KR830007698A - Method for preparing ammoniomethyl compound - Google Patents

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Method for preparing ammoniomethyl compound

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Claims (12)

a compound of formula (II) wherein n is 0 or 1, R ₁ is as defined in formula (I), 7β-amino group is optionally protected by the group undergoing acylation, and 4-carboxy group is optionally protected In which the 7β-amino group is acylated by reaction with an acylating agent which adds an acrylic group of the carboxylic acid of formula (III) in which Am, T and R ₂ are as defined in formula (I), and the functional group is optionally protected To prepare a compound of formula (I) wherein n is 0, Am, T, R ₁ and R ₂ are as defined in formula (I), and 4-carboxyl groups and other functional groups are optionally protected ( Isomerized to form the corresponding 3-cefe compound, or n is 0 or 1, Am, T and R ₁ are as defined in formula (I), 4-carboxyl group and It was the compound of formula (ⅴ) the other functional group is optionally protected group R ₂ is the same as defined in formula (I), Neunggi group is optionally protected formula H ₂ NOR ₂ (Ⅵ) hydroxylamine derivative and reaction to, or of, and n is 0 or 1 for R ₂ is the preparation of compounds of formula (I) hydrogen, Am, T and R ₁ is as defined in formula (I) and reacts a compound of formula IV wherein the 4-carboxyl group and other functional groups are optionally protected with a nitrogenating agent, or Am is a free or secondary amine group, and T To prepare a compound of formula (I) wherein a represents a 1,2,4-thiadiazole group bonded in the group of the formula-(C = NOR ₂ ) at the 5 position Am and the 3 position, n is -0 or 1, X ₁ represents hydrogen, halogen, or hydroxy, R ₁ is as defined in formula (I), and the compound of formula (VII) wherein 4-carboxyl group and other functional group is optionally protected Acid or isothiocyanate or hydrogen, reacted with dithiocyanogen, or n is 0 Or 1, Am, T and R ₂ are as defined in formula (I), X ₂ represents a group which may be substituted by nucleophilic substitution, and 4-carboxyl group and other functional group are optionally protected To react a compound of with a organic tertiary base corresponding to the group R ₁ or to prepare a compound of formula (I) wherein Am is a primary, secondary or tertiary amino group, n is 0 or 1, and T is , R ₁ and R ₂ are consistent with the definition of formula (I), and react a compound of formula (Y) wherein Y is hydrogen with ammonia or with primary or secondary amine Am-H or metal amides thereof If necessary, the compound of formula (I) is converted to a different compound of formula (I) or, if necessary, the compound of formula (I) with n is 0, Or a compound of formula (I) with n equal to 1 or a compound of formula (I) with n equal to 0 or In the product compound of formula (I), the functional group present in the protective form is converted into a free function group, or the product salt is converted into a free compound or another salt of formula (I), or a product glass structure having a salt-forming group ( 7β-aminothiadiazolylacetylamino-3-ammoniomethyl-3-cepem of formula (I), characterized in that the compound of I) is converted to a salt or the product mixture of this property is separated into their respective isomers. A process for preparing salts of -4-carboxylic acid compounds or their compounds having salt forming groups. In the above formula n is 0 or 1 Am represents unsubstituted or substituted amino, T is a thiadiazole group in which Am is bonded to one carbon atom and the structural formula-(C = NOR ₂ )-is bonded to another carbon atom. R ₁ represents an unsubstituted or substituted pyrazolio group, an unsubstituted or substituted