQASA-N (4-methoxyphenyl)methyl (6r,7r)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=C(CCl)CS[C@H]2N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1 KFCMZNUGNLCSJQ-NFBKMPQASA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960002129 cefixime Drugs 0.000 description 1
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention provides a method for preparing cefdinir, which comprises the following steps: directly condensing 7-amino-3-vinyl-3-cephem-4-carboxylic acid trichloroethyl ester serving as a cephalosporin skeleton raw material and 1- [ (Z) -2- (2-amino-4-thiazolyl) -2- (acetoxyl imino) acetoxyl ] benzotriazole serving as active ester. The invention has less steps and high yield and product purity.
Description
Technical Field
The present invention relates to a process for the preparation of cefdinir.
Background
Cefdinir is the third generation oral cephalosporin, which not only maintains the antibacterial effect of cefixime on G-bacteria, but also enhances the effect of the existing oral cephalosporin antibiotics on G + bacteria, especially the antibacterial effect on staphylococcus. The bacillus subtilis can inhibit more than 90% of clinical isolates, such as methicillin-sensitive staphylococcus aureus (MSSA), staphylococcus epidermidis (MSSE), streptococcus (including streptococcus pneumoniae), haemophilus influenzae, klebsiella pneumoniae, moraxella catarrhalis and escherichia coli, even has good curative effects on gonococcus, branhamella catarrhalis and indole-positive proteus, has great global market demand, and recently releases MAH system and DMF similar system solicitation comments, aiming at encouraging the development and transfer of technologies of scientific research institutes.
Through comprehensive retrieval, the preparation of cefdinir related to the prior art is hundreds, and mainly comprises three types, namely a cyclization method, an acyl chloride method and an active ester method. Wherein the active ester method is mainly prepared by condensing the active ester of 7-AVCA and aminothiazoly loximate:
the total yield of the method is not high, and one important reason is that the two raw materials involved in the method are prepared by multi-step reaction, taking 7-AVCA as an example, and taking ACA, penicillin G or GCLE as raw materials, the reaction steps are various, and the total yield is greatly reduced. In addition, the method has the defects of difficult solvent recovery, large pollution, complicated operation of post-treatment steps and the like, and a plurality of steps of operation and even column chromatography are needed in many cases, and some documents provide a high-purity product obtained by salification, for example, CN101974020B discloses dicyclohexylamine salt. In addition, the currently used active ester is basically thioester, and CN101798313B authorizes and protects a novel ester 1- [ (Z) -2- (2-amino-4-thiazolyl) -2- (acetoxyimino) acetoxy ] benzotriazole (AB-AE), and the stability of the novel ester is better.
Disclosure of Invention
The invention abandons the raw material combination of thioester and 7-AVCA used in the prior art, overcomes a certain technical bias and provides a method for preparing cefdinir with a brand new thought.
The preparation method of cefdinir comprises the following steps:
directly condensing 7-amino-3-vinyl-3-cephem-4-carboxylic acid trichloroethyl ester serving as a cephalosporin skeleton raw material and 1- [ (Z) -2- (2-amino-4-thiazolyl) -2- (acetoxyimino) acetoxy ] benzotriazole serving as active ester. The 7-amino-3-vinyl-3-cephem-4-carboxylic acid trichloroethyl ester is also called 7-AVCA trichloroethyl ester, can be purchased directly, and can also be prepared by directly condensing 7-AVCA and trichloroethanol.
Optionally, the molar ratio of the active ester to the cephalosporin skeleton raw material is 1.1-1.2: 1, such as 1.2: 1.
Optionally, the condensation reaction is carried out in the presence of dicyclohexylamine.
Optionally, the molar ratio of dicyclohexylamine to trichloroethyl 7-amino-3-vinyl-3-cephem-4-carboxylate is 1.1 to 1.5:1, such as 1.3: 1.
Optionally, the condensation reaction temperature may be 10 to 30 ℃, such as 20 ℃.
Optionally, the solvent of the condensation reaction comprises water and a polar organic solvent, such as water and tetrahydrofuran, and the volume ratio of water to tetrahydrofuran may be 1: 10.
Optionally, after the condensation reaction, ester hydrolysis is directly carried out without separation, and cefdinir dicyclohexylamine salt is obtained in situ in an alkaline system after the reaction by directly adding inorganic base for hydrolysis; the inorganic base may be sodium bicarbonate; the pH value of the hydrolysis reaction can be 7.5-8.0; the cefdinir dicyclohexylamine salt obtained in situ from the hydrolyzed alkaline system can be separated by cooling and crystallizing the reaction system, and the temperature can be reduced to below 0 ℃, for example, to about-20 ℃.
