DD151942A5 - PROCESS FOR THE PREPARATION OF AMINO-THIADIAZOLYL COMPOUNDS - Google Patents

Abstract

7 beta-Aminothiadiazolylacetamido-3-cephem-4-carboxylic acid compounds of the formula I, wherein Am represents an optionally protected amino group, R & ind1! is hydrogen, optionally substituted lower alkyl or cycloalkyl or optionally N-substituted carbamoyl, R & ind2! Hydrogen or lower alkoxy means R & ind3! represents hydrogen, acyloxy or heterocyclylthio, and R & ind4! represents an optionally protected carboxyl group, and salts of such compounds having a salt-forming group are prepared by various methods known per se. The compounds have excellent antibiotic properties. In the form of pharmaceutical preparations for parenteral administration, they can be used to treat bacterial infections.

Description

Berlin, 27.11. 1980 AP C 07 D / 222 421 57 771/18 </ P> <p> Process for the preparation of amino thiadiazolyl Compounds en </ P> The invention relates to a process for the preparation of novel 7β-aminothiadoxG.zolyl-acetamido-3-cephem-4-carboxylic acid compounds, pharmaceutical compositions containing such compounds and their use as antibiotics. </ P> <p> Characteristic of the known technical Loί </ P> <P> <I> In DE-OS 2 745 246 describes certain 7β-thiadiazolylacetamido-3-cephem-4-carboxylic acid compounds having an anti-biotic effect. </ P> The aim of the invention is the provision of new compounds with improved antibiotic activity. </ P> The object of the invention is to find compounds with the desired properties and to develop processes for their preparation. </ P> <p>, -Vft- 27.11.1980 </ P> <P> <Sup>; </ sup> AP G 07 D / 222 421 </ P> <p> 57 771/18 </ P> According to the invention, in particular 7β-aminothiadiazolyl-aeetamido-3-cephem-4 ° -carboxylic acid compounds of the formula </ P> <p>: Λ </ P> <P> Ν_ <Sub> e </ sub> _ c-- COlIH --- j 'Am- \ N N \ -. ^ ~ <Sup> Oil </ Sup> 2 ~ <Sup> K </ Sup> 3 </ P> <p> \ q / I I </ P> OR, R, </ P> <P> produced </ P> Compared to the known compounds, the compounds <I> the This invention is an improvement in that it is surprisingly distinguished by a particularly outstanding antibiotic activity. This excellent activity is particularly surprising because the compounds of the present invention are not among the preferred embodiments of DB-OS 2 745 246, </ P> <p> ~ Ί- 27.11 * 1980 </ P> <p> *, AP C 07 D / 222, 421 </ P> <p> 57 771 / Ί8 </ P> In Formula I, Am represents an optionally protected amino group, R. represents hydrogen, optionally substituted lower alkyl or cycloalkyl, or optionally n-substituted carbamoyl, Rr > R 1 represents hydrogen or acyl oxy or heterocyclylthio, and R 1 represents an optionally protected carboxyl group. Furthermore, salts of those compounds which have a salt-forming group are prepared pharmaceutical agents and their use * </ P> In the present specification of the invention, the term "lower" as used in the context of definitions of groups and compounds means "z" in groups of lower alkyl, lower alkyl, lower alkoxy, lower alkylanoyl or lower alkylamino or compounds such as lower Alcohol and the like, that the corresponding groups or compounds, unless expressly defined otherwise, contain up to 6, preferably up to 4 carbon atoms. « </ P> An optionally protected amino group Am is a primary, secondary or tertiary amino group, such as amino, lower alkylamino or di-lower alkylamino, where the primary or secondary amino groups, as indicated below, may be protected in a lower alkyl or lower alkyl group. </ P> <p> kylamino group contains lower alkyl 1-4 C atoms and is, for example, methyl, 'ethyl 1, propyl' or butyl. Am is preferably optionally protected amino or methylamino. </ P> <p> A lower alkyl group R, preferably contains 1-4. C atoms and is, for example, ethyl, propyl, butyl or especially methyl. </ P> <p> A cycloalkyl group R <Sub> 1 </ sub> preferably contains 3-8. primarily 3-6 ring members, and is e.g. Cyclobutyl, cyclopentyl or cyclohexyl, and especially cyclopropyl. </ P> <p> Substituents of substituted lower alkyl or cycloalkyl R are, inter alia. optionally etherified hydroxy, 2.B. Lower alkoxy, primary, secondary or tertiary amino era, e.g. Amino or Diniederalky lamino, optionally functionally modified, including esterified, amidated or protected carboxyl or sulfo, and optionally by lower alkyl N-substituted ureidocarbonyl. Preferably, the substituted lower alkyl and cycloalkyl groups are substituted by a carboxyl or sulfo group, preferably on the carbon atom connected to the oxygen atom of the oxyimino group. Such substituted lower alkyl and cycloalkyl groups R <Sub> 1 for example, 2-aminoethyl; 2-dimethylaminoethyl, carboxymethyl, 1- or 2-carboxyethyl, 1-, 2- or 3-carboxyprop-1-yl, 1-, 2- or 3-carboxyprop-2-yl, 1-carboxybut-1-yl, 1 -Carboxycycloprop-l-yl and 1-carboxycyclobut-1-yl / and corresponding sulfo-substituted lower alkyl and cycloalkyl groups. </ P> <p> The carboxy and sulfo groups in the radical R, can </ P> <P> <I> A- </ I> 11/27/1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <P>. , <Sub> J; </ sub> iff </ P> For example, by Ni'ederalkyl, such as methyl or ethyl, or, one of the physiologically cleavable groups, 2. B <Sub> 0 </ sub> pivaloyloxymethyl, esterified or by an aniine, vde IJH, or a primary or secondary am in, such as a mono - or di-lower alkylamino, or the methylol or ethylamine, or'dimethyl- or diethylamine be amidated, or, as indicated for R., in a primary eidocarbonyl group in the radical R <Sub> 1 The two nitrogen atoms can independently of each other by Ni ed er alkyl 5 v / ie methyl or ethyl <I> <Sub> t </ Sub> </ i> be substituted. Such groups are for example ureidocarbonyl or 1,3-dimethylureldocarbonyl </ P> Optionally N-substituted carbamoyl as R, is a group ~C (= O) -> NHR, v / orin R hydrogen, lower alkyl, <I> z <Sub> e </ Sub> </ I> B. Methyl, ethyl or 1- or 2-propyl, optionally protected carboxy-lower alkyl, z <Sub> e </ sub> carboxyethyl, 1- or 2-carboxyethyl or 1- <Sub> f </ Sub> <I> 2- </ i> or 3-carboxypropyl, wherein carboxy is protected by one of the usual carboxy-protecting groups, for example by lower alkyl, z, B <Sub> 0 </ sub> methyl, ethyl, · n ~ "or · iso-propyl, or n- or tert <Sub> 0 </ sub> Butyl may be esterified, optionally protected sulfonoloweralkyl <Sub> f </ sub> z. B <Sub> e </ sup> Su-methyl, 1- or 2-sulfatoethyl or 1-, 2- or 3-sulfopropyl, wherein SuIfo is protected by one of the usual sulfo protecting groups <Sub> f For example, by lower alkyl, z, B, methyl or ethyl, may be esterified, optionally protected hydroxy lower alkyl, ζ, B <Sub> c </ sub> hydroxymethyl <Sub> f </ sub> 2-hydroxyethyl or <I> 2- </ i> or 3-hydroxypropyl, wherein hydroxy may be protected by one of the usual hydroxy protecting groups, such as B * acylated, such as acetylated, optionally protected amino-lower alkyl <Sub> f </ sub> z. <Sub> e </ Sub> <I> B " 2-aminoethyl, 2-or 3-yn-inopropyl or 2-yl <Sub> s </ sub> 3- or 4-amino-butyl, wherein amino may be protected by one of the usual amino-protecting groups, may be acylated, such as acetylated, aryl-lower alkyl, for example phenyl-lower alkyl, z *. B <Sub> e </ sub> benzyl or 1- or 2-phenylethyl, halo-lower alkylene.1, for example, fluorine, chlorine or bromine </ P> <p> alkyl, e.g. 2-chloroethyl, 3-chloropropyl or 4-chlorobutyl, or wherein R is aryl, e.g. Phenyl or lower alkyl, e.g. • methyl, lower alkoxy, e.g. Methoxy, halogen, e.g. Chloro or nitro, mono- to trisubstituted phenyl. </ P> <p> A lower alkoxy group R <Sub> 2 It preferably contains 1-4 C atoms and is for example ethoxy, propoxy, butoxy, or in particular methoxy. </ P> <p> In an acyloxy group R <Sub> 0 For example, acyl is the acyl radical of an optionally substituted lower aliphatic carboxylic acid, a lower alkoxycarboxylic acid, a lower alkanesulfonic acid, an aromatic sulfonic acid, an aromatic carboxylic acid, an aryl-substituted lower alkanecarboxylic acid or an optionally N-substituted carbamic acid. </ P> <p> Such acyloxy groups R_ are, for example, lower alkanoyloxy, especially acetyloxy, furthermore formyloxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy, hexanyloxy, heptanoyloxy, pivaloyloxy, acetoacetoxy, oxalyloxy, succinyloxy and the like, lower alkoxycarbonyloxy, such as methoxycarbonyloxy, ethoxycarbonyloxy, propoxycarbonyloxy, l-cyclopropylethoxycarbonyloxy, isopropoxycarbonyloxy, butoxycarbonyloxy, tert-butoxycarbonyloxy, pentyloxycarbonyloxy, tert-pentyloxycarbonyloxy, hexyloxycarbonyloxy and the like, lower alkanesulfonyloxy such as mesyloxy, ethanesulfonyloxy, propanesulfonyloxy, isopropanesulfonyloxy, butanesulfonyloxy and the like, arenesulfonyloxy such as benzoxensulfonyloxy, tosyloxy and the like, aroyl such as benzoyl, toluoyl, naphthoyl, phthaloyl, indanecarbonyl and the like, aryl-lower alkanoyl, such as phenylacetyl and the like, where the above mentioned acyl radical has one or two suitable substituents. </ P> <p> such as halogen, e.g. Chlorine, bromine, iodine or fluorine, hydroxy, cyano, nitro, lower alkoxy, e.g. Methoxy, ethoxy, propoxy, isopropoxy and the like, lower alkyl, e.g. Methyl, ethyl, propyl, isopropyl, butyl and the like, lower alkenyl, e.g. Vinyl, allyl and the like or, for example, phenyl, ToIyX and the like. Suitable examples of the acyloxy having one or more of these substituents are preferably halo-lower alkanoyloxy, e.g. Chloroacetyloxy, dichloroacetyloxy, trichloro, acetyloxy., Or. Trifluoroacetoxy. </ P> In the acyl radical of an optionally N-substituted carbamic acid, N-substituents are optionally substituted by halogen, e.g. Chlorine, or by lower alkanoyl, e.g. Acetyl or propionyl, substituted lower alkyl, e.g. Methyl, ethyl, 2-chloroethyl, or 2-acetoxyethyl. Such acyloxy groups R <Sub> 3 </ sub> are e.g. Carbamoyloxy, N-methylcarbamcyloxy, N-Aethylcarbamoyloxy, N- (2-chloroethyl) -carbamoyloxy or .N- (2-acetoxyethyl) -carbamoyloxy. </ P> <p> In a keterocyclylthio group R <Sub> 3 </ sub> is heterocyclyl, in particular an optionally substituted one above. Ring carbon atom to the thio group bonded, heterocyclic radical having 1 to 4 ring nitrogen atoms and optionally another ring heteroatom of the group oxygen and sulfur. </ P> Such heterocyclyl residues are primarily optionally substituted, e.g. the below-mentioned substituents, monocyclic, five- or six-membered diaza-, triaza ™, tetraza-, thiaza-, thiadiaza-, thiatriaza-, oxaza- or oxadiazacyclische radicals aromatic or partially saturated .Charakters. </ P> Substituents of such heterocyclyl radicals are, i.a. Lower alkyl, in particular methyl, and ethyl, n-propyl, isopropyl or straight-chain or branched butyl, or hydroxy, esterified hydroxy, such as lower alkanoyloxy, halogen, such as chlorine, carboxy, esterified carboxy, such as lower alkoxycarbonyl, sulfo, amidated SuI-fo, amino , Mono- or di-lower alkylamino, acylamino, such as lower alkanoylamino, or lower alkyl substituted by substituted lower alkanoylamino substituted by carboxy or halogen, for example 2-hydroxyethyl, 2-acetoxyethyl, 2-chloroethyl, carboxymethyl, 2-carboxyethyl, ethoxycarbyclo! Methyl, 2- Aethoxycarbonyläthyl, SuI-fotnethyl, 2-sulfoethyl, sulfamylmethyl, 2-sulfamylethyl, 2-aminoethyl, 2-dimethylaminoethyl or 2-acetylaminoethyl. Further substituents of the heterocyclic radical are cycloalkyl, ζ.3. Cyclopentyl or cyclohexyl, aryl, optionally substituted by halogen, e.g. Chlorine, or nitro </ P> <p> substituted phenyl, Arylniederaikyl, z.3. 3enzyi, or keterccyclyl, such as Fury 1, ζ.3. 2-furyl, thienyl, <I> &gt;. ζ.Έ </ I> </ P> <p> 2-thienyl, or oxazolyl, e.g. 2- or 5-oxazolyl, or functional groups such as halogen, e.g. Fluoro, chloro or bromo, optionally, substituted amino such as, where appropriate, lower alkyl mono- or di-substituted amino, e.g. Amino, methylamino or dimethylamino, acylamino such as lower alkanoylaraino or lower alkanoylamino substituted by halogen or carboxy such as acetylaraino, 3-chloropropionylamino or 3-carboxypropionylamino, nitro hydroxy, lower alkoxy, e.g. Methoxy, ethoxy, n-butyloxy or 2-ethylhe: c7'loxy, or optionally functionally modified carboxy, such as carboxy, esterified carboxy, such as lower alkoxycarbonyl, e.g. Mathoxycarbonyl or Aethoxycarboriyl, optionally substituted, such as N-niono or'Ν, Ν-diederiederalkyliertes carbamoyl, e.g. N-methylcarbarioyl or Ν, Ν-dimethylcarbaaioyl, or cyano, </ P> <p> ^ Q "..." ef <I> GSSI </ i> Saw Si sa * s wi </ P> as well as oxo or oxido, where one or more such substituents, which are primarily associated with ring carbon atoms but also, in particular, lower alkyl and oxides, with ring nitrogen atoms, may be present. </ P> <p> Preferred heterocyclylthio groups ^ R. <I> wherein the heterocyclic moiety is a corresponding monocyclic, five-membered moiety, i.a. Imidazolylthlo, e.g. 2-imidazolylthio, optionally substituted by lower alkyl and / or phenyl triazolylthio, e.g. IH-I, 2,3-Trlazol-4 ~ ylthio <Sub> / </ sub> 1-methyl-1H-1 <Sub> / </ sub> 2,3-triazole-4-ylthio / IH-I, 2,4-triazole-3-ylthio <I> 5-Methyl-IH-1, 2,4-triazol-3-ylthio, 3-methyl-1-phenyl-1H-1, 2,4-triazol-5-ylthio, 4,5-dimethyl 4H ~ l, 2,4-triazol-3-ylthio or 4-carboxymethyl or 4-phenyl-4K-l, 2,4-triazol-3-ylthio, in particular optionally substituted as indicated tetrazolylchio, z.3. 1H-Tecrazol-5-ylthio, 1-methyl-1H-tetrazol-5-ylithio, 1-carboxyethyl-1H-tetrazol-5-ylchio, 1- (2-carboxyethyl) -H-tetrazol-5-ylthio, 1 Sulfomethyl-1K-tetrazol-5-ylthio, 1- (2-sulfoethyl) -1H-tetrazol-5-ylthio, 1- (2-dichloroaminoethyl) -1H-tetrazole = 5-ylthio, 1-phenyllH-tetrazole -5-ylthio or 1- (4-chlorophenyl) -lH-tetrazol-5-ylthio, optionally substituted by lower alkyl or thienyl-substituted thiazolylthio or isothiazolylthio, for example 2-thiasolylthio, 4- (2-thienyl) -2-thiazolylthio, 4,5-di · methyl-2-thiazolylthio, 3-isothiazolylthio, 4-isothiazolylthio or 5-isothiazolylthio, in particular also thiadiazolylthio optionally substituted as indicated, e.g. l, 2,3-thiadiazole-4-7lthio, 1,2,3-thiadiazol-5-ylthio, 1,3,4-thiadiazol-2-ylthio, 2-methyl-l, 3,4-thia- ' diazol-5-ylthio, <I> 2- </ i> (3-Carboxypropionylarnino) -1,3,4-thiadiazol-5-ylthio, 1, 2,4-thiadiazol-5-ylthio, 3-methyl-l, 2,4-thiadiazol-5-ylthio or 1,2,5-thiadiazole-3-ylthio, thiatriazolylthio, eg 1 <I>, 2, 3,4-Thiatriazolyl-5-ylthio, optionally substituted oxazolylthio as indicated </ P> <p> or isoxazolylthio, ζ .B. 5-oxazolylthio, 4-methyl-5-oxazolylthio, 2-oxazolylthio, 4,5-diphenyl-2-oxazolylthio or 3-methyl <Sup> IAE </ sup> -5-isoxazolylthio, or optionally as indicated, substituted oxadiazolylthio, e.g. 1,2,4-oxadiazol-5-ylthio, 2-methyl-1, 3,4-oxadiazol-5-ylthio, 2-phenyl-1,3,4-oxadiazol-5-ylthio, 5- (4-nitrophenyl ) -1,3,4-oxadiazol-2-ylthio or 2- (2-thlenyl) -1,3,4-oxadiazol-5-ylthio. </ P> <p> Preferred Eeterocyclylthio Groups R <I> in which the heterocyclic radical has a corresponding monocyclic, six-membered radical or a corresponding partially saturated radical <Sup> 1 </ sup> rest are </ P> <P> inter alia. optionally substituted by halogen 1-Oxidopyridylthio, z.3. 1-oxido-2-pyridylthio or 4-chloro-1-oxo-2-pyridylthio, optionally substituted by hydroxy-substituted pyridazinylthio, e.g. 3-Hydrox: * - 6-pyridazinylthio, optionally substituted by lower alkyl, lower alkoxy or halogen substituted N-oxido-pyridazinylthio, z.3. 2-oxido-6-pyridazinylchio, 3-chloro-l-oxido-6-pyridazinylthio, 3-methyl-2-oxido-6-pyridazinylthio, 3-menho: cy-loxido-6-pyridazinylthio, S-ethoxy-l oxido-o-pyridazinylthio, 3-n-butyloxy-l-oxido-6-pyridazinylthio, or 3- (2-ethylhe: r / loxy) -1-oxo-6-pyridazinylthio, or optionally lower alkyl, amino, di-lower alkylamino or carboxy substituted 2-oxo-l, 2-dihydro-pyriinidinylthio, for example 2-0xo-1-dihydro-A-pyrimidinylthio, 6-methyl-2-oxo-1-dihydro-A-pyriniidinylthio, 5-methyl-2-oxo-1-dihydro-A-pyridia-thio-thio-thio, 6-amino 2-oxo-1,2-dihydro-4-pyrimidinylthio, 6-dimethylamino-2-oxo-1,2-dihydro-4-pyriniidinylthio, 5-carbo-cyano-2-oxo-1,2-dihydro-4 -pyrimidinylthio or 6-carbo: c7-2-oxo-l, 2-dihydro-4-pyrimidinylthio or optionally substituted in the same way substituted 4-oxo-3,4 ~ dihydro-2-pyriinidinylthio, in particular the unsubstituted 4-oxo 3,4-dihydro-2-pyridiolidithio, or optionally lower alcyl, such as methyl or ethyl, and up to two oxo-substituted triazinyl </ P> <p> thio, especially N-lower alkyl-5,6-dioxo-l, 2,4-triazin-3-ylthio ,. For example, 1-, 2- or 4-methyl-5,6-dioxo-l, 2,4-triazin-3-yithio, or the tautomeric aromatic hydroxy compounds corresponding to the oxo compounds. </ P> The functional groups present in compounds of the Forrael (I), especially carboxyl and amino, furthermore hydroxy and sulfo groups, are optionally protected by protecting groups used in penicillin, cephalosporin and peptide chemistry. </ P> Protecting groups are light, that is to say, that undesirable side reactions take place, for example solvolytically, reductively, photolytically or even under physiological conditions, releasable. </ P> <p> Protecting groups of this type, as well as their cleavage, are described for example in "Protective Groups in Organic Chemistry", Plenum · Press, London, New York, 1973, also in "The Peptides", Vol. I, Schröder and Lübke, Academic Press , London, New York, 1965, as well as in "Methods <Sub> tw </ sub> of organic chemistry ", Kouben-'weyl, 4th edition, 3d. 15/1, Georg Thieme Verlag, Stuttgart, 1974. </ P> So are carboxyl groups, such as the carboxyl group R <Sub> 4 </ sub>, e.g. usually protected in esterified form, whereby such ester groups are readily cleavable under mild conditions. </ P> <p> Suitable protected carboxyl groups are, for example, lower alkoxycarbonyl, e.g. Mathoxy or ethoxycarbonyl, or especially tertiary-niaderalkoxy.carbonyl, e.g. tert, butyloxycarbonyl, polycycloalkoxycarbonyl, e.g. Adamantyloxycarbonyl, arylmethycxycarbonyl, wherein aryl preferably has one or two, optionally, e.g. by Niaderaikyi, especially tert-lower alkyl, e.g. tert-butyl, lower alkoxy »such as hethoxy, hydroxy, halo, e.g. Chlorine, and / or nitro mono or polysubstituted phenyl radicals </ P> <p>, as appropriate, e.g. substituted benzyloxycarbonyl as mentioned above, e.g. 4-nitro-benzyloxycarbonyl or 4-methoxybenzyloxycarbonyl, or optionally, for example, as mentioned above, substituted diphenylinethoxycarbonyl, e.g. Diphenylmethoxycarbonyl or di- (4-methoxyphenyl) methoxycarbonyl, or 2-halo-lower alkoxycarbonyl, e.g. 2,2,2-trichloroethoxycarbonyl, 2-chloroethoxycarbonyl, 2-bromoethoxycarbonyl or 2-iodoethoxycarbonyl, 2- (S.) (P <Sub> 2 </ Sub>) (S <Sub> 3 </ sub>) - silylethoxycarbonyl, wherein the substituents S., S <Sub> 2 </ sub> and S- independently of one another each an optionally substituted, e.g. by lower alkyl, lower alkoxy, aryl, halogen or nitro substituted aliphatic, araliphatic, cycloaliphatic or aromatic hydrocarbon radical with z.3. up to 15 carbon atoms, such as a corresponding optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl or aryl radical, z.3. 2-tri-lower alkylsilylethoxycarbonyi, such as 2-trimethylsilylethoxycarbonyl or 2- (dibutyl-methyl-silyl) -ethoxycarbonyl, or 2-triarylsilylethoxycarbonyl, 2-triphenylsilylethoxycarbonyl, or 1-loweralkoxy-loweralkoxycarbonyl, such as methoxymethoxycarbonyl, 1-methoxyethoxycarbonyl or 1-ethoxymethoxycarbonyl, or 1-lower alkylthio-lower alkoxycarbonyl, such as 1-methylthiomethoxycarbonyl or 1-ethylthioethoxycarbonyl or aroylmethoxycarbonyl, wherein the aroyl group is preferably optionally, for example by halogen, such as bromine, substituted benzoyl, e.g. Phenacyloxycarbonyl, or polyhaloaryloxycarbonyl, such as pentachlorophenyloxycarbonyl. Esterified carboxyl groups are also corresponding silyloxycarbonyl, in particular organic silyloxycarbonyl groups or corresponding stannyloxycarbonyl groups. In these, the silicon or tin atom preferably contains lower alkyl, in particular methyl, furthermore lower alkoxy, e.g. Methoxy, and / or halogen, e.g. </ P> <p> Chloro, as a substituent ^. Suitable silyl or SCanny1 protecting groups are, in the first place, tri-lower alkylsilyl, in particular trimethylsilyl, furthermore dimethyl-tart-butylsilyl, lower-alkoxy-lower-alkyl-halo-silyl, e.g. Methoxy-methyl-chloro-silyl, or di-lower alkyl-halosilyl, e.g. Dimethylchlorosilyl, or correspondingly substituted stannyl compounds, e.g. Tri-n-butyl-stannyl. </ P> Preferred protected carboxyl groups are tert-butyloxycarbonyl, optionally, 2.3. as mentioned "substituted B, enzyloxycarbonyl, 2.B. A-Nierobenzyloxycarbonyl and diphenylmethoxycarbonyl. </ P> <p> A physiologically cleavable esterified carboyl group is primarily an acyloxyniethoxycarbonyl group in which acyl ζ.3. the radical, an organic carboxylic acid, primarily an optionally substituted lower alkanecarboxylic acid, or wherein acyloxysaethyl forms the residue of a lactone. Such groups are NiederalkanoyloxTmethoxycarbcnyl, 2.3 "or Acetyloxynethylojcycarbonyl Pivaloylo. Cyraethoxycarbonyl, Aminoniederalkanoyloxymethoxycarbonyl, 'in particular a-amino-niederalkanoyloxymethoxycarbcnyl, Z.3 Glycyloxymethoxycarbonyl, L-Valyloxymethoxycarbonyl or L-Leucyloxyraethoxycarbonyl, further Phthalidyloxycarbonyl, for example 2-Phthalidyloxycarbonyl or indanyloxycarbonyl, for example. 5-indanyloxycarbonyl. </ P> A protected amino group, such as the group Am, may e.g. in the form of a slightly cleaved acylamino, mono-, di- or tri- aryl! methylamino, etherified mercaptoamino, 1-acyl-2-lower-alkylideneamino, silyl or stannylamino group or as azido group. · </ P> In a corresponding acylamino group, acyl is, for example, the acyl radical of an organic carboxylic acid ax. up to 18 C atoms, in particular one </ P> <p> optionally, e.g. by halogen or aryl, substituted aliphatic carboxylic acid or optionally, e.g. by halogen, lower alkoxy or nitro, substituted aromatic carboxylic acid, or a carbon monohydrate ester. Such acyl groups are, for example, lower alkanoyl, such as formyl, acetyl, propionyl, - halo-lower alkanoyl, such as 2-haloacetyl, in particular .2-chloro, 2-brosi-, 2-iodo, 2,2-dichloro or 2, 2, 2 -Trichlcracetyi, phenylacetyl, phenoxyacetyl, thienylacetyl, 3enzoyl, Α-chloro, 4-methoxy or 4-nitrobenzoyl, lower alkoxycarbonyl, especially Csrt.