GB2195334A - 1-Methanesulfonyloxy-6-trifluoromethyl-1H-benzotriazole and its use in preparing cephalosporin derivatives - Google Patents
1-Methanesulfonyloxy-6-trifluoromethyl-1H-benzotriazole and its use in preparing cephalosporin derivatives Download PDFInfo
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- GB2195334A GB2195334A GB08714764A GB8714764A GB2195334A GB 2195334 A GB2195334 A GB 2195334A GB 08714764 A GB08714764 A GB 08714764A GB 8714764 A GB8714764 A GB 8714764A GB 2195334 A GB2195334 A GB 2195334A
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- 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
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- 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
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
Abstract
An improved process for the acylation of cephalosporin which characterises reacting 2-oxo imino acetic acid of formula (II) having an unprotected amino group <IMAGE> with 7-amino-3-cephem-4-carboxylic acid derivatives in the presence of coupling reagent of formula (III> <IMAGE> wherein R4 is methyl or p-tolyl group. The coupling reagent of formula (III) is claimed per se.
Description
SPECIFICATION 1 -methanesulfonyluxy-6-trifluoromethyl-1 H-benzotriazole and its use in preparing cephalosporin derivatives
Background of the Invention
This invention relates to a method for preparing cephalosporin derivatives.
It is well known that the acylation process is carried out by using acid chloride or mixed anhydride, and also the process using reactive derivatives prepared from organic acid with 1hydroxy-succinimide or 1 -hydroxy- 1 H-benzotriazole has been developed.
Among those 1 -hydroxy- 1 H-benzotriazole is known the most favourable reagent to activate the organic acid.
However, the acylation using 1 -hydroxy-1 H-benzotriazole has disadvantage of taking long reaction time. For example, the acylation processes disclosed by West German Patent No. 3316798 and British Patent No. 2098216 using the reactive derivates prepard from 1 -hydroxy- 1 H-benzptri- azole hydrate require long reaction time. The reactive derivatives prepared for 3~4 hours have to be stirred for one night at room temperature to complete the acylation.
Brief Summary of the Invention
The object of the present invention is to provide a novel and improved acylation process using 1 -methanesulfonyloxy-6-trifluoromethyl- 1 H-benzotriazole with the superior reactivity to the conventional coupling reagents prepared from 1-hydroxy-1H-benzotriazole.
According to the present invention, a novel method for preparing a syn-isomer of compound of the general formula (I) is provided
wherein R is furyl, thiazolyl or thiadiazolyl, R1 is an alkyl, alkenyl, aikynyl or cycloalkyl containing less than six carbon atoms, Z is hydrogen or halogen atom, alkyl, cycloalkyl, alkoxy or alkylthio containing less than five carbon atoms, acetoxymethyl or carbomoyloxymethyl group, or -CH2-S-R2 or -CH2-R2, where R2 is a heterocycle of five or six ring members containing one to four heteroatom arbitrarily substituted from S and N, or
where R3 is hydrogen or an alkyl containing one to five-carbon atoms, ester, amide or organic acid group, M is hydrogen, alkali metal, alkaline earth metal, or ester group, or COOM group represents CO2, and also COO- when Z represents
The method of the present invention is characterised in that the reactive derivative obtained from compound of general formula (II) and coupling reagent of general formula (III) in the presence of organic base reacts with compound of the general formula (1V)
Where R, R1, Z, and M are the same as represented hereinbefore, R4 is alkyl or aryl group, X is a halogen atom, and n is an integer of zero to two. The most preferred R1 defined above is 2-furyl, 1,3-thiazole-4-yl, 2-amino-1, 3-thiazole-4-yl, or 5-amino-1,2,4,-thiadiozole-3-yl group.
Detailed Description
The processes of the present invention are proceeded by the following reaction:
The Coupling reagent of general formula (III) used in the present invention is a novel product, which can be produced at low price, and is also easy to handle.
It is possible to confirm in the examples described hereinafter that the reactive derivative of general formula (II) using the general formula (Ill) produced from the first stage of the process of the present invention has the structure of the following general formula (V):
The solvent dissolving organic acid of general formula (II) is N,N-dimethylformamide, N,Ndimethylacetamide, or N-methylpyrrolidone, and the reaction is carried out quantitatively at 0+5 C in a few minutes. As the base for neutralizing methanesulfonic acid produced during the reaction, triethylamine or pyridine is the most preferred.
