JPH0521911B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel cephalosporin derivative, and more particularly to a cephalosporin having excellent antibacterial activity represented by the following general formula (). [In the formula, R ₁ is

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One type selected from those represented by [Formula], R ₂ represents hydrogen or a methoxy group, and the organic residue in R ₁

When it has [Formula], R ₂ represents only hydrogen, R ₇ is a C ₁ to C ₆ alkyl group,

[Formula] (R _a and R _b may be the same or different and each is hydrogen or a C ₁ to _{C 4} alkyl group)}, R ₃ is hydrogen or a salt with an organic base, or a physiologically acceptable metal ion, R ₄ is a C ₁ -C ₆ alkyl group, R ₅ is hydrogen or a protecting group for an amino group, R ₆ is hydrogen or a salt with an organic base, or a physiologically acceptable metal ion. represents a protecting group for metal ions or carboxylic acids. ] An object of the present invention is to provide a cephalosporin that has excellent antibacterial activity against a wide range of pathogenic bacteria, mainly including Gram-negative bacteria and Gram-positive bacteria. Cephalosporin compounds are widely used for the treatment and prevention of infections caused by pathogenic bacteria. In many cases, it is desirable to use cephalosporin antibiotics that are active against both Gram-positive and Gram-negative bacteria, and various types of broad-spectrum cephalosporins are being developed. The cephalosporin of the present invention has an amino group, a protected amino group and a carboxyl group at the 3-position,
This is a new cephalosporin in which an imidazole derivative having a protected carboxyl group or the like as a substituent is S-bonded, and these cephalosporins have high antibacterial activity against Gram-positive bacteria and Gram-negative bacteria. R ₁ at the 7-position of the compound of the present invention is an aromatic phenyl group, a nuclear substituted aromatic phenyl group, an alkyl, a substituted alkyl, an alicyclic hydrocarbon, a substituted alicyclic hydrocarbon, nitrogen, oxygen,
4-6 containing 1-4 selected from sulfur
Represents an organic residue containing a membered heterocycle. For example, those having an aromatic phenyl group or a nuclear-substituted aromatic phenyl group include:

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[Formula] etc. are shown. Next, as alkyl and substituted alkyl,
NCCH ₂ −, NCCH ₂ S−CH ₂ −,

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[Formula] F ₃ CSCH ₂ −,

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[Formula] etc. In addition, as alicyclic hydrocarbons and substituted alicyclic hydrocarbons,

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[Formula] etc. Next, 1 to 1 selected from nitrogen, oxygen, and sulfur.
As a 4- to 6-membered heterocycle containing 4,

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[Formula] etc. are shown. Among these, those having an iminoether bond are preferably those having a syn configuration. Next, the third place part is where R ₄ is hydrogen or a C ₁ to _{C 6} alkyl group, a C ₁ to C ₆ substituted alkyl group, a C ₁ to _{C 6} branched alkyl group, a C ₁ to _{C 6} substituted branched alkyl group or an aromatic group, a substituted aromatic group, such as a phenyl group, a substituted phenyl group. R ₅ is hydrogen or an amino protecting group, such as formyl group, acetyl group, tert-butyloxycarbonyl group, benzyloxycarbonyl group, p-methoxybenzyloxycarbonyl group, p-toluenesulfonyl group, chloroacetyl group, etc. can give. R ₆ represents hydrogen or a salt with an organic base, or a physiologically acceptable metal ion or carboxylic acid protecting group. As the protecting group, for example, lower alkyl groups such as methyl, ethyl, propyl, benzyl group, p-nitrobenzyl group, tert-butyl group, methoxymethyl group, acetoxymethyl group, pivaloyloxymethyl group, etc. are used. . Next, the MICs of Gram-positive bacteria and Gram-negative bacteria for representative compounds () and () of the present invention are as follows.