-Niederaikoxycarbcnyl, ζ.3. tert-butyloxycarbonyl, folycycloalkoxycarboryl, z.3. Adanantyloxycarbonyl, arylisethoxycarbonyl, vcrin aryl preferably one or two, optionally, z.3. by lower alkyl, in particular tert-lower alkyl, z.3. tert-butyl, lower alkoxy, such as methoxy, hydroxy, halogen, z.3. Chlorine, and / or nitro, mono- or polysubstiruisrte phenyl radicals, such as optionally substituted Benzylcxycarbonyl, z.3. 4-nitrobenzyloxycarbonyl, or substituted diphenylniethoxycarbycarbonyl, e.g. 3-hydraoxycarbonyl or di- (4-methoxyphenyl) -rhreoxy-carbonyl, or 2-halo-lower alkoxycarbonyl, z.3. 2,2,2-trichloroethoxycarbonyl, 2-chloroethoxycarbonyr, 2-bromo- </ P> <p> ethoxycarbonyl or 2-iodo-carbonylcarbonyl <Sub> f </ sub> 2- (S,) (p <Sub> 2 </ sub>) (S ^ silyl-Mthoxycarbonyl, wherein the substituents S., S <Sub> 2 </ sub> and S. independently of one another each one optionally substituted, ζ.3 </ P> <p> by lower alkyl, lower alkoxy, aryl, halogen or nitro, substituted, aliphatic, araliphatic, cycloaliphatic or aromatic Kohlenwasserstoffrest nit z.3. up to 15 C atoms, such as a corresponding optionally substituted lower alkyl, Arylniadsraikyl-, cycloalkyl or aryl radical, .bedeuten, z.3. 2-trininedaralkylsilylethoxycarbonyl, as. 2-Trimethylsilyläthoxycar- </ P> <p> Bonyl or 2- (dibutylmethyl-s'ilyl) -ethoxycarbonyl, or 2-triethylsilylatoxycarbonyl, such as 2-tripheriylsilyl-5-carboxy-carbonyl, or aryl-line -oxycycloyl, in which the aryl group is preferably optionally, eg by halogen, such as bromine, substituted benzoyl, e.g. Phenacyloxycarbonyl. </ P> <p>, Further acyl groups in acylamino groups are radicals of organic phosphoric, phosphonic or phosphinic acids of the formula (R <Sup> 1 </ Sup>) (R <Sup> 2 </ sup>) P (= O) -, where R <Sup> 1 </ sup> and R <Sup> 2 </ sup> independently of one another represent a hydrocarbon radical etherified by a hydrocarbon radical or a hydrocarbon radical, the hydrocarbon radicals preferably containing up to 15 C atoms, for example aliphatic araliphatic cycloaliphatic or aroaromatic nature, for example are substituted by lower alkyl, lower alkoxy, aryl, halogen or nitro, and for example alkyl, in particular lower alkyl, such as methyl, ethyl, propyl, isopropyl or butyl, phenyl-lower alkyl, such as benzyl, p-nitro or p-chlorobenzyl, cycloalkyl, such as cyclopropyl , Cyclopentyl, cyclohexyl or cycloheptyl, or homoaryl, such as phenyl, ο-, m- or p-tolyl, ρ-methoxyphenyl, p-biphenylyl, p-chlorophenyl or p-nitrophenyl. Such radicals are, for example, dimethylphosphoryl, diethylphosphoryl, dipropylphosphoryl, diisopropylphosphoryl, dibenzylphosphoryl, di-p-nitrobenzylphosphoryl, dicy-clohe: &lt; ylphosphoryl, diphenylphosphoryl, phenoxyphenylphosphonyl, diethylphosphinyl and diphenylphosphinyl. </ P> In a mono-, di- or triarylmethylamino group, the aryl radicals are, in particular, optionally substituted phenyl radicals. Such groups include, for example, bensyl, di-phenylmethyl or tri-amino. </ P> An etherified Me.rcapto group in an atnino group Is protected in such a radical in the first arylthio or aryl-lower alkylthio, in which aryl in particular </ P> <p> particularly optionally, for example, lower alkyl, such as methyl or cert. butyl, lower alkoxy, such as methoxy, halogen, such as chlorine, and / or. Nitro is substituted phenyl. A corresponding amino protecting group is e.g. 4-nitrophenylthio. </ P> In a 1-acyl-2-lower alkylidene radical useful as an amine-protecting group, acyl is preferably the corresponding radical of a lower alkanecarboxylic acid, an optionally, e.g. by lower alkyl, such as methyl or tert-butyl, lower alkoxy, such as methoxy, halogen, such as chlorine, and / or nitro-substituted benzoic acid or a carbonic monoester, such as a carbonic acid lower alkyl. Corresponding protecting groups are primarily 1-lower alkanoyl-2-propylidene, e.g. 1-acetyl-2-propylidene, or 1-lower alkoxycarbonyl-2-propylidene, e.g. l-ethoxycarbonyl-2-propylidene. </ P> A silyl or stannylanino group is primarily an organic silyl or stannylairdnano group in which the silicon or tin atom is preferably lower alkyl, especially methyl, furthermore lower alkoxy, e.g. Methoxy, and / or halogen, e.g. Corresponding silyl or stannyl groups are in the first line tri-lower alkylsilyl, in particular trimethylsilyl, furthermore dimethyl-tert-butyl-silyl, lower alkoxy-lower alkyl-halo-silyl, for example. Methoxymethyl-chloro-silyl, or di-lower alkyl-halosilyl, e.g. Dimethyl-chloro-silyl, or appropriately substituted stannyl, e.g. Tri-n-butylstannyl. </ P> <p> An amino group can also be protected in protonated form; the anions are primarily those of strong inorganic acids, such as "hydrohalic acids, for example the chlorine or bromine anion, or of sulphonic acid, such as p-toluenesulphonic acid mure. </ P> Preferred amino-protecting groups are the acyl radicals of carbonic acid half tarn, especially tart.-Euty1oxycarbonyl, * optionally, e.g. substituted benzyloxycarbonyl or diphenylmethoxycarbonyl as indicated, or 2-halo-nisalkoxycarbonyl such as 2,2,2 "trichloroethoxycarbonyl. </ P> <p> Hydroxy protecting groups are e.g. Acyl radicals, such as 2,2-dichloroacetyl or, in particular, the acyl radicals mentioned in connection with a protected amino group, of carbon monhalotestane, in particular 2,2,2-trichloroethoxycarbonyl, or "organic methyl or stannyl radicals, and also readily cleavable 2-oxa or 2-thiaaliphatic or cycloaliphatic hydrocarbon radicals, in particular 1-lower-alkoxy-lower-alkyl or 1-lower-alkylthio-lower-alkyl, for example methoxyethyl, 1-methoxy-methyl, 1-ethoxy-ethyl, 1-ethylthiomethyl, 1-methylthio-ethyl or 1- Ethylthioethyl, or 2-0xa- or 2-Tniacycloniederalkyl with 5-7 ring atoms, such as 2-tetrahydrofuryl or 2-tetrahydropyranyl or corresponding Thiaanaloge, as well as easily cleavable, optionally substituted a-Phenylniederalkylreste, such as optionally substituted benzyl or Dipheny! Substituents of the phenyl radicals such as halogen, such as chlorine, lower alkoxy, such as methoxy and / or nitro come into question. </ P> A protected sulfo group is primarily a sulfo group esterified with an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or araliphatic alcohol, such as a lower alkanol, or with a silyl or stannyl radical, such as tri-lower alkylsilyl. In a sulfo group, the For example, hydroxy group may be etherified, such as the hydroxy group in an esterified carboxy group. </ P> <p> Salts are especially those of compounds of formula I with acidic groups, e.g. with free carboxyl and sulfo groups. Such salts are primarily metal or ammonium salts, such as alkali metal and alkaline earth metal, e.g. Sodium, potassium, magnesium or Cälciumsalze, and ammonium salts with ammonia or suitable organic amines, wherein primarily aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic primary, secondary or tertiary mono-, di- or polyamines, and heterocyclic bases for salt formation come into question, such as lower alkylamines, eg Triethylamine, hydroxycycloalkyl, e.g. 2-hydroxyethylamine, bis- (2-hydroxy-3-ethyl) -amine or tris- (2-hydroxyethyl) -amine, basic aliphatic esters of carboxylic acids, e.g. 4-amino-2-diethylaminoethylester, lower alkylene amines, e.g. 1-ethylpiperidine, cycloalkylamines, e.g. Dicyclohexylamine, or benzylamines, e.g. N.N'dibenzylnanyl.diamine, as well as pyridine-type bases, e.g. Pyridine, collidine or quinoline. Compounds of formula I having a basic group may include acid addition salts, e.g. with inorganic acids such as hydrochloric acid, sulfuric acid, or phosphoric acid, or with suitable organic carboxylic or sulphonic acids, e.g. Trifluoroacetic acid, as well as with amino acids such as arginine and lysine. In the presence of several acidic or basic groups, mono- or polysalts can be formed. Compounds of the formula I having a free carboxyl group and free amino group may also be present in Fora of internal salts, i. in zwitterionic form, or one part of the molecule may be present as an inner salt and another part as a normal salt. </ P> For isolation or purification it is also possible to use pharmaceutically unsuitable salts. For therapeutic use, only pharmaceutically acceptable salts, dia therefore preferred. </ P> <P> <Sup> 1 </ sup> U "fos </ P> <p> The group = N-O-R. may be in syn (Z) or anti (Ξ-0 form, with the syn form being preferred. </ P> <p> The aitiinothiadiazolyl group of the sub-formula </ P> <P> N- </ P> <p> β- </ P> <p> may also be in their tautomeric form as Iminothiadiazolinyl group of the sub-formula </ P> <P> ΗΝ </ P> <p> or as a mixture of both forms. The balance between the two tautomers depends on the nature of the substituents and external factors such as temperature, solvent or pH. In the context of the present invention, this group is referred to in the description and in the claims only as "" Aminothiadiazolyl ", although the Iminothiadiazolinylform is also to be included. </ P> The compounds of formula I in which protecting groups are removed, but wherein carboxyl groups are optionally esterified in physiologically cleavable form, and their pharmaceutically acceptable non-toxic salts are valuable antibiotic active substances used in particular as antibacterial antibiotics. v / can ground. For example, they are in vi <U> tro </ u> against gram-positive and gram-negative microorganisms, such as against cocci, e.g. Staphylococci such as Staphylococcus aureus, streptococci such as Streptococcus pyogenes and Streptococcus pnemaoniae, enterococci and micrococci, including Neisserla species, e.g. Neisseria aonorrhoeae, in minimal concentrations of · </ P> <P> <O, OO5 mcg / ml to about 3 2 mcg / ml, and to enterobacte-. ' riaceae, e.g. against <u> Escherichia coli </ u>, Klebslella, <U> Serratia </ u>,, <U> Enterobacter </ u> or <u> Proteus spp </ u>, as well as against <U> Pseudomonas </ u> aeruginosa, <u> Haemophilus influenzae </ u> and other gram-negative and gram-positive rod bacteria, in the minimum concentration of &Lt; 0.005 to about 16 mcg / ml, effective. <u> In vivo In mouse subcutaneous application, they are also against Gram-positive and Gram-negative bacteria, e.g. <U> staphylococci </ U> <u> Escherichia co </ O> li, <U>? Roteus </ u> and <U> Pseudomonas </ u> aeruginosa, in minimal doses of <fO, 15 to about 100 mg / kg. ''. </ P> <p> Certain preferred compounds are characterized by a particularly long residence time in the body. In the mouse, for example, the half-life is up to 60 minutes. </ P> The new compounds can therefore be suitably, e.g. in the form of antibiotically active preparations for the treatment of gram-positive or gram-negative bacteria and cocci, in particular by enterobacteria, such as <u> Escherichia coli </ u>, caused infections find use. </ P> <p> Highlighting groups are compounds of the formula I in which Am represents an optionally protected secondary or a tertiary amino group and R <Sub> 1 </ sub>, R <Sub> 2 </ sub>, R <Sub> 3 </ sub>, and R <Sub> 4 </ sub> have the meanings given under formula I, or wherein R is hydrogen, substituted lower alkyl or cycloalkyl, or optionally N-substituted carbamoyl, and Am, R <Sub> 3 </ sub>, R <Sub> 3 </ sub> -and R <Sub> 4 </ sub> have the meanings given under formula I, or wherein R <Sub> 2 </ sub> Lower alkoxy means and'Am, R <Sub> 1 </ sub>, R <Sub> 3 </ sub> and. R <Sub> 4 </ sub> have the meanings mentioned under formula I, and the salts of such compounds with salt-forming groups. </ P> a <£> a </ P> <p> Compounds of the formula I in which the functional groups are protected are used as starting materials for the preparation of compounds of the formula I. </ P> The present invention relates in the first place to those compounds of the formula I in which Am or. Methylamine, R-, hydrogen / lower alkyl, in particular methyl, carboxy-substituted lower alkyl or cycloalkyl, in particular 2-carboxy-2-propyl or 1-carboxy-lcyclopropyl, or a group -C (= O) -NHR, wherein R is hydrogen or Nied'eralkyi in particular. Methyl, R, means <Sub> 2 </ sub> is hydrogen or methoxy, R is lower alkanoyloxy, such as acetoxy, carbamoyloxy, N-lower alkylcarbamoyloxy, or optionally substituted heterocyclylthio bound to the thio group with a ring carbon atom, such as triazolylthio, tetrazolylthio, thiazolylthio, thiatriazolylthio, thiadiazolylthio, oxazolylthio, oxadiazolylthio, pyridazinylthio, Pyrimidinylthio or triazinylthio, in which the heterocyclic rings are partially hydrogenated and optionally substituted, for example by lower alkyl, such as methyl, Ν, Ν-di-lower alkylaminoniedex-alkyl, such as 2-N, N-dimethylaminoethyl, carboxy-lower alkyl, such as carboxymethyl or 2-carboxyethyl, sulfo-lower alkyl, such as sulfomethyl or 2-sulfoethyl, amino, carboxy-lower alkanoylamino, carbamoyl, oxo or hydroxy, and R. carboxyl or in physiologically cleavable form esterified carboxyl, eg Acyloxymethoxycarbonyl, pharmaceutically acceptable salts of such compounds, as well as the starting materials and intermediates useful in their preparation. </ P> Particularly noteworthy are compounds of the formula I in which Amino or methylamino, R is hydrogen,., methyl, 2-carboxy-2-propyl, 1-carboxy-1-cyclopropyl, carbamoyl or N-methylcarbamoyl, R 2 is hydrogen or methoxy , R 3 is acetoxy <Sub> f </ sub> carbamoyloxy, optionally lower alkyl, </ P> <p> - £ > - 27 * 11 * 1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <p> carboxy-lower alkyl, sulfo-lower alkyl or -U lower-alkyl-amino-lower alk-3'-substituted-1'-etrazolylthio, ζ, B 1-methyl-1'-tetrazol-5-ylthio, 1 ~ sulfomethyl-1H-tetrazol-5-ylthio, 1 (2 ~ <Sup> ö </ sup> sulfoethyl) -1H-tetrazol-5-ylthio, 1-carboxymethyl-III-tetrazol-5-ylthio, 1- (2-dimethylaminoethyl) -1H-tetrazol-5-ylthio, optionally thiol-substituted thiaoiazolylthio, such as 2 -Methyl-1,3,4-thia-thiazole-5-ylthio or 3-methyl-1,2,4-thiadiazol-5-ylthio, c <Sup> e </ sup> if necessary by hydroxy-substituted pyridazinylthio, <I> z, </ I> B. 3-hydroxypyridazin-6-yl-tlioi, optionally pyrimidinylthio substituted by hydroxy, ζ. Β <Sub> β </ sub> 4-Hyd'rozy-2-pyrimidinyl- or tautoinere 4-oxo-3,4-dihydro-2-pyrimidine5 <Sup> r </ sup>> thio, or by lower alkyl and two hydroxy-substituted triazinylthio, such as 2-lower alkyl-5,6-dihydroxy-1,2,4-triazin-3-ylthio, baw. to tautomeric 1,2,5,6-tetrahydro-2-lower alkyl-5,6-dioxo-1,2,4-triazin-3-ylthio, <i> z, B, 1,2,5,6-Tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazinyl-3-ylthio, and R. Carboxyl or in physiologically cleavable form esterified carboxyl, ζ. Β <Sub> β PjLvaloylmethoxycarbonyl, or phthaiidyloxycarbonyl, means pharmaceutically acceptable S <Sub> a </ sub> ize of such compounds and the starting materials and intermediates that can be used for their preparation » </ P> The invention relates in particular to the compounds of the formula I described in the examples, their pharmaceutically acceptable salts and the novel starting materials and intermediates described therein <Sub> o </ sub> - · ·. </ P> <P> <i> e-g s "j </ I> </ P> <p> - ^ te-. 27 <Sub> e </ sub> 11 .1 980 </ P> <p> AP C 07 D / 222 421 </ P> <P>. .. <Sub> Λ </ sub> \, 57 771/18 </ P> <p> 'ν "-ν · ** = </ P> <p> Particularly rich in antibiotics are the following compounds of general formula I; </ P> <p> 1,2,4-thiadiazol-3-yl) ~ 2 ~ Z -methoxyiminoaceta.rai · do / -3~ (1,2,5,6-tetrahydro-2-methyl-5,6-dioxo) 1 <Sub> s </ sub> 2 <Sub> f </ sub> 4-triazine-3 ™ yl'-thiomethyl) -3-cephem-4-carbonic acid; </ P> <P> i <I> <Sub> s </ sub> 2 <Sub> 9 </ Sub> 4-thiadiazol-3-yl) -2-Z, -hydroxyiminoaceta-diido-7-3- (1-methyl-tetrazol-5-yl-thiomethyl) -3-.CGphem ~ 4-carboic acid; </ P> <P> 7ß- / 2- (5- <Sup> A </ Sup> mino-1,2,4-thiadiasol-3 ~ yl) -2 ~ Z "methoxyiminoacetamidq7 ~ 3 acetoxyinethyl" 3 ~ 4 ~ cephera-carboxylic acid pivaloyloxymethyl ester; </ P> <P> 7ß- / 2- (5- <Sup> A </ sup> mino-1,2'-4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamide d7 ~ 3 "-carbamoyloxy-ethyl-3-cephera-4-carboxylic acid pivaloyloxy-ethyl ester; </ P> <p> o ~ 1, 2 <Sub> s </ sub> 4-thiadiazol-3-yl) -2-Z-methoxy-1-nitro-acetyl-arnido7-3- (1-methyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester; </ P> <p> 1,2,4-thiadia-ol-3-yl) -2-Z-methoxyiminoaceta-midq7-3 f 1 - / 2- (N, H -diethylethylino) ethyl-7-1H-tetrazol-5-ylylthio IJ 3 ~ cepliem-4-carboxylic acid e-pivaloylorymethyle st er; </ P> <p> 7β ~ / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-metlioxyirainoacetamide q7-3 ~ (1 -piva.loyloxyraethoxycarbonylmethyl-tetrazol-S-ylthylthio) thyl "-3 ~ <Sup> > </ sup> cephem- »4-carbons; -uric ~ pivaloylo." Myrnethyl ester; </ P> <p> 2- (5- <Sup> A </ sup> rain.o ~ 1, 2,4-thiaa: lasol ~ 3-yl) -2-Z-netho2: yiminoacet- </ P> <P> xo ~ 3 <Sub>? </ sub> 4 ~ dihydropyrimidine-2-yi-thiomethyl) <I> -3- </ I> cephem-4-carboxylic acid; </ P> <p> 27.11.1980. AP C 07 D / 222 421 47 771/18. </ P> <p> 7β-Z "2- (5-IT-methylamino-i, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido _ / - 3-acetoxymethyl-3-cephem-4-carboxylic acid; </ P> <P> 7.beta. ~ / "2- (5- <Sup> A </ Sup> mino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyl-0xyiminoacetamid ^ -3 ~ acetoxymethyl-3-cephem-4 ~ carbori3äure; </ P> <P> <I> 7ß- {2- </ i> (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-niethylcarbamoyloxy-difiinoacetaraidg7-3- (1-methyltetrazol-5-yl-thioraethyl) -3-cephem-4-carboxylic acid .Liure; </ P> <P> 7b-/ 2- (5- <Sup> A </ Sup> mino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyirainoacetaKiido7 ~ 3 ~ (1 ~ cai * bozyinethyl-tetrazol-5 ~ yl-tliiomethyl) -3-cephem ~ 4-carboxylic acid ; </ P> <P> 7.beta. ~ / 2- (5- <Sup> A </ sup> mino1,2,4-thiadiazol-3-yl) -2-Z-hydroxyiminoacetamido7-3- (1-carbo2-ymethyl-tetrazol-5-yl-thiomethyl) -3-cep2em ~ 4 ~ carbono . <Sup>: </ Sup> iure; </ P> <P> 7.beta.-Z2 ~ (5 ~ <Sup> A </ sup> mino-1,2,4-thiadiazol-3-yl) ~ 2 ~ Z-methylcarbamoyloxyiminoacetamido7-3- (i-sulfomethyl-tetrazol-5-yl-thio-ethyl) - '3-cephem ~ 4-carboxylic acid </ P> <p> 7β'- 2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-hydroxyiminoacetamido-7-3 ~ (1-sulfomethyl-tetrazol-5-yl-thiomethyl) -3-ceph -4-carboxylic acid </ P> <P> 7.beta. ~ <Sub> / </ sub> / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiraioacetamide <Sup> | r </ Sup> -3- (1-niethyltetrazol ~ 5-yl-thiomethyl) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester; </ P> <P> <i> Q 'O β O </ I> </ P> <P> <I> 15 </ I> ' <I> <Sub>: </ Sub> </ I> </ P> <p> - ^ ls- '27 * 11.1980 </ P> <p> * '· AP G O? D / 222 421 </ P> <p> 57 771/18 </ P> <p> 7B- / 2- (5-l \ f ~ methylamino-1 <Sub> f </ sub> 2, 4 ~ thiadiaol ~ 3-yl) -2-Z-methoxyiminoac et amldo_7 ~ 3- (1-carboxymethyl-etrazol-5-yl-tliylmethyl) 3-cephem-4-carboxylic acid ; </ P> <p> 7β- / 2- (5-N-Hethylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoaceto-niqq-7-3- (1-meth-yl-tetrazol-5-yl-tioioinethyl ) ° 3 ~ cepliem-4-carboxylic acid </ P> <p> 7β ~ / ^ "~ (5-tert-butoxycarbonylamino-1,2,4-thiaazol-3-yl) -2-Z ~ (2-carboxyprop-2-yloxy-amino) -acetamide-7α-acetozyme <Sup> i </ Sup> thyl-3-cephem-4-carboxylic acid; </ P> <P> 7.beta.-Z2 (5- <Sup> A </ sup> mino-1,2,4-thiadiazol-3-yl) -2-Z- (2-carboxyprop-2-yloxyimino) -acetamide q7-3 ~ (1-methyl-1, etra-oil-5-yl-thiomethyl) 3-cephem-4 "-earbonsäuxe; </ P> <p> 7β ~ / 2- (5α-Araino »1,2,4-thiadiazol-3-yl) -2-Z- (2-carboxy-prbp-2-yl-oxyimino) acetamido-7-3- / i - (2 ~ IT <Sub> f </ i> iJ-dimethyl thylaminoethyl) tetrazol-5-ylthiomethyl! <Sub> i </ Sub> 7 ~ 3 * cepehm-4-carboxylic acid; </ P> <p> as well as the pharmaceutically applicable <Sup> ü </ sup> alze of it » </ P> <p> • The compounds of the present invention are obtained by methods known per se, </ P> <p> Compounds of the formula I and salts of such compounds which. have a salt-forming group are prepared, for example, by </ P> <P> <I> ν * </ I> </ P> <p> a) in a compound of the formula </ P> <P> <I> IIS </ I> </ P> wherein R_ / R- and R have the meanings given above, and wherein the 7j3-amino group is optionally substituted by an acylation-permitting group, the 73-amino group. Treating with an acyl radical of a carboxylic acid of the formula </ P> <P> (Ill) </ P> <p> introducing acylating agents wherein Am and R have the meanings given above, acylated or </ P> <b> b) a compound of the formula </ P> <P>? 2 </ P> <P> / <Sup> S </ Sup> \ </ P> <p> CONH · ·? (Tv) </ P> <P> 27- </ P> <P> <I> -XX- </ I> </ P> in which Am, R 1, R <Sub> 3 </ sub> and R. have the meanings given above, iri ^ t a hydroxylamine of the formula H-N-O-R. (V), wherein R <Sub> 1 </ sub> has the meaning given above, or implements </ P> c) a 2-cephem compound of the formula </ P> <P>? 2 </ P> <P> On "" <i> β U. </ i> "N <Sub> n </ sub> / -CH <Sub> 2 </ Sub> -R <Sub> 3 </ sub> (VI), </ P> <p> S OR <Sub> 1 </ Sub> <I> Q </ I> - <I> <Sup> ά </ sup> * </ I> </ P> in which Am, R <Sub> 1 </ sub>, R <Sub> 3 </ sub>, R <Sub> 3 </ sub> and R <Sub> 4 </ sub> have the meanings given above, isornerated, or </ P> <d> d) for the preparation of a compound of the formula (I) in which Am denotes a primary or secondary amirio group · a compound of the formula </ P> <P>? 2 </ P> in which X is halogen or hydroxy and R ,, R- / R <Sub> 3 </ sub> and R <Sub> 4 </ sub> have the meanings given above, with a salt of Rhodanwasserstoffsäure, or with a Isorhodanwasserstoffester, or a compound of formula (VII) wherein X is hydrogen, treated with Rhodan / or </ P> <p> e) for the preparation of a compound of the formula (I) in which R. means hydrogen and in which Am, R, R and R have the meanings given above, a compound of the formula </ P> <P>? 