JPH07107069B2 - Novel derivative of cefalosporin compound, process for producing the same and pharmaceutical composition containing the derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to general formula (I) having antibacterial activity. [In the formula, R ¹ represents an amino group which may be substituted with a trityl group. R ² is an alkenyl group having 2 to 4 carbon atoms, 1 to 4 carbon atoms
Alkyl groups or groups (In the formula, R ⁶ and R ⁷ represent an alkyl group having 1 to 4 carbon atoms.

R ⁸ represents an alkali metal or a carboxyl group-protecting group. ) Is shown. A is a group forming an imidazolium ring (In the formula, R ³ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. R ⁴ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an alkyl group having 2 to 6 carbon atoms which may be substituted with a halogen atom. Having an alkenyl group, an alkynyl group having 2 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an alkanoyl group having 1 to 4 carbon atoms in the alkyl portion, a benzyl group, an acetyl group or a hydroxyl group on the phenyl ring Good phenyl group or group-CH ₂ COOR ⁹
(In the formula, R ⁹ represents an alkyl group having 1 to 4 carbon atoms or an alkali metal atom). X represents a halogen atom. ) B
Constitutes the imidazolium ring (In the formula, R ⁵ represents a hydrogen atom or an alkylamino group which may be substituted with a trityl group and whose alkyl moiety has 1 to 4 carbon atoms). n represents 0 or 1. However,
B is , R ² and R ⁴ must not both be methyl groups. ] To a novel cephalosporin compound in which the 3-position of cephem is substituted with an imidazolium ring, a pharmaceutically acceptable salt thereof, a method for producing the same, and a pharmaceutical composition containing them.

General formula In the cephalosporin compound represented by the formula (wherein R ¹ , R ² , n, A and B have the same meanings as described above) or a salt thereof, one such as an optical isomer due to the presence of an asymmetric carbon atom in the molecule, or More stereoisomers may exist,
Such isomers are included within the scope of this invention.

The salts of the object compound (I) of the present invention include pharmaceutically acceptable salts such as alkali metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (calcium salt,
Magnesium salt, etc., ammonium salt, organic amine salt (triethylamine salt, pyridine salt, etc.), inorganic acid addition salt (hydrochloride, hydrobromide, etc.), organic acid addition salt (formate, trichloroacetate, methanesulfone) Acid salts) and salts with basic or acidic amino acids (arginine salts, aspartates, glutamate, etc.).

In the general formula (I) of the present invention, R ¹ represents an amino group which may be substituted with a trityl group. R ² is an alkenyl group having 2 to 4 carbon atoms, an alkyl group having 1 to 4 carbon atoms or a group (In the formula, R ⁶ and R ⁷ represent an alkyl group having 1 to 4 carbon atoms.

R ⁸ represents an alkali metal or a carboxyl group-protecting group. ) Is shown. A is a group forming an imidazolium ring (In the formula, R ³ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. R ⁴ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an alkyl group having 2 to 6 carbon atoms which may be substituted with a halogen atom. Having an alkenyl group, an alkynyl group having 2 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an alkanoyl group having 1 to 4 carbon atoms in the alkyl portion, a benzyl group, an acetyl group or a hydroxyl group on the phenyl ring Good phenyl group or group-CH ₂ COOR ⁹
(In the formula, R ⁹ represents an alkyl group having 1 to 4 carbon atoms or an alkali metal atom). X represents a halogen atom. ) B
Constitutes the imidazolium ring (In the formula, R ⁵ represents a hydrogen atom or an alkylamino group which may be substituted with a trityl group and whose alkyl moiety has 1 to 4 carbon atoms). n represents 0 or 1. However,
B is , R ² and R ⁴ must not both be methyl groups. The cephalosporin compound (I) and salts thereof of the present invention can be produced by various methods, and if the preferred synthetic route is shown, they can be produced by the following two routes.

(In the formula, R ¹ and R ² have the same meanings as described above, R ¹⁰ represents a hydrogen atom,
When a metal atom, an ester residue, a salt-forming cation or COO forms an intramolecular or extramolecular salt with a cation pair, it exhibits an anionic charge. n represents 0 or 1, and X represents a group which can be substituted with a substituted or unsubstituted imidazole compound. ) Compound (II) or a salt thereof can be produced by reacting compound (VIII) or a reactive derivative at an amino group or a salt thereof with a reactive derivative at a compound (VI) or a carboxyl group or a salt thereof. Suitable salts of the compounds (VII) and (VI) include the same salts exemplified for the compound (I). Examples of the reactive derivative at the amino group of the compound (VII) include, for example, a silyl derivative formed by the reaction of the compound (VII) with a silyl compound [eg, bis (trimethylsilyl) acetamide, trimethylsilyl chloride, etc .; isocyanate; Thiocyanate; compound (VI
Examples include Schiff bases formed by the reaction of I) with a carbonyl compound (eg, aldehydes such as acetaldehyde and benzaldehyde and ketones such as acetone and methyl ethyl ketone) or enamine-type tautomers thereof.

Examples of the reactive derivative at the carboxyl group of the compound (VI) include acid halides such as acid chlorides and acid bromides: substituted phosphoric acid, dialkyl phosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, alkyl carbonate, organic carboxylic acid. Acid anhydrides and symmetrical acid anhydrides with amides; activated acid amides with imidazole, dimethylpyrazole, etc .; p-nitrophenyl ester, phenylthioester, carboxymethylthioester or N-hydroxypiperidine, N-hydroxysuccinimide , Active esters such as esters with N-hydroxy compounds such as N-hydroxyphthalimide.

Examples of the solvent used in this reaction include water,
A single or mixed solvent which does not adversely influence the reaction, such as acetone, dioxane, acetonitrile, chloroform, methylene chloride, benzene, ethyl acetate, N, N-dimethylformamide, pyridine and hexane can be used. The reaction temperature is not particularly limited, but is usually under cooling or heating, preferably about -20 to + 40 ° C.

This reaction can be carried out in the presence of an organic or inorganic base and the like. Examples of such a base include alkali metals such as lithium, sodium and potassium, calcium,
Alkaline earth metals such as magnesium, alkali metal hydroxides such as sodium hydroxide, alkali metal hydrides such as sodium hydride, alkaline earth metal hydrides such as calcium hydride, alkali metal carbonates such as sodium carbonate, Alkali metal hydrogen carbonate such as potassium hydrogen carbonate, alkali metal alkoxide such as sodium ethoxy, trialkylamine such as triethylamine,
Examples thereof include nitrogen-containing heterocyclic compounds such as pyridine, picoline, and quinoline. Of these, trialkylamines and nitrogen-containing heterocyclic compounds are preferably used. The amount of the base used is not particularly limited, but it is usually 25 equivalents or less, preferably 0.25 to 4 equivalents, relative to compound (VII).

The ratio of the compound (VII) to the compound (VI) used in the above reaction is not particularly limited and can be appropriately selected from a wide range, but usually the former: the latter is 1: 5 to 5: 1 (equivalent ratio), preferably It should be 1: 2 to 2: 1.

When compound (VI) is used in the form of a free acid or a salt thereof in this reaction, it is preferable to carry out the reaction in the presence of a condensing agent. Examples of the condensing agent include carbodiimide compounds such as N, N′-dicyclohexylcarbodiimide, keteneimine compounds such as diphenylketene-N-cyclohexylimine, unsaturated alkyl ether compounds such as ethoxyacetylene and β-chlorovinylethyl ether, and N-hydroxybenzoyl compounds. Sulfonic acid ester of triazole derivative [eg, 1- (4-chlorobenzenesulfonyloxy) -6-chloro-1H-benzotriazole, etc.], trialkylphosphite or triphenylphosphine and carbon tetrachloride, ethyl polyphosphate, trichloride In addition to phosphorus compounds such as phosphorus and thionyl chloride, so-called Vilsmeier reagents (N, N-dimethylformamide, N
-Formed by the reaction of an amide compound such as methylformamide with a halogen compound such as thionyl chloride, phosphoryl chloride or phosgene). The amount of the condensing agent used is usually 25 equivalents or less, preferably 0.25 to 4 equivalents, relative to the compound (VII).

(R in the formula¹, R², R^Ten, A, B, X And n are the same as above
Is the meaning. ) Next, a substituted or unsubstituted imida at the 3-position of compound (II)
When carrying out the substitution reaction with sol (III), water or
Cetonitrile, methanol, acetone, N, N-dimethyl
Formamide, tetrahydrofuran, etc., alone or as a mixture
Sodium carbonate, sodium hydrogen carbonate as a base in a solvent
Or triethylamine, etc.
In the presence of lenoxide, the reaction temperature is not particularly limited
However, usually under cooling or heating, preferably -10 ℃ ~ 40 ℃
It is good to do it in a degree.

In compound (IV), for example, R ¹ or R ¹⁴ has an amino protecting group or a carboxyl protecting group, or n
In the case of = 1, the compound (I)
Can be manufactured. This elimination reaction and reduction reaction can be carried out by a conventional method such as hydrolysis and reduction shown below.

(A) Hydrolysis Hydrolysis is preferably performed in the presence of an acid.

Examples of suitable acids include inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, and organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzenesulfonic acid and p-toluenesulfonic acid.

For hydrolysis, a single solvent or a mixed solvent which does not adversely influence the reaction, such as water, methanol, tetrahydrofuran, N, N-dimethylformamide, dioxane, benzene, and hexane can be used. When the above acid is a liquid, the acid itself can be used as a solvent.

The reaction temperature of this hydrolysis is not particularly limited, but it is usually carried out under cooling or heating.

(B) Reduction Reduction is carried out by a conventional method such as chemical reduction or catalytic reduction.

Examples of the chemical reducing agent include a metal or a metal compound such as tin, zinc, iron, chromium chloride and chromium acetate, and formic acid,
Examples thereof include those in combination with organic or inorganic acids such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid and hydrobromic acid, and phosphorus tribromide.

As the catalyst used for the catalytic reduction, for example, a usual catalyst containing a heavy metal such as platinum, palladium, rhodium, nickel, copper, cobalt and iron is used. For the catalytic reduction, usually, a single solvent or a mixed solvent which does not adversely influence the reaction such as water, methanol, N, N-dimethylformamide, hexane, benzene, dioxane and the like can be used. Also, when the above acid is a liquid, it can be used as a solvent.

The reaction temperature of this catalytic reduction is not particularly limited, but it is usually carried out under cooling or heating.

Synthetic route (2)(R in the formula¹, R², R^Ten, A, B, X And n are the same as above
Is the meaning. ) Compound (IV) or a salt thereof is compound (V) or
Compounds with reactive derivatives at the amino group or their salts
(VI) or a reactive derivative at the carboxyl group
Alternatively, it can be produced by acting a salt thereof.

Suitable salts of the compounds (V) and (VI) include the same salts exemplified for the compound (I).

Examples of the reactive derivative at the amino group of the compound (V) include the compound (VI
The same as mentioned in I) can be mentioned.

Examples of the reactive derivative at the carboxyl group of the compound (VI) include the same ones as described above.