[Table] Mouse (ICR-
In the acute toxicity test (mice, 5 weeks old), the LD ₅₀ showed the following values when administered intraperitoneally. Compound () LD ₅₀ 9-10 g/Kg Compound () LD ₅₀ 8-10 g/Kg Furthermore, in compounds () and (), intestinal absorption is improved as seen in the following examples. For example, when comparing the maximum blood concentrations of cefotaxime and compounds () and () after oral administration in rats, their effects are observed. Rat: Wistar rat 200-220g Dose: 30mg/Kg Blood concentration was measured by HPLC method and bioassay method (E. coli was used as the test organism). The compounds according to the present invention can be synthesized by approximately two routes. One example of this is the following method. In the synthesis method (i), R ₁ -COOH is reacted with a 7-ACA derivative in the presence of a suitable binder such as dicyclohexylcarbodiimide, or R ₁ -COOH is reacted with an activated form such as an active ester, a mixed acid, etc. There is a method of converting it into an anhydride or the like and then reacting it with a 7-ACA derivative. Furthermore, R ₁ −
It can also be reacted after being made into an acid chloride like COCl. In the above condensation, an organic solvent that does not participate in the reaction, such as tetrahydrofuran, dioxane, ethyl acetate, dimethylformamide, methylene chloride, acetone, etc., is selected. In addition, in reactions such as acid chloride,
It is also possible to use aqueous systems. Next, the conversion reaction of the acetoxymethyl group at the 3-position with the 2-mercapto-imidazole derivative is carried out by using sodium bicarbonate or triethylamine as a base in water or a mixed solvent such as methanol or acetone. PH 6~
The 3-position conversion reaction can be carried out by reacting at a temperature of 30 to 100°C for 1 to 20 hours, preferably 2 to 10 hours, while controlling the temperature to be around 7.7°C. During this time, the reaction system is preferably under a nitrogen atmosphere. Next, regarding route (ii), an example is shown below.
If the amino group of the 2-mercapto-imidazole derivative is free, it is protected, for example by t-butyloxycarbonylation, and then the acetoxymethyl group at the 3-position of 7-ACA (or its derivative) is removed in a mixed solvent system of water and acetone. Using sodium hydrogen carbonate or the like as a base, the reaction is carried out at 30 to 100°C for 1 to 20 hours while controlling the pH to 6 to 7. If the carboxyl group at the 4-position of the obtained compound 7-ACA derivative and the carboxyl group at the 3-position of the imidazole derivative are free, they are trimethylsilylated or left free.
Condensation with R ₁ COOH or its carboxylic acid activated form (eg, active ester, mixed acid anhydride, acid chloride). Thereafter, the desired product can be obtained by removing BOC using trifluoroacetic acid, formic acid, or the like. Furthermore, in the synthesis of the following compounds, etc., they can also be produced by the following synthetic route. (Y represents a halogen atom, R ₄ , R ₅ , R ₆ , R ₇
has the same meaning as above. ) Example 1 5 g of 2-methoxyimino-2-(2-chloroacetylamido-4-thiazolyl)acetic acid was added to 20 ml of thionyl chloride, and a reaction was carried out at 40°C for 30 minutes. After the reaction is complete, thionyl chloride is distilled off under reduced pressure, and the residue is dissolved in 20 ml of acetone. Next, 6 g of 7-aminocephalosporanic acid, 4.8 g of sodium bicarbonate
The acid chloride obtained by the above method was added dropwise to a solution prepared by dissolving G in 30 ml of water and 5 ml of acetone while maintaining the pH at 7 at 5 to 10°C, and the mixture was stirred for 40 minutes. After the reaction was completed, the reaction solution was adjusted to pH 2 with 6N hydrochloric acid, acetone was distilled off, water was partially distilled off, concentrated, and purified using an XAD- column, resulting in 7β-[(Z) 3.9 g of -2-(2-chloroacetamido-4-thiazolyl)-2-(methoxyimino)acetamide]cephalosporanic acid are obtained. Next, this product was dissolved in 30 ml of water, 1 g of thiourea was stirred at 20°C for 6 hours, and the reaction solution was mixed with XAD-
The dechloroacetylated product is separated and purified using a column. Next, 2-mercapto-4-amino-5-carboxy-N-methylimidazole, which becomes the 3-position moiety