The second stage of the present invention is the acylation process of the reactive derivative with compound of general formula (IV), and the reaction is completed within one hour at room temperature.
After completing the reaction, the product can be isolated in a usual method with a high yield.
Comparing with the conventional acylation process, the present invention has the following advantages:
1. Sulfonic ester of general formula (III) prepared from low cost methanesulfonychloride or tosylchioride, is novel coupling reagent which is stable and easy to handle.
2. The acylation process is carried out quantitatively in one hour without protecting the amino group of amino acid, and
3. The product can be isolated by simple operation.
According to the the method of the present invention, various cephalosporin derivatives can be obtained, the following compounds of which are not mentioned in the examples.
7-[(2-amino-4-thiazolyl)-2-methoxymino acetamido]ceph-3-m-4-carboxylic acid, syn-isomer, alkali metal or alkaline earth metal, ammonium, salt consisting of amino organic base, and ester with degradable group.
7-[(2-amino-4-thiazolyl)-2-methoxyimino acetamid]-3-[(1-methyl-1-pyrrolidinium)methyl]-3-ce- phem-4-carboxylate, syn-isomer.
7-[(2-fur-2-yl)-2-methoxyiminoacet amido]-3-carbamoyloxymethylceph-3-m-4-carboxylic acid, syn-isomer, salts thereof, and ester with degradable group.
7-[(2-(4-thiazolyl)-2-(carboxymethoxyimino) acetamido]ceph-3-m-4-carboxylic acid.
N-[7-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2-methoxymino acetamido]-3-cephem-3-ylmethyl]-pyridinium-4-carboxylate, syn-isomer and salt thereof.
The present invention will be described more specifically through the following examples.
Example 1
6.8g (33.5 millimole) of 1-hydroxy-6-trifluromethyl-1H-benzotriazole is suspended in 200ml of distilled water, and dissolved in 36ml of 1N sodium hydroxide solution. After slowly adding 2.8ml (36.2 millimole) of methane sulfonylchloride to the solution under freezing condition, 20ml of ethylchloride is added, and then reacted for 2hrs at room temperature.
After organic phase is decanted, the aqueous phase is extracted with ethyl acetate (20minx2), and then combined with the organic phase. The combined phase is- dried over magnesium sulfate anhydride and crystaliized with petroleum ether after removing solvent by distillation under reduced pressure. After filtering and drying, white 1-methanesulfonyloxy-6-trifluormethyl
1H-benzotriazole is obtained.
Yield: 8.8g (93%)
Melting Point: 98--100"C IR (ajax KBr, CN-1): 1300 (S=0) NMR(DMSO-d6,J): 2.65(3H,S), 7.60 7.80(1H,m), 8.00 8.30(ZH,m) Example 2
8.129 (40 millimole) of 1-hydroxy-6-trifluromethyl-1H-benzotriazole is suspended in 5ml of water, and dissolved in 45ml of 1 H sodium hydroxide.
After slowly adding 8.0g (40.3 millimole) of P-toluenesulfonyl chloride under the freezing condition, 100ml of ethyl acetate is added, and then reacted at room temperature for 1 hour.
The organic phase is decanted, washed with distilled water (50m1x2), dried over magnesium sulfate anhydride, crystallized with petroleum ether after removing solvent by distillation under reduced pressure. After filtering and drying, white 1-(P-toluenesulfonyoxy)-6-trifluromethyl-1Hbenzotriazole is obtained.
Yield: 13.69 (95.3%)
Melting Point: 99--102"C IR (imam, KBr, Cm-1): 1310 NMR(DMSO-d6.d): 2.3(3H,S), 7.05 7.55(4H,ABq), 7.45--8.05(1H,m) 8.05--8.25(2H,S) Example 3
To the solution of 4.09 (20 millimole) of 2-(2-amino-4-thiazolyl)-2-syn-methoxyiminoacetic acid dissolved in 40m of N,N-dimethylformamide, 3.1 ml (22 millimoles) of trithylamine is added dropwise under freezing condition, and 6.1g (22 millimoles) of 1-methanesulfonyloxy-6-trifluoro- methyl-1H-benzotriazole is added at the same temperature, and then reaction mixture is stirred for 30 minutes. The reaction solution is poured into icy water to crystallize.