As the solvent used in this reaction, the same solvent as used in the above synthetic route (1) can be used. The reaction temperature is not particularly limited, but usually under cooling or heating,
It is preferably about -20 to + 40 ° C.

This reaction can be carried out in the presence of an organic or inorganic base and the like. As such a base, the same bases as in the above synthetic route (1) can be used. The amount of the base used is not particularly limited, but it is usually 25 equivalents or less, preferably 0.25 to 4 equivalents, relative to compound (V).

The ratio of the compound (V) to the compound (VI) used in the above reaction is not particularly limited and can be appropriately selected from a wide range. Usually, the former: the latter is 1: 5 to 5: 1 (equivalent ratio), preferably It should be 1: 2 to 2: 1.

When compound (VI) is used in the form of a free acid or a salt thereof in this reaction, it is preferable to carry out the reaction in the presence of a condensing agent. As the condensing agent, the same one as described in the above synthetic route (1) can be used. The amount of the condensing agent used is usually 25 equivalents or less, preferably 0.25 to 4 equivalents, relative to the compound (V).

In compound (IV), For example, when an amino-protecting group or a carboxyl-protecting group is present, or when n = 1, the compound (I) can be produced by subjecting each of the amino-protecting group and the carboxyl-protecting group to a elimination reaction or a reduction reaction. As the elimination reaction and the reduction reaction, the same reaction as the above-mentioned synthetic route (1) can be used.

The compound (I) of the present invention has high antibacterial activity and is useful as a prophylactic or therapeutic agent for bacterial infections.

When the compound (I) of the present invention and a salt thereof are administered for the purpose of prevention and treatment, the compound is contained as an active ingredient, and an organic or inorganic, solid or solid compound suitable for oral, parenteral and external administration It is used in a conventional formulation mixed with a pharmaceutically acceptable carrier such as a liquid excipient. The formulation may be in solid form such as tablets, granules, powders, capsules or in liquid form such as solutions, suspensions, syrups, emulsions, lemonades and the like. If necessary, in the above formulation,
Auxiliary substances, stabilizers, lubricants and other conventional additives such as lactose, magnesium stearate, white clay, sucrose, corn starch, talc, stearic acid,
Gelatin, agar, pectin, peanut oil, olive oil,
Cocoa butter, ethylene glycol, etc. may be mixed.

The dose of compound (I) is selected according to the patient's age, condition, type of disease, type of compound (I) to be administered, and the like. Generally, an amount of 1 mg to about 4000 mg per day or even more can be administered to a patient. To treat pathogenic infections,
The average dose of compound (I) is about 50 mg, 10
Amounts of 0 mg, 250 mg, 500 mg, 1000 mg, 2000 mg can be used.

(Examples) Next, examples and test examples of the present invention will be described below, but the present invention is not limited thereto. In the following, Tr is a trityl group and tBu is a tertiary butyl group.

Example 1 A solution of 7-amino-3-chloromethyl-3-cem-4-carboxylic acid p-methoxybenzyl ester p-toluenesulfonate (700 mg) in methylene chloride (20 ml) was added to triethylamine (0.19 ml) under ice cooling. ) Was added and stirred, and (Z) -2- (2-allyloxyimino) -2- (2-trimethylaminothiazole-4) was further added to this solution.
-Yl) acetic acid (600 mg) was added and stirred to obtain a uniform solution.
1-Hydroxybenzotriazole (265 mg) and then dicyclohexylcarbodiimide (270 mg) were added to this solution with stirring under ice cooling. The mixture was stirred under ice cooling for a further 3 hours. The mixture was filtered and the white solid washed with a little acetone. The filtrate and washings were combined and concentrated, the solvent was distilled off under reduced pressure, and the residue was eluted with chloroform-methanol (volume ratio 8: 1) through a silica gel column. The product-containing eluate was collected and then concentrated to give 7- [2- (2-propenyloxyimino) -2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-chloromethyl-3-cefm-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (90
0 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 3.50 (2H, s), 3.78 (3H, s), 4.45 (2H, d, J = 12Hz), 4.5
8 (2H, d, J = 5.5Hz), 4.96 (1H, d, J = 5.0Hz), 5.1 to 5.4
(4H, m), 5.8 ~ 6.1 (2H, m), 6.7 (1H, s), 7.08 ~ 7.84
(20H, m), 8.13 (1H, s) Example 2 7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3-chloromethyl-3-cefm-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (890 m
g) in acetone (50 ml), add sodium iodide (237
(mg) and sodium carbonate (157 mg) were added, and the mixture was heated under reflux for 1 hr with stirring. The mixture was returned to room temperature, filtered, and the filtrate was concentrated under reduced pressure.
l) dissolved in 5% sodium thiosulfate aqueous solution (30 ml)
Washed in. The organic phase obtained was concentrated under reduced pressure to give 7- [2
-(2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3-
Iodomethyl-3-cefm-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (820 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 3.50 (2H, m), 3.82 (3H, s), 4.32 (2H, s), 4.70 (2H, d,
J = 5.5Hz), 4.90 (1H, d, J = 5.0Hz), 5.1 to 5.4 (4H, m),
5.8 ~ 6.1 (2H, m), 6.7 (1H, s), 7.08 ~ 7.84 (20H, m),
8.13 (1H, s) Example 3 7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cem-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (5.0
g) and methylene chloride (160 ml) in a solution of m-chloroperbenzoic acid (1.5 g) in methylene chloride (40 g) under cooling at 0 ° C.
ml) solution is added dropwise over 10 minutes, and further stirred at the same temperature for 50 minutes. After returning to room temperature, it was washed with an aqueous solution of sodium carbonate, water and saturated saline, dehydrated with magnesium sulfate, and the organic phase was evaporated under reduced pressure to remove the solvent. -2- (2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-
Methoxybenzyl ester (syn isomer) (5.1 g) was obtained.

NMR δ ppm (CDCl ₃ ): 3.54 (2H, m,), 3.78 (3H, s), 4.41 (2H, m), 4.44 (1H,
m), 4.73 (2H, m), 4.97 to 5.42 (2H, m), 5.22 (2H, s),
5.65 ~ 6.21 (2H, m), 6.64 (1H, s), 7.08 (4H, m), 7.25
(16H, s) Example 4 7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) in THF (5 ml) and chloroform ( 2.5m
l) The mixed solution of 1) and ice-cooled 1- (2-propenyl)
-Add imidazole (64.8 mg). After the addition is complete, warm to room temperature and stir for an additional 3 hours. After evaporating the solvent under reduced pressure, the residue was pulverized with diethyl ether and purified with a silica gel column (chloroform / methanol volume ratio 8: 1).
Then, by collecting the eluate of the desired content and distilling off the solvent,
7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (375.1 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.75 (2H, m), 3.80 (3H, s), 4.60 (2H, m), 4.88~5.47
(9H, m), 5.60 ~ 6.30 (3H, m), 6.81 (1H, s), 7.14 (4H,
m), 7.32 (15H, s), 7.66 (2H, m), 8.74 (1H, s), 8.94
(1H, m), 9.06 (1H, s) Example 5 7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( (Syn isomer) (359.6 mg) was dissolved in acetone (20 ml), cooled to -40 ° C with a dry ice-acetone refrigerant, phosphorus tribromide (270 µl) was added dropwise, and the mixture was stirred for 1 hour. Under the same cooling, an aqueous solution of potassium carbonate (500 mg) (3 ml) was added, the mixture was warmed to room temperature, water (60 ml) was added, and the mixture was extracted twice with ethyl acetate (100 ml), and the organic phase was anhydrous magnesium sulfate. After dehydration at 7, the ethyl acetate was distilled off to give 7-
[2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide]-
3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (292.8 mg)
Got

NMR δ ppm (DMSO-d ₆ ): 3.50 (2H, s), 3.78 (3H, s), 4.56 (2H, m), 4.84 (2H, s)
m), 5.01 to 5.60 (9H, m), 5.60 to 6.40 (3H, m), 6.72 (1
H, s), 7.15 (4H, m), 7.31 (15H, s), 7.62 (2H, m), 9.05
(1H, s), 9.20 (1H, s), 9.53 (1H, m) Example 6 7- [2- (2-propenyloxyimino) -2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (380m
g) was dissolved in 80% acetic acid aqueous solution (3 ml) and stirred at 35-40 ° C for 2 hours, then the solvent was distilled off by freeze-drying, diethyl ether was added to the residue, and the precipitated powder was collected by filtration. 7- [2
-(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- [3-
(2-Propenyl) -1-imidazoliomethyl] -3-
Cefme-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (209.2 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.54 (2H, s), 3.76 (3H, s), 4.58 (2H, m), 4.83 (2H, s)
m), 5.0 to 5.54 (9H, m), 5.61 to 6.35 (3H, m), 6.78 (1H,
s), 6.83 (2H, s), 7.13 (4H, m), 7.68 (2H, m), 9.22 (1
H, s), 9.63 (1H, s) Example 7 7- [2- (2-aminothiazol-4-yl) -2-
(2-Propenyloxyimino) acetamide] -3-
[3- (2-propenyl) -1-imidazoliomethyl]
-3-Cephem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (190 mg) in a mixed solvent consisting of methylene chloride (3 ml), trifluoroacetic acid (930 μl) and ansole (650 μl), ice After stirring under cooling for 2 hours, the solvent was distilled off under reduced pressure, and diethyl ether (100 ml) was added to the residue to precipitate a powder. This was collected by filtration, neutralized with an aqueous solution of potassium hydrogencarbonate, and freeze-dried to obtain a crude yellow powder. This is Sefadex LH
-20 column (methanol) was used to obtain the target eluate, and the solvent was distilled off under reduced pressure to give 7- [2- (2-aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamide. ] -3- [3- (2-propenyl)-
1-Imidazoliomethyl] -3-cephem-4-carboxylate (68.4 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.65 (2H, m), 4.57 (2H, m), 4.82 (2H, m), 5.01 to 5.5
(7H, m), 5.55 to 6.35 (3H, m), 6.83 (1H, s), 7.17 (2H,
s), 7.63 (2H, m), 9.23 (1H, s), 9.35 (1H, d, J = 8.0H
z) Example 8 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Il) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-benzylimidazole (94.8 mg) were added to 7- [ 2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-benzyl-
1-Imidazolyomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (418.3 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.65 (2H, m), 3.28 (3H, s), 4.56 (2H, m), 4.97 (1H,
m), 5.01 to 5.60 (8H, m), 5.51 to 6.30 (2H, m), 6.80 (1
H, s), 7.12 (4H, m), 7.32 (15H, s), 7.43 (5H, s), 7.62
(1H, s), 7.73 (1H, s), 8.73 (1H, s), 8.91 (1H, m), 9.
40 (1H, s) Example 9 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-benzyl-1-imidazo according to Examples 5, 6 and 7. Riomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester
From iodide (syn isomer) (408.3 mg) to 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenioloxyimino) acetamido] -3- (3-benzyl-1-imidazoliomethyl) -3-cefm-4
-Carbonoxylate (syn isomer) (37.2 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.47 (2H, m), 4.68 (2H, m), 4.80-5.50 (5H, m), 5.41
(2H, s), 5.60 ~ 6.23 (2H, m), 6.93 (1H, s), 7.37 (5H,
s), 7.67 (2H, m), 9.23 (1H, s) Example 10 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Il) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-tert-butoxycarbomethylimidazole (109.2 mg) , 7-
[2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide]-
3- (3-tert-Butoxycarbomethyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (447.4 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 2.97 (9H, s), 3.63 (2H, m), 3.78 (3H, s), 4.07 (2H, s)
m), 4.86 (2H, s), 4.91 to 5.54 (7H, m), 5.70 to 6.35 (2
H, m), 6.81 (1H, s), 7.17 (4H, m), 7.37 (15H, s), 7.22
(2H, m), 8.74 (1H, s), 8.83 (1H, m), 9.12 (1H, s) Example 11 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-tert-butoxycarbomethyl) according to Examples 5, 6 and 7. -1-Imidazoliomethyl) -3-
From cefm-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (425.9 mg), 7-
[2- (2-aminothiazol-4-yl) -2- (2
-Propenyloxyimino) acetamide] -3- (3
-Carboxymethyl-1-imidazoliomethyl) -3-
Cefm-4-carboxylate (syn isomer) (50.3
mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.50 (2H, m), 4.70 (2H, m), 4.95~5.61 (7H, m), 5.67
~ 6.41 (2H, m), 6.98 (1H, s), 7.74 (2H, s), 9.21 (1H,
s) Example 12 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
7- [2] -(2-Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-vinyl-1
-Imidazoliomethyl) -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (380 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.75 (2H, m), 3.80 (3H, s), 4.60 (2H, m), 4.85 to 5.47
(9H, m), 7.32 (15H, s), 7.66 (2H, m), 8.74 (1H, s),
8.94 (1H, m), 9.06 (1H, s) Example 13 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-vinyl-according to Examples 5, 6 and 7
From 1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (350 mg), 7- [2- (2-aminothiazol-4-yl) 2- (2-Propenyloxyimino) acetamide] -3- (3-vinyl-1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) (29 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.75 (2H, m), 4.60 (2H, m), 4.80-5.47 (9H, m), 6.78
(1H, s), 6.83 (2H, s), 7.17 (2H, s), 9.23 (1H, s), 9.
35 (1H, d, J = 8.0Hz) Example 14 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 4-imidazoleacetophenone (100 μl) were added to give 7- [2- (2-
Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-
Acetophenyl-1-imidazoliomethyl) -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (330 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, s), 3.75 (2H, m), 4.50 (2H, m), 4.56 (2H, m)
m), 5.0 (2H, m), 5.15 (4H, m), 6.60 (1H, s), 7.32 (18
H, m), 9.30 (1H, d, J = 8.0Hz) Example 15 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-acetophenyl-1-imidazo according to Examples 5, 6 and 7. Lyomethyl) -3-cefm-1
-Oxido-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (310 mg) to give 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- (3-acetophenyl-1-imidazoliomethyl) -3-cephem-4-carboxylate (53 mg) was obtained. It was