Optionally, the preparation method further comprises adding acid to the dicyclohexylamine salt according to a conventional method to obtain cefdinir free base, wherein the acid can be inorganic acid, such as hydrochloric acid, and the pH value can be rapidly adjusted to about 3 by the acid.
As an example, the preparation method of the present invention comprises:
1 equivalent of 7-AVCA trichloroethyl ester dissolved in water: adding 1.1-1.5 equivalents of dicyclohexylamine into a solvent of tetrahydrofuran 1:10(V/V), adding 1.1-1.2 equivalents of AB-AE, condensing at 20 ℃, then dropwise adding a sodium bicarbonate aqueous solution until full hydrolysis, controlling the pH of the system after reaction to be about 7.5, then cooling to-20 ℃, continuing stirring to fully separate out cefdinir dicyclohexylamine salt, washing the obtained salt with tetrahydrofuran, and drying.
The beneficial effects of the invention are mainly as follows:
the invention develops a new way, abandons the combination of the common raw materials in the prior art, namely thioester and 7-AVCA, and unexpectedly discovers a specific 7-AVCA carboxylic ester which is not necessarily converted into 7-AVCA in advance and can be directly condensed with a specific active ester of the aminothiazoly loximate, the reaction steps are less, the yield is improved by dozens of percentage points, and the method greatly exceeds the expected range of people in the field; in addition, the method is carried out under the alkaline condition, the product does not contain E-type isomer of cefdinir dicyclohexylamine salt basically, the post-treatment is simple, the purity of the product is high, the obtained dicyclohexylamine salt can be converted into free alkali by simple treatment according to the quality requirements of various countries, and the method is very suitable for division and cooperation or technical transfer under the recent medical policy; the invention further researches the influence of the material proportion on the yield and the purity.
Detailed Description
Example 1:
dissolving 60mmol of 7-amino-3-vinyl-3-cephem-4-carboxylic acid trichloroethyl ester in a mixed solution of 200ml of tetrahydrofuran and 20ml of water, stirring, adding 66mmol of dicyclohexylamine for dissolving, then adding 66mmol of 1- [ (Z) -2- (2-amino-4-thiazolyl) -2- (acetoxyimino) acetoxyl ] benzotriazole, stirring at 20 ℃ until the HPLC monitoring reaction is completed, keeping the temperature at 20 ℃, dropwise adding a sodium bicarbonate aqueous solution under stirring for full hydrolysis, controlling the pH of a system after the reaction to be about 7.5, then cooling to-20 ℃, and continuing stirring until solids are fully separated out. The resulting solid was separated, washed with 50ml tetrahydrofuran and dried to give 34.6g of solid identified as cefdinir dicyclohexylamine salt, which was free of E isomer impurities and 90% pure by standard control.
1H-NMR(DMSO-d6):9.4(d,1H)；7.2(s,2H)；7.0(dd,1H)；6.7(s,1H)；5.6(dd,1H)；5.2(d,1H)；5.1(d,1H)；5.0(d,1H)；3.6,3.4(ABd,1H)；3.2(m,2H)；2.1(m,4H)；1.8(m,4H)；1.6(m,2H)；1.2-1.4(m,10H)
Examples 2-4 and comparative examples:
in the above experiment, referring to example 1 except the conditions listed in the table, the reaction conditions of the comparative example were the diphenylmethyl 7-AVCA ester, i.e., the ester of 7-AVCA and diphenylmethanol, and it is clear that the yield and purity of the comparative example are very poor and low compared with the embodiments of the present invention.
Claims (15)
1. A process for preparing cefdinir, comprising:
directly condensing 7-amino-3-vinyl-3-cephem-4-carboxylic acid trichloroethyl ester serving as a cephalosporin skeleton raw material and 1- [ (Z) -2- (2-amino-4-thiazolyl) -2- (acetoxyimino) acetoxyl ] benzotriazole serving as an active ester, directly hydrolyzing without separation after condensation reaction to obtain an addition salt of cefdinir and alkali, and further adding acid to treat the addition salt to obtain the cefdinir.
2. The method as claimed in claim 1, wherein the molar ratio of the active ester to the raw material of the cephalosporin skeleton is 1.1-1.2: 1.
3. The process according to claim 1 or 2, characterized in that the condensation reaction is carried out in the presence of dicyclohexylamine.