2 </ P> <p> N "-CH - CONH -.- ·. </ P> <P> <Sup> 1 </ Sup> J <I>% <Sup> 2 </ sup> i </ i> Λ i-CF-R (V <Sup> T </ sup> TI), </ P> <P> S <I> 0 <Sup> / </ Sup> </ I> </ P> in which Am, R / R <Sub> 3 </ sub> and R have the meanings given above, treated with a nitrosating agent, or </ P> <f> For the preparation of a compound of formula (ϊ) wherein R is optionally substituted lower alkyl or cycloalkyl or optionally N-substituted carbamoyl and wherein Am, R <Sub> 2 </ sub>, R <Sub> 3 </ sub> and R. have the abovementioned meaning, in a compound of the formula: </ P> <P>? 2 </ P> <p> IM M. A .1-CH. </ P> <P> If- </ P> <P> OH <I> \ </ I> </ P> in which Am, R, R <Sub> 3 </ sub> and R. have the meanings given above, the hydroxyimino group handles agents, or </ P> <p> the hydroxyimino group with the radical R, introducing </ P> <p> g) for the preparation of a compound of formula (I) wherein R_ is lower alkoxy and wherein Am, R,, R <Sub> 3 </ sub> and R <Sub> 4 </ sub> have the meanings given above, in a compound of the formula '. , · </ P> <P> jl9 </ P> <p> Ν-- «C-CONH» <I> V --- / </ I> </ P> <P> On <Sup>] </ sup> i ii <i> ύ J \ </ I> </ P> <p> Ν-- «C-CONH» <I> V --- / </ I> \ </ P> <P> <Sup>] </ sup> i ii. <i> ύ J ~ \ <i> CH-R (Ig), V OR <Sub> 1 </ Sub> &lt; / 'j <I> <sup> Δ ό </ sup>. </ I> </ P> in which Am, R, R and R have the meanings given above, where functional groups are in protected form, in, 7α-position introduces a lower alkoxy group, or </ P> (h) for the preparation of a compound of formula (I) wherein R-J is heterocyclithio and wherein Am, R, R and R are as defined above, a compound of formula </ P> <P>? 2 </ P> <P> / <Sup> S </ Sup> </ P> <P> On - "-. J Μ ο -, - ά i-CH <Sub> 9 </ sub> -R ° (Ih), </ P> in which Am, R, R and R have the meanings given above, and <I> R ° </ i> represents a residue which can be replaced by a heterocyclylthio radical R, with a mercaptan H-R-, </ P> <p>, or.,. </ P> i. for the preparation of a compound of formula J <Sub> 3 </ sub> J), where R is acyloxy and where Am, R, R <Sub> 9 </ sub> and R. have the meanings given above, a compound of the formula </ P> <P>? 2 </ P> <P> i-CH <Sub> 2 </ sub> -OH (ii), </ P> in which Am, R ,, R <Sub> 2 </ sub> and R have the meanings given above, treated with an acylating agent, or </ P> <p> j) for the preparation of a compound of formula (I) wherein R represents free carboxyl and wherein Am, R, R and R have the meanings given above in a compound of formula </ P> <P>? 2 </ P> <p> β-C-CONH- • • <Sup> / </ sup> ^ * </ P> in which Am, R., R <Sub> 2 and R_ have the meanings given above and R is a protected carboxyl group, the carboxyl protecting group is removed and replaced by hydrogen, or </ P> <p> k) for the preparation of a compound of the formula (I) in which R represents an esterified carboxyl group and in which Am, R, R and R have the meanings given above, in a compound of the formula </ P> <P> COOH </ P> <p> V7orin Am, R,, R <Sub> 2 </ sub> and R- have the meanings given above, the 4-carboxy group, ester, or <Sub> v </ Sub> </ P> <p> 1) for the preparation of compounds of formula (I) wherein Am is a primary, secondary or tertiary amino group, a compound of formula </ P> <P> fl- <I> IC </ I> c-CONH-f- <Sup> X </ Sup> <Sub> T </ Sub> </ P> <p>. "J Il ^ <Sup> e </ Sup> -N <Sub> v </ sub> - ^ - CH-R, (XVIII) </ P> <p> S N CT * <I> <sup> Δ ό </ Sup> </ I> </ P> <P> OR <Sub> 1 </ Sub> <Sup> R </ Sup> 4 </ P> in which y is halogen and R, "R <Sub> 2 </ sub>, R <Sub> 3 </ sub> and R. have the meanings given above, with ammonia or a primary or secondary amine Am-H, or a metal amide thereof, and, if necessary, splits off undesired protective groups in a compound obtained, and / or if desired, converting a salt-forming group-having compound into a salt, or a salt obtained, into a free compound or other salt. </ P> <P> <u> Process a) (A Optionally existing radicals which substitute the amino group and permit their acylation, radicals in a starting material of the formula II are, for example, organic silyl or stannyl groups, and also ylidene groups which form a Schiff base together with the amino group. The said organic silyl or stannyl groups are z, .B. the. which are also able to form a protected carboxyl group with the 4-carboxyl group on the cephem ring. In the silylation or stannylation of a carboxyl group in a starting material </ P> <P> 13 </ P> <P> of Formula II, using an excess of the silylation or stannylating agent, the amino group may also be silylated or stannylated. </ P> <p> The mentioned ylidene groups are primarily. Arylmethylengruppen ,. wherein aryl is in particular a carbocyclic, primarily monocyclic aryl radical, e.g. is optionally substituted by nitro or hydroxy, substituted phenyl. </ P> The remaining functional groups present in the starting materials of the formula II can be protected by the protective groups already mentioned among the compounds of the formula I. Preference is given to all reactive functional groups which do not participate in the acylation reaction, but in particular, if appropriate, precursors. ne, acylatable amino, hydroxy and mercapto groups, protected. </ P> The acylating agents which introduce the acyl radical of a carboxylic acid of the formula III are, for example, the carboxylic acid itself or reactive functional derivatives thereof. </ P> If a free acid of the formula III, in which all functional groups except the reactive carboxyl group may be protected, is used for acylation, it is customary to use suitable condensing agents, such as carbodiimides, for example N, N'-diethyl, Ν, Ν ' -Dipropyl, N, N'-dicyclohexyl or N-ethyl-N <Sup> 1 </ sup> -3-dimethylaminopropyl-carbodlimide, suitable carbonyl compounds, for example carbonyldiimidazole, or isoxazolinium-3'-sulphonate and N-tert-butyl-5-methylisoxazolinium perchlorate, or an acylamino compound, e.g. 2-ethoxy-1-ethoxycarbonyl-l, 2-dihydro-chlnolin. </ P> The condensation reaction is preferably carried out in an anhydrous reaction medium, preferably in the presence of a solvent or diluent, e.g. Methylene chloride, dimethylformamide, acetonitrile or tetrahydrofuran, if desired or necessary, with cooling or heating and / or in an inert gas atmosphere. </ P> <p> A reactive, i. Amide-forming functio-. The neat derivative of an acid of formula III, wherein all functional groups other than the reacting acid group can be protected, is primarily an anhydride of such an acid, inclusive and preferably a mixed anhydride. Mixed anhydrides are e.g. those with. inorganic acids, such as hydrohalic acids, i. the corresponding acid halides, e.g. chlorides or bromides, further with hydrazoic acid / i. the corresponding acid azides, with a phosphorous acid, e.g. Phosphoric acid, diethylphosphoric acid or phosphorous acid, or with a sulphurous acid, e.g. Sulfuric acid, or with hydrocyanic acid. Other mixed anhydrides are e.g. those with organic carboxylic acids, such as with optionally, e.g. by halogen, such as fluorine or chlorine, substituted lower alkanecarboxylic acids <I> </ I> e.g. Pivalic acid or trichloroacetic acid, or with half-esters, especially lower alkyl halides of carbonic acid, such as the Aethy1 ™ or isobutyl half-ester of carbonic acid, or with organic, in particular aliphatic or aromatic, sulfonic acids, e.g. p-toluenesulfonic acid. </ P> Further acid derivatives suitable for reaction with the amino group in an acid of the formula III in which all functional groups other than the reactive carboxyl group may be protected are activated esters, such as esters with vinylogous alcohols (ie enols, such as vinylogous loweralkenols) , or Iiairiomethylesterhalogeniden, such as Dimethyliminomethylesterchlorid (prepared from the carboxylic acid and dimethyl-chloromethyliden-iminium chloride of the formula [(CK <Sub> 3 N = CHCl] ^ Cl ^), or aryl esters such as 4-nitrophenyl or 2,3-dinitrophenyl esters, heteroaromatic esters such as benztriazole, e.g. 1-benztriazole ester, or diacyl-nino-ester, bis-succinylimino or phthalylimino esters. </ P> The acylation with an acid derivative, such as an anhydride, especially with an acid halide, is preferably carried out in the presence of an acid-binding agent, for example an organic base, such as an organic amine, e.g. a tertiary amine such as tri-lower alkylamine, e.g. Trimethylamine, triethylamine or acetyl-diisopropylamine, or Ν, Ν-di-lower alkyl-aniline, 2.B. Ν, Ν-dimethylaniline, or a cyclic tertiary amine, such as an N-lower alkylated morpholine, such as N-methylmorpholine, or a Fyridine-type base, e.g. Pyridine, an inorganic base, for example an alkali metal or alkaline earth metal hydroxide, carbonate or bicarbonate, e.g. Sodium, potassium or calcium hydroxide, carbonate or bicarbonate, or an oxirane, for example, a lower 1,2-Alkylenj such as ethylene oxide or Przpylenoxid performed. </ P> <p> 4 21 </ P> The above acylations are preferably carried out in an inert, preferably anhydrous solvent or solvent mixture, for example in a carboxamide, such as a formamide, ζ, Β. Dimethylformamide, a halogenated hydrocarbon, e.g. Methylene chloride, carbon tetrachloride or chlorine, benzene, a ketone, e.g. Acetone, an ester, 2.B. Ethyl acetate, or a nitrile, z, B. Acetonitrile, or mixtures thereof, at room temperature, if necessary, at reduced or elevated temperature, for example at -40 ° to about 100 °, preferably at -10 ° to + 40 °, and / or in a. Inert gas, e.g. Nitrogen atmosphere. </ P> The acylation can also be carried out in the presence of an acylase producing the desired amide bond. Such acylases are known. And are formed by a number of microorganisms, e.g. by Acetobacter, such as Acetobactet aurantium, Achrcxnobac ter, such as Achrctncbac ter aeris, Aeromonas, such as Aeromonas hydrophila, or Bacillus meg'aterium, e.g. 400. Into the enzymatic acylation are in particular amides, esters or thioesters, such as corresponding lower alkyl, e.g. Methyl or ethyl ester, the carboxylic acid of formula III used. The enzymatic acylation is carried out in a nutrient medium containing the microorganism, in a filtrate of the culture broth or, if appropriate, after isolation of the acylase, including after adsorption to a medium at 30-40 °, in a aqueous medium optionally containing a buffer. preferably at about 37 °. , </ P> In an acylating acid of the formula III or in an acid derivative thereof, a protected amino group may also exist in ionic form, i. the starting material of formula III may be in the form of an acid addition salt, preferably with a strong inorganic acid such as a hydrohalic acid, e.g. Hydrochloric acid, or sulfuric acid can be used. </ P> Further, an acid derivative may be added if desired <U> situ </ u> are formed. Thus, for example, a mixed anhydride by treating an acid of formula III, with appropriately protected functional groups, or a suitable salt thereof, such as an ammonium salt, z.3. with an organic amine such as pyridine or 4-methylmorpholine, or a metal, e.g. Alkali metal salt, with a suitable acid derivative, such as a corresponding acid halide of an optionally substituted lower alkanecarboxylic acid, e.g. Trichloroacetyl chloride, with a half ester of a carbonyl halide, e.g. Ethyl chloroformate or isobutyl ester, or with a halide of a di-alkyl alcohol, e.g. Dläthylphosphorbromidat, and uses the thus obtained mixed anhydride without isolation. </ P> <P> <u> Process b) (conversion of the oxomethylene group with hydroxyl </ U> amines); In a compound of formula IV wherein functional groups are optionally protected, the oxo group in the 7β-acylamido group is converted to a hydroxyiminomethylene or R-substituted hydroxyiminomethylene group by treatment with hydroxylamine or a substituted hydroxylamine of formula H "N-O-R (V). </ P> <P> <I> 2 &gt; 1 </ I> </ P> <p> The reaction of the oxo group mi% of the hydroxylamine compound is carried out in a usual manner, e.g. by mixing the two reactants in a solvent such as water or an organic solvent such as an alcohol, e.g. Methanol, at a slightly elevated or reduced temperature, such as between about -20 ° to about + 100 °, preferably at about 0 ° to about 30 °, optionally in an inert gas such as Stickstoffatrüosphäre react; The hydroxy raminverbindung, also in situ, from one of its salts, for example a Hydrohaiogenid such as hydrochloride, by treatment with an inorganic base such as an alkali metal hydroxide, z.3. Sodium hydroxide, or an organic base such as a tertiary azin, e.g. a tri-lower alkylamine such as tri-lower alkylamine such as triethyl &amp; sin or ethyl-diisopropylamine, or a heterocyclic tertiary base such as pyridine. </ P> <P> a </ P> <p> 2-Cephem compound of the formula VI, the optionally protected carboxyl group in the 4-position preferably has the α-configuration. </ P> <p> 2-CeOHEM compounds of formula VT are isomerized by treating them with a weakly basic agent and isolating the corresponding 3-cephem compound. Suitable isotyping agents are e.g. organic, nitrogenous bases, in particular tertiary heterocyclic bases of aromatic character, </ P> <P> 3ί </ P> <p> primarily pyridine-type bases such as pyridine itself * as well as collidines or lutidines, further Chin.ölin, tertiary aromatic bases, e.g. those of the aniline type, such as N, N-di-lower alkyl anilines, e.g. N, N-dimethyl, aniline or Ν, Ν-diethylaniline, or tertiary aliphatic, azacycloaliphatic or araliphatic bases, such as Ν, Ν, Ν-tri-lower alkylamines, for example N, N, N-triethylamine, N, N-diisopropyl-N Ä'thylamin, N-lower alkyl azacycloalkanes, eg N-methyl-piperidine, or N-phenyl-lower alkyl-N, N-lower alkylamines, e.g. N-benzyl-N, N-dimethylamine, as well as mixtures thereof, such as the mixture of a pyridine-type base and a Ν, Ν, Ν-tri-lower alkylanine, e.g. Pyridine and triethylamine. Further, inorganic or organic salts of bases, especially of medium to strong bases with weak acids, such as alkali metal or ammonium salts of lower alkanecarboxylic acids, e.g. Sodium acetate, triethylammonium acetate or N-methyl-piperidine acetate, as well as other analogous bases or mixtures of such basic agents. </ P> <p> Isomerization with basic agents is preferably carried out in anhydrous medium, in the presence or absence of a solvent, such as an optionally halogenating, e.g. chlorinated, aliphatic, cycloaliphatic or aromatic hydrocarbon, or a Lösungsmitteigemisches, which can be used as Reaktionsmittei used under the reaction conditions 3asen at the same time as a solvent, under KQhlen, at room temperature or with heating, preferably in a temperature range from about -30 C to about +100 C, in an inert gas, eg Nitrogen atmosphere, and / or in a closed vessel. </ P> <P> <I> Sun </ i> available 3-cephem compounds <I> "sefa. </ i> in a manner known per se, e.g. by adsorption and / or crystallization, of any remaining 2-cephem ~ compounds. </ P> The isomerization of 2-cephem compounds of the formula VI is preferably carried out by oxidizing them in the 1-position, if desired separating an available mixture of isomers of the 1-oxides, and thus obtaining the 1-oxides of the corresponding 3-oxides. Cepheni Ver. reduced in quantity. </ P> As suitable oxidants for the oxidation in the position of 2-cephem compounds, inorganic inorganic peracids which have a reduction potential of at least +1.5 volts and consist of non-metallic elements, organic peracids or mixtures of hydrogen peroxide and acids, in particular organic </ P> <p> Carboxylic acids, with a dissociation constant of * - 5 </ P> <p> at least 10 in question. Suitable inorganic peracids are periodic acid and persulfuric acid. Organic peracids are corresponding percarboxylic and persulphonic acids which may be added as such or formed by use of at least one equivalent of hydrogen peroxide and a carboxylic acid in situ. It is expedient to use a large excess of the carboxylic acid, if e.g. Acetic acid is used as a solvent. Suitable peracids are e.g. Performic acid, peracetic acid, trifluoroperacetic acid, perrnalic acid, perbenzoic acid. acid, 3-chloroperbenzoic acid, monoperphthalic acid or p- </ P> <P> Toluolpersulfonsäure. · </ P> <P> to </ P> The oxidation can also be carried out using hydrogen peroxide. catalytic amounts of an acid having a dissociation constant of at least 10 ° C., it being possible to use low concentrations, for example 1-2% or less, but also larger amounts of the acid, the effectiveness of the mixture being primarily dependent on the starch the acid. Suitable mixtures are e.g. those of hydrogen peroxide with acetic acid, perchloric acid or trifluoroacetic acid. <Sub> t </ sub>. , </ P> <p> The above oxidation can be in the presence of </ P> For example, the oxidation with percarboxylic acids can be catalyzed by the presence of an acid having a dissociation constant of at least 10, the effectiveness of which depends on its strength Acids suitable as catalysts are, for example, acetic acid, perchloric acid and trifluoroacetic acid. Usually, at least equimolar amounts of the oxidizing agent are used, preferably a slight excess of from about 10% to about 20%, although larger excesses, ie up to 10 times the amount of the oxidizing agent or more, can be used , z.3 at temperatures of about -50 <Sup> 0 </ sup> C to about +100 <Sup> 0 </ sup> C, preferably about -10 <Sup> 0 </ sup> C to about +40 <Sup> 0 </ sup> C performed. , </ P> The reduction of the 1-oxides of 3-cephem compounds can be carried out in a manner known per se by treatment with a reducing agent, if necessary in the presence of an activating agent. Suitable reducing agents are, for example: </ P> <p> Catalytically activated hydrogen, using noble metal catalysts containing palladium, platinum or rhodium, which are optionally combined. </ P> <p> men rait a suitable support material, such as coal or ^ barium sulfate, - uses; reducing tin, iron, copper or manganese cations, which are in the form of corresponding compounds or complexes of inorganic or organic type, z, B, as stannous chloride, fluoride, acetate or formate, iron-IT-chloride , sulfate, oxalate or succinate, copper x-chloride, benzoate or oxyde, </ P> <p> • or manganese IX chloride, sulfate, acetate or oxide, or as complexes »e.g. with ethylenediaminetetraacetic acid or Nitrolotriessigsäure »are used; reducing dithionites, J.od or ferrous cyanide anions, which may be in the form of corresponding inorganic or organic salts, such as alkali metal, z, B. Sodium or potassium di-thionite, sodium or potassium iodide or iron II cyanide, or in Fortn the corresponding acids, such as Iodic acid used; reducing trivalne inorganic or organic phosphorus compounds, such as phosphines, furthermore esters, amides and halides of phosphorous, phosphonous or phosphorous acid, as well as phosphorus-sulfur compounds corresponding to these phosphorus oxygen compounds, wherein organic. Radicals are primarily aliphatic, aromatic or araliphatic radicals, e.g. optionally substituted lower alkyl, phenyl or phenyl-lower alkyl groups, e.g. Triphenylphosphine, tri-n-butylphosphine, diphenylphosphinacetic acid ester, diphenyl chlorophosphine, phenyl </ P> <p> 'dichlorophosphine, Benzolphosphonigsäuredimethyles ter, Butanphosphonigsäuremethy! ester, Phosphorigsäuretripheny1 ester, Phosphorigsäuretrime methyl ester, Phosphor trichlor id, Phosphortribroniid, etc.'; reducing halosilane compounds which have at least one hydrogen atom bonded to the silicon atom and which are other than halogen, such as chlorine, bromine or iodine, and organic radicals, such as aliphatic or aromatic groups, e.g. gegebenen- </ P> <p>, <U> fftw </ U> t <U> JB- </ u> MMOV U <I> VuS </ I> </ P> <p> -5 & -27.11.1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <p> if substituted him ed he alley 1- or phenyl groups may have, such as chlorosilane, bromosilane, di- or trichlorosilane <Sub>} Di-or '' -ribromosilane, diphenylchlorosilane, dimethylchlorosilane, dimethyliodosilane or halosilane compounds in which all hydrogens are replaced by organic radicals, vde '-Praniederalkylhalogensilan, z «B«, trimethyliodosilane, or cyclic, sulfur-containing silanes, such as 1,3-dithia-2,4-disilacyclobutane or 1,3,5-trithia-2,4,6-trisila-cyclohexane, whose silicon atoms are substituted by hydrocarbon radicals, in particular lower alkyl radicals, z »B <Sub> e </ sub> 2,2,4,4-tetramethyl-1,3-dithia-2,4-disilacyclobutane or 2,2,4,4,6,6-hexaniethyl-1,3,5-trithia-2, 4,6-trisilacyclohexane, etc .; reducing quaternary chloroethyleneimine salts, in particular chlorides or bromides, in which the imino group is represented by a bivalent or two inonovalent organic radical, <I> \ D.E. optionally substituted lower alkylene or lower alkyl groups, such as K-chloromethylene-1,1-di-ethyliminium chloride or N-chloro-ethylenepyrrolidinium chloride; and complex tetrahydrate hydrides, sodium borohydride, in the presence of suitable activators, such as cobalt (II) chloride, and borane dichloride, </ P> <p> As activating agents used together with those of the above-mentioned reducing agents which do not themselves have Lewis acid properties, d. hu, which are used primarily together with the dithionite, iodine or iron (II) cyanide and the non-halogenous trivalent phosphorus reducing agents or in the catalytic reduction, are in particular organic carboxylic and sulfonic acid halides, furthermore sulfur, Phosphorus or silicon halides having the same or greater second order hydrolysis constant than benzoyl chloride, z, B, phosgene, oxalyl chloride, acetic acid </ P> <p> chloride or broride, chloroacetic acid chloride; Pivalic