The synthesis of [Formula] is carried out by the following method. Dissolve 12g of ethyl cyanoacetate in 20ml of glacial acetic acid,
Cool to around 5°C. A solution of 8.7 g of sodium nitrite dissolved in 20 ml of water is added dropwise to the above solution while stirring over 30 minutes. The temperature during the reaction should be around 20°C. After reacting for an additional hour, 50 ml of water was added to the reaction solution, and the mixture was stirred at 20°C for 2 hours. This solution is extracted three times with 50 ml of ether. This ether solution is washed with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. By distilling off the ether, 12 g of white crystals are obtained. Next, add this to formic acid.
Dissolve in a mixed solvent of 120 ml and 50 ml of water, and cool in an ice bath. 12 g of zinc powder was added to the above solution over 10 minutes, and the reaction was carried out at around 5°C for 3 hours with stirring.
The reaction solution is then concentrated to 1/4 (volume) under reduced pressure. This solution is extracted five times with 50 ml of ether, and the ether solution is dried over anhydrous sodium sulfate. After distilling off the ether and formic acid, 7.2 g of crystals were obtained.
Dissolve this in 15 ml of ether, and while stirring, add 7.2 g of methyl isothiocyanate dissolved in 10 ml of ether. The reaction solution becomes homogeneous, so leave it at 20°C for 2 days. When the reaction solution is concentrated to 1/2 (volume) and allowed to cool, crystals will precipitate.
4.8g of the target product is obtained. Next, this product is suspended in 50 ml of a 10% aqueous sodium hydrogen carbonate solution, and boiled under reflux while stirring to form a homogeneous solution. The reaction is continued for an additional hour and then cooled. After separating the insoluble matter, the target substance is separated using a column packed with XAD- resin, and 2-mercapto-
2.5 g of 4-amino-5-carboxy-N-methylimidazole are obtained. Next, 7β-[(Z)-2-
(2-amino-4-thiazolyl)-2-(methoxyimino)acetamide]cephalosporanic acid 1.5
g, 1.0 g of sodium hydrogen carbonate and 0.9 g of 2-mercapto-4-amino-5-carboxy-N-methylimidazole were added to 50 ml of water, and while controlling the pH to 6.0 to 6.7 under a nitrogen atmosphere, 65
The reaction is carried out for 5 hours at °C. After the reaction is complete, 1NHCl
Adjust the pH to 2-3 with
0.8 g of acetamido]-3-[4-amino-5-carboxy-N-methylimidazol-2-ylthiomethyl]-3-cephem-4-carboxylic acid was obtained. The target product was confirmed by NMR. (Measured in DMSO- _d6 ) s...Singlet d...Double line m...Multiple line

[Table] Example 2 In the method for synthesizing 2-amino-2-carboxy-N-methylimidazole obtained in Example 1, using 8.6 g of ethyl isothiocyanate instead of 7.2 g of methyl isothiocyanate,
By the same method as Matsutaku, 2-mercapto-4
3.1 g of -amino-5-carboxy-N-ethylimidazole was obtained. Next, 7β-[(Z)-2 obtained in Example 1
-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamide]cephalosporanic acid
1.5 g, 1.2 g of sodium hydrogen carbonate and 2-meltocapto-4-amino-5 obtained by the above method.
1.2 g of -carboxy-N-ethylimidazole is placed in 50 ml of water, and the reaction is carried out at 60 to 70° C. for 4 hours under a nitrogen atmosphere while controlling the pH to 6.0 to 6.7. After the reaction is complete, adjust the pH to 2-3 with ¹ N HCl.
After concentration and purification using an XAD column, the target product 7β-[(Z)-2-(2-
0.9 g of amino-4-thiazolyl)-2-(methoxyimino)acetamide]-3-[4-amino-5-carboxy-N-methylimidazol-2-ylthiomethyl]-3-cephem-4-carboxylic acid was obtained. . The target product was confirmed by NMR. (measured by DMSO- _d6 )

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[Table] Example 3 3.5 g of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oximino)acetamidocephalosboranic acid,
2-mercapto-4-amino-5-carboxy-
150 ml of an aqueous solution containing 1.5 g of N-methylimidazole and 4.9 g of sodium bicarbonate was reacted at 65° C. for 5 hours under a nitrogen atmosphere. Meanwhile, the reaction solution
Control pH between 6.3 and 6.8. After the reaction is complete,
After partially distilling off water and concentrating, the residue was isolated and purified by XAD-column chromatography to obtain 2.1 g of the target product. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