After filtering and drying under reduced pressure, light yellowish 2-(2-amino-thiazolyl-2-synmethoxyimino nitric acid-5-trifluromethyl- 1 H-benzotriazole- 1 -yI) ester is obtained.
Yield: 7.3(95%) Melting Point: 198"C (decomposed)
IR (lax, KBr, Cm1): 1850 (C=O) NMR(DMSO-d6b) 3.90(3H,S), 6.84(1H,S) 7.56~8.25 (3H,m)
Example 4
To the solution of 1 .96g (2 millimoles) of 7-amino-3-[(2,3)-cyclopenteno-1-pyridinio)methyl]-3- cephem-4-carboxylate iodic acid hydride dissolved in 10ml of N,N-dimethylformamide, 0.819 (2.1 millimoles) of 2-(2-amino-4-thiazolyl)-2-syn-methoxyiminoacetic acid-5-trifluoromethyl-1 H-benzotria- zole-yl ester is added under the freezing condition.
After stirring at room temperature for one hour, the insoluble material is filtered off, and solvent is removed by distillation under reduced pressure (--2mmHg). 10ml of isopropyl alcohol is added to the residue to crystallise, which is stirred for 30 minutes under the freezing condition. After filtering, and drying under reduced pressure, light yellowish 7-[2-(2-amino-4thiazolyl)-2-syn-(methoxyimino) acetamide]-3-[(2,3-cyclopenteno- 1 -pyridinio) methyl]-3-cephem-4carboxylate iodic acid is obtained.
Yield: 1.2g (93.4%)
Melting Point: 178- 181 0C (decomposed)
IR (;lax. KBr, Cm ): 1785 (lactam C=O)
NMR (CF3 COOD.J): 2.30--2.85(2H,m), 3.10-- 4.05(6H,m), 4.41(3H,S),
5.21~6.23(4H,m). 8.11(1H,S), 7.65--8.70(3H,m).
Example 5
To the solution 1.989 (6.8 millimoles) of 1-methanesulfonyioxy-6-trifluoromethyl-1H-benzotriazole dissolved in 9ml of N,N-diethylformamide, the solution of 1.29 (6 millimole) of 2-(2-amino-4thiazolyl)-2-syn-methoxyiminoacetic acid dissolved in 12ml of N,N-dimethylformamide is added dropwise to solution hereinbefore under freezing condition and 0;9ml (6.6 millimole) of triethylamine is slowly added. After stirring for 30 minutes under freezing condition, 2.69 (5.4 millimoles) of 7-amino-3-[2,3-cyclopenteno-1-pyridinio) methyl]-3-cephem-carboxylate iodic acid hydroxide is added to the reactant, and then stirred for 1 hour at room temperature.
After treatment with same procedure described in Example 3, 3.29 (92%) of light yellowish 7 [2-(2-amino-4-thiazolyl)-2-syn-(methoxyimino) acetamido]-3-(2,3 cyclopenteno- 1 -pyridinio) methyl-3 cephem-4-carboxylate iodic acid is obtained. IR and NMR data are the same as Example 3.
Example 6
To the solution of 1.49,(6.9 millimoles) of 1-hydroxy-6-trifluoromethyl-1H-benzotriazole dissolved in 8ml of N,N-dimethylformamide 0.9ml (6.6 millimoles) of triethylamine is added at --5C, and the mixture of 0.64ml (8.3 millimoles) of methanesulfonyl chloride and 4ml of N,N-dimethylformamide is added dropwise at the same temperature. After stirring for 30 minutes under freezing condition and adding 0.84ml of triethylamine, a clear solution of 1.29 (6 millimoles) of 2-(2-amino-4-thiazolyl)-2-syn-methoxyimino acetic acid and 18ml of N,N-dimethylformamide is added dropwise, and then reacted for 30 minutes at the same temperature.