NMR δ ppm (DMSO-d ₆ ): 3.75 (2H, m), 4.50 (2H, m), 5.0 (2H, m), 5.50 (1H,
m), 6.65 (1H, s), 7.0 (2H, s), 9.06 (1H, d, J = 8.0Hz) Example 16 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 4-imidazoleacetophenone (88 μl) were added to give 7- [2- (2-Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3-
(4-Hydroxyphenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p
-Methoxybenzyl iodide (syn isomer) (310m
g) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, s), 3.75 (2H, m), 4.50 (2H, m), 4.56 (2H, m)
m), 5.75 ~ 6.10 (4H, m), 7.0 ~ 7.32 (17H, m), 9.20 (1
H, d, J = 8.0 Hz) Example 17 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3- (4-hydroxyphenyl) according to Examples 5, 6 and 7 (Enyl) -1-imidazoliomethyl] -3-
Cefm-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (290 mg) to 7
-[2- (2-aminothiazol-4-yl) -2-
(2-Propenyloxyimino) acetamide] -3-
[3- (4-Hydroxyphenyl) -1-imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) (53 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.75 (2H, m), 4.50 (2H, m), 4.56 (2H, m), 5.75~6.10
(4H, m), 7.2 (6H, m), 9.20 (1H, d, J = 8.0Hz) Example 18 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Iyl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-propynylimidazole (58 μl) were added to give 7- [2 -(2-Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3- (2-
Propynyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (325 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.9 to 4.4 (2H, m), 4.6 (2H, s), 4.85 (1H, d, J = 5.0H)
z), 5.45 (1H, m), 6.72 (1H, s), 7.25 (15H, s), 9.45
(1H, d, J = 8.0Hz) Example 19 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3- (2-propynyl) according to Examples 5, 6 and 7. -1-Imidazoliomethyl] -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (315 mg) to 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- [3- (2
-Propynyl) -1-imidazoliomethyl] -3-cem-4-carboxylate (38 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.9 to 4.4 (2H, m), 4.6 (2H, s), 4.85 (1H, d, J = 5.0H)
z), 5.45 (1H, m), 6.72 (1H, s), 7.10 (2H, s), 9.45 (1
H, d, J = 8.0 Hz) Example 20 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
7- [2] -(2-Propenioloxyimino) -2- (2-tritylaminothiazole)
Acetamido] -3- [3- (2-butenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4
-Carboxylic acid p-methoxybenzyl iodide (syn isomer) (365 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.7 (3H, d, J = 6.0), 3.9 to 4.4 (2H, m), 4.6 (2H, s), 4.
85 (1H, d, J = 5.0Hz), 5.45 (1H, m), 6.72 (1H, s), 7.25
(15H, s), 9.45 (1H, d, J = 8.0Hz) Example 21 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazole) acetamido] -3- [3- (2-butenyl)-according to Examples 5, 6 and 7.
1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (353 mg) to 7- [2- (2-aminothiazole-
4-yl) -2- (2-propenyloxyimino) acetamido] -3- [3- (2-butenyl-1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) (57 mg) Got

NMR δ ppm (DMSO-d ₆ ): 1.7 (3H, d, J = 6.0), 3.9 to 4.4 (2H, m), 4.6 (2H, s), 4.
85 (1H, d, J = 5.0Hz), 5.45 (1H, m), 6.73 (1H, s), 7.10
(2H, s), 9.45 (1H, d, J = 8.0Hz) Example 22 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
7- [2] -(2-Propenioloxyimino) -2- (2-tritylaminothiazole)
Acetamido] -3- [3- (3-butenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4
-Carboxylic acid p-methoxybenzyl iodide (syn isomer) (353 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 2.28 (2H, m), 3.85 (2H, m), 4.6 (2H, s), 4.85 (1H, d, J
= 5.0Hz), 5.45 (1H, m), 6.76 (1H, s), 7.25 (15H, s),
9.20 (1H, d, J = 8.0Hz) Example 23 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3- (3-butenyl) according to Examples 5, 6 and 7. -1-Imidazoliomethyl] -3-cefm-
1-oxide-4-carboxylic acid p-methoxybenzyl
From iodide (syn isomer) (348 mg), 7- [2-
(2Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- [3- (3-
Butenyl) -1-imidazoliomethyl] -3-cem-4-carboxylate (syn isomer) (51 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 2.28 (2H, m), 3.85 (2H, m), 4.6 (2H, s), 4.85 (1H, d, J
= 5.0Hz), 5.45 (1H, m), 6.76 (1H, s), 7.01 (2H, s),
9.20 (1H, d, J = 8.0Hz) Example 24 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
YI) acetamido] -3-iodomethyl-3-cem-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1- (3,4,4, trifluoro-3-)
From butenyl) imidazole (100 μl), 7- [2
-(2-Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3
-[3-3,4,4-trifluoro-3-butenyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl iodide (syn isomer) (213 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 2.7 to 3.0 (2H, m), 4.0 (2H, m), 4.6 (2H, s), 4.85 (1H,
d, J = 5.0Hz), 5.45 (1H, m), 6.70 (1H, s), 7.30 (15H,
s), 9.30 (1H, d, J = 8.0Hz) Example 25 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3-3,4,4 according to Examples 5, 6 and 7. , -Trifluoro-3-butenyl) imidazoliomethyl] -3
-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl iodide (syn isomer) (200 mg) to 7- [2- (2-aminothiazol-4-yl)-
2- (2-Propenyloxyimino) acetamide]-
3- [3- (3,4,4, -trifluoro-3-butenyl)-
1-imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) (21 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 2.7 to 3.0 (2H, m), 4.0 (2H, m), 4.6 (2H, s), 4.85 (1H,
d, J = 5.0Hz), 5.45 (1H, m), 6.70 (1H, s), 7.10 (2H,
s), 9.32 (1H, d, J = 8.0Hz) Example 26 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Il) acetamido] -3-iodomethyl-3-cem-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-methylimidazole (50 μm
1) to 7- [2- (2-propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-methyl-1-imidazoliomethyl) -3 -Chem-1-oxid-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (336 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.65 (2H, m), 3.73 (3H, s), 3.85 (3H, s), 4.64 (2H, m)
m), 4.97 (1H, m), 5.0 ~ 5.50 (6H, m), 5.6 ~ 6.40 (2H,
m), 6.92 (1H, s), 7.07 (4H, m), 7.31 (15H, s), 7.60
(2H, m), 8.80 (1H, s) Example 27 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-methyl-according to Examples 5, 6 and 7
From 1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (300 mg), 7- [2- (2
-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- (3-methyl-
1-imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) (25.1 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.48 (2H, m), 3.85 (3H, s), 4.17 (2H, s), 4.90-5.50
(5H, m), 5.86 (1H, m), 5.70 ~ 6.40 (1H, m), 7.65 (2H, m)
s), 9.10 (1H, s) Example 28 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-butylimidazole (63 μl), 7- [2 -(2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-butyl-1-
Imidazoliomethyl) -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (310 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.40 (9H, s), 1.6 to 2.11 (4H, m), 3.68 (3H, s), 4.8 (2
H, m), 5.1 to 5.6 (4H, m), 5.80 (1H, m), 6.68 (1H, s),
7.25 (15H, s), 9.4 (1H, d, J = 8.0Hz) Example 29 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-butyl-according to Examples 5, 6 and 7
From 1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (300 mg), 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- (3-butyl-1-imidazoliomethyl] -3-cefm-4-carboxylate (21 mg) was obtained. It was

NMR δ ppm (DMSO-d ₆ ): 1.40 (9H, s), 1.6 to 2.11 (4H, m), 3.68 (3H, s), 4.8 (2
H, m), 5.1 to 5.6 (4H, m), 5.80 (1H, m), 6.68 (1H, s),
7.10 (2H, s), 9.4 (1H, d, J = 8.0Hz) Example 30 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-acetylimidazole (50 μl), 7- [2 -(2-Propenioloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-acetyl-1-imidazoliomethyl) -3-cefm-1-oxide-4 -Carboxylic acid p-methoxybenzyl ester
Iodide (syn isomer) (302 mg) was obtained.