4. The process as claimed in claim 3, wherein the molar ratio of dicyclohexylamine to the cephalosporin skeleton material is 1.1-1.5: 1.
5. The process as claimed in claim 3, wherein the molar ratio of dicyclohexylamine to cephalosporin material is 1.3: 1.
6. The method as set forth in claim 1, wherein the solvent for the condensation reaction contains water and a polar organic solvent.
7. The method as set forth in claim 1, wherein the solvent for the condensation reaction contains water and tetrahydrofuran.
8. The method as set forth in claim 1, wherein the hydrolysis is carried out by adding an inorganic base.
9. The method according to claim 8, wherein the inorganic base is sodium bicarbonate.
10. The process according to claim 1, wherein the addition salt is cefdinir dicyclohexylamine salt.
11. The process as claimed in claim 10, wherein the separation of the cefdinir dicyclohexylamine salt is carried out by cooling the system for crystallization.
12. The method of claim 11, wherein said cooling is to below 0 ℃.
13. The method of claim 12, wherein said cooling is to-20 ℃.
14. A process according to any preceding claim, wherein the condensation reaction temperature is from 10 to 30 ℃.
15. The method of claim 14, wherein the condensation reaction temperature is 20 ℃.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710399331 | 2017-05-31 | ||
| CN2017103993310 | 2017-05-31 | ||
| CN201810556431.4A CN108546270B (en) | 2017-05-31 | 2018-05-31 | The method for preparing Cefdinir |
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|---|---|---|---|
| CN201810556431.4A Division CN108546270B (en) | 2017-05-31 | 2018-05-31 | The method for preparing Cefdinir |
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| CN111039958A CN111039958A (en) | 2020-04-21 |
| CN111039958B true CN111039958B (en) | 2022-05-20 |
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| CN201911331229.2A Expired - Fee Related CN111039958B (en) | 2017-05-31 | 2018-05-31 | Preparation method of cefdinir |
| CN201810556431.4A Expired - Fee Related CN108546270B (en) | 2017-05-31 | 2018-05-31 | The method for preparing Cefdinir |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995033753A1 (en) * | 1994-06-03 | 1995-12-14 | Marcham Trading & Investment Ltd. | Process for the preparation of trihydrated cefixime |
| CN1251590A (en) * | 1997-04-04 | 2000-04-26 | 生物化学有限公司 | Crystalline amine salt of cefdinir |
| CN101798313A (en) * | 2010-02-22 | 2010-08-11 | 浙江永宁药业股份有限公司 | New preparation method of Cefdinir |
| CN101974020A (en) * | 2010-11-19 | 2011-02-16 | 苏州中联化学制药有限公司 | Method for synthesizing cefdinir |
| CN102010427A (en) * | 2010-11-19 | 2011-04-13 | 苏州中联化学制药有限公司 | Method for preparing cefdinir |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992007840A1 (en) * | 1990-11-02 | 1992-05-14 | Taisho Pharmaceutical Co., Ltd. | Thiazole thioester derivative |
| US20040242556A1 (en) * | 2003-06-02 | 2004-12-02 | Ramesh Dandala | Novel crystalline form of cefdinir |
| US7105659B2 (en) * | 2003-06-02 | 2006-09-12 | Aurobind - Pharma Ltd. | Process for preparing cefdinir |
-
2018
- 2018-05-31 CN CN201911331229.2A patent/CN111039958B/en not_active Expired - Fee Related
- 2018-05-31 CN CN201810556431.4A patent/CN108546270B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995033753A1 (en) * | 1994-06-03 | 1995-12-14 | Marcham Trading & Investment Ltd. | Process for the preparation of trihydrated cefixime |
| CN1251590A (en) * | 1997-04-04 | 2000-04-26 | 生物化学有限公司 | Crystalline amine salt of cefdinir |
| CN101798313A (en) * | 2010-02-22 | 2010-08-11 | 浙江永宁药业股份有限公司 | New preparation method of Cefdinir |
| CN101974020A (en) * | 2010-11-19 | 2011-02-16 | 苏州中联化学制药有限公司 | Method for synthesizing cefdinir |
| CN102010427A (en) * | 2010-11-19 | 2011-04-13 | 苏州中联化学制药有限公司 | Method for preparing cefdinir |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111039958A (en) | 2020-04-21 |
| CN108546270B (en) | 2019-11-08 |
| CN108546270A (en) | 2018-09-18 |
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