2.8g (5.9 millimoles) of 7-amino-3-[(2,3-cyclopenteno-1-pyridinio) methyl]-3-cephem-4-carboxyl ate iodic acid hydride is added to the reactant and stirred for 1 hour at room temperature. After treatment with the same procedure described in Example 3.
3. 5g (92%) of 7-[2-(2-amino-4-thiaxolyl)-2-syn-(methoxyimino) acetamido]-3-(2,3 cyclopenteno1-pyridinio methyl)-3-cephem-4-carboxylate, iodic acid is obtained. IR and NMR data are the same as Example 3.
Example 7
To the solution 2.09 (10 millimoles) of 2-(2-amino-4-thiazolyl)-2-syn-methoxyimino acetic acid dissolved in 20ml of N,N-dimethylacetamide, 3.939 (11 millimoles) of 1-toxyloxy-6-trifluorome thyl-l H-benzotriazQle is added under freezing condition, and 1.54ml (11 millimoles) of triethylamine is added dropwise. After stirring for 30 minutes at the same temperature, 3.659 (10 millimoles) of 7-amino-[3-( 1-methyl- 1 H-tetrazole-5yl) thiomethyl]-3-cephem-4-carboxylate hydrochloride salt dissolved in 20ml of N,N-dimethylacetamide is added dropwise, and then reacted for 1 hour at room temperature.
This solution is poured into icy water, then the pH thereof is adjusted to 1.5 with 2Nhydrochloric acid solution, and the precipitate formed is filtered off. After drying under reduced pressure, light yellowish 7-[[2-(2-amino-4-thiazole)-2-syn-methoxyimino acetamido]-3-[( 1-methyl- 1H-tetrazole-5-yl) thiomethyl]-3-cephem-4-carboxylic acid is obtained.
Yield: 4.69 (90%) IR (KBr.Cm-'): 1780
NMR (D20/NaHCO3.J): 3.84(2H,d), 4.01(3H,S), 4.05(3H,S), 5.20(1H,d), 5.77(1H,d), 7.01(1H,S).
EXAMPLE 8
To the solution of 2.0g (10 miliimoles) of 2-(2-amino-4-thiazoleyi)-2-syn-methoxyiminoacetic acid dissolved in 20ml of N,N-dimethylformamide, 3.05g (11 millimoles) of 1-methanesulfonyloxy6 trifluoromethyl-1H-benzotriazole is added under freezing condition, and 1.54ml (11 millimoles) of triethylamine is slowly added at the same temperature.
And also 4.89 (10 millimoles) of 7-amino-3-[(2.5-dihydro-6-hydroxy-2-methyl-5-oXotriazine-3-yl) thomethyl]-3-cephem-4-carboxylate hydrochloride salt dissolved in 20ml of N,N-dimethylformamide is added dropwise to the mixture, and stirred for 1 hour at room temperature.
After completing the reaction, N,N-dimethylformamide is removed by distillation under reduced pressure (2mmHg), and the pH of the residue is adjusted to 4.5 by addition of water under freezing condition. The pH of the solution is adjusted to 3.0 after saturating with salt, the precipitate being formed.
After stirring for 1 hour, filtered and dried the solution under reduced pressure, then white 7 [[2-(2-amino-4-thiazole)-2-syn-methoxyiminoj acetamido]-3-[(2. 5-dihydro-6-hydroxy-2-methyl-5-ox- otriazine-3-yl) thiomethyl]-3-cephem-4-carboxylic acid is obtained.
Yield: 5.09 (90%)
IR (Amaxm KBr, Cm l): 1780 (lactam C=O)
NMR (DJ/NaHCO3.b): 3.20(2H,d), 3.62(3H,S), 3.95(3H,S), 4.21(2H,d),
5.17(1H,d), 5.72(1H,d), 6.95(1H,S).
EXAMPLE 9
To the solution of 2.09 (10 millimoles) of 2-(2-amino-4-thiazoleyl)-2-syn-methoxyimino acetic acid dissolved in 20 ml of N,N-dimethylformamide, 3.05g (11 millimoles) of 1-methanesulfony loxy-6-trifluoromethyl-1H-benzotriazole is added under freezing condition, 1.54ml (11 millimoles) of trimethylamine is added at the same temperature.