NMR δ ppm (DMSO-d ₆ -TFA-d): 1.90 (3H, s), 3.5 to 3.8 (2H, m), 4.8 (2H, m), 5.1 to 5.6.
(4H, m), 5.80 (1H, m), 7.0 (1H, s), 7.25 (15H, s) Example 31 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-acetyl-1-imidazo according to Examples 5, 6 and 7. Riomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester
From iodide (syn isomer) (290 mg), 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- (3-acetyl-1-imidazoliomethyl-3-cefm-4-carboxylate (syn isomer) ( 24 mg).

NMR δ ppm (DMSO-d ₆ ): 1.90 (3H, s), 3.5 to 3.8 (2H, m), 4.8 (2H, m), 5.1 to 5.6
(2H, m), 5.80 (1H, m), 6.69 (1H, s), 7.20 (2H, s), 9.
4 (1H, d, J = 8.0Hz) Example 32 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.6 g) and 1- (2- From propenylno-imidazole (79 mg), 7- [2-methoxyimino-2
-(2-Tritylaminothiazol-4-yl) acetamide] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester -Iodide (syn isomer) (390 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 3.77 (3H, s), 4.0 (3H, s) <4.95 (1H, d, J = 4Hz), 5.6
~ 6.5 (2H, m), 6.65 (1H, s), 6.7 ~ 7.5 (19H, m), 7.7
(1H, s), 9.7 (1H, s) Example 33 7- [2-methoxyimino-2- (2-tritylaminothiazol-4-yl) according to Examples 5, 6 and 7
Acetamide] -3- [3- (2-propenyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
From 4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (320 mg), 7- [2- (2-
Aminothiazol-4-yl) -2-methoxyiminoacetamido] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) (26 mg) Obtained.

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, s), 4.48-6.25 (m8H), 6.65 (1H, s), 7.1 (2
H, s), 7.6 (1H, s), 7.95 (1H, s), 9.25 (1H, s), 9.4 (1
H, d, J = 8.0 Hz) Example 34 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Iyl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (1.58 g) and imidazole (4
5 μl) and 7- [2- (2-propenioloxyimino) -2- (2-tritylaminothiazole-4-)
Il) acetamido] -3- (1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p
-Methoxybenzyl ester iodide (syn isomer) (250 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.80 (3H, s), 4.95 (1H, d, J = 4.0Hz), 5.50 (1H, m), 6.
70 (1H, s), 6.80 to 7.75 (20H, m), 9.40 (1H, d, J = 6.0H
z) Example 35 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- (1-imidazoliomethyl) -according to Examples 5, 6 and 7. 3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (200 mg) to 7- [2- (2-aminothiazol-4-yl) -2- (2- Propenyloxyimino) acetamido] -3- (1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) (19 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.80 (3H, s), 4.95 (1H, d, J = 4.0Hz), 5.50 (1H, m), 6.
70 (1H, s), 7.5 (1H, s), 7.30 (1H, s), 7.70 (1H, s),
9.4 (1H, d, J = 6.0Hz) Example 36 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.6 g) and 1- (propynylimidazole) (88 mg) and 7- [2-methoxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propynyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (330 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 2.75 (1H, m), 3.75 (3H, s), 4.0 (3H, s), 4.75 (1H, d, J
= 3.0Hz), 4.8 to 5.5 (6H, m), 6.0 to 6.3 (1H, m), 6.70
(1H, s), 6.8 to 7.75 (20H, m), 9.8 (1H, s) Example 37 7- [2-methoxyimino-2- (2-tritylaminothiazol-4-yl) according to Examples 5, 6 and 7
Acetamido] -3- [3- (2-propynyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester (syn isomer) (300 mg) to 7- [2- (2-aminothiazol-4-yl) -2-methoxyiminoacetamide]
-3- [3- (2-Propinyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) (52 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, s), 4.75 to 5.25 (5H, m), 5.5 (1H, m), 6.65
(1H, s), 7.1 (2H, s), 7.65 (1H, s), 7.95 (1H, s),
9.35 (1H, d, J = 8.0Hz), 9.45 (1H, s) Example 38 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamide] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.54 g) and 1-butylimidazole (8
0 mg) to 7- [2-methoxyimino-2- (2-
Tritylaminothiazol-4-yl) acetamide]
-3- (3-Butyl-1-imidazoliomethyl) -3-
Cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (365m
g) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.8 (3H, s), 4.0 (3H, s), 6.2 (1H, m), 6.7 (1H, s),
6.8 to 7.5 (19H, m), 7.75 (1H, s), 9.7 (1H, s) Example 39 7- [2-methoxyimino-2- (2-tritylaminothiazol-4-yl) according to Examples 5, 6 and 7
Acetamide] -3- (3-butyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (350 mg) to 7- [2 -Aminothiazole-
4-yl) -2-methoxyiminoacetamide] -3-
(3-Butyl-1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) (60 g) was obtained.

NMR δ ppm (DMSO-d ₆ ): 0.78 to 1.8 (9H, m), 3.75 (3H, s), 4.95 (1H, d, J = 4.0H
z), 5.50 (1H, m), 6.70 (1H, s), 7.10 (2H, s), 7.70 (1
H, s), 8.0 (1H, s), 9.25 (1H, s), 9.4 (1H, d, J = 8.0H
z) Example 40 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl (syn isomer) (1.37 g) and 1-methylimidazole (120 μl) ) And 7- [2-methoxyimino-2- (2-tritylimidazol-4-yl) acetamide] -3- (3-
Butyl-1-imidazoliomethyl) -3-cefm-1
-Oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (650 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.74 (3H, s), 3.80 (3H, s), 3.82 (3H, s), 4.95 (1H, d,
J = 4.0Hz), 5.75 (1H, m), 6.75 (1H, s) Comparative Example 1 According to Examples 5, 6 and 7, 7- [2-methoxyimino-2- (2-tritylaminothiazole-4)
-Yl) acetamido] -3- (3-methyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-
Carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (600 mg) to 7- [2- (2-aminothiazol-4-yl) -2-methoxyiminoacetamide] -3- (3-methyl-1) -Imidazoliomethyl) -3-cephem-4-carboxylate (42g) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.8 (3H, s), 5.0 (1H, d, J = 4.0Hz), 5.6 (1H, m), 6.7
(1H, s), 7.2 (2H, s), 7.7 (s, 1H), 7.9 (1H, s), 9.2
(1H, s), 9.4 (1H, d, J = 8.0Hz) Example 42 (Example 41 is a missing number) According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-ceem-4-carboxylic acid p-methoxybenzyl (syn isomer) (0.5 g) and imidazole (45 μl) were added to give 7- [ 2-Methoxyimino-2- (2-tritylimidazol-4-yl) acetamide] -3- (1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (331mg)
Got

_{NMR δ ppm (DMSO-d 6} ): 3.80 (3H, s), 4.95 (1H, d, J = 4.0Hz), 5.50 (1H, m), 6.
70 (1H, s), 7.25 (15H, s), 7.30 (1H, s), 7.70 (1H,
s), 9.4 (1H, d, J = 6.0Hz) Example 43 7- [2-methoxyimino-2- (2-tritylaminothiazol-4-yl) according to Examples 5, 6 and 7
Acetamide] -3- (1-imidazoliomethyl) -3
-Chem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (32
0 mg) to 7- [2-aminothiazol-4-yl)
2-Methoxyiminoacetamide] -3- (1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) (38 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.80 (3H, s), 4.95 (1H, d, J = 4.0Hz), 5.50 (1H, m), 6.
70 (1H, s), 6.80 (2H, s), 7.15 (1H, s), 7.30 (1H, s),
7.70 (1H, s), 9.4 (1H, d, J = 6.0Hz) Example 44 7- [2- (2-tert-butoxycarbonyl) prop-
2-Oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3
-Chem-1-oxid-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.6 g) was added to THF (5 m
l), the solution dissolved in chloroform (2.5 ml) was cooled to 0 ° C., 1- (2-propenyl) imidazole (70 mg) was added, and then the mixture was heated and stirred at room temperature for 3 hours. Was distilled off and the residue was triturated with diethyl ether (50 ml) and eluted with a silica gel column (chloroform: methanol, volume ratio 8: 1) to give 7- [2- (2-tert-butoxycarbonyl) prop- 2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (412.2 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.36 (15H, s), 3.75 (2H, m), 3.79 (3H, s), 4.83 (2H, s)
m), 5.00 (1H, m), 5.07 ~ 5.53 (6H, m), 5.75 ~ 5.95 (2
H, m), 6.73 (1H, s), 7.18 (4H, m), 7.23 (15H, s), 7.70
(2H, m), 8.75 (1H, s), 9.23 (1H, m), 9.42 (1H, s) Example 45 According to Examples 5 and 6, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamide] -3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (400 mg) to 7- [2- (2-aminothiazol-4-yl) -2- (2-tert-butoxycarbonyl) prop-2-oxyiminoacetamide] -3-
[3- (2-propenyl-1-imidazoliomethyl]-
3-Chem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (230 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.37 (9H, s), 1.49 (3H, s), 1.52 (3H, s), 3.50 (2H, s)
s), 3.76 (3H, s), 4.82 (2H, m), 4.90 to 5.52 (7H, m),
5.72 ~ 6.31 (2H, m), 6.69 (1H, s), 7.13 (4H, m), 7.22
(2H, s), 7.66 (2H, m), 9.21 (1H, s), 9.30 (1H, m) Example 46 7- [2- (2-aminothiazol-4-yl) -2-
(2-tert-Butoxycarbonyl) prop-2-oxyiminoacetamide] -3- [3- (2-propenyl-
1-imidazoliomethyl] -3-cephem-4-carboxylic acid p-methoxybenzyl iodide (syn isomer)
(220 mg) to methylene chloride (3 ml) and anisole (2.2 m
l), and trifluoroacetic acid (3.1 ml) was added dropwise under cooling at 0 ° C. After stirring at 0 ° C for 2 hours and then at 10 ° C for 4 hours, the solvent was distilled off under reduced pressure, and the residue was diluted with diethyl ether (50
(ml) was pulverized and collected by filtration, neutralized with an aqueous solution of potassium hydrogen carbonate and freeze-dried to obtain a yellow powder. This was eluted with Sephadex LH-20 (methanol) to give 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} as a white powder. -3- [3-
(2-Propenyl-1-imidazoliomethyl] -3-cem-4-carboxylate (syn isomer) (53.2m
g) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.38 (3H, s), 1.43 (3H, s), 3.50 (2H, s), 4.83 (2H, s)
m), 4.91 to 5.60 (5H, m), 5.75 to 6.37 (2H, m), 6.68 (1
H, s), 7.07 (2H, s), 7.58 (1H, s), 7.48 (1H, s), 9.46
(1H, s), 12.13 (1H, m) Example 47 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.5g) and 4-imidazole acetophenone (100μ
l) and 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3
-Acetophenyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (340 mg)
Got