acid, A-methoxybenzoic acid chloride »4-cyanobenzoic acid chloride, p-toluenesulfonic acid chloride, methanesulfonyl chloride, thionyl chloride, phosphorus oxychloride, phosphoric chloride, phosphorus tribromide ,. Ph-enyldichlorophosphine, .Benzolphosphonigsäuredichl-orid, DimeChylchlorsilan or trichlorosilane, further suitable acid anhydrides, such as trifluoroacetic anhydride, or cyclic sultones, such as Aetbansulton, 1, 3-Prppansulton, 1, 4-Bu sansulton. or 1,3-HexanesulEOn. </ P> The reduction is preferably carried out in the presence of solvents or mixtures thereof, the choice of which is determined primarily by the solubility of the starting materials and the choice of the reducing agent, e.g. Lower alkanecarboxylic acids or esters thereof, such as acetic acid and ethyl acetate, in the catalytic reduction, and e.g. optionally substituted such as halogenated or nitrated aliphatic cycloaliphatic, aromatic or araliphatic hydrocarbons, e.g. Benzene, methylene chloride, chloroform or nitromethane, suitable acid derivatives such as lower alkanecarboxylic acid esters or nitriles, e.g. Acetic acid "ethyl ester or acetonitrile, or amides of inorganic or organic acids, e.g. Prosthy! Formamide or hexametylphosphoridnide, ether, e.g. Diethyl ether, tetrahydrofuran or dioxane, ketones, e.g. Acetone, or sulfones, especially aliphatic sulfones, e.g. Dimethyl-oralanone or tetraraetbylene sulfone, etc., together with the '. chemical reducing agents, these solvents. preferably no water. It usually works at temperatures of about -20 ° C to about 100 ° C. <Sub> 5 </ sub> where the reaction can be carried out at lower temperatures when using highly reactive activating agents. ·. </ P> <P> <u> Process d) (thiadiazole ring formation) In a compound of the formula VII, X, as halogen, is, for example, chlorine, iodine or, preferably, bromine. Suitable salts of hydroxydic acid (thiocyanic acid) are for example alkali, alkaline earth or also heavy metal salts, e.g. the sodium, potassium,. , Magnesium or lead salt, or ammonium salts derived from ammonia or organic nitrogen bases, e.g. the ammonium salt, or mono-, di-, tri- or Tetraniederalkylammoniumsalze, wherein lower alkyl is methyl, ethyl, isopropyl or the like. </ P> Suitable isorhodanhydrates are, for example, isorhodanhydride lower alkyl esters, also referred to as lower alkyl isothiocyanates, such as methyl, ethyl, propyl or butyl isothiocyanate. </ P> The condensation of compounds of formula VII with a salt of rhodanilic acid or with rhodane gives compounds of formula (I) wherein Am is a free, primary amino group, while the condensation with a Isorhodanwasserstoff acid ester gives a compound of formula (I) in which Am is a free secondary amino group, for example a lower alkylamino group. </ P> The reaction is preferably carried out in an inert solvent such as a lower alcohol, e.g. Methanol, ethanol, propanol or isopropanol, an ether, such as diethyl ether, dioxane or tetrahydrofuran, an amide, such as dimethylformamide, an aliphatic or aromatic hydrocarbon, such as hexane, benzene or toluene and the like, or in mixtures thereof, optionally with cooling or heating, ie at temperatures between about -80 ° to about + 100 °, preferably between about -20 ° to about 20 °, optionally in an inert gas atmosphere. </ P> <p> A compound of formula VII wherein X is halogen may also be prepared in situ, optionally in the presence of the rhodan sulfate salt, for example by dissolving a compound of formula VII in which X is hydrogen in one of said Solvent with a hypohalite, for example '' 'sodium or' 'potassium hypobromite, or with a halogen and an alkali metal base, such as a hydroxide, carbonate or alkoxide, eg with bromine and sodium methylate or potassium carbonate. This halogenation takes place, preferably with cooling, e.g. at about -15 ° to about 0 ° instead. </ P> <p> A compound of formula VII wherein X is hydroxy can also be used in_ <U> situ are prepared, for example, by treating a compound of formula VII wherein X is hydrogen with an oxidizing agent such as hydrogen peroxide. </ P> The reaction of a compound of the formula VI. where X is hydrogen with the rhcdan also takes place in one of said inert solvents and under similar reaction conditions. Optionally, an acid addition salt of a compound of formula VII which is converted to the free compound in situ may also be employed, or the rhodan may be formed in ethyl acetate, e.g. from a Rhodanld, e.g. Blelorhodanide, and a halogen, e.g. Bromine. </ P> <P> <U> method </ u> e) (National Federation d <u> he me </ U> thylengruppe); In a compound of formula VIII, the functional groups are preferably protected. </ P> <P> • FRFC </ P> <Suitable> Nitrosating agents are nitrous acid and derivatives derived therefrom, such as nitrosyl halides, e.g. Nitrosylchloride or nitrosylbromide, salts of nitrous acid, such as alkali metal salts, e.g. Sodium or potassium nitrite, or in particular esters of nitrous acid, such as lower alkyl esters, e.g. Butyl, pentyl or especially iso-amyl nitrite. </ P> If a salt of nitrous acid is used as the nitrosating agent, the reaction is preferably carried out in the presence of a strong inorganic or else organic acid, such as hydrochloric acid, sulfuric acid, formic acid or acetic acid. When using an ester of nitrous acid, the reaction is preferably carried out in the presence of a strong base such as an alkali metal alkylate. </ P> The nitrosation is carried out in a suitable solvent such as water, a carboxylic acid, e.g. Acetic acid, a lower alcohol, ζ.B..methanol or ethanol, an ether, e.g. Dioxane or tetrahydrofuran, or a hydrocarbon, e.g. Hexane or benzene, or in mixtures thereof, under cooling or heating, in particular at about -15 ° to room temperature, carried out. </ P> <P> <u> Method f) (Alkylation and Carbamoyl </ U> l <u> ierung of Hydroxyjminogruppe) In the starting material of the formula If are alkylatable or carbamoylatable groups, except. reactive hydroxyimino group, preferably protected. </ P> The etherification of the free hydroxy group is carried out with a conventional * etherifying agent introducing the desired, optionally substituted lower alkyl or 'cycloalkyl R' radical. </ P> Suitable etherifying agents are, for example, diazo compounds such as diazo-lower alkanes or cycloalkanes, e.g. Diazomethane, diazoethane or diazo-n-butane, which may optionally be substituted in the alkane moiety. These reagents are dissolved in the presence of a suitable inert solvent, such as an aliphatic cycloaliphatic !! or aromatic hydrocarbon such as hexane, cyclohexane, benzene or toluene, a halogenated aliphatic hydrocarbon, e.g. Methylene chloride, or an ether such as a di-lower alkyl ether, e.g. Diethyl ether, or a cyclic ether / e.g. Tetrahydrofuran or dioxane, or a solvent mixture, and depending on the diazo reagent, with cooling, at room temperature or with gentle heating, further, if necessary, in a closed vessel and / or under an inert gas, for example Nitrogen atmosphere, brought to application. </ P> Further suitable etherifying agents are esters of corresponding alcohols, primarily those with strong inorganic or organic acids, such as mineral acids, e.g. Hydrohalic acids such as hydrochloric, hydrobromic or hydroiodic acid, furthermore sulfuric acid or hydrosulfuric acid, e.g. Fluorosulfuric acid, or strong organic sulfonic acids, as appropriate, e.g. by halogen, such as fluorine, substituted lower alkanesulphonic acids, or aromatic sulphonic acids, e.g. optionally, for example. benzenesulfonic acids substituted by lower alkyl, such as methyl, halo, such as bromo or nitro, for example methanesulfonic, trifluorororoethanesulfonic or p-toluenesulfonic acid, e.g. </ P> <P> Mi </ P> di-lower alkyl sulfates such as dimethyl sulfate, furthermore fluorosulfonic acid lower alkyl esters e.g. Fluorosulfonic acid methyl ester or optionally halogen-substituted methanesulfonic acid lower alkyl ester, e.g. They are usually prepared in the presence of an inert solvent, such as a given halogenated, such as chlorinated aliphatic, cycloaliphatic or aromatic hydrocarbon, <I> e.g. methylene chloride, an ether, such as dioxane or tetrahydrofuran, or a mixture. It is preferred to employ suitable condensing agents, such as alkali metal carbonates or bicarbonates, e.g. Sodium or potassium carbonate or bicarbonate (usually together with a sulfate), or organic bases such as, usually sterically hindered, tri-lower alkylamines, e.g. Ν, Ν-diisopropyl-N-ethyl-amine (preferably together with lower alkyl-halo-sulphates or optionally halo-substituted methanesulphonic acid-lower alkyl esters), whereby with cooling, at room temperature or with heating, e.g. at temperatures of about -20 <Sup> 0 </ sup> C to about 50 ° C </ P> <p> - and, if necessary, in a closed vessel and / or in an inert gas, 'ζ.B. Nitrogen atmosphere is worked. </ P> Further etherifying agents are corresponding acetals, e.g. gem-Niederalkoxynjederalkane, such as 2,2-di- </ P> <P>. methoxy-propane, which in the presence of a strong organic :! Sulfonic acid, such as p-toluenesulfonic acid, and a suitable </ P> <p> Solvent, such as a di-lower alkyl or lower alkylene sulfoxide, e.g. Dimethyisulfoxyd apply, or <Sup> 1 </ sup> Orthoester, e.g. Ortho-formic acid trinuclear alkyl ester, e.g. Orthoformic acid triethyl esters which are obtained in the presence of a strong mineral acid, e.g. Sulfuric acid, or a strong organic sulfonic acid, such as p-toluenesulfonic acid, and a suitable solvent, such as an ether, e.g. Dioxane, to be used. </ P> Other medications include corresponding tri-R-, oxonium salts (so-called seaweed salts), Di-R <Sub> 1 </ sub> -O-carbenium salts or di-R, -Haloniumsalze, wherein R- represents the introduced radical, for example Triniederalkyloxoniunsalze, and Diniederalkoxycarbenium- or Diniederalkylhaloniumsal2e, in particular the corresponding salts with complex, fluorous acids, such as the corresponding tetrafluoroborates, hexafluorophosphates , Hexafluoroantimonates or hexachloroantimonates. Such reagents are e.g. Trimethy1oxenium or triethyloxonium hexafluoroantimonate, hexachloroantimonate, hexafluorophosphate, or tetrafluoroborate, dimethoxycarbenium hexafluorophosphate or dimethylbromonohexa-fluoroanoninate. It is preferable to use these etherifying agents in an inert solvent such as an ether or a halogenated hydrocarbon, e.g. Diethyl ether, tetrahydrofuran or methylene chloride, or in a mixture thereof, if necessary, in the presence of a base such as an organic base, e.g. a, preferably sterically hindered, tri-lower alkylamine, e.g. N, N-diisopropyl-N-ethyl-amine, and with cooling, at room temperature or with gentle heating, e.g. at about -20 ° C to about 50 ° C, if necessary, in a closed vessel and / or in an inert gas, e.g. Nitrogen · atmos oxygen ·. </ P> <P> </ P> <p> - \ & - 27.11.1980 </ P> <p> ΛΡ C 07 D / 222 421. 57 771/18 </ P> Finally, further etherifying agents are corresponding "1-R-3-aryl triazene compounds, in which R.sup..the radical to be introduced and aryl preferably denotes an optionally substituted phenyl radical, B.sub.2 N-alkylkylphenyl, such as 4-methylphenyl ~ Aryl ~ 1-lower alkyl-triazenes, a * B. 3 ~ (4-methylphenyl) -1-ethyl-triazene, these reagents are usually in the presence of inert solvents, such as optionally halogenated hydrocarbons or ethers, for example, benzene , or solvent mixtures, and with cooling, at room temperature and preferably at elevated temperature, z, at about 20 <Sup> 0 </ sup> C to about 100 C, if necessary, in a closed vessel and / or in an inert gas, eg nitrogen atmosphere. </ P> <p> The introduction of a carbonyl group ~ C (= O) -NHR instead of the hydrogen atom is done in a known manner by carbamoylation. For this purpose, a compound of formula (If) in which all reactive groups which are not to be carbamoylated or which would consume and destroy the reagents are in protected form, optionally treated stepwise with a carbamoylating agent. Suitable carbamoylating agents are reactive derivatives of the carbamic acids R-HH-C (= O) OPI, in particular the isocyanates R-N = C = O or the mixed anhydrides, eg. B * the carbamic acid chlorides R-ITH-CC = C) Cl, which are also in situ from phosgene and an Ami η R -IJH <Sub> 2 </ sub> can be produced « </ P> The conversion with the isocyanates is carried out in one of the customary inert solvents, for example an optionally halogenated hydrocarbon, for <Sub> e B, benzene, xylene or methylene chloride, an ether, e.g. B * diethyl ether, dioxin </ P> <p> xan or tetrahydrofuran, or an ester, e.g. Ethyl acetate, optionally in the presence of a basic catalyst, for example a tertiary amine, e.g. Triäthyl- '' amine or pyridine, at room temperature or slightly reduced or elevated temperature, for example between -20 ° and + 50 °. </ P> <p> For conversion with a mixed anhydride of the carbamic acid, the alcohol group is advantageously first metallized, for example with an alkali metal hydride, e.g. Sodium or lithium hydride. The compound of the formula If) which has been metallated at the hydroxyl group can also be reacted first with phosgene "and then with the amine R-NH <Sub> 2 be treated </ sub> and gradually carbamoylated in this way. These reactions also take place in an inert solvent and at the temperatures given above. </ P> <p> Method g) (alkoxyification of 7a-position); In a compound of the formula If in which all functional groups are in protected form, the 7a-lower alkoxy group R <Sub> 2 in a manner known per se, for example by sequentially mixing said intermediate with an anion-forming agent, an N-halogenating agent and a lower alkanol. treated. </ P> A suitable anion-forming agent is primarily an organometallic base, especially an alkali metal, primarily a lithium-organic base. Such compounds are especially appropriate. Alcoholates, such as suitable lower alkyl lower alkanolates, primarily lithium ethylate, or corresponding metal hydrocarbon bases <Sub> s </ sub> such as lithium lower alkanes and lithium phenyl. The reaction with the anion-forming organometallic base is usually carried out with cooling, e.g. from about 0 ° C to about -80 ° C, and in the presence of a suitable solvent or diluent, <I> z. </ I> B. one </ P> <P> <I> SI </ P> <p> -KZ- </ I> </ P> ethers, such as tetrahydrofuran, using lithium methylate also in the presence of methanol, and, if desired, in a closed vessel and / or in an inert gas, e.g. Nitrogen atmosphere, recommended. </ P> As an N-halogenating agent, it is customary to use a hindered organic hypohalite, especially chlorite, and especially a corresponding aliphatic hypohalite, e.g. -chloric acid, such as a tert-lower alkyl hypochalogenite, e.g. -chlorit. In the first line, tert-butyl hypochlorite is used, which is reacted with the non-isolated product of the anionization reaction. </ P> <p> The N-halogenated intermediate compound is converted to a 7-acyliminocephem compound in the presence of an excess of the anion-forming base, in particular lithium ethylate, under the reaction conditions and without being isolated, and converted into a Ta-lower alkoxy compound by addition of the lower alkanol. cephem compound transferred. If necessary, must be removed from the N-halogenated intermediate, the elements of hydrogen halide, especially hydrochloric acid; this is done by adding a hydrogen halide split-off base, such as a suitable alkali metal lower alkanolate. e.g. Lithium tert-butoxide, which reaction usually takes place under the conditions of the anion and N-halogen compound-forming reaction, wherein one can work in the presence of methanol and instead of the acylimino directly the 7a-lower alkoxy-cephem compound can be obtained. One usually starts from a compound of the formula If in which functional groups are present in protected form, these are reacted with an excess of the anion-forming agent, e.g. Lithium methylate or phenyllithium, in the presence of methanol, then treated with the N-type coagulant, z.3. tert. "hypochlorite, </ P> <P> 5i </ P> <p> and thus directly obtains the desired compound of formula I in which functional groups are protected. You can also add the Nlederalkanol subsequently added, wherein the dehydrohalogenation and the addition of the lower alkanol at. , slightly higher temperatures than the anion, and <Sub>; </ sub> N-halogeno-linking reactions, e.g. at about O <Sup> 0 </ sup> C to about -20 <Sup> 0 </ sup> C, if necessary, in a closed vessel and / or in an inert gas, e.g. Nitrogen atmosphere, can perform. <Sup> 1 </ Sup> </ P> <p> In the above reactions conducted under basic conditions, 3-cephem compounds, optionally partially, can isomerize to 2-cephem compounds. A 2-cephem compound obtained or a mixture of a 2- and a 3-cephem compound can be isomerized in a manner known per se to the desired 3-cephem compound. </ P> <P> <U> AV </ U> a to hear h) (Th </ U> i <U> olisier </ u> u-ng); In a starting material of the formula Ih, a suitable Rf which can be replaced by a heterocyclylthio group is, for example, one of the cited acyloxy groups R <Sub> 3 </ sub>, such as a hydroxy group esterified by an optionally substituted lower aliphatic carboxylic acid, or one of the said sulfonyloxy groups R_. Such esterified hydroxy groups R ° are in particular acetyloxy, furthermore formyloxy and acetoacetyl; as well as mesyloxy or tosyloxy. </ P> The reaction of such a compound with a heterocyclic mercaptan compound H-R- may be in the presence under neutral or weakly basic conditions. Water and optionally a water-miscible organic solvent. The basic conditions 'can' be achieved, for example, by adding an inorganic base / such as an alkali metal or alkaline earth metal. </ P> <P> <i> K ti </ I> <I> </ I> JS </ P> <p> metal hydroxide, carbonate or bicarbonate, e.g. as organic solvents, for example water-miscible alcohols, for example lower alkanols, such as methanol or ethanol, ketones, for example lower alkanones, such as acetone, amides, for example lower alkanecarboxamides The reaction is carried out at room temperature or, depending on the reactivity, under cooling or gentle heating, optionally the thiolation may be carried out in the presence of water-soluble salts of the formula (II) Hydroiodic acid and / or thiocyanic acid, such as corresponding alkali metal, alkaline earth metal, ammonium or quaternary ammonium salts, including phase-transferring salts Suitable salts include, for example, lithium, potassium, magnesium, calcium, and especially sodium and tetra-n .butylammonium iodide The reaction is then preferred in concentrated aqueous solutions of these salts. </ P> <Heading> <i> Method i) (Acylation of 3-hydroxymethyl group): </ U> </ Heading> In a starting material of the formula If, all acylatable groups, except the 3-hydroxymethyl group to be acylated, are preferably present in protected form. </ P> The acylation is carried out according to methods known per se by treatment with an acylating agent introducing the desired acyl radical Suitable acylating agents are the free acid itself or a reactive functional derivative thereof, such as an anhydride, including a mixed anhydride or an internal anhydride. or an activated ester. </ P> <p> If a free acid H-R, is used for acylation, suitable condensing agents are used, such as carbodiimides, for example M, N <Sup> 1 </ sup> -Dläthyl-, Ν, Ν'-di- </ P> <p> propyl, N, N'-dicyclohexyl or N-ethyl-N <Sup> 1 </ sup> -3-dimethylaminopropjl-carbodiimide, suitable carboxyl compounds, for example, carbonyldiimidazole, or "isoxazoliniuin-3 <Sup>: </ sup> - sulfonate and N-tert-butyl-S-methylisoxazolinium perchlorate, or an acylamino compound, e.g. 2 ~ ethoxy ~ l ~ l-ethoxycarbonyl, 2-dihydroquinoline. </ P> The condensation reaction is preferably carried out in an anhydrous reaction medium, preferably in the presence of a solvent or diluent, z. Methylene chloride, dimethylformamide, acetonitrile or Tetrahy & rofu-s ran, if desired or necessary, carried out under cooling or heating and / or in an inert gas atmosphere. </ P> A reactive, i.e., ester-forming, functional derivative of an acid is primarily an anhydride of such an acid, inclusive, and preferably a mixed anhydride, but also an internal anhydride, i. a corresponding ketene or a corresponding isocyanate. Mixed anhydrides are e.g. those with inorganic acids, such as hydrohalic acids, i. the corresponding acid halides, e.g. chlorides or bromides, further with hydrazoic acid, i. the corresponding acid azides, with a phosphorus acid, e.g. Phosphoric acid or phosphorous acid, or with a sulfur-containing acid, e.g. Sulfuric acid, or, with hydrogen cyanide acid. Other mixed anhydrides are e.g. those with organic carboxylic acids, such as with optionally, e.g. halogenated, such as fluorine or chlorine, substituted lower alkanecarboxylic acid, <I> z. </ I> B. Pivalic acid or trichlorethylene. acetic acid, or mit'Halbestern, in particular Niederalkylhalbestefn "of carbonic acid, such as the Aethyi- or isobutyl </ P> <p> semi-esters of carbonic acid, or with organic, in particular aliphatic or aromatic, sulfonic acids, z.3. p-toluene sulfonic acid. </ P> <p> Activated esters suitable for reaction with the hydroxy group are e.g. Esters with vinylogous alcohols (i.e., enols), such as vinylogous lower alkenols, or iminomethyl ester halides, such as dimethyliminomethyl ester chloride (prepared from the carboxylic acid and dimethylchloromethyl-iminium chloride of the formula [(CH <Sub> 3 N = CHCl] S ^ or aryl esters such as 4-nitrophenyl or 2,3-dinitrophenyl esters, heteroaromatic esters such as senzriazole, e.g. </ P> <p> 1-Benzotriazole esters, or diacylimino esters, such as succinyl-irino or phthalyl-imino esters. </ P> The acylation with an acid derivative, such