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[Table] Example 4 7β-[(Z)-2-(2
-amino-4-thiazolyl)-2-(methoxyimino)acetamide] 1.5 g of cephalosporanic acid,
1.3 g of 2-mercapto-4-amino-5-ethoxycarbonyl-N-methylimidazole, also obtained in Example 1, and 1.0 g of sodium hydrogen carbonate.
Put g in 50 ml of water and adjust the pH to 6.0~ under nitrogen atmosphere.
6. Carry out the reaction at 65°C for 5 hours while controlling the temperature. After the reaction, the pH was adjusted to 3 with ¹ N HCl, concentrated, and purified using an XAD column to obtain the target product, 7β-[(Z)-2-(2-amino-4-thiazolyl)-2- 0.8 g of (methoxyimino)acetamido]-3-[4-amino-5-ethoxycarbonyl-N-methylimidazol-2-ylthiomethyl]-3-cephem-4-carboxylic acid was obtained. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

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[Table] Example 5 15 ml of methylene chloride containing 3.2 g of bromine is dropped into 20 ml of methylene chloride containing 1.7 g of diketene cooled to -30°C and stirred for 15 minutes. Next, 5 g of 7-aminocephalosporanic acid,
Add the above solution containing 3-oxobutyryl bromide to 70 ml of methylene chloride to which 4 g of triethylamine has been added while keeping the solution at -30°C. The reaction solution was allowed to react for 1 hour while being gradually heated to 20°C. Next, the solvent was distilled off, the residue was shaken with 50 ml of ethyl acetate and 50 ml of 5% hydrochloric acid, the ethyl acetate layer was dried over anhydrous magnesium sulfate, the ethyl acetate was distilled off, and recrystallization was performed from ether. , 3.6 g of 7-(4-bromo-3-oxobutyrylamino)cephalosporanic acid are obtained. next,
Add 0.6g of thiourea and 0.66g of sodium bicarbonate to water.
100ml, dissolved in 50ml of tetrahydrofuran, 7-
Add 3.6 g of (4-bromo-3-oxoptyrylamino)cephalosporanic acid, and react at 20°C for 1 hour. When the reaction solution is concentrated to 1/3 and allowed to cool, crystals precipitate and are separated to obtain 2.4 g of 7-[2-(2-aminothiazol-4-yl)acetamido]cephalosporanic acid. Next, this 7-[2-(2-aminothiazole-
4-yl)acetamido]cephalosporanic acid
2.4 g of sodium bicarbonate, 3.6 g of 2-mercapto-4-amino-5-carboxy-N-methylimidazole and 1.6 g of 2-mercapto-4-amino-5-carboxy-N-methylimidazole were added to 100 ml of water, and the reaction system was heated at 65° C. for 5 hours under a nitrogen atmosphere. During this time, the pH of the reaction solution is controlled at 6.4 to 6.7. Next, the reaction solution is concentrated, and then isolated and purified by XAD-column chromatography to obtain 1.1 g of the target product. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

[Table] Example 6 Put 4 g of tetrazole acetic acid into 30 ml of thionyl chloride, add 1 ml of dimethylformamide, and add 1 ml of dimethylformamide.
Boil at reflux for an hour. Next, thionyl chloride is distilled off under reduced pressure, and the residue is dissolved in 10 ml of acetone. Next, add 8.5 g of 7-ACA to 70 ml of water and 70 ml of acetone.
and add 7.9 g of sodium hydrogen carbonate to make a homogeneous solution. The above acetone solution of tetrazole acetate chloride was added dropwise to this solution under ice cooling, and the reaction was carried out for 1 hour. After the reaction is complete, ¹ H
After adjusting the pH to 3 with HCl and distilling off the acetone, extract with 100 ml of ethyl acetate. After washing the ethyl acetate with water,
After drying over anhydrous magnesium sulfate, ethyl acetate is distilled off to obtain 5.2 g of 7-[1-( ¹ H)tetrazolylacetamide]cephalosporanic acid. A similar product was obtained in condensation of 7-ACA with the triethylamine salt after conversion of tetrazole acetic acid into the p-nitrophenyl ester. Next, add 3.2 g of 2-mercapto-4-amino-5-carboxy-N-ethylimidazole and 3.0 g of sodium hydrogen carbonate to 30 ml of water, and add 7-
5.2 g of [1-( ¹ H)tetrazolylacetamide] cephalosporanic acid is added and the reaction is carried out at 60° C. for 6 hours. During this time, the reaction is carried out under a nitrogen atmosphere while controlling the pH at 6.4. After the reaction is completed, the solution is heated to remove some of the water.
Purify by XAD-column chromatography. 3.1 g of the target product was obtained. The target product was confirmed by NMR. (DMSO- _d6 , measured in trifluoroacetic acid)