NMR δ ppm (DMSO-d ₆ ): 1.36 (15H, s), 3.75 (2H, m), 3.60 (3H, s), 4.83 (2H, s)
m), 6.73 (1H, s), 7.18 (4H, m), 7.25 (15H, s), 9.42
(1H, d, J = 8.0Hz) Example 48 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) pup-2-oxyimino-2- (2-
Tritylaminothiazol-4-yl) acetamide]
-3- (3-acetophenyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p
-Methoxybenzyl ester iodide (syn isomer) (330 mg) to give 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3 -(3-Acetophenyl-1-imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) (53 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.60 (3H, s), 4.83 (2H, m), 6.69 (1H, s), 7.13 (2H, s)
s), 7.66 (2H, m), 9.30 (1H, d, J = 8.0Hz) Example 49 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From (0.6 g) and 1-butylimidazole (80 mg), 7
-[2- (2-tert-butoxycarbonyl) prop-2
-Oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-butyl-1-
Imidazoliomethyl) -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (410 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 0.97 (3H, m), 1.40 (9H, s), 1.53 (6H, s), 1.6 to 2.11
(4H, m), 3.68 (3H, s), 4.00 (2H, s), 4.13 (2H, m), 4.
97 (1H, d), 5.21 (2H, s), 5.48 (2H, m), 6.22 (1H, m),
6.52 (1H, s), 7.13 (4H, m), 7.25 (15H, s), 7.26 (1H,
s), 9.72 (1H, s) Example 50 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (3-butyl-1-imidazoliomethyl]-
3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (38
5 mg) to give 7- {2- (2-aminothiazole-4-
Yl) -2- [potassium (2,2-dimethylacetate)
Oxyimino] acetamido} -3- (3-butyl-1)
-Imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) (51 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 0.85 (3H, m), 1.36 (3H, s), 1.40 (3H, s), 3.46 (2H,
s), 4.12 (2H, m), 5.67 (1H, m), 6.64 (1H, s), 7.10 (2
H, s), 7.64 (1H, s), 7.9 (1H, s), 9.46 (1H, s), 11.95
(1H, m) Example 51 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.6 g) and 1-n-hexyl imidazole (80 mg) to give 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide. ] -3- (3-n-Hexyl-1-imidazoliomethyl) -3-cefm-1
-Oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (360 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 0.88 (3H, m), 1.05 to 2.15 (8H, m), 1.39 (9H, s), 2.04
(6H, s), 3.76 (3H, s), 5.02 (1H, m), 5.43 (2H, m), 6.
14 (1H, m), 6.48 (1H, s), 7.02 (4H, m), 7.24 (15H,
s), 7.73 (1H, s), 9.64 (1H, s) Example 52 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (3-n-hexyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p
-Methoxybenzyl ester iodide (syn isomer) (345 mg) to give 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide}- 3- (3-
n-Hexyl-1-imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) (23 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 0.82 (3H, t, J = 6.5Hz), 4.08 (2H, t, J = 6.5Hz), 0.98-
2.05 (4H, m), 4.93 (1H, d, J = 5.0Hz), 1.34 (3H, s), 5.
63 (1H, d, d, J = 5.0Hz, J = 8.0Hz), 1.38 (3H, s), 6.64
(1H, s), 3.43 (2H, s), 7.07 (2H, s), 7.62 (1H, s), 7.
92 (1H, s), 9.39 (1H, s), 11.75 (1H, d, J = 8.0Hz) Example 53 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.5g) and 1-n-dodecanyl imidazole (127mg)
And 7- [2- (2-tert-butoxycarbonyl)
Prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-n
-Dodecanyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (296 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 0.84 (3H, m), 0.9 to 2.3 (20H, m), 1.33 (9H, s), 1.40
(6H, s), 3.60 (2H, m), 3.74 (3H, s), 4.96 (1H, m), 5.
22 (2H, s), 5.84 (1H, m), 6.73 (1H, s), 7.25 (15H,
s), 7.75 (1H, s), 8.07 (1H, m), 9.01 (1H, s) Example 54 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamide] -3- (3-n-dodecanyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomerism Body) (290 mg), 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (3-n
-Dodecanylate-1-imidazoliomethyl) -3-
Cefm-4-carboxylate (syn isomer) (31.5
mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 0.84 (3H, m), 0.96 to 2.05 (20H, m), 1.35 (3H, s), 1.40
(3H, s), 3.50 (2H, s), 3.68 (2H, m), 4.93 (1H, m), 4.
98 (2H, m), 5.64 (1H, m), 6.65 (1H, s), 7.08 (2H, s),
7.64 (1H, s), 7.95 (1H, s), 9.35 (1H, s), 11.50 (1H,
m) Example 55 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.5g) and 1- (2-propynyl) imidazole (57m
g) and 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- [3
-(2-Propinyl) -1-imidazoliomethyl] -3
-Chem-1-oxid-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (294m
g) was obtained.

NMR δ ppm (CDCl ₃ ): 1.41 (9H, s), 1.57 (6H, s), 3.80 (3H, s), 5.24 (2H,
s), 6.40 (1H, m), 6.57 (1H, s), 7.06 (4H, m), 7.28 (1
5H, s) Example 56 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (2-propynyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (290 mg), 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- [3
-(2-Propinyl) -1-imidazoliomethyl] -3
-Chem-4-carboxylate (syn isomer) (3
4.2 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.40 (3H, s), 1.45 (3H, s), 3.62 (2H, s), 3.72 (1H,
m), 4.50-5.45 (5H, m), 5.32 (1H, m), 6.74 (1H, s),
7.15 (2H, s), 7.64 (1H, s), 7.96 (1H, s), 9.15 (1H,
s), 11.88 (1H, m) Example 57 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.6 g) and 1-benzylimidazole (101 mg) to give 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide]- 3- (3-Benzyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (409 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.36 (15H, s), 3.65 (2H, m), 3.73 (3H, s), 4.85 to 5.32
(5H, m), 5.42 (2H, s), 5.72 (1H, m), 6.63 (1H, s), 7.
13 (4H, m), 7.28 (15H, s), 7.42 (5H, s), 7.71 (2H,
m), 8.76 (1H, s), 9.23 (1H, m), 9.32 (1H, s) Example 58 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (3-benzyl-1-imidazoliomethyl)
-3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer)
(480 mg), 7- {2- (2-aminothiazole-
4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamido} -3- (3-benzyl-1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) ( 38.9 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.34 (9H, s), 1.43 (6H, s), 3.50 (2H, s), 5.45 (2H, s)
s), 5.68 (1H, m), 6.72 (1H, s), 7.12 (2H, s), 7.42 (5
H, s), 7.64 (1H, s), 8.03 (1H, s), 9.65 (1H, s), 12.01
(1H, m) Example 59 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From (0.6 g) and 1-benzylimidazole (50 μl), 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide]- 3- (3-Methyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester
Iodide (syn isomer) (339 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.36 (15H, s), 3.70 (2H, m), 3.75 (3H, s), 3.83 (3H, s)
s), 4.80 to 5.46 (5H, m), 5.68 (1H, m), 6.67 (1H, s),
7.22 (15H, s), 8.26 (1H, s), 9.08 (1H, s), 9.23 (1H,
m) Example 60 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamide] -3- (3-methyl-1-imidazoliomethyl]-
3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (32
0 mg) to 7- {2- (2-aminothiazole-4-
Yl) -2- [potassium (2,2-dimethylacetate)
Oxyimino] acetamido} -3- (3-methyl-1)
-Imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) (50.9 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 1.39 (3H, s), 1.45 (3H, s), 3.48 (2H, s), 4.84 (3H,
s), 4.97 (1H, m), 4.99 (2H, m), 5.73 (1H, m), 6.71 (1
H, s), 7.12 (2H, s), 7.57 (1H, s), 7.95 (1H, s), 9.48
(1H, s), 12.06 (1H, m) Example 61 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From (0.5 g) and imidazole (50 μl), 7- [2-
(2-tert-Butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- (1-imidazoliomethyl)
-3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer)
(280 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.34 (9H, s), 1.42 (6H, s), 3.53 (2H, m), 3.75 (3H,
s), 5.26 (2H, s), 5.86 (1H, m), 6.75 (1H, s), 7.09 (1
H, s), 7.26 (15H, s), 7.42 (1H, s), 7.60 (1H, s), 8.02
(1H, m), 8.63 (1H, s) Example 62 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (270 mg) ,
7- {2- (2-aminothiazol-4-yl) -2-
[Potassium (2,2-dimethylacetate) oxyimino] acetamido} -3- (1-imidazoliomethyl)
-3-Chem-1-carboxylate (syn isomer)
(30 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.36 (3H, s), 1.41 (3H, s), 3.46 (2H, s), 4.91 (1H,
m), 5.50 (1H, m), 6.67 (1H, s), 7.05 (2H, s), 7.20 (1
H, s), 7.61 (1H, s), 12,00 (1H, m) Example 63 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
(0.5 g) and 1-methylbenzimidazole (71.3 mg) to give 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide. ] -3- (Benz-
3-N-Methyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (294 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.32 (9H, s), 1.37 (6H, s), 3.60 (2H, m), 3.69 (3H, s)
s), 3.80 (3H, m), 4.10 (3H, s), 5.22 (2H, s), 5.45 (2
H, s), 5.86 (1H, m), 6.70 (1H, s), 7.09 (14H, m), 7.19
(15H, s), 8.60 (1H, s) Example 64 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (benz-3-N-methyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (280 mg), 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (benz-3-N) -Methyl-1-imidazoliomethyl) -3
-Chem-1-carboxylate (syn isomer) (12
mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.41 (3H, s), 1.45 (3H, s), 3.80 (3H, m), 4.89 (1H,
m), 5.17 (2H, m), 5.52 (1H, m), 6.72 (1H, s), 6.73 ~
7.42 (2H, m), 7.12 (2H, s), 8.32 (1H, s), 12.06 (1H,
m) Example 65 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From (0.5 g) and benzimidazole (67 mg), 7-
[2- (2-tert-butoxycarbonyl) prop-2-
Oxyimino-2- (2-tritylaminothiazole-
4-yl) acetamido] -3- (benz-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (354 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.32 (9H, s), 1.37 (6H, s), 3.60 (2H, m), 3.69 (3H, s)
s), 4.96 (1H, m), 5.22 (2H, s), 5.45 (2H, s), 5.86 (1
H, m), 6.70 (1H, s), 7.09 (4H, m), 7.19 (15H, s), 8.60
(1H, s) Example 66 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (benz-1-imidazoliomethyl) -3-
Cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (345m
From g), potassium 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (benz-
1-Imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) (21.2 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 1.41 (3H, s), 1.45 (3H, s), 3.47 (2H, s), 4.89 (1H,
m), 5.17 (2H, m), 5.52 (1H, m), 6.72 (1H, s), 6.73 ~
7.42 (2H, m), 7.12 (2H, s), 8.32 (1H, s), 12.06 (1H,
m) Example 67 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamide] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (0.5 g) and 1-methylbenzimidazole (70 mg) to give 7- [2-methoxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (benz-3-N-methyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) (285 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, m), 4.10 (3H, s), 4.90 (1H, m), 5.2-5.6 (6
H, m), 6.60 (1H, s), 7.0 to 7.3 (15H, s), 9.2 (1H, d, J =
8.0Hz) Example 68 7- [2-methoxyimino-2- (2-tritylaminothiazol-4-yl) according to Examples 5, 6 and 7
Acetamide] -3- (benz-3-N-methyl-1-
Imidazoliomethyl) -3-cefm-1-oxide-
From 4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (279 mg), 7- [2- (2-
Aminothiazol-4-yl) -2-methoxyiminoacetamido] -3- (benz-3-N-methyl-1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) (20.5 mg) Got