as an anhydride, especially with an acid halide, is preferably carried out in the presence of an acid-binding agent, for example an organic base, such as an organic amine, e.g. a tertiary amine such as tri-lower alkylamine, e.g. Triethylamine, triethylamine or ethyl-diisopropylamine, or Μ, Ν-di-lower alkyl-aniline, z.3. N, N-dimethylaniline, or a cyclic tertiary amine, such as an N-lower alkylated morpholine, such as N-methylmorpholine, or a pyridine-type base, z.3. Pyridine, an inorganic base, for example, an alkali metal or alkaline earth metal hydroxide. carbonates or bicarbonates, e.g. Sodium, potassium or calcium hydroxide, carbonate or bicarbonate, or an oxlane, for example a lower 1,2-alkylene oxide, such as ethylene oxide or propylene oxide. </ P> The above acylations are preferably carried out in an inert, preferably anhydrous solvent or solvent mixture, for example in a carboxamide, such as a formamide, e.g. Dimethylformamide, a halogenated hydrocarbon, z.3. Methylene chloride, carbon tetrachloride or chlorobenzene, a ketone, e.g. Acetone, an ester, e.g. Ethyl acetate, or a nitrile, e.g. Acetonitrile, or mixtures thereof, </ P> <p> at room temperature, if necessary, at reduced or elevated temperature, such as from -40 ° to about + 100 °, preferably at -10 ° to + 40 °, and / or in an inert gas, such as nitrogen atmosphere. </ P> Further, an acid derivative may, if desired, be included in <U> situ </ u> are formed. Thus, for example, a mixed anhydride by treating an acid H-R- with appropriately protected functional groups, or a suitable salt thereof, such as an ammonium salt, e.g. with an organic amine, such as pyridine or 4-methylmorpholine, or a metal, e.g. Alkali metal salt, with a suitable acid derivative, such as a corresponding acid halide of an optionally substituted lower alkanecarboxylic acid, e.g. Trichloroacetyl chloride, with a half ester of a carbonyl halide, e.g. Chloroformic acid ethyl ester or isobutyl ester, or with a halide of a di-lower alkyl phosphoric acid, e.g. Diäthylphosphorbromidat, and uses the thus obtained mixed anhydride without isolation. </ P> To introduce a carbamoyl group, the compound of formula If is reacted with a suitable carbonic acid derivative, especially with an isocyanate or carbamic acid compound such as a silyl isocyanate, e.g. Silyl tetraisocyanate, a sulfonyl isocyanate, e.g. Chlorosulfonyl isocyanate, with a carbamic acid halide, e.g. chloride (resulting in N-unsubstituted 3-aminocarbonyloxymethyl linkages) or then with an N-substituted isocyanate or with an N-mono- or N, N-disubstituted carbamic acid compound such as a corresponding carbamic acid halide, e.g. chloride, usually in the presence of a solvent or diluent, and, if necessary, with cooling or heating, in a closed vessel and / or in an inert gas, e.g. Nitrogen breath, works. </ P> <P> 27,11.1980 </ P> <p> APC 07 D / 222 421 </ P> <p> 57 771/18 </ P> <p> Procedures j) (Overtraining "the" <i> e e </ U> </ P> In a starting compound of the formula I, the protected carboxyl group R. is obtained in a manner known per se, such as by solvolysis, in particular hydrolysis, alcoholysis or cydolysis, or by reduction, in particular hydrogenolysis or chemical reduction , optionally in stages and optionally equilateral with other protected functional groups released. </ P> <p> So you can z. B, an optionally in 2 ~ position by a Siiylgruppe or in 1- <Sup> ü by lower alkyl or lower alkylthio-substituted lower alkoxycarbonyl group, a polycycloalkoxycarbonyl or a diphenylmethoxycarbonyl group by treatment with a suitable acidic agent, such as formic acid or 'J-difluoroacetic acid, optionally with the addition of a nucleophilic compound, such as phenol or <Sup> A </ sup> nisole into the free carboxyl group. An optionally substituted - enzyloxycarbonylgruppe can, for. B, by hydrogenolysis by treatment with hydrogen in the presence of a hydrogenation catalyst, such as a palladium catalyst, released. Perner can be selected from certain benzyloxycarbonyl groups, ie from 4-bisbenzyloxycarbonyl, also by means of chemical reduction, eg. B <Sub> 4 </ sub>, by treatment with an alkali metal, e.g. B * sodium dithionite, or with a reducing metal, e.g. <Sub> o B. Zinc, or metal salt, such as a H'rom II salt, e.g. For example, chromium (II) chloride, usually in the presence of a hydrogen donating agent which is capable of producing nascent hydrogen with the metal, such as an acid, primarily a carboxylic acid or hydroxycarboxylic acid, especially acetic acid, formic acid, glycolic acid , Diphenylglycolsäure, Liil-ch, acid, Ivia.nd el acid, p-chloromandelic acid, V7einsäure, and the like or an alcohol or <Sup> > J </ sup> -hiols, whereby </ P> Add water, adding '*' to the free carboxyl group. By treating with a reducing metal or metal salt as described above, one may also convert a 2-halo-lower alkoxycarbonyl group (optionally after conversion of a 2-bromo-lower alkoxycarbonyl group to a 2-iodo-lower alkoxycarbonyl group) or an aroylmethoxycarbonyl group into the free carboxyl group an aroylmethoxycarbonyl group may also be cleaved by treatment with a nucleophilic, preferably salt-forming, reagent, such as sodium thiophenolate or sodium ajodide. A substituted silylethoxycarbonyl group may also be prepared by treating with a hydrofluoric acid salt which provides fluoride anion, such as an alkali metal fluoride, e.g. Sodium or potassium fluoride, in the presence of a macrocyclic poly-ether ("crown ether"), or with a fluoride of an organic quaternary base, such as tetraalkylammonium fluoride or trialkylarylanxmonium fluoride, e.g. Te.craäthylaamoniuxQ »fluoride or Tetrabutylanancniumfluorid, in the presence of an aprotic polar solvent, such as dimethyl sulfoxide or Ν, Ν-dimethylacetamide, in the free carboxyl group .Übergeführt. A polyhaloaryloxycarbonyl group, such as the pentachlorophenyloxycarbonyl group, is saponified to the free carboxyl group under mild basic conditions, such as dilute sodium hydroxide or organic bases in the presence of water. </ P> <p> An e. g. by silylation or stannylation </ P> <p> protected carboxyl group can be prepared in a conventional manner, for example ' by treatment with water or an alcohol, free </ P> <p>. , </ P> <P> FCoE </ P> <P> <u> Process k) (esterification of 4-carboxyl group): The conversion of the free carboxyl group in a compound of the formula Ik into an esterified carboxyl group, in particular into one which is cleavable under physiological conditions, takes place by esterification methods known per se, for example by reacting a compound of the formula Ik, wherein other functional groups such as amino, hydroxy or sulfo groups, optionally in protected form, or a functional derivative thereof reactive with the esterifying carboxyl group, or a salt thereof, are esterified with a corresponding alcohol or a reactive functional derivative thereof , </ P> <p> Suitable reactive functional derivatives of the carboxyl group to be esterified are anhydrides, especially mixed anhydrides, and activated esters. </ P> The esterification of the free carboxyl group with the desired alcohol is carried out in the presence of a condensing agent. </ P> Common condensing agents are carbodiimides, for example N, N'-diethyl, N, N'-dipropyl, N, N <Sup> 1 </ sup> -Dicyclohexyl- or N-ethyl-N <Sup> 1 </ sup> -3-dimethylamino-1-carbodiimide, suitable carbonyl compounds, for example carbonyldiimldazole, or isoxazolinium-3'-sulphonate and N-tert-butyl-5-methylisoxazolinium perchlorate, or an acylamino compound, e.g. 2-ethoxy-1-ethoxyoxycarbonyl-1,2-dihydroquinoline. , · ' </ P> The condensation reaction is preferably carried out in an anhydrous reaction medium, preferably in the presence of a solvent or diluent, e.g. methylated </ P> </ P> lenchloride, dimethylformamide, acetonitrile or tetrahydrofuran, if desired or necessary, with cooling or heating and / or in an inert gas atmosphere </ P> For example, mixed anhydrides are those with inorganic acids, such as hydrohalic acids, i. the corresponding acid halides, e.g. chlorides or · bromides, further with hydrazoic acid, i. the corresponding acid azides, with a phosphorus acid, e.g. Phosphoric acid, diethylphosphoric acid or phosphorous acid, or with a sulphurous acid, e.g. Sulfuric acid, or with hydrocyanic acid. Other mixed anhydrides are e.g. those with organic carboxylic acids, such as with optionally, e.g. halogen, such as fluorine or chlorine, substituted lower alkanecarboxylic acids, e.g. Pivalic acid or trichloroacetic acid, or with half esters, especially lower alkyl halides of carbonic acid, such as the ethyl or Isobutylhalbester of carbonic acid, * or with organic, especially aliphatic or aromatic, sulfonic acids. e.g. p-toluene sulfonic acid. </ P> <p> Activated esters suitable for reaction with the alcohol are e.g. Esters with vinylogous alcohols (i.e., eno-len), such as vinylogous lower alkenols, or iminomethyl ester halides, such as dimethyliminomethyl ester chlorite (prepared from the carboxylic acid and dimethyl chloromethylidene iminium chloride of the formula [(CH) <Sub> 2 N, CHC1 !, ClCl), or aryl esters, such as 4-nitrophenyl or 2,3-dinitrophenyls, heteroaromatic esters, such as benzotriazole, e.g. l-benzotriazole esters, or diacylimino esters such as succinylimino or phthalylinoin esters. </ P> The acylation with an acid derivative, such as an anhydride, especially with an acid halide becomes </ P> <p> preferably in the presence of an acid-binding agent, for example an organic base such as an organic amine, e.g. a tertiary amine such as tri-lower alkylamine, e.g. Trimethylamine, triethylamine or ethyl-diisopropylamine, or Ν, Ν-di-lower alkyl-aniline, e.g. Ν, Ν-dimethylaniline, or a cyclic tertiary amine such as an N-lower alkylated morpholine, such as N-methylmorpholine, or a pyridine-type base, e.g. Pyridine, an organic base, for example an alkali metal or alkaline earth metal hydroxide, carbonate or bicarbonate, e.g. Sodium, potassium or calcium hydroxide, carbonate or bicarbonate, or an oxirane, for example a lower 1,2-alkylene oxide, such as ethylene oxide or propylene oxide. </ P> The above acylations are preferably carried out in an inert, preferably anhydrous solvent or solvent mixture, for example in a carboxylic acid amide, such as a formamide, e.g. Dimethylformamide, a halogenated hydrocarbon, e.g. Methylene chloride, carbon tetrachloride or chlorobenzene, a ketone, e.g. Acetone, an ester, e.g. Ethyl acetate, or a nitrile, e.g. Acetonitrile, or mixtures thereof, at room temperature, if necessary, at reduced or elevated temperature, for example at -40 ° to about + 100 °, preferably at -10 ° to + 40 °, and / or in an inert gas , eg Nitrogen atmosphere. </ P> Further, if desired, the acid derivative may be incorporated in <U> situ </ u> are formed. Thus, for example, a mixed anhydride by treating the carboxylic acid with appropriately protected functional groups, or a suitable salt thereof, such as an ammonium salt, e.g. with an organic amine, such as pyriolin or 4-methylmorpholine, </ P> <p> 27.11.1 S80 </ P> <p> AP C 07 D / 222 421 </ P> <p> 57 771/18 </ P> <p> or a metal, z * B «alkali metal salt, .with a suitable acid derivative, such as a corresponding acid halide of an optionally substituted lower alkanecarboxylic acid, e.g. B. richloroacetylchlorid, with a half ester of a Kohlensäurehaiblialogenids, z »B" ethyl chloroformate or -isobutylester, or with a halide of a Diniederalkylpliosphorsäure, e.g. Biophylphosphorbromidat, and uses the thus obtained mixed anhydride without isolation, </ P> <p> Method 1) <U> (From </ u> Exchange .V <Sub> 1 </ sub> Qn Y vs.., Amine AmH) J <Sub> n In a compound of the formula XVIII, Y is bromine, iodine or preferably chlorine. </ P> The amines Am-H are in free form, i <Sub> e </ sub> h. as ammonia, lower alkylamine, such as methyl, ethyl, propyl or butylamine, or di-lower alkylamine, such as dimethyl, diethyl, dipropyl, ditmethyl, ethyllethyl, ethyl-propyl, methylbutyl, propyl Butylamine or the like or in the form of metal amides thereof, for example as .Alkalimetallamidej such as lithium, sodium or potassium amides, used » </ P> The exchange reaction preferably takes place in an inert organic solvent, such as benzene, toluene, dimethylformamide, tetrahydrofuran, or the like, or, when Y is exchanged for MIp, also in liquid ammonia, whereupon the acid HY is intercepted, such as tertiary amines, <I> Z <Sub> 9 </ Sub> </ I> B <Sub> 8 </ sub> ethyl-diisopropylamine, pyridine or the like can be added » </ P> <p> The reaction is, ever <I> by </ i> Reactivity, at room temperature or with cooling or heating, between about -70 <Sup> 0 </ sup> C and about +100 <Sup> 0 </ sup> C, preferably between about -70 <Sup> 0 </ sup> C and about +50 <Sup> 0 </ Sup> C <Sub> β </ sub>. </ P> <P> <I> bif </ I> </ P> <P> Abspa <u> Protection of protecting groups In a resulting compound of formula I wherein one or more functional groups are protected, these, e.g. protected carboxyl, amino, hydroxy, mercapto and / or sulfo groups, in a conventional manner, such as by solvolysis, in particular hydrolysis, alcoholysis or'Acidolyse, or by reduction, in particular hydrogenolysis or chemical reduction, optionally released stepwise or simultaneously become. </ P> The transfer of a protected into a free carboxyl group can be carried out according to process j). </ P> <p> A protected amino group, e.g. Am, is known per se and depending on the nature of the protecting groups in a variety of ways, e.g. by solvolysis or reduction, released. A 2-halo-lower alkoxycarbonylamino group (optionally after conversion of a 2-bromo-lower alkoxycarbonyl group to a 2-iodo-lower alkoxycarbonyl group), an acylmethoxycarbonylamino group or a 4-nitrobenzyloxycarbonylamino group can be e.g. by treating with a suitable chemical reducing agent such as zinc in the presence of a carboxylic or α-hydroxy carboxylic acid such as aqueous acetic acid, an aroylmethoxycarbonylamino group also by treating with a nucleophilic, preferably salt-forming reagent such as sodium thiophenolate, and a 4-nitro-benzyloxycarbonylamino group also by Eehandeln with an alkali metal, eg Natriuindithionit, a Diphenylmethoxycarbonylaaino-, tert-Niederalkoxycarbonylamino-, 2- (S. <Sub> 1 </ Sub>) (S <Sub> 2 </ sub>) (S ^) - Silyläthoxycarbonylaaiino- or Folycycloälkoxycarbonylaminogruppe by treating e.g. mii: ants or trifluoroacetic mure, an optionally substituted benzyloxycarbonylamino group 2.3. </ P> <p> 65 "- ^ </ P> by hydrogenolysis by treatment with hydrogen in the presence of a hydrolyzate catalyst, such as a palladium catalyst, a triarylmethyl group, e.g. by treating * with: aqueous mineral acid, and an axaiyl group protected with an organic silyl or stannyl group, e.g. be released by hydrolysis or alcoholysis. An amino group protected by 2-haloacetyl, such as 2-chloroacetyl, may be prepared by treatment with thiourea in the presence of a base, or. with a thiolate salt, such as an alkali metal thiolac <I> the </ i> thiourea and subsequent solvolysis, such as alcoholysis or hydrolysis, <I> the </ i> resulting condensation product are released. An amino group protected by a substituted-silylethoxycarbonyl group may also be converted to the free amino group by treatment with a salt of hydrofluoric acid which provides fluoride anions, as indicated above for the release of a suitably protected carboxyl group. A phosphorus, phosphine or phosphinamido group may be prepared by treatment with a phosphorus-containing acid, such as a phosphorous phosphonic or phosphinic acid, e.g. Orthophosphoric acid or polyphosphoric acid, an acidic ester thereof, z.3. Monomethyl, monoethyl, dimethyl or Diathylphosphat or monomethylphosphonic acid, or an anhydride thereof, such as phosphorus pentoxide, and the like, are converted to the free amino group. ' </ P> A protected in the form of an azido Arainogruppe is converted in a conventional manner by reduction, in the free amino group, for example by catalytic hydrogenation with hydrogen and a hydrogenation catalyst such as platinum oxide, palladium, or Raney nickel, or by Zinc and acid, such as acetic acid. </ P> The catalytic hydrogenation is preferred in e.einer. th solvents, such as a halogenated hydrocarbon, e.g. Methylene chloride, or in water or a mixture of water and an organic solvent such as an alcohol or IJioxan, at about 20 to 25 °, or at reduced or elevated temperature, performed. </ P> <p> A hydroxy group protected by an acyl group, a silyl or stannyl group or by an optionally substituted α-phenyl-lower alkyl group is liberated as a correspondingly protected amino group. A hydroxy group protected by 2,2-dichloroacetyl is released by acid hydrolysis and a hydroxy group protected by a 2-oxa or 2-thia-aliphatic or -cyclic-aliphatic hydrocarbon radical is liberated by acidity. </ P> <p> A protected sulfo group is released analogously to a protected carboxyl group. , · </ P> Preferably, the protecting groups are selected so that they can all be simultaneously cleaved, for example acidolytically, as by treatment with trifluoroacetic acid or formic acid, or reductively, as by treatment with zinc and glacial acetic acid, or with hydrogen and a hydrogenation catalyst, such as a palladium / Coal catalyst. </ P> The described cleavage reactions are carried out under conditions known per se, if necessary with cooling or heating, in a closed vessel and / or in an inert gas, e.g. Nitrogen · atmosphere. , - </ P> <P>. '-63- AP C 07 D / 222 421 </ P> <p> 57 771/18 </ P> Salts of compounds of the formula I having salt-forming groups can be known per se <Sup> w Thus, one can prepare salts of compounds of the formula I with acidic groups, eg <Sub> e form B, by treatment with metal compounds, such as alkali metal salts of suitable carboxylic acids, the sodium bicarbonate of cG-Aethyleapronsäure or IJatriumbicarbonat, or with ammonia or a suitable organic amine, wherein preferably stoichiometric amounts or only a small excess of the salt-forming agent, acid addition salts of compounds of formula I are obtained in the usual way, z <Sub> e </ B> B, by treatment with an acid or a suitable anion exchange reagent. Internal salts of compounds of the formula I which contain a free carboxyl group can z * B * by neutralizing salts, such as acid addition salts, to the isoelectric point, z, B <Sub> e </ sub> with weak bases, or by treatment with liquid ion exchangers. </ P> Salts can be converted into the free compounds in customary manner. Metal salts and ammonium salts z, B, by treatment with suitable acids, and acid addition salts, eg <Sub> e </ B> B, by treatment with a suitable basic agent, </ P> The process also encompasses those embodiments according to which starting compounds used as intermediates are used as starting materials and the remaining process steps are carried out with them, or the same is experienced on any one of them <Sup> ö </ sup> tufe is canceled; Further, iron may be used in the form of derivatives or formed during the reaction. </ P> <p> Preferably, such starting materials are used and the .Reaktionsbedingungen chosen so that one arrives at the compounds listed above as particularly preferred. </ P> <P> <u> Preparation of the starting compounds </ U>: </ P> <p> Starting compounds of the formula II and corresponding compounds having protected functional groups are known or can be prepared in a manner known per se. </ P> <p> Starting compounds of the formula III and processes for their preparation have not been previously known. These compounds can be prepared according to the following reaction scheme: </ P> <p> N. · -CH. </ P> <p> - if JL Am- · N </ P> <P> IX </ P> <P> Level </ P> <P> On </ P> <P> <Sup> 1 </ Sup> - </ P> <P> <u> Level 2 </ U> </ P> <P> V * </ P> <p> N · -CH <Sub> 0 </ Sub> -COOH </ P> <P> At the "-V <I> β </ I> </ P> <P> XI </ P> <P> ο <i> </ I> <Sup> ww </ sup> "* ί ίι-i- <Sup> COOH </ Sup> <u> Stage 4a) </ U> </ P> <P> <U> Level </ U> <I> <U> X </ U> </ I> On <Sup> 1 </ sup> - · N O </ P> <P> XII </ P> <p> Level 4b) </ P> <p> HN = C C -COOH X-N = C C r COOH </ P> <P> OR <Sup> 0 </ sup> N <U> Level </ U> <I> <U> 6, </ U> </ i> NH, ν level 4c) </ P> <P> <I> K </ I>; , or </ P> <P> XV </ P> <p> Level 5 </ P> <P> <Sub> N </ Sub> = c-C-COOH </ P> <p> XIII Level 7 </ P> <p> μ ,, "£ -COOH ν ν </ P> <P> <Sup> y </ Sup> " <Sup> e </ Sup> \ <Sub> e </ sub> / ¥ <Sub> D </ sub> Stage 4d). in </ P> <p> S OR-j ^ </ P> <P> XIV </ P> <P> XIX </ P> <p> - 5-5- </ P> <p> Step 1: Compounds of the formula IX are known or can be prepared in a manner known per se. * </ P> <p> In the known compounds of formula IX, a primary or secondary amino group is prepared by one of the usual methods, e.g. Acylation or silylation and the like, or alkylation, converted to a protected or tertiary amino group Am. A protected amino group Am <Sup> 1 </ sup> is one of the protected amino groups listed under Am, in particular one of said Acy! amino groups, in particular tert.Butoxycarbonylamino or N-methyl-tert.butoxycarbonylamino. A tertiary amino group Am <Sup> 1 </ sup> is e.g. one of the di-lower alkylamino groups mentioned. In the alkylation, the alkyl group may optionally initially go to the ring nitrogen atom in the 4-position, followed by heating to about 100 °, a transalkylation in the exo-amino group occurs. Such alkylation and rearrangement occurs, for example, also in the methylation of 5-amino-3-methyl-1,2,4-thiadiazole. </ P> <21> A compound of formula XI, optionally in esterified form, is obtained by carboxylating a compound of formula X. The carboxylation is carried out in a manner known per se by metallizing a compound of formula X and treated with carbon dioxide. In particular, organolithium