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[Table] Example 7 2.7 g of sodium bicarbonate and 3.1 g of cefapirin sodium are added to 1.7 g of 2-mercapto-4-amino-5-carboxy-N-methylimidazole. After purging the reaction system with nitrogen, the reaction temperature was raised to 65°C and the reaction was carried out for 6 hours. During that time, the pH of the reaction solution was 6.0.
Control to ~6.8. After the reaction was completed, part of the water in the reaction solution was distilled off, and after concentration, the product was isolated and purified by XAD-column chromatography to obtain 1.9 g of the target product. (Measured in DMSO- _d6 )

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[Table] Example 8 To 2.7 g of 2-mercapto-4-amino-5-carboxy-N-ethylimidazole are added 2.0 g of sodium bicarbonate and 3.7 g of cephalothin sodium. The reaction system was purged with nitrogen, the reaction temperature was raised to 65°C, and the reaction was carried out for 5 hours. During that time, the pH of the reaction solution was 6.2.
Control to ~6.6. After the reaction was completed, part of the water was distilled off, the residue was concentrated, and then isolated and purified by XAD-column chromatography to obtain 2.1 g of the target product. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

Table Example 9 4.5 g of furanglioxylic acid are placed in 50% alcohol and 3.1 g of methoxyamine hydrochloride dissolved in 10 ml of water are added to this solution. Then 20
While keeping the mixture at 0.degree. C., diluted caustic soda solution is added to adjust the pH to 4 to 5, and the mixture is stirred at 20.degree. C. for 15 hours to carry out the reaction. The alcohol was distilled off under reduced pressure, and the reaction solution was
% caustic soda solution and wash with ether, and the aqueous phase is brought to pH 2 with concentrated hydrochloric acid. Next, the mixture is extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and ethyl acetate is distilled off under reduced pressure to obtain an oily product. Recrystallization from toluene yields syn-α-methoxyimino-2-furyl acetic acid.
Obtain 1.2g. Next, 0.6 g of sodium is added to 40 ml of methanol, and once the sodium has completely dissolved, the mixture is cooled to 3°C and 10 ml of a methanol solution containing 1.2 g of syn-α-methoxyimino-2-furylacetic acid is added. After stirring at 20°C for 20 minutes and distilling off the solvent, the residue was thoroughly dried. 0.65 g of sodium syn-α-methoxyfuryl acetate obtained here was suspended in 30 ml of benzene,
Add 0.3 ml of oxalyl chloride and incubate at 25 °C for 30 min.
After stirring for several minutes, benzene is distilled off under reduced pressure to obtain acid chloride. Dissolve this in 15 ml of acetone, add an acetone solution of acid chloride to a solution of 0.8 g of 7-aminocephalosporanic acid, 0.7 g of sodium bicarbonate, 5 ml of acetone, and 30 ml of water, and stir while maintaining the pH at 30 mm at 20°C. continue. After the reaction, adjust the pH to 2 with 6N hydrochloric acid,
Purification using an XAD-column (manufactured by Organo) yields 0.8 g of 7-α-methoxyiminofrylacetamidocephalosporanic acid. Next, 0.8 g of this compound, 2-mercapto-4
-Add 0.5 g of amino-5-carboxy-N-methylimidazole and 0.5 g of sodium bicarbonate to 40 ml of water,
Under a nitrogen atmosphere, while maintaining pH = 6.0 to 6.5,
The reaction is carried out at 60°C for 5 hours. After the reaction was completed, the reaction solution was adjusted to pH 2 with ¹ N hydrochloric acid, and then part of the water was distilled off. After concentration, it was purified by an XAD column to obtain the target product 7-(α-methoxyiminofrylacetamido)-3-[4-amino-5-carboxy-N-methylimidazole-2.
0.4 g of -ylthiomethyl]-3-cephem-4-carboxylic acid was obtained. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