4. lug (10 millimoles) of 7-amino-3-[2-(5-methyl- 1 ,2,3,4-tetrazoleyl) methyl]-3-cephem-4-pivaloyloxymethyl) carboxylate, hydrochloride salt dissolved in 20ml of N,N-dimethylformamide is added dropwise to the mixture, and then reacted for 1 hour at room temperature.
After addition of the mixture of water and ethylacetate to the reactant completed the reaction the organic phase was separated by adjusting the pH to 7.0 under freezing condition.
After removing solvent by distillation under reduced pressure, ethylether is poured into the residue, and then crystallised.
Filtering, and drying under reduced pressure, there is obtained 7-[2-(2-amino-4-thiazoleyl)-2syn-methoxyimino acetamido]-3-[2-(5-methyl-1,2,3,4-tetrazoleyl) methyl]-3-cephem-4-(pyvaloyloxymethyl) carboxylate.
Yield: 5.3g (90%)
Melting Point: 127--128"C (decomposed)
IR (KBr.Cm-1): 1780.1743.1675 NMR(DMSO-d6b): 1.1 7(9H.S), 2.46(3H.S), 3.55(2H,6S), 3.96(3H.S),
5.19(1H.d), 5.30~6.00 (5H.n), 6.96(1H.S)
EXAMPLE 10
To the solution of 2.0g (10 millimoles) of 2-(2-amino-4-thiazoleyl)-2-syn-methoxyimino acetic acid dissolved in 20ml of N,N-dimethylformamide, 3.23g (11 millimoles) of 1-tosyloxy-6-trifluoromethyl-1H-benzotraizole is added under freezing condition and 1.54ml (11 millimoles) of triethylamine is added at the same temperature. 3.239 (10 millimoles) of 6-amino-3-[2-(5-methyl1 ,2,3,4-tetrazoleyl) methyl]-cephem-4-carboxylate hydrochloride salt is added dropwise to the reaction mixture, and reacted for 1 hour at room temperature.
After removing solvent by distillation under reduced pressure. 10ml of isopropyl alcohol is added to the residue to crystallise, which is stirred under freezing condition for 30 minutes, filtering, and drying under reduced pressure, there is obtained light yellowish 7-[2-(2-amino-4thiazoleyl)-2-syn-methoxyimino acetamido]-3-[2-(5-methyl- 1 ,2,3,4-tetrazoleyl) methyl]-3-cephem-4carboxylate.
EXAMPLE ii To the solution of 1.37g (5 millimoles) of 7-2-(2-aminothiazole-4-yl)-2-syn-(2-t-butoxywarbonyl- prop-2-oxyimino) acetic acid dissolved in 20ml of DMF, 0.7ml (5 millimoles) of triethylamine is added dropwise.
1.499 (5.3 millimoles) of 1-methanesulfonyloxy-6-trifluoromethyl-1H-benzotriazole is added to the solution under freezing condition, and then stirred at the same temperature for 30 minutes.
And the solution of 1.819 (5 millimoles) of 7-amino-3-(1-pyridiniummethyl)-3-cephem-4-carboxylate, bis hydrochloride salt dissolved in 20 ml of DMF is added dropwise to the reaction mixture, and reacted for 1 hour at room temperature. After removing solvent by distillation under reduced pressure, 20ml of 90% formic acid is added to the residue, which is stirred at room temperature for 40 minutes. After removing solvent by distillation under reduced pressure, 30ml of acetone is added to the residue of organic phase to crylstallise. After filtering and drying under reduced pressure, 7-[2-(2-aminothiazole-4-yl)-2-syn-(2-carboxyprop-2-oxyimino) acetamido]-3-(1-pyrridini- ummethyl)-3-cephem-4-carboxylate, bis hydrochloride salt is obtained.
Yield: 2.729 (88%)
NMR (D2O/NaHCQ.J): 1.45 (6H.S), 6.26 (1H.d, J=5.0 Hz) 5.84
(1H.d, J=5.0 Hz), 6,90 (1H,S), 8.05 9.05 (5H.m).
Claims (6)
1. A coupling reagent of the formula (III)
wherein R4 is methyl or p-tolyl group.