compounds such as lower alkyllithium, e.g. Methyl, ethyl or butyl lithium <Sub> r </ sub> Aryllithium, e.g. Phenyl lithium, or lithium amides such as lithium lower alkyl amides, e.g. Lithium diisopropylamide, and the like. The metallation is carried out in an inert solvent such as an ether, e.g. Diethyl ether, dioxane or tetrahydrofuran, or a hydrocarbon, e.g., hexane, benzene, or a tertiary amine or diamine, e.g. Tetramethylethylenediamine, and the like, at reduced temperatures. </ P> <p> temperatures, for example at 0 ° to -80 ° performed. Subsequently, carbon dioxide is introduced at the same temperature or the metallation mixture is poured onto dry ice. If, instead of carbon dioxide, a haloformate is used, an ester of an acid of the formula XI is obtained. </ P> <p> You can get an ester. also obtained, optionally only as a by-product, when carboxylating compounds of formula X, wherein Am <Sup> 1 </ sup>> is a secondary amino group protected by esterified carboxyl. In this case, the acyl protecting group can migrate from the amino group to the methylcarbanion in the 3-position, so that after working up a compound of formula XI results, wherein Am <Sup> 1 </ sup> is a free secondary amino group and wherein the carboxyl group is in esterified form. For example, 5- (N-methyl-N-tert-butoxycarbonylamino) -3-methyl-1,2,3,4-thiadiazole gives, upon treatment with lithium diisopropylamide, the 2- (5-methylamino-1, 2,4-thiadiazole-2-one yl) acetic acid tert-butyl ester. The workup of the reaction mixture is carried out by treatment with water and acid or base and extraction in a conventional manner. </ P> <P> <u> Stage 3 An α-keto compound of formula XII or an ester thereof is obtained by treating a compound of formula XI or an ester thereof with a suitable oxidizing agent. Numerous such oxidizing agents are known. Preferably, selenium dioxide is used. The reaction is carried out in an inert solvent such as an ether, e.g. Dioxane or tetrahydrofuran, an amide, e.g. Dimethylformamide, or a tertiary amine, e.g. Pyridine, or the like, at reduced or elevated temperature, at about 0 ° to about 100 °, preferably at room temperature up to <I> _ </ i> performed about 80 °. </ P> <p> Step 4a: One. A compound of the formula III or an ester thereof, wherein Am is a protected or tertiary amino group Am <Sup> 1 </ sup> is obtained by reacting a compound of formula XII </ P> <p> or an ester thereof with a hydroxylamine of the formula. H <Sub> 9 </ Sub> N-O-R <Sub> 1 </ sub> (V). The reaction can be carried out as described under process b). </ P> <4> stage): A compound of the formula III or an ester thereof in which Am represents a protected or tertiary amino group Am 'can also be obtained by nitrosating a compound of the formula XI or an ester thereof and, if desired, a compound obtained of formula III, wherein R is hydrogen, is converted into a compound of formula III, wherein R is optionally substituted lower alkyl. The "nitrosation can be carried out as described under method e) and the alkylation as described under method f). </ P> <P> <u> Level 4c) </ U>; A compound of the formula III or an ester thereof in which Am represents a free primary or secondary amino group can also be obtained by reacting a compound of the formula XIII or an ester thereof in which X is halogen or hydroxy and R. the meaning given above has, with a salt of Rhodanwasserstoffsäure, or a Isorhodanwasserstoffester or a compound of formula XIII, wherein X is hydrogen, treated with Rhodan. The ring-closure reaction with the salt of hydroxydic acid or with rhodan is carried out as described under process d). </ P> <p> Step 4d): A compound of the formula III or an ester thereof in which Am represents a primary, secondary or tertiary amino group can also be obtained by reacting a compound of the formula XIX or an ester thereof wherein Y is halogen and R, as defined above, is reacted with ammonia or a primary or secondary amine Am-H, or a meta-amide thereof. The replacement of halogen Y, e.g. of chlorine, against the amino group Arn takes place as </ P> <p> under method 1). </ P> In a compound of formula III, a protected amino group Am <Sup> 1 </ sup> into a free amino group or in <Sub>; </ sub> a differently protected amino group are converted, or if R, is hydrogen, the group = N-OH can be etherified or carbamoylated analogously to process f). Obtained esters of compounds of the formula III are converted in a manner known per se into the free carboxylic acids. </ P> Reactive derivatives of compounds of the formula III which are suitable for acylation are prepared in a manner known per se, optionally <U> situ </ u>, manufactured. </ P> <p> Compounds of the formula XIII are obtained starting from compounds of the formula XIV via compounds of the formula XV according to the steps 6 and 7. </ P> <P> <U> Level </ U> <I> <U> S </ u> '· </ i> Compounds of the formula XV, wherein R <Sup> 0 is lower alkyl, and R is as defined above, and wherein the carboxyl group is optionally protected, can be obtained by. to a compound of formula XIV, wherein R, which has the abovementioned meaning and the functional groups are optionally protected, the alcohol HOR ° attached. The addition of the alcohol to the nitrile is carried out in a manner known per se in the presence of an acid, e.g. a hydrogen halide acid, such as hydrochloric acid,. at reduced or elevated temperature, preferably between about -30 ° to + 40 °, in particular about 0 °. The reaction is carried out in some inert solvent, preferably in the alcohol HORO itself. The acid addition salt of the iminoester of the formula XV or a protected derivative thereof is obtained. </ P> <p> Level _6_; A compound of formula XV wherein R is <Sup> 0 </ sup> is lower alkyl and R, which has the meaning given above, is a derivative </ P> <p> vat thereof, wherein functional groups are protected or an acid addition salt thereof, is converted by treatment with ammonia into a compound of formula XIII, wherein X is hydrogen and wherein functional groups are optionally protected. Instead of ammonia, it is also possible to use ammonium hydroxide or ammonium chloride. The reaction with ammonia takes place in an aqueous or non-aqueous solvent at temperatures between about -30 ° to about + 40 °. In a compound of formula XIII, wherein X is hydrogen, it may be substituted by halogen as described under method d). </ P> <P> S Step 7 </ U>; Compounds of formula XIX, wherein Y is halo and R has the meaning given above, esters or salts thereof are obtained by reacting a compound of formula XIII, wherein X is hydrogen, or an ester or a salt thereof, with a perhalomethyl mercaptan of Formula Y ^ CSY, where Y has the above meaning, implements. </ P> In the starting material and in the product of the formula XIX, y- is preferably chlorine. The reaction is carried out in the presence of a base neutralizing the resulting hydrogen halide H-Y in an organic or organic-aqueous solvent or solvent mixture. As bases, organic bases such as tertiary amines, e.g. Tri-lower alkylamines, such as trimethylamine, ethyldiisopropylamine, or aromatic amines, such as pyridine or inorganic bases, e.g. The solvents used are water, organic solvents such as alcohol, for example methanol or ethanol, halogenated hydrocarbons such as methylene chloride or chloroform, amides such as dimethylformamide , Sulfoxides, such as dimethylsulfoxide, ethers, such as dioxane, tetrahydrofuran, or the like, </ P> <p> or optionally mixtures or aqueous emulsions thereof, to which an emulsifier, such as sodium dodecyl sulfate, can optionally be added for better emulsification. The reaction is carried out at room temperature, with cooling or gentle heating, depending on the reactivity, i. at about -15 ° to about + 50 °, preferably at about -10 ° to about + 20 °. ·. </ P> <p> Compounds of formula IV are obtained by acylation of compounds of formula II with compounds of formula XII or a reactive functional derivative thereof. </ P> <p> Compounds of formula VI can be obtained as by-products in the preparation of compounds of formula I under basic conditions. They need not be in pure form, but can be used in admixture with compounds of formula I. </ P> <p> Compounds of the formula VII are obtained by acylation of compounds of the formula II with compounds of the formula XIII <Sub> 7 or a reactive functional derivative thereof, or analogously to steps 6 and 7, starting from compounds of the formula </ P> <P> (SVI) </ P> <p> via compounds of the formula </ P> <p> HN = C C - CONH - * - &Lt;? </ P> <P> R <Sup> 0 </ Sup> </ P> <P> '' R </ P> <p> which in turn can also be obtained by acylation of compounds of the formula II with compounds of the formula XIV or XV, or reactive functional derivatives thereof. </ P> <p> Compounds of formula VIII can be obtained from compounds of formula II by acylation with compounds of formula XI, or reactive functional derivatives thereof, according to process a), optionally the groups Am, R ", R <Sub> 3 </ sub> and R. in other groups Am, R- / R <Sub> 3 </ sub> or R. can be converted, wherein methods can be applied, as indicated for corresponding reactions for the preparation of compounds of formula I. Compounds of formula VIII wherein R is <Sub> 4 carboxy and their pharmaceutically acceptable salts and their physiologically cleavable esters have similar antibiotic properties as the active compounds of the formula I. These compounds and the processes for their preparation are also provided by the present invention. </ P> <p> Compounds of the formulas (If) to (Ik) fall under the general formula I and can be obtained according to one of the processes a) to e). Also in these compounds, existing groups Am, R, R, R or R can be converted into other groups Am, R <Sub> 1 </ sub>, R <Sub> 2 </ sub>, R <Sub> 3 </ sub> or R, wherein, by analogy, methods can be used, as indicated for corresponding reactions for the preparation of compounds of formula I. </ P> <P>. Compounds of the formula XVIII can be prepared in various ways, for example analogously to the process a), c), f), i), j) or k) or the step 7, in particular by reacting, analogously to process a), in a compound of Formula II wherein R-, R <Sub> 3 </ sub> and R <Sub> 4 </ sub> have the meanings given, and wherein the 7/3 amino group is optionally substituted by an acylating group, the 7β-amino group is treated by treatment with an acyl radical of a carbon ™ </ P> Acylated acylating agent of formula XIX, or by analogously to step 9, a compound of formula VII, wherein X is hydrogen and R <Sub> 1 </ sub>, R <Sub> 7 </ sub>, R ^ and R <Sub> 4 </ sub> have the meanings indicated, or a salt thereof, with a perhalomethyl mercaptan of the formula Y. <Sub> 3 </ sub> C-S-Y, and if desired, carrying out the subsequent operations mentioned in the preparation of the compounds of the formula I. </ P> The new intermediates and starting compounds and processes for their preparation are also the subject of the present invention. </ P> <p> The pharmacologically useful compounds of the present invention may be e.g. be used for the preparation of pharmaceutical preparations containing an effective amount of the active ingredient together or in admixture with inorganic or organic, solid or </ P> <p> liquid, pharmaceutically acceptable excipients </ P> <p>, which are suitable for external, rectal, oral or preferably for parenteral administration. Suitable forms of such preparations are ointments, suppositories, tablets, dragees, capsules or ampoules. <Sub>% </ i> i * </ P> Preferably, the pharmacologically active compounds of the present invention are used in the form of injectable, e.g. intramuscular or intravenous, administrable or infusion solutions. Such solutions are preferably isotonic aqueous solutions or suspensions, e.g. from lyophilized preparations containing the active ingredient alone or together with a carrier material, e.g. Mannitol, can be prepared before use. The pharmaceutical preparations may be sterilized and / or adjuvants, e.g. Preservatives, stabilizers, wetting agents and / or emulsifiers, solubilizers, salts for regulating the Asian pressure and / or buffers. The present pharmaceutical compositions which, if desired, may contain other pharmacologically valuable substances, are prepared in a manner known per se, e.g. </ P> <P> 27,11.1980 </ P> <p> AP 'C OT D / 222, 421 </ P> <p> 57 771/18 </ P> <p> by conventional solution or lyophilization methods, prepared and containing about 0.1 <I>% </ i> to 100 <I>%, </ i> in particular of about 1 <I>% </ i> until about 50 <I>% * </ i> Lyophilisates up to 100 <I>% Depending on the nature of the infection and condition of the infected organism, one uses daily doses of about 0.5 g to about 5 g s <Sub> e </ Sub> c <Sub> e </ sub> for the treatment of warm-blooded animals weighing about 70 kg » </ P> <P> Ausführungabeispiel </ P> The following examples serve to illustrate the invention; Temperatures expressed in degrees Celsius * </ P> <p> The following abbreviations are used in the examples: </ P> BOC: tert-butyloxycarbonyl P,: melting point </ P> <p> Thin-layer chromatography: Op-ti-UPC ^ -Pls-tten of Pa, Antec are silica-coated glass plates, where the silica gel was treated with dodecyltrichlorosilane (for reversed phase chromatography), </ P> <p> Preparation of the starting compounds </ P> <P> <U> In </ u> play a): 5-tert <Sub>? </ sub> Butoxycarbonylamino-3-methyl-1 »2,4-thiadiazole </ P> A suspension of 20.0 g (0.174 McI) of 5-amino-3-methyl-1,2,4-thiadiazoin (DBP-955 684) in 100 ml of BOC anhydride is added at 100.degree <Sup> 0 </ sup> C (bath temperature) for 12 hours. The Re- </ P> <P>. 27.11.1980 </ P> <p> AP C 07 D / 222 421 '. 57 771/18 </ P> <p> The reaction mixture is cooled, the volatiles are removed in vacuo, and the partially crystalline residue is purified by recrystallization from isopropyl alcohol. This gives 18.2 g of the title compound of Rf 'fl'ert Of 65 (silica gel, ethyl acetate), UV spectrum (ethanol): Λmax (£) 222 (4000); 245 (825Q) nm <Sub> e </ sub> IR spectrum </ P> <p> (Nujol): characteristic absorption bands at 5.90; 6.45? 8.75 u; F .: 136-7 °. </ P> <P> <u> Example -b); 2- (5-tert.Butoxycarbonylamlno-1,2,4-thiadlazol-3-yl) acetic acid. </ U> </ P> <p> A freshly prepared solution of lithium diisopropylamide in 100 ml abs. Tetrahydrofuran [from 26 ml (0.184 mol) of diisopropylamine and 104 ml (0.208 mol) of a ca. 2 N solution of butyl lithium in hexane] is treated at -78 ° under nitrogen with 10.0 g (0.046 mol) of 5-tert-butoxycarbonylamino 3-methyl-l, 2,4-thiadiazole in 50 ml abs. Tetrahydrofuran and stirred for 30 min. At this temperature. After heating the reaction mixture to -30 ° C for 30 min <Sub> 2 </ sub> initiated. The solution is mixed with 100 ml of water and diluted with 50 ml of diethyl ether .. The organic phase is separated, the aqueous phase with 2 N hydrochloric acid to pH 2.0 and extracted with ethyl acetate. The organic phase is separated, washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. The backlog will be out. Diethyl ether like. The title compound is obtained at Rf 0.40 (silica gel, chloroform: methanol: glacial acetic 85: 12: 3); F .: 163-5 °; UV spectrum (methanol): Amax (£) 215 (5250); 245 (8250) nm; IR spectrum (Nujol): characteristic absorption bands at 2.85; 2.90; 3.15; 6.45 <I> μ. </ I> </ P> <P> 27.11.1980 </ P> <p> AP C 07 D / 222 421 57 771/18. </ P> <p> Example _c): 2 ~ (5- ° tert. </ P> <p> A suspension of 5.0 g (19.25 m mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetic acid and 4.2 g of selenium dioxide in 100 ml abs, dioxane becomes 80 for 3 h <Sup> 0 After filtration of the reaction mixture, the filtrate is concentrated in vacuo. The residue is diluted with 150 ml of ethyl acetate and extracted with aqueous sodium bicarbonate solution, the ethyl acetate phase is separated off, washed with aqueous sodium chloride solution Magnesium sulphate, dried and concentrated. This gives uniform 5-tert-butoxycarbonylamino-3-formyl-1,2,4-thiadiazole of purity 0.65 (silica gel, chloroform: methanol: glacial acetic acid 85:12; 3) IR- pectum (CHpClp): characteristic absorption bands at 2.90 ;, 5.80; ..6.15, 6.50; 8.70 / U. <I> ®ie </ i> aqueous sodium bicarbonate phase is adjusted to pH 1.0 with 2 N hydrochloric acid and extracted with ethyl acetate. The organic. Phase is separated, washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. This gives uniform <Sup> 1y </ sup> - it is a compound in the form of a foam of Rf value 0.30 (silica gel, chloroform: methanol: glacial acetic acid 85: 12: 3); UV spectrum (methanol: ^ max ($) 219 (7150); 243 (7900) nm; IR spectrum (ITuj oil): characteristic absorption bands 3.10, 5.80, 6.15, 6.45, 8.60 / U ·. </ P> <P> <u> Example d): 2- (5-tart.Butoxycarbonylamino-1, 2,4-thiadiazol-3-yl) -2 (Z) -methoxy-aminoacetic acid. </ U> </ P> <p> A suspension of 3.4 g (12.4 m mol) of 2- (5-tert-butoxycarbonylaraino, -!, 2,4-thiadiazol-3-yl) -2-oxoacetic acid, 1.11 g ( 13.3 5 m mol) of methoxyamine hydrochloride and 1.1 ml of pyridine in 70 ml of 95% ethanol is stirred for 3 hrs. At room temperature. The reaction mixture is concentrated in vacuo. The residue is diluted with 100 ml of ethyl acetate and 100 ml of water, the aqueous phase is adjusted to pH 2N HCl <Sup>! </ sup> 2 and then extracted with ethyl acetate. The organic phase is separated, washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. The residue consists of a ca. 9: 1 Z / E isomer mixture. The title compound is obtained as a unitary product by fractional crystallization from methylene chloride. Rf value: 0.30 "(silica gel, s-butanol / glacial acetic acid / water 67:10:23); mp: 137-39 °° (decomposition); IR spectrum: characteristic absorption bands at 2.75; 2, 90; 5.85; 6.18; 6.45; 9.60; i; UV spectrum (methanol): λmax (£): 234 (22250) nm. </ P> <P> Example e): 5- (N-Me </ U> thyl-N-ter <U> t.Butoxycarbonylam </ U> i <U> no) -3-methyl-1,2,4-thiadiazole </ U> </ P> <p> A suspension of 15 g (116.3 m mol) of 5-N-methyl-3-methyl-l, 2,4-thiadiazole in 55 ml of BOC anhydride is stirred at 100 ° (bath temperature) for 4 hours. The reaction mixture is cooled, the volatiles are removed in vacuo and the residue is chromatographed (silica gel, toluene / increasing proportions of ethyl acetate) to give 22.3 g of the title compound of Rf 0.65 (silica gel, Toluene / ethyl acetate 1: 1), mp 4.7-48 °, IR spectrum (CK <Sub> 0 </ Sub> CL <Sub> 9 </ sub>): characteristic absorption bands at 5.90; 6,55: 8,80 <I> μ. </ I> </ P> <P> <u> Example f); 2- (5-N-Methylamino-1,2,4-thiadiazol-3-yl) - </ U> essigsä <U> acid tert-butyl ester </ U> </ P> <p> A freshly prepared solution of lithium diisopropylamide in 30 ml abs. Tetrahydrofuran [from 7.8 ml (55.2 m mol) of diisopropylamine and 30 ml of a ca; 2 N solution of butyllithium in hexane] at -78 ° under nitrogen with 3.15 g (13.8 mol) of 5- (N-methyl-N-tert-butoxycarbonylamino) -3-methyl-l, 2,4 thiadiazole in 15 ml abs. Tetrahydrofuran and stirred for 50 min. At this temperature. The reaction mixture is stirred with solid CO <Sub> 2 </ sub> poured and stirred for 30.min. The solution is mixed with 60 ml of water and extracted with diethyl ether. The aqueous phase is adjusted to pH 2.0 with 2N hydrochloric acid and reextracted with ethyl acetate. The combined organic phases are washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. </ P> After chromatography of the residue on silica gel with toluene / increasing proportions of ethyl acetate gives the uniform title compound of Rf 0.50 (silica gel, ethyl acetate) F. 91-92 °. IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 2.90, 5.80; 8.65 ^. </ P> <P> <u> Example g); 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2- </ U> o_xo_-e <U> ssigsäure tert. butyl ester </ u>, </ P> <p> A suspension of 2.3 g (10.0 mol) of 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -acetic acid tert-butyl ester and 3.0 g of selenium dioxide in 50 ml abs. Dioxane is stirred for 3 hours at 90 °. After filtering the reaction mixture, the filtrate is concentrated in vacuo. The residue is triturated with diethyl ether. This gives the title compound of Rf V 0.45 (silica gel, chloroform / methanol 9: 1). IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 2.90? 3.10? 