NMR δ ppm (DMSO-d ₆ ): 3.80 (3H, m), 4.10 (3H, s), 4.90 (1H, m), 5.2-5.6 (3
H, m), 6.60 (1H, s), 7.0 (2H, s), 7.6 (2H, m), 7.8 (1
H, m), 9.2 (1H, d, J = 8.0Hz) Example 69 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From (0.6 g) and 1-methyl-5- (2-tritylamino) ethylimidazole (234 mg), 7- [2- (2-t
ert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- [3-methyl-4- (2-tritylamino) ethyl-1-imidazoliomethyl] -3-Cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (432 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 1.42 (9H, s), 1.55 (6H, s), 2.30 to 2.92 (4H, m), 3.70
(3H, s), 3.80 (3H, s), 4.02 (2H, s), 4.98 (1H, m), 5.
21 (2H, s), 5.29 (2H, m), 6.22 (2H, m), 6.57 (1H, s),
7.12 (4H, m), 7.21 ~ 7.43 (30H, s), 7.02 ~ 7.64 (4H,
m), 9.17 (1H, s) Example 70 According to Examples 43 and 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3-methyl-4- (2-tritylamino)
Ethyl-1-imidazoliomethyl] -3-cefm-1
-Oxido-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (400 mg) to 7-
{2- (2-Aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- [3-methyl-4- (2-aminoethyl-1-imidazolio) Methyl] -3-cem-4-
The carboxylate (syn isomer) (59.4 mg) was obtained.

NMR δ ppm (DMSO-d ₆ -TFA-d): 1.56 (6H, s), 2.53 to 3.31 (4H, m), 3.52 (2H, s), 3.82
(3H, s), 4.98 (1H, m), 5.17 (2H, m), 5.91 (1H, m), 6.
81 (1H, s), 7.02 (2H, s), 7.51 (2H, s), 8.10 (1H, s),
9.17 (1H, s), 11.85 (1H, s) Example 71 From 7-phenylacetamido-3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cem-4-carboxylic acid p-methoxybenzyl ester (syn isomer) by known imino ether method. Obtained 7-amino-3- [3- (2-propenyl) -1-imidazoliomethyl] -3-cem-4-carboxylic acid (0.56 g)
Is suspended in dry ethyl acetate (20 ml), bis (trimethylsilyl) acetamide (4.8 g) is added, and the mixture is stirred at room temperature (solution A). Meanwhile, phosphorus oxychloride (0.6g) under ice cooling 2
-Propenyloxyimino-2- (2-aminothiazol-4-yl) acetic acid (syn isomer) (0.53 g) was added and 20
Stir for minutes (solution B).

Next, drop the solution B into the solution A at -20 ° C, and then add -10 ° C-
Stir at 20 ° C. for 1 hour 30 minutes. -20 ℃ ~-
Under cooling at 30 ° C., ice water (30 ml) is added, ethyl acetate (50 ml) is further added, and the mixture is stirred. The precipitated insoluble matter is removed by filtration and the organic phase is separated. A saturated aqueous sodium hydrogen carbonate solution is added to this organic phase to adjust the pH to 7.5, and the aqueous layer is separated and washed with methylene chloride. The aqueous layer was adjusted to pH 2 with 10% hydrochloric acid, the precipitate was collected by filtration, dried, and then dissolved in a 5% aqueous potassium hydrogen carbonate solution, which was obtained in Example 7 using Sephadex LH-20 (H ₂ O). -[2
-(2-Aminothiazol-4-yl) -2- (2-propenoxyimino) acetamido) -3- [3- (2-
The same compound (18 mg) as propenyl) -1-imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) was obtained.

Example 72 7- obtained by subjecting the compound obtained according to Example 34 to reduction with phosphorus tribromide as in Example 7
[2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide]-
3- (imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester
Dissolve iodide (syn isomer) (230 mg) in a solvent consisting of acetonitrile (5 ml) and chloroform (2.5 ml), add propylene oxide (0.5 ml) to it, and add methyl iodide (2 ml) to room temperature. After stirring for 18 hours, the solvent and excess methyl iodide are distilled off under reduced pressure to give 7- [2- (2-propenyloxyimino) -2-
(2-Tritylaminothiazol-4-yl) acetamido] -3- (3-methyl-1-imidazoliomethyl)
-3-Cephem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (205 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.65 (2H, m), 3.73 (3H, s), 3.85 (3H, s), 4.64 (2H, m)
m), 4.97 (1H, m), 5.0 ~ 5.50 (6H, m), 5.6 ~ 6.40 (2H,
m), 6.92 (1H, s), 7.07 (4H, m), 7.31 (15H, s), 7.60
(2H, m), 8.80 (1H, s) Example 73 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-methyl-1-) according to Examples 6 and 7.
From imidazoliomethyl) -3-cephem-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (200 mg), 7- [2- (2-aminothiazol-4-yl) -2- (2 -Propenyloxyimino)
Acetamide] -3- (3-methyl-1-imidazoliomethyl) -3-cefm-4-carboxylate (syn isomer) (18 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.48 (2H, m), 3.85 (3H, s), 4.17 (2H, s), 4.90-5.50
(5H, m), 5.86 (1H, m), 5.70 ~ 6.40 (1H, m), 7.65 (2H, m)
s), 9.10 (1H, s) Example 74 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-methyl-1-) obtained in Example 26
Imidazoliomethyl) -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (400 mg) in acetonitrile (3 ml)
And dissolved in a mixed solvent consisting of chloroform (1.5 ml) and propylene oxide (0.5 ml) added to this concentration,
After adding methyl iodide (0.78 ml) and stirring at room temperature for 18 hours, the solvent and excess methyl iodide were distilled off under reduced pressure to give 7- [2- (2-propenyloxyimino)-
2- (2-Tritylaminothiazol-4-yl) acetamido] -3- (3-dimethyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester diiodide ( Syn isomer) (363 mg) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.65 (2H, m), 3.73 (3H, s), 3.85 (6H, s), 4.64 (2H, m)
m), 4.97 (1H, m), 5.0 ~ 5.50 (6H, m), 5.6 ~ 6.40 (2H,
m), 6.92 (1H, s), 7.07 (4H, m), 7.31 (15H, s), 7.60
(2H, m), 8.80 (1H, s) Example 75 7- [2- (2-Propenyloxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (3-dimethyl-according to Examples 5, 6 and 7)
1-imidazoliomethyl) -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester diiodide (syn isomer) (350 mg) to 7- [2-
(2-Aminothiazol-4-yl) -2- (2-propenyloxyimino) acetamido] -3- (3-dimethyl-1-imidazoliomethyl) -3-cem-4-
Carboxylate iodide (syn isomer) (18mg)
Got

NMR δ ppm (DMSO-d ₆ ): 3.48 (2H, m), 3.85 (6H, s), 4.17 (2H, s), 4.90-5.50
(5H, m), 5.86 (1H, m), 5.70 ~ 6.40 (1H, m), 7.65 (2H, m)
s), 9.10 (1H, s) Example 76 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 500 mg and 1-vinylimidazole 68 mg, 7- [2
-(2-tert-Butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazole-4-
There was obtained 317.5 mg of p-methoxybenzyl iodide (syn isomer) of (yl) acetamide] -3- (3-vinyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid.

NMR δ ppm (CDCl ₃ ): 1.39 (9H, s), 1.55 (6H, s), 3.71 (3H, s), 4.07 (2H,
m), 4.97 (1H, d, J = 5.0Hz), 4.75 to 5.91 (4H, m), 5.21
(2H, s), 6.10 (1H, dd, J = 5.0,8.0Hz), 6.72 (1H, s),
7.05 (4H, dd, J = 8.0,35.0Hz), 6.61-8.09 (5H, m), 7.2
5 (15H, s), 9.68 (1H, s) Example 77 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamide] -3- (3-vinyl-1-imidazoliomethyl)-
3-Chem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 300 m
From g, 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (3-vinyl-1-
25.9 mg of imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.38 (3H, s), 1.44 (3H, s), 3.10 to 3.77 (2H, m), 4.65
~ 5.50 (4H, m), 4.98 (1H, d, J = 5.0Hz), 5.64 (1H, dd, J
= 5.0, 8.0Hz), 6.75 (1H, s), 6.90 to 7.60 (1H, m), 7.12
(1H, s), 7.98 (1H, s), 8.11 (1H, s), 9.70 (1H, s), 1
2.06 (1H, d, J = 8.0Hz) Example 78 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 500 mg and 1-cyclohexylimidazole 220 mg,
7- [2- (2-tert-butoxycarbonyl) prop-
2-Oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- (3-cyclohexyl-1-imidazoliomethyl) -3-cefm-1-
185.8 mg of oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 1.35 (9H, s), 1.50 (6H, s), 0.95 to 2.30 (11H, m), 3.73
(3H, s), 4.08 (2H, m), 4.92 (1H, d, J = 5.0Hz), 5.17
(2H, s), 5.0 to 5.92 (2H, m), 6.08 (1H, dd, J = 5.0,8.0H
z), 6.61 (1H, s), 7.04 (4H, dd, J = 8.0,37.5Hz), 7.24
(15H, s), 7.05 to 7.94 (4H, m) 9.65 (1H, s) Example 79 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamide] -3- (3-cyclohexyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) ) From 185 mg, 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (3-cyclohexyl-1-imidazoliomethyl] 8.8 mg of 3-Cephem-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.41 (3H, s), 1.44 (3H, s), 0.81 to 2.36 (11H, m), 3.10
~ 3.75 (2H, m), 4.97 (1H, d, J = 5.0Hz), 5.05 ~ 5.45 (2
H, m), 5.50-5.85 (1H, m), 6.69 (1H, s), 7.10 (2H,
s), 7.58 (1H, s), 8.00 (1H, s), 9.46 (1H, s), 12.13
(1H, d, J = 8.0Hz) Example 80 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 350 mg and 1- (4-hydroxyphenyl) imidazole 65 mg, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3-
160.9 mg of [3- (4-hydroxyphenyl) -1-imidazoliomethyl] -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 1.37 (9H, s), 1.54 (6H, s), 3.76 (3H, s), 4.13 (2H, s)
m), 4.99 (1H, d, J = 5.0Hz), 5.24 (2H, s), 5.05 to 5.85
(2H, m), 6.14 (1H, dd, J = 5.0,8.0Hz), 6.63 (1H, s),
7.07 (4H, dd, J = 8.0,37.5Hz), 6.65 ~ 8.10 (9H, m), 7.2
3 (15H, s), 9.71 (1H, s) Example 81 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [3- (4-hydroxyphenyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 160 mg was used to give 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide. } -3
9.0 mg of-[3- (4-hydroxyphenyl) -1-imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.39 (3H, s), 1.41 (3H, s), 3.20 to 3.72 (2H, m), 4.95
(1H, d, J = 5.0Hz), 5.05 to 5.40 (2H, m), 5.47 to 5.84 (1
H, m), 6.72 (1H, s), 6.23 ~ 8.25 (9H, m), 9.47 (1H,
s), 12.03 (1H, d, J = 8.0Hz) Example 82 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 500 mg and 121 mg of 1-benzylbenzimidazole, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- ( Benz-3
288.5 mg of -N-benzyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 1.39 (9H, s), 1.54 (6H, s), 3.75 (3H, s), 4.16 (2H,
m), 5.13 (1H, d, J = 5.0Hz), 5.23 (2H, s), 6.10 (2H,
s), 5.75 (2H, m), 6.11 (1H, dd, J = 5.0,8.0Hz), 7.02
(4H, dd, J = 8.0,42.5Hz), 7.25 (15H, s), 7.37 (5H,
s), 6.70 to 8.10 (7H, m) Example 83 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N-benzyl-1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) from 280 mg, 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (benz-3-N-benzyl) -1-Imidazoliomethyl) -3
-Chem-4-carboxylate (syn isomer) 30.1
to obtain mg.