thiaziolio group, a tert-lower alkyl amonioser group or a pyridinio group of the formula (A), R ₂ represents hydrogen, unsubstituted or substituted loweralkyl or cycloalkyl or unsubstituted or substituted carbamoyl, R ^a is substituted with cycloalkyl, phenyl, hydroxy, lower alkoxy, halogen, cyano, carbamoyl, carboxyl or sulfosubstituted lower alkyl, unsubstituted lower alkenyl or lower alkylthio, or lower alkenyl or carboxyl Carbamoyl monosubstituted with amino, di-loweralkylamino, loweralkylhydroxy-loweralkyl, loweralkoxy, hydroxy or cyano, monosubstituted with substituted lower alkylthio, lower alkyl, lower alkanoyl or aminobenzenesulfonyl, Thiocarbamoyl, cycloalkyl, phenyl, hydroxy, lower alkoxy, halogen, lower alkoxycarbamoyl, lower alkanoyloxy, lower alkanoyl, carboxyl, sulfo, cyano, nitro or hydroxy sulfo-lower alkyl, R ^b is the same as carbamoyl or hydrogen or R ^a , R ^c is the same as hydrogen or R ^a . 2. A compound according to claim 1, wherein n is 0, Am is amino, lower alkylamino, di-lower alkylamino or protected amino and T is at one carbon atom of Am and the other carbon atom of the formula-(C = NOR ₂ )- A thiadiazole group bonded to a group, R ₁ is 2-lower alkyl-1-pyrazolo, 2-carboxy-lower alkyl-1-pyrazolo, 1-carboxy-lower alkyl-1-pyrazolo, 2 Lower alkoxycarbonyl-lower alkyl-1-pyrazolo, 3-lower alkyl-1-triazolethio and R ^a is cycloalkyl, phenyl, hydroxy lower alcohol group, halogen, cyano, carbamoyl, carboxyl, Or lower alkyl substituted by sulfo, unsubstituted lower alkenyl or lower alkylthio or lower alkylthio substituted by lower alkenyl or carboxyl, unsubstituted amino or lower alkyl, lower alkanoyl or aminobenzenesulfonyl Substituted amino, di-lower alkylamino, lower alkyl, hydroxy lower alkyl, lower alkoxy, DE hydroxy or cyano single substituted carbamoyl, di-lower alkyl carbamoyl; Thiocarbamoyl; Cycloalkyl; Phenyl; Hydroxy; Lower alkoxy; halogen; Lower alkoxycarbonyl; Lower alkanoyl; Carboxyl; Sulfo; Cyano; Nitro or hydroxy sulfo-lower alkyl, R ^b represents carbamoyl or hydrogen or is the same as R ^a, and R ^c is hydrogen, and R ₂ is hydrogen, unsubstituted or substituted lower alkyl or cyanoalkyl, or unsubstituted Or a method of preparing a pharmaceutically toxic salt of the formula (I) having a substituted carbamoyl, in particular a compound of formula (I) representing a group of formula = NOR ₂ having a Syn (or Z) structure or a salt forming group . 3. A compound according to claim 2, wherein n is 0, Am is amino, lower alkylamino (e.g. methylamino) or protected amino, and T is a structural formula-(C = NOR ₂ )- A group to which a thiadiazole group is bonded, R ₁ is 2-lower alkyl-1-pyrazolethio (e.g. 2-methyl-1-pyrazolethio), 2-carboxy-lower alkyl-1-pyrazolio ( Eg, 2-carboxy-methyl-1-pyrazolo), 1-carboxy-lower alkyl-1-pyrazoloio (eg, 1-carboxymethyl-1-pyrazolo), 2-lower alkoxycarbonyl-lower Alkyl-1-pyrazolio (e.g. 2-methoxycarbonylmethyl-1-pyrazolio), 3-lower alkyl-1-triaziole (e.g. 3-methyl-1-triaziolio) or hydride The oxy-lower alkylpyridinio (eg 3- or 4- hydroxy methyl pyridinio) values are given by the pyridinio group of the formula (A), the lower alkoxy-lower alkylpyridinio (eg 4-methoxymethyl Pyridinio), cyano-uvbalkylpyridinio (eg, 3-cyanomethylpyridi O), carboxy-lower alkylpyridinio (e.g. 3-carboxymethylpyridinio), sulfo-lower alkylpyridinio (e.g. 4- (2-sulfoethyl) -pyridinio), carboxy lower alkenyl Pyridinio (e.g. 3- (2-carboxyvinyl) -pyridinio), carboxy-lower alkylthiopyridinio (e.g. 4-carboxymethylthiopyridinio), thiocarbamoylpyridinio (e.g., 4-thiocarbamoylpyridinio), halopyridinio (e.g. 3-bromo- or 4-bromo-pyridinio), carboxypyridinio (e.g. 4-carboxypyridinio), sulfopyrididi Nio (e.g. 3-sulfopyridinio), cyanopyridinio (e.g. 3-cyanopyridinio), carboxy-lower alkylcarbamoylpyridinio (e.g. 