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[Table] Example 10 7β [(Z)-2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetamide]-3-acetoxymethyl-3-cephem-4
-carboxylic acid 3.0g, 2-mercapto-4-amino-5-carboxy-N-ethylimidazole
After dissolving 1.6 g and 4.5 g of sodium hydrogen carbonate in 70 ml of water, the reaction was carried out at 65° C. for 5 hours in a nitrogen atmosphere. During this time, the pH of the reaction solution is controlled at 6.3 to 6.7. After the reaction was completed, part of the water was distilled off, the residue was concentrated, and then isolated and purified by XAD-column chromatography to obtain 1.4 g of the target product. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

[Table] Example 11 In the method for synthesizing 2-mercapto-4-amino-5-carboxy-N-methyl-imidazole in Example 1, 7.2 g of methyl isocyanate
Using 10 g of propyl isothiocyanate instead, 3.0 g of 2-mercapto-4-amino-5-carboxy-N-propylimidazole was obtained in a similar manner. Add this to 40 ml of 50% dioxane, 0.8 g of triethylamine, 2-tert-
3.7 g of butyloxycarbonyloxyimino-2-phenylacetonitrile was added and the reaction was carried out at 10°C for 7 hours. After the reaction is complete, add ethyl acetate 30
ml of 2-tert-butyloxycarbonyloxyimino-2-phenylacetonitrile. After adjusting the aqueous layer to pH 2 with ¹ N HCl, the desired product is extracted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, and concentrated to dryness. 3.1 g of tert-butyloxycarbonylated 2-meltocapto-4-amino-5-carboxy-N-propylimidazole are obtained. Next, 3.0 g of 7-ACA and 3.1 g of the compound obtained by the above method were placed in 40 ml of water and 30 ml of acetone.
The reaction is carried out at 60°C for 5 hours while controlling the pH to 6.0 to 6.7. After the reaction is complete, the acetone is distilled off and the target product is detected using XAD-column chromatography.
2.3g was obtained. Next, put this material in 50 ml of tetrahydrofuran, and add 1.3 equivalents of bis(trimethylsilyl)acetamide, which is a trimethylsilylating agent. next,
Add 0.8 g of 2-thienyl acetic acid and 1.3 g of N,N-dicyclohexylcarbodiimide to the reaction system,
React for 10 hours at ℃. After separating the precipitate and adding 5 ml of water to the solution, the solvent was distilled off under reduced pressure, the residue was dissolved in 40 ml of formic acid, the reaction was carried out at 10°C for 2 hours, and the formic acid was distilled off. Adding ether to the oily residue solidifies it. XAD−
7-(2-ethienylacetamido)-3-[4-amino-5-carboxy-N-propylimidazol-2-ylthiomethyl]-3-cephem-4-carboxylic acid 1.6
I got g. The target product was confirmed by NMR. (Measured in DMSO- _d6 )

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Claims (1)

[Claims] 1 General formula () [In the formula, R ₁ is [formula] [formula] [formula] [formula] [Formula] One type selected from those represented by [Formula] [Formula], R ₂ represents hydrogen or a methoxy group {However, if the organic residue in R ₁ has [Formula], R ₂ represents only hydrogen, R ₇ is a C ₁ to C ₆ alkyl group,
[Formula] (Ra and Rb may be the same or different and each represents hydrogen or a C ₁ to C ₄ alkyl group)}, R ₃ is hydrogen, a salt with an organic base, or a physiological _R4 is a _C1 - _C6 alkyl group, _R5 is hydrogen or a protecting group for an amino group, _R6 is hydrogen or a salt with an organic base, or a physiologically acceptable metal ion. Represents a protecting group for ions or carboxylic acids. ] A cephalosporin compound and physiologically acceptable inorganic and organic salts.