NMR δ ppm (DMSO-d ₆ ): 1.35 (3H, s), 1.40 (3H, s), 3.08 to 3.76 (2H, m), 4.93
(1H, d, J = 5.0Hz), 5.45 (2H, s), 5.77 (2H, s), 5.46 ~
5.82 (1H, m), 6,66 (1H, s), 6.85 ~ 8.50 (9H, m), 7.07
(2H, s), 10.13 (1H, s), 11.84 (1H, d, J = 8.0Hz) Example 84 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
350 mg and 1- (2-propynyl) benzimidazole 64 m
From g and 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- [benz-3-N- (2 209.1 mg of -propynyl) -1-imidazoliomethyl] -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 1.38 (9H, s), 1.52 (6H, s), 2.47 (1H, t, J = 2.8Hz), 3.
72 (3H, s), 4.07 (2H, m), 4.88 (2H, d, J = 2.8Hz), 5.16
(1H, d, J = 5.0Hz), 5.25 (2H, s), 6.03 (2H, m), 6.23
(1H, dd, J = 5.0,8.0Hz), 6.59 (1H, s), 7.01 (4H, dd, J
= 8.0,42.5Hz), 7.26 (15H, s), 6.62 ~ 8.10 (6H, m), 1
0.31 (1H, s) Example 85 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-propynyl) -1
-Imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) from 217.6 mg, 7- {2- (2-
Aminothiazol-4-yl) -2- [potassium (2,2
-Dimethylacetate) oxyimino] acetamide}
36.5 mg of -3- (benz-3-N- (2-propenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.38 (3H, s), 1.42 (3H, s), 3.35 to 3.86 (2H, m), 4.96
(1H, d, J = 5.0Hz), 5.05 to 5.82 (5H, m), 6.67 (1H, s),
7.10 (2H, s), 6.96 ~ 8.50 (4H, m), 10.06 (1H, s), 11.1
7 (1H, d, J = 8.0Hz) Example 86 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 500 mg and 1- (2-methyl-2-propenyl) benzimidazole 100 mg, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-methyl-propenyl) -1-imidazoliomethyl] -3-cefm-1-
268.9 mg of oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 1.40 (9H, s), 1.54 (6H, s), 1.75 (3H, s), 2.76 (3H,
s), 4.17 (2H, m), 4.66 (2H, s), 4.85 ~ 5.40 (3H, m),
5.21 (2H, s), 5.75 (2H, m), 6.20 (1H, dd, J = 5.0,8.0H
z), 6.59 (1H, s), 7.02 (4H, dd, J = 8.0,42.5Hz), 7.25
(15H, s), 6.70-8.15 (7H, m) Example 87 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-methyl-propenyl) -1-imidazoliomethyl] -3-cefm-1-
From 265 mg of oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer), 7- {2-
(2-Aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamido} -3- [benz-3-N- (2-propenyl)-
30.8 mg of 1-imidazoliomethyl] -3-cephem-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.37 (3H, s), 1.42 (3H, s), 2.24 (3H, s), 3.32 to 3.75
(2H, m), 4.55 to 5.25 (2H, m), 4.95 (1H, d, J = 5.0Hz),
5.15 (2H, s), 5.42 (2H, s), 5.62 (1H, dd, J = 5.0,8.0H
z), 6.67 (1H, s), 7.07 (2H, s), 6.81 to 8.46 (4H, m),
9.99 (1H, s), 11.58 (1H, d, J = 8.0Hz) Example 88 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
350 mg and 1- (3-butenyl) benzimidazole 70 mg
And 7- [2- (2-tert-butoxycarbonyl)
Prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N (3-butenyl) -1-imidazoliomethyl]
-3-Chem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 21
4 mg was obtained.

NMR δ ppm (CDCl ₃ ): 1.38 (9H, s), 1.52 (6H, s), 2.72 (2H, q, J = 6.0Hz), 3.
80 (3H, s), 4.14 (2H, m), 4.48 (2H, t, J = 6.0Hz), 5.20
(2H, s), 4.80 to 5.26 (3H, m), 5.67 (2H, m), 5.70 to 6.2
0 (1H, m), 6.17 (1H, dd, J = 5.0,8.0Hz), 6.58 (1H, s),
7.02 (4H, dd, J = 8.0,42.5Hz), 7.24 (15H, s), 6.75 ~ 8.
08 (6H, m), 10.6 (1H, s) Example 89 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-butenyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
From 210 mg of 4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer), 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide } -3
25.3 mg of-[benz-3-N- (3-butenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.36 (3H, s), 1.41 (3H, s), 2.66 (2H, q, J = 6.0Hz), 3.
30 to 3.75 (2H, m), 4.58 (2H, t, J = 6.0Hz), 4.92 (1H, d,
J = 5.0Hz), 5.04 (2H, s), 5.25 to 6.22 (4H, m), 6.67 (1
H, s), 7.07 (2H, s), 7.35 to 8.47 (4H, m), 10.3 (1H,
s), 11.91 (1H, d, J = 8.0Hz) Example 90 According to Example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazole) acetamide] -3-iodomethyl-3-cefm-1-oxide- 4-carboxylic acid p
-Methoxybenzyl ester (syn isomer) 350mg and 1
-Butylbenzimidazole 71 mg, 7- [2-
(2-tert-Butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (benz-3-N-butyl-
198 mg of 1-imidazoliomethyl) -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (CDCl ₃ ): 0.97 (3H, t, J = 6.0Hz), 1.48 (9H, s), 1.52 (6H, s), 1.
70 to 2.25 (4H, m), 3.75 (3H, s), 4.18 (2H, m), 4.40 (2
H, t, J = 6.0Hz), 5.16 (1H, d, J = 5.0Hz), 5.22 (2H, s),
5.72 (2H, m), 6.17 (1H, dd, J = 5.0,8.0Hz), 6.58 (1H,
s), 7.02 (4H, dd, J = 8.0,42.5Hz), 7.24 (15H, s), 6.65
~ 8.20 (7H, m) Example 91 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (benz-3-N-butyl-1-imidazoliomethyl) -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide ( Syn isomer) 195 mg, 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide} -3- (benz-3-N-butyl) 24.0 mg of -1-imidazoliomethyl) -3-cephem-4-carboxylate (syn isomer) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 0.92 (3H, t, J = 6.0Hz), 1.37 (3H, s), 1.41 (3H, s), 1.
27 (2H, m), 1.83 (2H, m), 3.15 to 3.75 (2H, m), 4.48 (2
H, t, J = 6.0Hz), 4.93 (1H, d, J = 5.0Hz), 5.42 (2H, s),
5.30 ~ 5.83 (1H, m), 6.67 (1H, s), 6.95 ~ 8.48 (4H,
m), 7.07 (2H, s), 10.00 (1H, s), 11.83 (1H, d, J = 8.0H
z) Example 92 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
350 mg and 1- (2-propenyl) benzimidazole 65 m
From g and 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3- (benz-3-N- (2 -Propenyl) -1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) (224.3 mg) was obtained.

NMR δ ppm (CDCl ₃ ): 1.40 (9H, s), 1.54 (6H, s), 3.66 (3H, s), 4.11 (2H,
m), 4.76 (2H, d, J = 6.3Hz), 5.02 (1H, d, J = 5.0Hz), 5.
23 (2H, s), 5.05 ~ 6.14 (2H, m), 6.37 ~ 6.70 (4H, m),
6.61 (1H, s), 7.04 (4H, dd, J = 8.0,42.5Hz), 7.26 (15
H, s), 6.65 to 8.15 (7H, m) Example 93 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-propenyl) -1
-Imidazoliomethyl] -3-cephem-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 200 mg, 7- {2- (2-aminothiazol-4-yl) -2 − [Potassium (2,2-
Dimethyl acetate) oxyimino] acetamide}-
11.5 mg of 3- [benz-3-N- (2-propenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.37 (3H, s), 1.39 (3H, s), 3.12 to 3.77 (2H, m), 4.87
(2H, d, J = 6.0Hz), 4.93 (1H, d, J = 5.0Hz), 5.02 to 5.74
(3H, m), 5.40 (2H, s), 5.74 to 6.34 (1H, m), 6,65 (1H,
s), 6.41 to 8.46 (4H, m), 7.10 (2H, s), 9.91 (1H, s), 1
1.90 (1H, d, J = 8.0Hz) Example 94 According to Example 4, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) 450 mg and 1- (2-propenyl) benz From 87 mg of imidazole, 7- [2-methoxyimino-2-
(2-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-propenyl)-
130 mg of 1-imidazoliomethyl] -3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.75 (3H, s), 3.80 (3H, s), 4.1 to 4.3 (2H, m), 4.45 (2
H, s), 4.90 to 5.10 (2H, m), 5.22 (4H, s), 5.45 (2H,
s), 5.5 to 5.65 (1H, m), 6.75 (1H, s), 7.25 (15H, s),
9.20 (1H, s) Example 95 7- [2-Methoxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-propenyl)-according to Examples 5, 6 and 7. 1-imidazoliomethyl] -3-cefm-1-
Oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 120 mg to 7- [2-
(2-Aminothiazol-4-yl) -2-methoxyiminoacetamido] -3- (benz-3-N- (2-propenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn 17 mg) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.10~3.70 (2H, m), 3.80 (3H, s), 4.1~4.3 (2H, m),
4.40 to 4.50 (2H, m), 4.98 (2H, d, J = 8.0Hz), 5.22 to 5.4
5 (4H, m), 6.75 (1H, s), 12.5 (1H.d, J = 8.0Hz) Example 96 According to Example 4, 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazole-4-)
Yl) acetamido] -3-iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer) (460 mg) and 1- (2-propenyl) benzimidazole (87 mg) -(2-
Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-propenyl) -1-imidazoliomethyl] -3-cephem-1-oxide -4-carboxylic acid p
-140 mg of methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (DMCO-d ₆ ): 3.75 (3H, s), 4.2 to 4.3 (4H, m), 4.45 (2H, s), 5.05 to
5.15 (4H, m), 5.22 ~ 5.45 (6H, m), 5.5 ~ 5.6 (2H, m),
6.75 (1H, s), 7.08 to 7.15 (4H, m), 7.25 (15H, s), 9.20
(1H, s) Example 97 7- [2- (2-Propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamide] -3- [benz-3-N according to Examples 5, 6 and 7.
-(2-Propenyl) -1-imidazoliomethyl] -3
-Chem-1-oxid-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 130 mg
From 7- [2- (2-aminothiazol-4-yl)
-2- (2-Propenyloxyimino) acetamide]
26 mg of -3- [benz-3-N- (2-propenyl) -1-imidazoliomethyl] -3-cefm-4-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 3.60 to 3.65 (2H, m), 4.2 to 4.3 (4H, m), 4.45 (2H, s),
5.05 ~ 5.15 (4H, m), 5.22 ~ 5.45 (4H, m), 5.5 ~ 5.6 (2
H, m), 6.75 (1H, s), 12.5 (1H, d, J = 8.0Hz) Example 98 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
502 mg and 1- (2-butenyl) benzimidazole 103 mg
And 7- [2- (2-tert-butoxycarbonyl)
Prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-butenyl) -1-imidazoliomethyl] -3-cephem-1- Oxide-4-carboxylic acid p
-410 mg of methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.34 (9H, s), 1.44 (3H, s), 1.7 (3H, s), 4.7-4.85 (3
Hm), 5.30 (2H, s), 5.5 ~ 5.9 (3H, m), 6.60 (1H, s),
7.25 (15H, s), 9.20 (1H, s) Example 99 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- [benz-3-N- (2-butenyl) -1-
Imidazoliomethyl] -3-cefm-1-oxide-
4-Carboxylic acid p-methoxybenzyl ester / iodide (syn isomer) 280 mg was used to prepare 7- {2- (2-aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamide. } -3
21.5 mg of-[benz-3-N- (butenyl) -1-imidazoliomethyl] -3-cefm-1-carboxylate (syn isomer) were obtained.