3-carboxymethyl-4-carbamoyl Pyridinio), aminocarbomoylpyridinio (e.g. 2-amino-5-carbamoylpyridinio), carboxycarbamoylpyridinio (e.g. 3-carboxy-4-carbamoylpyridinio), sia No-halomethylpyridinio (eg 3-cyano-4-tri Fluoromethylpyridinio), or aminocarboxypyridinio (e.g. 2-amino-3-carboxypyridinio), R ₂ is hydrogen, lower alkyl (e.g. methyl), carboxy-lower alkyl (e.g. , 2-carboxy-propyl), carbamoyl, lower alkylcarbamoyl (e.g. methylcarbamoyl), or amino lower alkyl (e.g. 2-aminoethyl), general formula = NOR ₂ group with Syn (or Z) structure A process for preparing a salt of a pharmaceutically toxic compound of formula (I) having a compound of formula (I) or a salt forming group. The method of claim 3, n represents 0, Am represents amino, T represents a 1,2,4-thiadiazole group in which the structural formula-(C = NOR ₂ ) -group is bonded at the 5 position Am and the 3 position, R ₁ is 2-hibibalkyl- ₁ -pyrazoloio (e.g. 2-methyl-1-pyrazoloio), 2-carboxy-lower alkyl-1-pyrazoloio (e.g. 2-carboxymethyl-1-pyra) Zolio), 2-lower alkoxycarbonyl-lower alkyl-1-pyrazoloio (e.g. 2-methoxy-carbonylmethyl-1-pyrazolio), 3-lower alkyl-1-thiazio (e.g. Pyridinio groups of the formula A, such as 3-methyl-1-triazioio) or hydroxy-uvalkylpyridinio (eg 4-hydroxymethylpyridinio), carboxy-lower alkylpyridinio (eg , 3-carboxymethylpyridinio), sulfo-lower alkylpyridinio (e.g. 4- (2-sulfoethyl) -pyridinio), halopyridinio (e.g. 3-bromopyridinio), carboxy Pyridinio (eg 4-carboxypyridinio), sulfopyridinio (eg 3-sulfopyridinio) or aminocarbamoylpyridinio (eg 2-amino-5-carbamoylpyridinio) , R ₂ is hydrogen, lower alkyl (eg methyl), carboxy-lower alkyl (eg 2-carboxy-2-propyl), carbamoyl or lower alkyl carbamoyl (eg methyl carbamoyl), Syn (or Z) structure formula = process for preparing a salt of a non-toxic compound with a pharmaceutical compound or formula (I) of formula (I) represents a group of NOR ₂ having a. The method of claim 4 n represents 0, Am represents amino T represents a 1,2,4-thiadiazole group in which the structural formula-(C = NOR ₂ ) -group is bonded at the 5 position Am and the 3 position, R ₁ is a structural formula such as 2-lower alkyl- ₁ -pyrazoloio (e.g. 2-methyl-1-pyrazoloio) or hydroxy-uvbalkylpyridinio (e.g. 4-hydroxymethyl-pyridinio) A pyridinio group of A, a carboxy-lower alkylpyridinio (eg, 3-carboxymetapyridinio), a halopyridinio (eg, 3-bromopyridinio), or a carboxypyridinio (eg, 4 Carboxypyridinio), R ₂ is lower alkyl (eg methyl) or carboxy-lower alkyl (eg 2-carboxy-2-propyl) or aminocarbamoylpyridinio (eg 2-amino-5-carbamoylpyridinio), Syn (Or Z) A process for preparing a salt of a compound of formula (I) or a pharmaceutically toxic compound of formula (I), which represents a group of structure = NOR ₂ -having a structure. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (4-carboxypyridine according to claim 5 Process for preparing dinimethyl) -3-cepem-4-carboxylate. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-carboxyprop-2-yloxyiminoacetamido-3- (3-carboxymethylpyridiniomethyl-3-cepem-4-carboxylate. 7β- [2- (5-amino-1, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (2-methyl- A process for preparing 1-pyrazolomethyl) -3-cepem-4-carboxylate. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (4- (2) -Sulfoethyl) -Pyridiniomethyl) -3-cepem-4-carboxylate. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (2-amino- 5-Carbamoylpyridiniomethyl) -3-cepem-4-carboxylate. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (3-bromofur according to claim 5 Process for preparing lidiniomethyl) -3-cepem-4-carboxylate. 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (4-hydroxy according to claim 5 Method for preparing methylpyridiniomethyl) -3-cepem-4-carboxylate. ※ Note: The disclosure is based on the initial application.