2. A process for the production of syn-isomer of formula (I)
in which R is furyl, thiazalyl or thiadiazolyl, R1 is an alkyl, alkenyl, alkynyl or cycloalkyl containing less than six carbon atoms, Z is hydrogen or halogen atom, an alkyl, cycloalkyl, alkoxy or alkylthio containing less than five carbon atoms, acetoxymethyl or carbamoyloxymethyl group, or -CH2-S-R2 or -CH2-R2, where R2 is a heterocycle of five or six ring members containing one to four heteroatom arbitrarily substituted from S and N, or
where R3 is hydrogen or an alkyl containing one to five carbon atoms, ester, amide or organic acid group, M is hydrogen, alkali, alkaline earth metal, or ester group, and COOM group represents CO2, and also COO- when Z represents
in which Ra is as defined above and pharmaceutically acceptable salts thereof, which comprises reacting a syn-isomer of formula (II)
in which R and R1 are as defined above with a compound of formula (IV)
in which Z and M are as defined above, and X is halogen and n is an integer of zero to two, in the presence of coupling reagent of the formula (III)
in which R4 is as defined in Claim 1.
3. Syn-isomers of formula (V)
in which R and R1 are as defined in Claim 2, active intermediate produced by the reaction of a syn-isomer of formula (II) with coupling reagent (III).
4. A coupling reagent substantially as described with reference to Examples 1 to 11.
5. A process for the production of syn-isomer substantially as described herein with reference to Examples 1 to 11.
6. Syn-isomers substantially as described herein with reference to Examples 1 to 11.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019860005101A KR890002107B1 (en) | 1986-06-25 | 1986-06-25 | Process for preparing cephalosporin derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8714764D0 GB8714764D0 (en) | 1987-07-29 |
| GB2195334A true GB2195334A (en) | 1988-04-07 |
Family
ID=19250716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08714764A Withdrawn GB2195334A (en) | 1986-06-25 | 1987-06-24 | 1-Methanesulfonyloxy-6-trifluoromethyl-1H-benzotriazole and its use in preparing cephalosporin derivatives |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS6322570A (en) |
| KR (1) | KR890002107B1 (en) |
| DE (2) | DE3744772A1 (en) |
| GB (1) | GB2195334A (en) |
| IT (1) | IT1205178B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR890100706A (en) * | 1989-10-31 | 1992-03-20 | Han Mi Pharma Ind Co Ltd | Method of preparation of cepheme derivatives |
| AT398764B (en) * | 1992-01-28 | 1995-01-25 | Lek Tovarna Farmacevtskih | METHOD FOR PRODUCING CEFTRIAXONDINATRIUM SALZHEMIHEPTAHYDRATE |
| AT399877B (en) * | 1992-02-20 | 1995-08-25 | Biochemie Gmbh | NEW METHOD FOR PRODUCING CEFTRIAXONE |
| WO1996012712A1 (en) * | 1994-10-24 | 1996-05-02 | Miwon Co., Ltd. | Reactive phosphate derivatives of thiazolylacetic acid and process for preparing cephalosporin antibiotics using the same |
| KR100197788B1 (en) * | 1995-06-30 | 1999-06-15 | 김충환 | Processes for manufacturing cephem derivatives |
-
1986
- 1986-06-25 KR KR1019860005101A patent/KR890002107B1/en not_active IP Right Cessation
-
1987
- 1987-06-22 JP JP62155237A patent/JPS6322570A/en active Pending
- 1987-06-23 DE DE19873744772 patent/DE3744772A1/de active Pending
- 1987-06-23 IT IT21014/87A patent/IT1205178B/en active
- 1987-06-23 DE DE19873720681 patent/DE3720681A1/en not_active Withdrawn
- 1987-06-24 GB GB08714764A patent/GB2195334A/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| GB8714764D0 (en) | 1987-07-29 |
| DE3720681A1 (en) | 1988-01-28 |
| KR880000448A (en) | 1988-03-25 |
| JPS6322570A (en) | 1988-01-30 |
| IT8721014A0 (en) | 1987-06-23 |
| KR890002107B1 (en) | 1989-06-19 |
| DE3744772A1 (en) | 1989-02-02 |
| IT1205178B (en) | 1989-03-15 |
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