NMR δ ppm (DMSO-d ₆ ): 1.38 (3H, s), 1.41 (3H, s), 1.7 (3H, s), 4.7-4.85 (3
H, m), 5.30 (2H, s), 5.5 ~ 5.9 (3H, m), 6.60 (1H, s),
9.80 (1H, s), 12.50 (1H, d, J = 8.0Hz) Example 100 According to example 44, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-tritylaminothiazol-4-yl) acetamide] -3
-Iodomethyl-3-cefm-1-oxide-4-carboxylic acid p-methoxybenzyl ester (syn isomer)
From 502 mg and 1- (3-methyl-2-butenyl) benzimidazole 111 mg, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2-
Tritylaminothiazol-4-yl) acetamide]
-3- [benz-3-N- (3-methyl-2-butenyl) -1-imidazoliomethyl] -3-cefm-1-
380 mg of oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.34 (9H, s), 1.39 (6H, s), 1.80 (6H, s), 4.7-4.85
(3H, m), 5.30 (2H, s), 5.3 to 5.6 (2H, m), 6.60 (1H,
s), 7.25 (15H, s), 9.20 (1H, s) Example 101 According to Examples 45 and 46, 7- [2- (2-tert-butoxycarbonyl) prop-2-oxyimino-2- (2
-Tritylaminothiazol-4-yl) acetamido] -3- (benz-3-N- (3-methyl-2-butenyl) -1-imidazoliomethyl) -3-cefm-1
-Oxide-4-carboxylic acid p-methoxybenzyl ester iodide (syn isomer) 260 mg, 7- {2
-(2-Aminothiazol-4-yl) -2- [potassium (2,2-dimethylacetate) oxyimino] acetamido} -3- [benz-3-N- (3-methyl-2-)
12.6 mg of butenyl) -1-imidazoliomethyl] -3-cefm-1-carboxylate (syn isomer) was obtained.

NMR δ ppm (DMSO-d ₆ ): 1.38 (6H, s), 1.80 (6H, s), 4.7-4.85 (3H, m), 5.30
(2H, s), 5,3 to 5,6 (2H, m), 6,60 (1H, s), 9.80 (1H,
s), 12.50 (1H, d, J = 8.0Hz) Example 102 7- [2- (2-propenyloxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3-iodomethyl-3-cefm-4-carboxylic acid p-obtained in Example 2 214.4 g of methoxybenzyl ester (syn isomer) was dissolved in a mixed solvent of chloroform (600 ml) and acetonitrile (1000 ml), and 1- (2-
Propenyl) imidazole (41.1 g) is added. After the addition is complete, warm to room temperature and stir for an additional 4 hours. After distilling off the solvent under reduced pressure, the residue was purified with a silica gel column (chloroform-methanol, volume ratio 3: 1) and the eluate containing the target substance was collected and the solvent was distilled off to give 7- [2- (2-propenyl Oxyimino) -2- (2-tritylaminothiazol-4-yl) acetamido] -3- [3- (2
-Propenyl) -1-imidazoliomethyl] -3-cem-4-carboxylic acid p-methoxybenzyl ester
268 g of iodide (syn isomer) was obtained.

_{NMR δ ppm (DMSO-d 6} ): 3.55 (2H, s), 3.77 (3H, s), 4.58 (2H, d, J = 5.0Hz), 4.
87 (2H, d, J = 5.0Hz), 4.98 ~ 5.60 (9H, m), 5.62 ~ 6.35
(3H, m), 6.76 (1H, s), 7.12 (4H, dd, J = 8.0Hz, 32.5H
z), 7.32 (15H, s), 7.68 (1H, s), 7.75 (1H, s), 9.28
(1H, s), 9.27 (1H, s), 9.58 (1H, d, J = 8.0Hz) Next, in order to show the usefulness of the compound (I) of the present invention, typical compounds of the compound (I) of the present invention The test data of the in vitro antibacterial activity of is shown below.

Test: In vitro antibacterial activity Test compound: A: compound of Example 7 B: compound of Example 15 C: compound of Example 17 D: compound of Example 19 E: compound of Example 73 F: of Example 33 Compound G: Compound of Example 37 H: Compound of Example 46 I: Compound of Example 48 J: Compound of Example 52 K: Compound of Example 56 L: Compound of Example 64 M: Compound of Example 77 N: compound of Example 79 O: compound of Example 81 P: compound of Example 83 Q: compound of Example 85 R: compound of Example 87 S: compound of Example 89 T: compound of Example 91 : Compound of Example 93 V: Compound of Example 95 W: Compound of Example 97 X: Compound of Example 99 Y: Compound of Example 101 Test method In vitro antibacterial activity was determined by the following double agar plate dilution method. I asked. 0.005 ml of the test strain (the number of surviving bacteria: about 10 ⁸ / ml), which was obtained by culturing each test strain in the broth for sensitivity measurement for 20 hours.
Was inoculated into an agar medium for sensitivity measurement containing various concentrations of antibacterial agents, and after incubating at 37 ° C for 20 hours, the minimum inhibitory concentration (MI
C) was measured in units of μg / ml. The results are shown in Table 1.

Test Example No. 17 above except that the compounds of Example 39 and Comparative Example 1 were used.
By the same test method as described on page 4, the minimum inhibitory concentration (MI
C) was measured in units of μg / ml. The results are shown in Table 2.
The compound of Comparative Example 1 is the compound of Example 3 of JP-A-60-97982.

As described above, there is a large difference in antibacterial activity in Staphylococcus aureus 209P of Gram-positive bacteria, and other Gram-negative bacteria are not particularly large, but overall the compound of Example 39 It is clear that the antibody activity is better.

Front page continuation (72) Inventor Akihiro Shimabayashi 463 Kagasuno, Kawauchi Town, Tokushima City, Tokushima Prefecture (56) In the Tokushima Plant of Otsuka Chemical Co., Ltd. (56) Reference JP-A-60-97984 (JP, A) JP-A-60 -97982 (JP, A) JP-A-58-4789 (JP, A) JP-A-48-19591 (JP, A) JP-B-40-6467 (JP, B1)

Claims (4)

[Claims] 1. A general formula [In the formula, R ¹ represents an amino group which may be substituted with a trityl group. R ² is an alkenyl group having 2 to 4 carbon atoms, 1 to 4 carbon atoms
Alkyl groups or groups (In the formula, R ⁶ and R ⁷ represent an alkyl group having 1 to 4 carbon atoms. R ⁸ represents an alkali metal or a carboxyl group-protecting group.) A is a group forming an imidazolium ring (In the formula, R ³ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. R ⁴ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an alkyl group having 2 to 6 carbon atoms which may be substituted with a halogen atom. Having an alkenyl group, an alkynyl group having 2 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an alkanoyl group having 1 to 4 carbon atoms in the alkyl portion, a benzyl group, an acetyl group or a hydroxyl group on the phenyl ring Good phenyl group or group-CH ₂ COOR ⁹
(In the formula, R ⁹ represents an alkyl group having 1 to 4 carbon atoms or an alkali metal atom). X represents a halogen atom. ) B
Constitutes the imidazolium ring (In the formula, R ⁵ represents a hydrogen atom or an alkylamino group which may be substituted with a trityl group and whose alkyl moiety has 1 to 4 carbon atoms). n represents 0 or 1. However,
B is , R ² and R ⁴ must not both be methyl groups. ] The cephalosporin compound and the pharmacologically acceptable salt which the 3rd position of the cephem shown by these was substituted by the imidazolium ring. 2. General formula (II)(R in the formula¹, R²And n have the same meanings as above, R^Ten
Is hydrogen atom, metal atom, ester residue, salt forming cation
Or COO^-Forms an intra- or extra-molecular salt with a cation pair
When it shows an anion charge. X is a substituted or unsubstituted i
Halogen substitutable by imidazole compound (III)
An atom or a group such as an acid residue)
General formula (III)(Wherein A and B have the same meanings as described above)
General formula (IV)(R in the formula¹, R², R^Ten, A, B, X And n are the same as above
Meaning) Cefalosporin compound or salt thereof
And further cephalosporin represented by the general formula (IV)
Reduction or deprotection of compounds or their salts as necessary
General formula (I) characterized by being attached to a group reaction(R in the formula¹, R², n, A and B have the same meanings as above.
Or a salt thereof
Manufacturing method. 3. General formula (V)(R in the formula^Ten, A, B, X And n have the same meanings as described above.
A) and a general formula (VI)(R in the formula¹And R²Is the same meaning as above)
General formula (IV)(R in the formula¹, R², R^Ten, A, B, X And n are the same as above
Cefalosporin compound represented by
Of the cephalos of the general formula (IV)
If necessary, reduce porin compounds or their salts or
General formula (I) characterized by being attached to a deprotecting group reaction, etc.(R in the formula¹, R², n, A and B have the same meanings as described above.
Of the cephalosporin compound or its salt
Production method. 4. The general formula (I) A prophylactic / therapeutic agent for bacterial infection, which comprises a cephalosporin compound represented by the formula (wherein R ¹ , R ² , n, A and B have the same meanings as described above) or a salt thereof.