Biochemie Gesellschaft M.b.h

Sandoz Ag

Sandoz Gmbh

Siegfried Wolf

Johannes Ludescher

Hubert Sturm

Peter Kremminger

Bernhard C Prager

Julia Greil

Klaus Totschnig

Harald Summer

Rainer Pucher

Werner Veit

Martin Decristoforo

Ludwig Miller

This invention provides processes for preparing cefepime, including crystalline intermediates of Formula V. 

Processes for the preparations of cefepime

7-[2-(2-aminothiazol-4-yl)-2-(methylcarbonyloxyimino)acetamido]-3-vinyl-cephem-4-carboxylic acid of formula (I), in the form of a crystalline salt and use thereof, e.g. in the preparation of pure cefdinir. In another aspect this invention relates to the compound of formula (I) in the form of a salt, optionally in crystalline form, wherein the salt is selected from the group consisting of phosphate, hydrogen phosphate, mesylate, tosylate, sulfate, hydrogen sulfate and sulfamate. 

Cefdinir intermediate

A salt of PACA with an amidine and its use in the production of cefprozil.

Intermediates in cefprozil production

7-[2-(2-aminothiazol-4-yl)-2-(methylcarbonyloxyimino)acetamido]-3-vinyl-cephem-4-carboxylic acid of formula I in the form of a crystalline salt and use thereof, e.g. in the preparation of pure cefdinir. In another aspect this invention relates to the compound of formula I in the form of a salt, optionally in crystalline form, wherein the salt is selected from the group consisting of phosphate, hydrogen phosphate, mesylate, tosylate, sulfate, hydrogen sulfate and sulfamate.

The novel intermediate compound crystalline 7-[2-(2-fomylaminothiazol-4-yl)-2 -(Z)-(methoxyimino)acetamido]-3-methoxymethyl-3-cephem-4-carboxylic acid-1 -(isopropoxy/crystallization of cefpodoxime proxetil. The crystallization process comprises dissolving or suspending the intermediate in the presence of a nitrile or a ketone or mixtures thereof; at a ratio of 1 gm of the intermediate to 2-15 ml nitrile; or at a ratio of 1 gm of the intermediate to 3-15 ml ketone; in the presence of 5-80 ml water; and thereafter isolating the intermediate in crystalline form and converting the intermediate by splitting off the formyl group from the amino group attached to the thiazolyl group, to obtain the desired product cefpodoxime proxetil, in the form of a diastereoisomeric mixture in a ratio of B/(A+B) of 0.5 to 0.6.

Crystalline &#x3b2;-lactam intermediate

Cephalosporin intermediates

Process for the preparation of cefpodoxime proxetil diastereoisomers

Cefdinir in the form of a salt with dicyclohexylamine, a process for its production and its use in the purification of impure cefdinir.

Crystalline amine salt of cefdinir

The invention relates to a new process for the depletion of 7-amino-3-&lsqb;(E)-1-propen-1-yl&rsqb;-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-&lsqb;(Z)-1-propen-1-yl&rsqb;-3-cephem-4-carboxylic acid and 7-amino-3-&lsqb;(E)-1-propen-1-yl&rsqb;-3-cephem-4-carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-&lsqb;(z/E)-1-propen-1-yl&rsqb;-3-cephem-4-carboxylic acid or by adsorption chromatography.

Process for the purification of a 3-cephem-4-carboxylic acid derivative

Crystalline 2-(amninothiazol-4-yl)-2-(tert.butoxycarbonylmethoxyimino)acetic acid-S-mercapto-benzo-thiazolylester in form of an N,N-dimethylacetamide solvate; a crystalline salt of a 7-&lsqb;2-(aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido&rsqb;-3-vinyl-3-cephem-4-carboxylic acid with an amine of formula N(R,)(R,)(R,), wherein R,, R,, and R,have various meanings, a crystalline sulphuric acid addition salt of a 7-&lsqb;2-(2-aminothiazol-4-yl)-2-carboxymethoxyimino)acetamido&rsqb;-3-vinyl-3-cephem-4-carboxylic acid; and the use of these salts in the production of cefixime, e.g. in form of a trihydrate.

Purification process

Separation of cephalosporin isomers

The invention relates to a new process for the depletion of 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-[(Z)-1-propen-1-yl]-3-cephem-4-carboxylic acid and 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-[(Z/E)-1-propen-1-yl]-3-cephem-4-carboxylic acid or by adsorption chromatography.

The invention relates to a new process for the depletion of 7-amino-3-�(E)-1-propen-1-yl!-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-�(Z)-1-propen-1-yl!-3-cephem-4-carboxylic acid and 7-amino-3-�(E)-1-propen-1-yl!-3-cephem-4 carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-�(Z/E)-1-propen-1-yl!-3-cephem-4-carboxylic acid or by adsorption chromatography.

A p-toluenesulphonic acid salt of 7-�2-(2-aminothiazol-4-yl)-2-(Z)-hydroximino-acetamido!-3-N,N-dimethylcarb amoyloxymethyl-3-cephem-4-carboxylic acid (isopropoxycarbonyloxy)ethylester, e.g. of formula ##STR1## its use in the production of other salts and a pharmaceutical composition containing it.

Purification of a cephalosporin salt

A p-toluenesulphonic acid salt of 7-[2-(2-aminothiazol-4-yl)-2-(Z)-hydroximino-acetamido]-3-N,N-dimethylcarb amoyloxymethyl-3-cephem-4-carboxylic acid (isopropoxycarbonyloxy)ethylester, e.g. of formula ##STR1## its use in the production of other salts and a pharmaceutical composition containing it.

Growing community of inventors

Brixlegg, Austria

Siegfried Wolf