5.80; 5.90; 6.25; 9.35; 9.70 <I> μ. </ I> </ P> <P> fifes </ P> <Heading> <u> Example h): 2- (5-N-Methylamino-l, 2,4-thiadiazol-3-yl) -2-Z </ U> </ Heading> <P> <u> methoxyimino-acetic acid tert-butyl ester </ u>. ". </ P> <p> A suspension of 2.0 g (8.0 m MoI) 2- (5-methylaminol, 2 <Sub> / 4-thiadiazol-3-yl) -2-oxoacetic acid tert -butyl ester, 0.736 g (8.64 m MoI) of methoxyamine hydrochloride and 0.72 ml of pyridine in 50 ml of 95% ethanol are stirred for 3 hours at room temperature , then concentrated in vacuo. The residue, which consists of the two Z and Ε isomers of the title compound, is fractionally crystallized from a mixture of methylene chloride / ethyl acetate. The uniform Z isomer of Rf value 0.75 (silica gel, chloroform / methanol 9: 1) is obtained. F .: 153-155 °. IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 2.90; 3:10; 5.80; 6.25; 9.50 u. Preparative layer chromatography of the mother liquor (silica gel, chloroform / methanol 95: 5) gives the E isomer of Rf 0.70 (silica gel, chloroform / methanol 9: 1). </ P> <P> <i> Example i): 2- (5-N-Methylamino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetic acid </ U> </ P> <p> A mixture of 1.5 g (6.24 m mol) of 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetic acid tert-butyl ester in 15 ml of methylene chloride is added at room temperature with 15 ml of trifluoroacetic acid and stirred for 40 min, then stirred into 200 ml of diethyl ether / hexane 1: 2 stirred. The precipitate is isolated by filtration, dissolved in water and the aqueous phase is adjusted to pH 5.3 with aqueous sodium bicarbonate solution. The aqueous solution is partially concentrated and then with abs. Aethanol'versetzt. The precipitate is isolated by filtration and washed with </ P> <p> washed with diethyl ether. The title compound is obtained at Rf 0.35 (slug gel, s-butanol / glacial acetic acid / water 67:10:23). IR spectrum (Nujol): characteristic absorption bands at 2.80; 3.05; 5.85; 6.20; 6.40; 9.50 ^ first </ P> The compound of example i) can also be prepared according to the following examples j) to m): </ P> <P> Ex <i> ielj): 2- (5-N-methyl-N-tert-butoxycarbonylamino-1,2, </ U> 4- <U> thiadiazol-3-yl) acetate tert.buty! Ester </ u> and <u> 2- (5-N-Methyl-1,2 ', 4-thiadia'zol-3-yl) -acetic acid-tert. </ U> - <U> butyl </ U> </ P> A freshly prepared solution of lithium diisopropylamide in 200 ml of abs. tetrahydrofuran [from 26 ml (0.184 mol) of diisopropylamine and 110 ml of a ca. 2 M solution of butyl lithium in hexane] is stirred at -78 ° under nitrogen at 21.0 g (92.0 mmol) of 5- (N-methyl-N-tert-butoxycarbonylamino) -3-methyl-1,2,4-thiadiazole in 100 ml of abs. Tetrahydrofuran and stirred for 1 hr. At this temperature, then warmed to -20 ° and treated with 200 ml of water. The mixture is diluted with ethyl acetate, washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue is chromatographed (silica gel, toluene / increasing proportions of ethyl acetate). </ P> The uniform tert-butyl 2- (5-N-methyl-N-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetate of Rf 0.80 ( Silica gel, ethyl acetate). IR spectrum (CH-Ci <Sub> 9 </ sub>): characteristic absorption bands at 5.78; 5.85; 6.60 <I> μ, and uniform 2- (5-N-Methylaminb-1,2,4-thiadiazol-3-yl) -acetic acid tert-butyl ester of Rf value 0.50 (silica gel, ethyl acetate). </ P> <P> <I> * $ &amp; </ I>. 27.11.1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <P> <U> Step Example </ u> l k): 2 ~ (-5 ~ H ~ Met <U> hyi ~ l! T ~ tert.buto3c </ U> ycarbonylainino ~ 1 <Sub> i > </ Sub> 2 <Sub> r </ sub> 4 ~ thiadi% zol-3-y ^ </ P> From 5.0 s (15.2 mmol) of 2- (5-H-methyl-1-tert-butoxy-carbonyl-amino-1,2,4-thiadiazol-3-yl) -acetic acid tert-butyl ether and 4.2 g of selenium dioxide in 75 ml of dioxane are obtained analogously to Example g), the 'i' title compound of Rf 0.70 SjLlicagel, chloroform / methanol 95: 5). F .: 96 to 98 <Sup> 0 </ Sup> C. IR spectrum (CHgCl <Sub> 2 </ sub>): characteristic absorption bands at 5.80; 5.90; 6.60 / U. </ P> <p> Example 1): 2- (5-N &Lt; -methyl ~ lJ-tert <Sub> &gt; </ Sub> Butox <U> ycarbony </ u> lamino-1,2,4-thiadiazole 3-yl) ~ 2 ~ Z-methoxyimino-3-tert-butyl acetate </ P> <p> From "6.3 g (18.3 mmol) of 2- (5-N ~ l, diethyl-, 1-butoxy-carbonylamino-1,2,4-thiadiazol-3-yl) -2-oxo tert-butyl acetate, 1.65 g of methoxyimine hydrochloride and 1.6 ml of pyridine in 40 ml of 95% ^ -ethanol are obtained analogously to Example h) the title compound of Rf value 0.80 (silica gel, chloroform / methanol 99: 1 ). P .: 125 Ms 127 <I>% </ i> IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 5.78; 5.90; 6.62; * 8.90 / U. </ P> <P> <U> Beis </ u> piel m): 2- (5 <u> -l · T-I let hylamino-1,2,4-thiadia-aol-3-y <U> l) -2 ~ Z ~ </ u> methoxyimine acetic acid </ P> The title compound can also be prepared analogously to Example i) from 0.5 g (1.34 mmol) of 2- (5-K-methyl-U-tert, butoxycarbonylamino-1,2,4-thiadiazol-3-yl) 2-Z-methoxyiminoacetic acid tert-butyl ester and 5 ml trifluoroacetic acid are obtained </ P> <p> • Example n): 2- (5-N-methyl-IT-tert.'butoxycarbonylamino-1 <Sub> | t </ Sub> 2 <Sub> T </ Sub> 4 ·· </ P> <p> thiadiaz ql <Sub> 11 </ Sub> -3,37J <Sub> 1 </ sub> J. 2-Z-methoxyimino-siglylic acid. · ·. </ P> <P> A. Solution. Of 500 mg (2.30 mmol) of 2- (5-l-methylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetic acid in </ P> <p> - ίΜ, - </ P> <p> 7.5 ml of water are added to 0.48 ml of triethylamine in 7.5 ml of dioxane and stirred for 10 min. At room temperature, then with 615.5 mg of 2- (tert.Butoxycarbonylox'y imino) -2-phen. ylacetonitrile and stirred for 4 hours at 40 °. After addition of a further 300 mg of 2- (tert-butoxycarbonyloxyimino) -2-phenylacetonitrile is stirred for a further 16 hours at 40 °, then diluted with diethyl ether and extracted with water. The aqueous phase is adjusted to pH 3.0 with 20% citric acid and extracted with ethyl acetate. The combined organic extracts are dried over magnesium sulfate and concentrated in vacuo. The title compound of Rf 0.60 (silica gel, s-butanol / glacial acetic acid / water 67:10:23) is obtained. </ P> <P> <u> Example 6): 2- (5-tert-Butoxycarbonylamino-1,2,4-thiadiazole </ U> - <U> 3-yl) essigsäuremethvlester </ U> </ P> A mixture of 30.0 g (0.115 mol) of 2 - '(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetic acid in 350 ml of methylene chloride is added successively with 26.16 g of N, N-dicyclohexylcarbodiimide, 5.13 ml of abs. Methanol and 1.71 g of 4-pyrrolidinopyridine and stirred for 3 hours at room temperature. After addition of another 0.5 ml of abs </ P> <p> 2.6 g of N, N-dicyclohexylcarbodiimide is stirred for another 60 min. The precipitate is filtered off with suction, the filtrate is washed successively with aqueous sodium bicarbonate solution, water and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is triturated with diethyl ether. The uniform title compound of Rf 0.50 (silica gel, toluene-ethyl acetate 1: 1). IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): - characteristic absorption bands at 2.90; 5.75; 5.85; 6.50; 8.70 <I> μ. </ I> </ P> <P> <u> Example ρ); 2- (5-t-butoxycarbonylamino-l, 2,4-thiadiazol · </ U> - <U> 3-yl) -2-oxo-acetic acid methylester </ U> </ P> <p> A suspension of 20.0 g * (73.18 mmol) of 2- {5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetic acid methyl ester and 22.0 g of selenium dioxide in 330 ml abs .Dioxan is stirred for 3 hours at 95 °, After filtering the reaction mixture, the filtrate is concentrated in vacuo. The residue is diluted with ethyl acetate, washed successively with water, aqueous sodium bicarbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. The title compound is obtained in the form of a foam of Rf 0.35 (silica gel, toluene-.Aethylacetat 1: 1). IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 2.95; 5.75; 5.85; 6,50 u. </ P> <P> <u> Example q): 2- (5-tert-Butoxycarbonylamino-1, 2,4-thiadiazole </ U> - <U> 3-yl) -2-hydroxyiminoacetic acid-methyl-ester </ U> </ P> <p> A suspension of 21.8 g (75.88 mmol) of 2- (5-tert-butoxycarbonylamino-l, 2,4-thiadiazol-3-yl) -2-oxoacetic acid methyl ester, 7.48 g of hydroxylamine hydrochloride and 9 , 8 ml of pyridine in 300 ml of 95% ethanol is stirred for 3 hours at room temperature. The reaction mixture is concentrated in vacuo. The residue is dissolved in ethyl acetate and the solution is extracted successively with dilute hydrochloric acid, water and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is crystallized from diethyl ether. The title compound is obtained of Rf 0.30 (silica gel, chloroform: methanol 95: 5). F. 131-132 °. IR spectrum ('CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): · characteristic absorption bands at 2.85; 5.75; 5.85; 6,50 ;, 8,70; 8.90 ^. </ P> <P> Step Example <r> l r): 2 ~ "(5-tert-Butoxycarbonylamino-1,2,4-thiadiazole </ U> - <u> 3-yl) -2-hydrox </ U> y <U> imino acetic acid </ U> <I> ',, </ I> </ P> A solution of 8.0 g (26.46 mmol) of 2- (5-tert-butoxycarbonylamino-l, 2,4-thiadiazol-3-yl) -2-hydroxyiminoacetic acid methyl ester in 175 ml of 95% ethanol is treated with 8 , 6 g of potassium hydroxide and 70 ml of water and stirred for 5 hours at 40 °. The reaction mixture is concentrated in vacuo, the residue dissolved in water, the solution with dilute hydrochloric acid to pH 8.5 and extracted with ethyl acetate. The aqueous phase is separated off, adjusted to pH 2.0 with 2N HCl and extracted with ethyl acetate. The organic phase is separated off, washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is crystallized from diethyl ether to yield the unitary title compound of Rf 0.60 (silica gel, s-butanol / glacial acetic acid / water 67:10:23), mp 158-160 ° (dec.), IR Spectrum (Nujol): characteristic absorption bands at 3.10-5.85; 8.65 p. </ P> <P> <u> Example s): 2- (5-tert-Butoxycarbonylamino-1,2,3-thiadiazole </ U> - <U> 3-yl) -2-2-methylcarbamoyloxyiminoessigsäure </ U> </ P> <p> A solution of 2.85 g (8.95 mmol) of 2- {5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-hydroxyiminoacetic acid in 20 ml of tetrahydrofuran is added at 0-5 ° with 10 ml of methyl isocyanate and stirred at this temperature for 2 hours. The reaction mixture is mixed with η-hexane and the resulting precipitate is filtered off with suction. After recrystallization of the precipitate from methylene chloride, the unitary title compound of Rf 0.25 (UPCI plates, water / acetonitrile 6: -I) is obtained. F. 124-127 °. IR spectrum (Nujol): characteristic absorption bands at 5.75; 5.85; 6,40p. </ P> <P> <i> Βία the </ i> _ «» «« '«*" </ P> <p> 27.11.1980 AP C 07 D / 222 421 57 771/13 </ P> <p> Example t); 2 ~ (5-tert "-butoxycarbonyl <U> amino-1,2,4-thiadiazol </ U> </ P> <P> in ^^ </ P> <P> methylester </ P> <p> A solution of 1.4 (6.27 mmol) of 2-bromo-isobutyric acid tert-butyl ester and 1.94 g (14.03 mmol) of finely powdered potassium carbonate in 12.50 ml of dimethyl sulfoxide is added at room temperature under nitrogen with a solution of "1.70 g (5.62 mmol) of methyl 2- (5-tert-ε-uterotycarbonylamino-1,2,4-thiadiazol-3-yl) -2-hydrox-yiminoacetate in 7 × 5 ml Dimethylisulfoxide and stirred for 14 h at this temperature <Sup> 0 </ sup> C in a high vacuum to dryness. The residue is taken up in 200 ml of ethyl acetate and washed successively with water, dilute hydrochloric acid (1 N), water and saturated sodium chloride solution, dried over magnesium sulphate and evaporated to dryness in vacuo. The residue is crystallized from ca, 5 nil ether to give the title compound of melting point 142 to 144 <Sup> 0 </ Sup> C. </ P> <P> <U> s </ U> p <u> iel u): 2- </ U> ( <U> g tert "Butoxycarbon </ U> yla <U> rnino-1,2,4-thiadiazol </ U> Λ - ^ - ^ Τ <Sup> 2 </ Sup> <u> "(2-tert" but o xycai-bonylprop-2-yloxyimino) e <U> ssigsau </ U> re ^ </ P> <p> A solution of 11 g (22.55 mmol) of 2 "(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z- (2-tert-butoxycarbonylprop-2-yl). yloxyiinino) acetic acid methyl ester in 290 ml of methanol and 96 ml of 2N sodium hydroxide solution at a temperature of 50 <Sup> 0 </ sup> C 6 <Sup> 1 </ sup> / 2 hours left to stir. The reaction mixture is evaporated at 35 ° C in a high vacuum to dryness. The residue is taken up in 200 ml of water (distilled) and extracted once with 200 ml of ethyl acetate. The aqueous phase is covered with 200 ml of ethyl acetate and made acidic with concentrated hydrochloric acid. The ethyl acetate phase is washed successively with water and saturated sodium chloride solution, dried over magnesium sulfate and </ P> Concentrated in vacuo to give the title compound is crystalline. TLC Rf 0.2 (silica gel, chloroform / methanol 4: 1); IR spectrum (dioxane): characteristic absorption bands at 5.81; 5.74; 3.3 <I> μ. F: 180-183 °. </ P> <Heading> <u> Preparation of compounds of the formula I. </ U> </ Heading> <P> <u> Example 1: 73- [2- (5-tert-3-methoxycarbonylamino-1,2,4-thiadiazol-3-yl) - ^ - Z -methoxyl.Tiinoacetamldo] -3-acetoxy-ethyl-3-cephem-4 ca ^ bonsäuredlphenylrnethylester. </ U> </ P> <p> a) A solution of 1.5 g (4.96 mol) of 2- (5-tert-butoxycarbonyl-amino-1,2,4-thiadiazol-3-yl) -2-methoxylinino-acetic acid in 20 ml Methylene chloride and 0.44 ml of pyridine. At -15 ° under nitrogen with 0.88 ml (6.0 m mol) Diäthylphosphorbromidat and stirred for 30 min. At this temperature. After addition of 2.1 g (4.70 m mol) of 7ß-amino-3-acetoxymethy1-3-cephem-4-carboxylic acid diphenyl methyl ester at -15 °, the reaction mixture is stirred at room temperature for 2.5 hrs, then diluted with 2 50 ml of methylene chloride, washed successively with dilute sulfuric acid, water, aqueous sodium bicarbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is purified by preparative layer chromatography on silica gel with chloroform. The unitary title compound of Rf 0.40 (silica gel, toluene / ethyl acetate 1: 1) is obtained; IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 3.10; 5.65; 5.80; 5.95; 6.40; 8,2Ou; UV-Sectrum (methanol): X, max (£.) 232 (26280). nm. </ P> <p> The same compound can also be prepared as follows. , .., »·", </ P> b) A solution of 200 mg (0.28 m mol) of 7/3 - [2- (5-tert-butoxycarbonylamino-1, 2,4-thiadia2ol-3-yl) -2-hydroxyimino-acetamido ] -3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester in 15 ml of methanol "is added dropwise with a 0 ° -cold solution of diazomethane in diethyl ether until the reaction is complete and at 0-5 ° for 30 min. The reaction mixture is concentrated under reduced pressure and the residue is purified by preparative layer chromatography on silica gel with chloroform to give the title compound of Rf 0.40 (silica gel, toluene / ethyl acetate 1: 1). </ P> <P> <U> Beispi </ U> e <u> l 2; 7.beta. ~ [2- </ U> ( <5> Amino-1,4,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3-acetoxymethyl-3-cephem-4-carboxylic acid (sodium salt) </ U> </ P> <p> A solution of 3.8 g (5.23 mol) of 7j3- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetamido] -3 Acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester in 8.5 ml of methylene chloride and 2.8 ml of anisole is added at room temperature with 39 ml of trifluoroacetic acid and stirred for 25 min, then stirred into 900 ml diethyl etherhexane 1: 2 stirred. The precipitate consisting of the trifluoroacetate of the 73- [2- (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -S-acetoxymethyl-S-cephem * carboxylic acid becomes isolated by filtration, dissolved in methanol-containing water (10 ml of methanol / 500 ml of water) and the aqueous phase with aqueous sodium bicarbonate solution to pH 6.8. The solution is lyophilized and the resulting sodium salts are chromatographed on S'ilicagel "Opti UPC, <Sub> 2 Antec) with water / acetonitrile 6: 1 to give the uniform title compound of Rf 0.30 (UPC, - plates, water / acetonitrile 6: 1); from 150 ° (decomp.); </ P> <p> 24 2 </ P> <p> UV spectrum (methanol): Λ max { <I> ί </ i>): 234 (12240) nm; IR spectrum (Nujol): characteristic absorption bands at 3.00; 5.65; 5.95? 6.20? 6.52; 'δ, 1Ο; 9.60 ^. </ P> <P> <3> Example 3: 73- [2- (5-Tert-butoxycarbonylamino-L, 2,4-thiadiazol-3-yl </ U>) - <U> 2-Z-methoxyimlnoacetainido] -3- (1-methyl-2-ol tetrahydro-5-yl-thiomethyl ·) -3-cephem-4-carboxylic acid diphenyl: nethyl </ U> ester. </ P> <p> a) From 575 mg (1.90 m mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetic acid, 880 mg (1.8 μmol) 7 ( 3-Amino-3- (1-methyltetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid diphenylmethyl ester and 0.33 ml (2.30 moles) of diethylphosphorobromidate in 10 ml of methylene chloride and 0.17 ml of pyridine the homogeneous title compound of Rf value 0.30 (silica gel, toluene / ethyl acetate 1: 1) is obtained analogously to Example 1, IR spectrum (CH-Cl-): characteristic absorption bands at 2.90, 5.65, 5.85 ; 5.95; 6.10; 6.45; 8.60 μ. </ P> ai) By preparative layer chromatography on silica gel with toluene / ethyl acetate 1: 1 is also obtained 7ß- [2 ~ (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido ] -3- (1-methyltetrazol-5-yl-thiomethyl) -2-cephem-4-carboxylic acid diphenylmethyl ester of Rf. 0.35 (silica gel, toluene / ethyl acetate 1: 1). </ P> <p> The 3-cephem title compound can also be obtained as follows: </ P> b) A suspension of 0.50 g (1.65 m mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetic acid and 0.152 g (0.825 m Mol) cyanuric chloride in 30 ml of acetone is heated for 30 min. At 40 °, with a solution. After addition of 0.166 g (1.65 m mol) of triethylamine </ P> <p> the solution is stirred for 3 hours at room temperature. After addition of 0.815 g (1.65 m mol) of 7ß-amino-3- (1-methyltetrazol-5 ^ yI-thiomethyl) .- 3-cephem-4-carboxylic acid diphenyl methyl ester is stirred for a further 2 hours at room temperature , then concentrated in vacuo, diluted with 50 ml of water and extracted with methylene chloride. The organic phase is washed successively with 1: phosphate buffer pH 8.0 and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue contains the title compound of Rf 0.30 (silica gel, toluene / ethyl acetate 1: 1). </ P> <p> c) 0.50 g (1.65 m mol) of 2- (5-tert-butoxycarbonylaminol, 2,4-thiadiazol-3-yl) -2-methoxyiminoacetic acid and 7 ml of ethyl acetate become at -5 ° to a stirred suspension of a Vilsmeier reagent (prepared from 0.25 g (1.98 mol) of oxalyl chloride and 0.15 ml of Ν, Ν-diraethylformamide in 1 ml of dry ethyl acetate.The mixture is stirred at 0 ° for 45 min After addition of 0.81 g (1.65 m mol) of 7β-amino-3- (1-methyltetrazol-5-yl-thiomethyl) -3-cephem-4-c, arbonsäure-diphenylme The 1-ester is stirred for 2.5 hours at 0 °, then diluted with 50 ml of ethyl acetate and washed successively with water, phosphate buffer pH 8.0 and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo Acetone-hexane to give the title compound of Rf. 0.30 (silica gel, toluene / ethyl acetate 1: 1). </ P> <P> <3) A suspension of 629 mg {0.84 m mol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-oxo-acetamido-3 { 1-ethyltetrazol-5-yl-thioriethyl) -3-cephein-4-carboxylic acid diphenylmethyl ester, 0.75 g (0.90 mole) of methoxyamine hydrochloride and 0.7 ml of pyridine in 40 ml of 95% ethanol is added during 3 hrs. at room temperature touched. The reaction mixture is concentrated in vacuo. The residue is with </ P> <p> 27.11.1980 AP C 07 D / 222 421 • 57 771/18 </ P> 25 ml of ethyl acetate are diluted and washed successively with water, dilute sulfuric acid and aqueous sodium chloride solution, washed over magnesium sulfate and concentrated in vacuo. The residue is purified by preparative layer chromatography on silica gel with toluene / ethyl acetate 3: 2. The title compound is obtained of Rf 0.30 (silica gel, toluene / ethyl acetate 1: 1), </ P> <P> e) <Sup> A 185 mg (0.26 mmol) of 7β- / f 2 - (5-tert-butoxy-carbonyiamino-1,2,4-thiadazazol-3-yl) -2-hydroxyiminoacetamido. - 3- (1-methyltetrazole -5-yl-thiomethyl) ~ 3 ~ cephem-4-carboxylic acid diphenylmethyltester in 15 ml of methanol and a solution of diazomethane in Diäthyiher be obtained analogously to Example 1b), the title compound of Rf 0.30 (silica gel, toluene / ethyl acetate 1: 1). </ P> <p> f) A solution of 187 mg (0.25 mmol) of 7β- / 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyaminoacetamaxo / 3 ~ O ~ methyltetrazol-5-yl ~ thiomethyl) ~ 2-cephem-4 · carboxylic acid diphenylmethyl ester in 4 ml of methylene chloride is cooled to 0 C, at this temperature with 50 ml of m-chloroperbenzoic acid (about 90 / uig) and Stirred for 30 min. Subsequently, excess peracid is destroyed by the addition of sodium thiosulfate. The reaction solution is extracted successively with aqueous ITatriumbicarbonat- and aqueous ITatriumchloridlösung, dried over sodium sulfate and concentrated. The residue is precipitated from acetone / diethyl ether. There is obtained 7β ~ ^ 2 ~ (5- "tert -butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiniinoacetam d ^ o} -3- (1-methyltetrazol-5-yl "-thiomethyl" -3 "cephem-4" -carboxylic acid diphenylmethyl ester-1-oxide of Rf ~ V / ert 0.35 (silica gel, ethyl acetate) » </ P> A solution of 115 mg (0.15 mmol) of the 1-oxide in 3 ml of ίΙ, ΙΪ-dimethylformamide is added to -10 <Sup> 0 Chilled, with 0.04 ml (Oj30 mmol) of phosphorus trichloride and stirred for 35 min. </ P> <P>. 22242 </ P> <p> The reaction solution is on ice. poured and diluted with 20 ml of ethyl acetate; The separated organic phase is extracted successively with aqueous Na'triumbicarbonatlösung and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated. After preparative layer chromatography on silica gel with toluene / ethyl acetate 1: 1, the uniform title compound of Rf 0.30 (silica gel, toluene / ethyl acetate 1: 1). </ P> <P> <u> Example 4: </ U> <I> <U> ISS </ U> </ I> <u> [2- (5-Amino-1,2,4-thiolazol-3, -yl) -2-Z-methoxyl-minbiacoacetyl] -3- (1-methyltetrazol-5-yl-thiomethyl) -S- cep </ U> Hemm <u> -carboxylic acid (sodium salt). </ U> </ P> <P> <Sub> a From 650 mg (0.87 mmol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] 3- ( 1-methyltetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid diphenylmethyl ester in 1.4 ml of methylene chloride, 0.47 ml of anisole and 6.5 ml of trifluoroacetic acid are obtained analogously to Example 2, the title compound of the Rf Value 0.25 (UPC <Sub> 32 </ sub> plates, water / acetonitrile 6: 1); üV spectrum (methanol): X max (£ j 232 (25200) nm; IR spectrum (Nujol): characteristic absorption bands at 3.00, 5.70, 6.25, 6.55, 9.62 <I> μ. </ I> </ P> <P> <I>. </ i> The same connection can also be made as follows: </ P> b) A suspension of 0.478 g (1.0 mol) of 73- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3-acetoxymethyl 3-cephem-4-carboxylic acid sodium salt, 0.207 g (1.5 x m mole) of 1-methyltetrazor-5-yl-thiol, 0.369 g (1.0 mole) of tetrabutylammonium iodide and 2.0 g of potassium iodide 2 ml of water is stirred at 70 ° for 2.5 hours, then diluted with water and extracted with ethyl acetate. The aqueous phase is concentrated and chromatographed (UPC, <Sub> 2 </ Sub> ~ <Sup> p </ Sup> l <Sup> atten </ sup> 'Water: </ P> <p> acetonitrile 6: 1). The unitary title compound of Rfr 0.35 (UPCI plates, water / acetonitrile 6: 1) is obtained. </ P> <P> Beispi <5> 7g- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyimino-acetamido] -3-carbainoyloxy </ U> meth <U> yl · -3-cephem-4-methyl carbonsäuredipheΓxyl · · ester. </ U> </ P> <p> From 575 mg (1.9 m mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetic acid, 1.10 g (1.8 m mol) 70-Ammurium-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid diphenylirate ethyl ester tosylate and 0.4 ml of diethyl phosphoroborate in 15 ml of methylene chloride and 0.3 ml of pyridine give, analogously to Example 1, the titer compound of Rf value 0, 60 (silica gel, ethyl acetate); UV spectrum: Amax (* c) 230 (sh) nm; IR spectrum (Nujol): characteristic absorption bands at 2.90; 3:10; 5.60; 5.80; 6.25; 6,45 ^ u. </ P> <P> <U> Ex </ U> i el. 6: 73- [2- (5-amino-1, 2 </ U> <I> <U> </ U> </ I> <u> t-thiadiazol-S-yl) -2-Z-methoxyiminoacetamidol-3-carbamoyloxy-ethyl-3-cephem-4 </ u> carboxylic acid (sodium salt). </ P> From 700 mg (0.95 m mol) of 7β- [2- (5-tert-butoxycarbonylaraino-l, 2,4-thiadiazol-3-yl) -2-methoxymiminoacetamido] -S-earbamoyloxyrnethyl-S-cephem ^ -carboxylic acid-diphenylinethyl ester in 1.5 ml of methylene chloride, 0.5 ml of anisole and 7.1 ml of trifluoroacetic acid are obtained analogously to Example 2, the title compound of Rf value 0.50 (UPC plates, water / acetonitrile 6: 1); F.: about 215 ° (decomposition); .UV spectrum (methanol); Ps, max 230 sh; IR spectrum (Nujol): characteristic absorption bands at 2 <Sub> f </ Sub> 85; 3.05; 5.60; 5.80; 6.25; 6.45 <I> μ. </ I> </ P> <P> Example 7: 7g- [2- (5-tert-Butoxycarbonylamino-l, 2,4, thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (1,2,5,5,6 tetrahydro-2-methyl-5,6-dioxo-1, </ U> <I> <U> 1, </ U> </ I> <u> 4-triazine-3-yl-thiomethyl ·) -ceph-3-em-4-carbonic acid </ U> </ P> A solution of 0.74 g (2- (5-tert-butoxycarbonylamino) -1,2 4-thiadiazol-3-yl) -2-Z-methoxyiminoacetic acid in 5 ml of ethyl acetate and the now clear solution is stirred for 45 minutes at 0.degree .. After addition of a solution of 0, adjusted to pH 7.5 with 1 ml of 2N sodium hydroxide solution , 74 g of 7β-amino-3- (1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-l, 2,4-triazine-3-yl-thiomethyl) -3-cephem 4-carboxylic acid in 5 ml of water, the reaction mixture is 3 hours at 0 <Sup> 0 C., while keeping to pH 7.5 by dropwise addition of 2N sodium hydroxide solution. After addition of 100 ml of ethyl acetate, the aqueous phase is adjusted to pH 1.5 with 2N hydrochloric acid and extracted 3 times with 100 ml of ethyl acetate. The combined extracts are washed with sodium chloride solution, dried with magnesium sulfate and crystallized after concentration under injection with ethyl acetate. The title compound is obtained, which decomposes above 180 °. IR spectrum (nujol): characteristic absorption bands at: 3.12; 5.63; 5.78; 6.11; 6.46; a; UV spectrum (ethanol): Λ max ( <i> £) </ i>: 238 (35800) nm. </ P> <P> <I> Λί </ I>. 27.11.1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <p> "" 3- em- 4-carb onsä </ P> <P> jgajbriumqalz </ P> <p> 0.52 g of 7β ~ / 2- (5-tert-butoxycarbonylamino-1,2,4,3-yl) -2-Z-methoxyiminoacetamidec> 7-3 ~ (1,2,5,6-tetrahydro-2-yl) methyl-5,6 ~ dioxo ~ 1, <I> 2 4-triazine-3-yl-thiomethyl-3-cephem-4-carboxylic acid are dissolved in 5 ml of trifluoroacetic acid and stirred at room temperature for 5 minutes. The mixture is isolated as in Example 2 and the <Sup> 1 </ sup> It is the connection of the Rf value 0.2 (UPC <Sub> 12 </ sub> plates, water / acetonitrile 4: 1); P <Sub> e </ sub>: approx <Sub> e </ sub> 21Q " <Sup> 0 </ sup> C (Zers.); IR spectrum (Nujöl): characteristic absorption bands at 2.92; 5.67; 5.99; 6.29; 6.53 <I>, u, </ I> </ P> <P> For example, <I> 3% </ i> 7β- / 2- (5-A <Sub> m yimirioac ^ ^ -beta et.oa.mid .-: _ (3 ~ methyl </ sub> ino-1,2,4-thiadinsol) ~ 2 "Z ~ methoa <I> \ <Sub> 1 </ Sub> 2 </ i>, 4,1-thiadiazole-5, -yl-thip.-rn e t hy I) - 3-c ephem-4-c arb ori <I> sliur </ i> e -ITa tr i um salt </ P> A suspension of 1.43 g (30 mLIol) of 7β- / 2- (5-nino-1,2,4-thiadiazol-3-yl). 2- <Sup> z </ sup> -methoxyiminoacetamido-7-3-acetoxymethyl-3-cephem-4-carboxylic acid llatrium mine salt and 0.44 g (3.6 ml) of 3-methyl-1,2,4-thiadiazol-5-yl-thiol in 10 ml aqueous sodium bicarbonate solution is stirred at 70 C and a pH of 6.0 to 6.5 for 2.5 h, then brought to pH 7.0 with solid IT sodium bicarbonate and extracted with ethyl acetate. The aqueous phase is concentrated in vacuo. Hach chromatography on Siücagei "Opti UPC ^" <Sup> rfl acetonitrile: water 1: 9 gives the unitary title compound of Rf 0.40 (UPC <Sub> 1 </ Sub> O-Pl <Sup> 3 </ Sup> ^ e <Sup> 11 </ sup> J water-acetonitrile 4: 1). P .: from 185 <Sup> 0 </ sup> C (Zers <Sub> e </ Sub>) <Sub> β </ sub> 'UV spectrum (IJethanol): Λmax (g): 230 (25050); 272 (17700) nm; IR ~ S <Sub> pe </ sub> ktrum CTuJöl): characteristic absorption bands at 3 <Sub>} </ Sub> 0; 5 <Sub> f </ Sub> 65? 6.0; 6.55; 9.60 / u. </ P> <P> _ <Sub> M </ sub> _ 22 24 2t </ P> <P> Example 10: 7β- [2- (5-Amino-1, 2,4-thiadia2ol-3-yl) - </ U> 2-Z-meth <U> oxyiminoacetamido] -3 ~ (l-carboxymethyl-tetrazol-S-yl-thiomethyl) -3-cephem-4-carboxylic acid * Natriumsal </ U> z </ P> <p> a) A suspension of 0.478 g (1.0 mol) of 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxy-thio-acetoacetamido] -3-acetoxymethyl 3-cephem-4-carboxylic acid sodium salt, 0.240 g (1.5 m mol) of 1-carboxymethyltetrazol-S-yl-thiol, 0.370 g of tetrabutylammonium iodide and 2.0 g of potassium iodide in 2 ml of water are stirred at 70 ° for 2 hours , then diluted with water and extracted with ethyl acetate. The ethyl acetate extracts are washed with aqueous sodium bicarbonate solution. The combined aqueous phases are adjusted to pH 1.5 in the cold with 4N hydrochloric acid solution and extracted with ethyl acetate. The ethyl acetate extracts are washed with aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is triturated with ethyl acetate, the solid product is filtered off with suction and washed with ethyl acetate-ether 1: 1. The residue is dissolved in methanol-containing water and adjusted to pH 7 with solid sodium carbonate. After lyophilization of this solution and chromatography of the residue on silica gel "Opti UPC, <I> <Sub> 7 </ Sub> " With acetonitrile: water 1: 6 gives the uniform title compound of Rf value 0.6-5 (UPC <Sub> 12 </ sub> plates, water-acetonitrile 6: 1). F.ca.210 ° (decomp.). IR spectrum (Nujol) characteristic absorption bands at 3.00; 5.68; 6.20; 6.55; 9.62 ju; UV spectrum (methanol): A max <I> (ξ) </ i> 232 (24450) nm. </ P> <p> The same compound can also be made as follows: </ P> b) A suspension of 0.570 g (1 M mole) of 70- [2- (5-ammonium-1,2,4-thiadiazol-3-yl) -2-Z-methoxyimine-acetamido] -3-acetoxymethyl 3-cephem-4-carboxylic acid trifluoroacetate and 0.160 g (1 M MoDl-carboxymethyl-tetrazol-S-yl-thiol in 5 mL aqueous sodium bicarbonate solution at pH 6.0-6.5 for 2 hours at 70 ° stirred, then brought to pH 7.0 with solid sodium bicarbonate and extracted with ethyl acetate The aqueous phase is concentrated in vacuo After chromatography on silica gel "Opti UPC <Sub> 2 </ sub> "(Antec Co.) with acetonitrile water 1: 6 gives the uniform title compound of Rf value 0.65 (UPC, 2 plates, water, acetonitrile 6: 1). </ P> <P> Example 11: 70- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazole-S-yD-methoxyiminoacetamido] -3- </ U> <I> <U> (1- </ U> </ I> <U> f2-N, N-dimethyl) ethyl] -lH-tetra2ol-5-yl-thiomethyl ·) -3-cephem-4-carboxylic acid tetrafluoroborate </ U> </ P> <p> 0.298 g (0.99 mol) of 2- (5-tert-butoxycarbonylamino-1, <I> 2, 4-thiadiazol-3-yl) -2-methoxyiminoacetic acid is added at -5 ° to a stirred suspension of a Vilsmeier reagent (prepared from 0.1 ml (1.2 m mol) of oxalyl chloride and 0.09 ml of Ν , Ν-dimethylformamide in 4 ml of dry ethyl acetate) and the mixture is stirred at this temperature for 30 min (solution 1). On the other hand, a mixture of 0.473 g (1.0 mol) of 70-amino-3- {1- [2- (N, N-dimethylamino) ethyl] -1H-tetrazol-5-yl-thiomethyl) -3-cephem 4-carboxylic acid tetrafluoroborate, 1.1 ml of N, O-bis (trimethylsilyl) acetamide and 5 ml of dry ethyl acetate stirred for 30 min. At room temperature and then cooled to -15 ° (solution 2). Solution 1 is added to the -15 ° C solution 2 and the mixture is stirred at this temperature for 3.5 hours, then diluted with 40 ml of ethyl acetate and extracted with water. The aqueous extracts are concentrated and lyophilized. Part of the lyophilizate is chromatographed (UPC2 plates) <I> </ i> water: acetonitrile 1: 1). · The uniform title </ P> <p> _ <Sub> w </ sub> _ 22242t </ P> <p> Compound of Rf 0.30 (UPC <Sub> 12 </ sub> plates, water-acetonitrile 1: 1) IR spectrum (KBr): characteristic absorption bands at 2.95; 5.62 ;. 5, 'δ5; 6.00; ' 6.45 <I> μ; UV spectrum (methanol): Λ max (0 235 (174OO) nm. </ P> <P> Example 12: 76 - [- 2- (5-Amino-1, </ U> <I> <U> 2 </ U> </ I> <u>, 4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3 ^ 1- [2-N, N-dimethylaminoethyl] -IH-tetrazol-S-yl; thiomethyl-3-cephem-4-carboxylic acid sodium salt </ U> </ P> <p> A solution of 2.1 g (2.77 m mol) of 70- [2- (5-tert-butoxycarbonylamino-1'-thiadiazol-S-yl) -2-methoxyiminoacetamido] -3- (1 - [2- (Ν, Ν-dimethylammoniumethyl] -LH-tetrazol-5-ylJ thiomethyl-3-cephem-4-carboxylic acid tetrafluoroborate in 4.7 ml of methylene chloride is added at room temperature with 21 ml of trifluoroacetic acid and stirred for 30 min , then stirred into 1.0 ml of diethyl ether / hexane 1: 2. The precipitate is isolated by filtration, dissolved in 50 ml of methanol and adjusted to pH 7.0 with a methanolic about 3N sodium 2-ethylhexanoate solution ml of ether, the precipitate formed is filtered off with suction and chromatographed (silica gel "Opti UPC <Sub> 12 </ sub> ", water / acetonitrile 9: 1). The uniform title compound of Rf 0.35 (UPC, <Sub> 2 </ sub> plates, water / acetonitrile 4: 1). F. 190 ° (dec.). IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.65; 5.95; 6.20; 6.45 Uf UV spectrum (methanol) λ <Sub> mav </ sub> = 231 nm (^ = 27800). </ P> <P> Example 13: 73- [2- (5-tert-Butoxycarbonylamino-1,2,4-thia </ U> diazole ~ 3 ~ <U> yl) acetamido] -3 ~ acetpxymethyl-3-cephem-4-carboxylic </ u> 'Acid diphenylmethyl ester' ' </ P> <p> A solution of 500 mg (1.90 m mol) of 2- (5-tert-butyloxycarbonylamino-1,2,4-thiadiazol-3-yl) acetic acid and 83 mg of 0.90 g (1.90 g) m mol) 7ß-Amino-3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester in 10 ml of dry tetrahydrofuran at 0 ° with 210 mg of 1-hydroxybenzotriazole and 475 mg (2.30 moles) N, N <Sup> 1 </ sup> -Dicyclohexylcarbodiimid added in 6 ml of dry tetrahydrofuran, While stirring for 3.5 hr. At '0 ° and then warmed to room temperature. After filtering the reaction mixture, the filtrate is diluted with 50 ml of ethyl acetate and washed successively with aqueous sodium bicarbonate and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is purified by preparative layer chromatography on silica gel with 95: 5 chloroform / methanol. The result is the uniform title compound of Rf value 0.65 (silica gel, chloroform / methanol 95: 5). UV spectrum (methanol): A (£) 248 (14500 </ P> <P> max </ P> <P> nm; IR spectrum (methylene chloride): characteristic absorption bands at 3.0; 5.57; 5.80; 6.45; 8,15 u. </ P> <P> For example, <u> 14: 70- [2- (5-tert-Butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-hydroxyiminoacetamido] -S-acetoxymethyl-S-cephem-4-carboxylic acid diphenyl methacrylate </ U> </ P> <p> A solution of 3 40 mg (0.5 mol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -acetamido] -3-acetoxymethyl-3 cis -acetic acid -cephem-4-carboxylate in 3 ml of glacial acetic acid at 38 ° C (0.55 m mol) of sodium nitrite is added at 10-15 ° and stirred for 30 min. At this temperature. The reaction mixture is washed with 20 ml of ethyl acetate </ P> <p> 22 24 21 </ P> The reaction mixture is washed successively with water, aqueous sodium bicarbonate and aqueous sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure, the residue is purified by preparative layer chromatography on silica gel with ethyl acetate 0.30 (silica gel, ethyl acetate) IR spectrum (Nujol): characteristic absorption bands at 3.05, 5.65, 5.85, 5.90, 6.45, 9.05 <I> jx. </ I> </ P> <P> Example 15: 7g- [2- (S-tert-Butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -acetamido] -3- (1-methyltetrazol-5-yl-thiomethyl) - 3-cephem-4-carboxylic acid diphenylmethy! ester </ U> </ P> From 518 mg (2.0 m mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetic acid, 940 mg (1.90 m mol) of 7β-amino-3 - diphenylmethyl (L-methyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylate, 210 mg of 1-hydroxybenzotriazole and 475 mg (2.30 moles) of N, N <Sup> 1 </ sup> -Dicyclohexylcarbodiimide in 30 ml of tetrahydrofuran is obtained analogously to Example 13, the uniform title compound of Rf value 0.60 (silica gel, chloroform / methanol / glacial acetic 85: 12: 3). IR spectrum (methylene chloride) characteristic absorption bands at 3.0; 5.65; 5.90; 6.45 <I> yx. </ I> </ P> <P> Example 16: 7ß- [2- (S-tert-Butoxycarbonylamino-l, 2,4-thiadiazol-3-yl) -2-hydroxyiminoacetamido] -3- (1-methyltetrazol ^ 5-yl-t </ U> h <i> iomethyl) - 3 -cephem-4-carboxylic acid e-dipheny line thy! ester </ U> </ P> From 258 rag (0.38 m mol) of 7β- [2- (5-tert-butoxycarbonylaminol-1,2,4-thiadiazol-3-yl) -acetamido] -3- (1-methyltetrazole) </ P> <p> 5-yl-thiomethyl) -3-cephem-4-carboxylic acid diphenylmethyl ester and 29 mg. (0.42 mol) of sodium nitrite in 2.5, ml of glacial acetic acid are obtained analogously to Example i4 the title compound of Rf value 0 , 30 '(silica gel, toluene / ethyl acetate 1: 1). IR spectrum (Nujol) characteristic absorption bands at 2.90; 5.60; 5.85 ;. 5.95; 6.20; 6:45; 9.10 ^ u. ' </ P> <P> Example 17; 73- </ U> <I> <U> [2- </ U> </ I> <U> (5-t-butoxycarbonylamino-l, 2,4-thiadlazol-3-yl) -2-oxo-acetamido] -3- (l-methyl tetra </ U> z <U> ol-5-yl </ U> thio <U> methyl) -3-cephem-4-carboxylic acid dlphenylmethylester </ U> </ P> <p> 0.683 g (2.50 mol) of 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-oxoacetic acid and 12 ml of ethyl acetate become a stirred suspension at -5 ° of a Vilsmeier reagent (prepared from 0.38 g (3.0 m mol) of oxalyl chloride, 0.20 ml of Ν, Ν-dimethylformamide in 1.5 ml of dry ethyl acetate). The mixture is stirred at 0 ° for 35 min. After addition of 1.235 g (2.50 m mol) of 7ß ~ Amlno-3- (1-methyl-tetrazol-5-yl-thiomethyl) -S-cephem ^ -carboxylic diphenylmethylester is stirred for 3 hours at 0 °, therein with 50th ml of ethyl acetate and washed successively with water, phosphate buffer solution pH 8.0 and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The residue is purified by preparative layer chromatography on silica gel with chloroform / ethyl acetate / glacial acetic acid 100/100 / 0.5. The uniform title compound of Rf 0.60 (silica gel, chloroform / ethyl acetate / glacial acetic acid 100: 100: 0.5). IR spectrum (CH <Sub> 2 </ Sub> Cl <Sub> 2 </ sub>): characteristic absorption bands at 2.75; 5.60; 5.85; 6.10; 6.45; , 8,50 ^ u. </ P> <P> <I> -Λθζ-. </ I> </ P> <p> 2 2 2 4 2 </ P> <P> Example 18; 7G [2- (5-amino-l ·, 2,4-thiadiazol-3-yl ·) -2-Z-hydroxyiminoacetamido1-3- (l-methyltetrazol-5-yl-thiomethyl) -3-cephein ~ 4 -carboxylic acid Natriuiusalz </ U> </ P> <p> From 355 mg (0.5 mol) of 7β- [2 ~ (5-tert-butoxycarbonylamino-1, 2, 4-thiadiazol-3-yl) -2-hydroxyiminoacetamido] -3- (1-methyltetrazole 5-yl-thiomethyi) -3-cephem-4-carboxylic acid diphenylmethyl ester in 0.80 ml of methylene chloride, 0.27 ml of anisole and 3.75 ml of trifluoroacetic acid are obtained analogously to Example 2, the uniform title compound of Rf value 0.15 (UPC, - "plates, water / acrylonitrile 9: 1) <Sup> 7 </ sup> P .: from 185 ° (Zers.). IR spectrum (Nujol): characteristic absorption bands at 3.0Qi 5.65; 5.95; 6.25; 6.55; 9.10 <I> μ. </ I> </ P> <P> <u> Example 19 </ U> <I> <U> ' </ U> </ I> <U> 7ot-methoxy-7ß- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadlazol-3-yl) -2-Z-methoxyiminoacetamido] -3-acetoxymethy1-3-cephem-4-carboxylic acid -dipheny! methylester </ U> </ P> <p> A solution of 2.18 g (3.0 m mol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] - 3-acetoxymethyl-3-cephem-4-carbonic acid diphenylmethyl ester in 200 ml of absolute tetrahydrofuran is cooled to -75 ° (dry ice-acetone bath) and a precooled solution of lithium methoxide in methanol (83 mg of lithium dissolved in 9 ml of methanol) within 2 minutes are added dropwise, the temperature rises to -70 ° and an orange-colored solution is formed. The reaction mixture is stirred for a further 2 minutes at -75 °, then added 0.25 'ml of tert-butyl hypochlorite and stirred at -75 °. After 8 minutes, the solution is treated with a further 0.2 ml of tert-butyl hypochlorite. After 30 minutes, </ P> 3.3 ml of glacial acetic acid and a solution of 1.5 g of sodium thiosulfate in 1.9 ml of water were added dropwise to the reaction mixture. The cooling bath is removed and the solution warmed to room temperature. The mixture is concentrated in vacuo and diluted with ethyl acetate. The ethyl acetate solution is successively with </ P> <P> 27.11.1980 </ P> <p> AP C 07 D / 222 421 </ P> <p> 57 771/18 </ P> water, aqueous sodium bicarbonate solution and water, dried over magnesium sulphate and concentrated in vacuo The crude product is purified by chromatography <Sup> s </ sup> silica gel with methylene chloride and increasing proportions of ethyl acetate is purified. <Sup> il </ sup> with the compound of Rf 0.30 (silica gel, toluene / ethyl acetate 3: 2) <Sub> e </ sub> IR spectrum (methylene chloride): characteristic absorption bands at 2.95; 5 »6O; 5.85; 5.95; 6.45; 9,50 / U, </ P> <p> Example 20: <I> 7A-Methpx £ -J] Jr / (£ rs! ?? Jt $ ipPrl * 2.t. </ I> 4-thiadiaaol > -3 - yl) - </ P> <p> bjonsα ur <I> e ^ </ I> JTA. salt </ P> <p> From 0.44 g (1.01 mLIol) 7 < t-Methoxy-7β-Z2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-metho: >: yiminoacetamide Q7-3 ~ acetoxy2-methyl-3-cephem-4 ~ carbonic acid ~ diphenylrnethylester in 3 ail methylene chloride, 1 ml of anisole and 14.2 ml · trifluoroacetic acid is obtained analogously to Example 2, the '^ itelverbindung of Rf value / 0.45 (UPC <Sub> 1 </ sub> 2-plates, water / acetonitrile 9: 1). P, ": from 190 ° C (Zers.) <Sub> e </ sub> IR spectrum (ITu oil): characteristic absorption bands at 3.0; 5.60; 5.95; 6.20; 6.55; 9 * 55 / U. </ P> Example 21: 7ß-Z2- (5) <Sup> A </ Sup> mino- <Sub> i </ Sub> 1,2,4-t M </ P> <P> methoxyirainoac ^ </ P> <p> ^ urepiyalpylpx ^ metliyleater, </ P> <p> Mixture of 1.91 g (4.0 mmol) of 7β ~ / 2 ~ (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido-7-3-acetoxymethyl-3 ~ cephem-4-carboxylic acid sodium salt in 22 ml of N, N-dimethylformamide is at 0 <Sup> 0 </ sup> C with 0.9 ml (3 <Sub> S </ sub> 85 mmol) of iodomethyl pivalate and stirred for 60 min at this temperature, then poured into 120 ml of phosphate buffer solution (pH 7.0) and extracted with ethyl acetate / acetone 4: 1. The organic extracts are washed with aqueous sodium chloride solution Washed, dried over magnesium sulfate and concentrated in vacuo </ P> The residue is triturated with diethyl ether, the solid is filtered off with suction and with diethyl ether / hexane 1: 1. rewashed. you </ P> <p> sift · <i> &amp; </ I> </ P> <p> obtains the title compound of Rf 0.80 (silica gel, s-butanol / glacial acetic acid / water 67:10:23). IR spectrum (.Nujol): characteristic absorption bands at 3.0? 5.60; 5.70; 5,9O; <Sub> s </ sub> 6.15; 6:45 <I> μ. </ i>, .., " </ P> <P> Example 22: 70- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -S-carbamoyloxymethyl-S-cephem ^ -carboxylic acid pivaloyloxymethyleste, r </ u>, '..., </ P> From 2.39 g (5.0 moles) of 7β- [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3-carbamoyloxyniethyl-3 -Qephem-4-carboxylic acid sodium salt and 1.13 ml (4.81 m mol) of iodomethyl pivalate in 25 ml of Ν, Ν-dimethylformamide obtained analogously to Example 21, the title compound of Rf 0.70 (silica gel, s-butanol / glacial acetic acid / Water 67:10:23). IR spectrum (Nujol): characteristic absorption bands at 3.05; 5.60; 5.72; 5.95; 6.25 ;. 6,45 u. </ P> <P> <u> Example 23: </ U> <I> <U> ISS [2- </ U> </ I> <U> (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (l-methyltetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid pivaloyloxymethy! ester </ U> </ P> From 4.27 g (8.0 mmol) of 73- [2- (5-amino-1,2,4-thiadiazol-3-yl] -2-Z-methoxyiminoacetmido-3- (1-methyl) tetra-zol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid sodium salt and 1.8 ml (7.70 m mol) of iodomethyl pivalate in 45 ml of Ν, Ν-dimethylformamide are obtained analogously to Example 21, the title compound of the Rf Value 0.80 (silica gel, acetone / glacial acetic acid / water / ammonia 20: 8: 5: 1) IR spectrum (Nujol): characteristic absorption bands at 2.95, 5.65, 5.80, 5.95, 6 , 45 u. </ P> <P> Example 24: 7β- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-Z-meth </ U> oxyimi <u> noacetamido] -3-Jl- [2- (N, N-dimethylamino) ethyl] -jLH-tetra-2Ql-5-yl-thiomethyl-S-cephem-carboxylic acid pivaloyloxymethyl </ U> e <U> ster-hydrochl </ U> ORID </ P> From 3.5 g (5.91 m mole) of 7/3 - [2- (5-amino-1, 2,4-thiadazole-3-yl) -2-Z-methoxyiminoacetamido] -3 - (1- [2- (N, N-dimethylamino) ethyl] -1H-tetrazol-5-yl-thiomethyl-3-cephem-4-carboxylic acid, sodium salt and 1.35 ml (5.78 moles) of iodomethyl pivalate in 30 ml of Ν, Ν-dimethylformamide the title compound, which is isolated as the hydrochloride, is obtained analogously to Example 21. Rf value: 0.60 (acetone / glacial acetic acid / water / ammonia 20: 8: 5: 1). Nujol): characteristic absorption bands at 3.0, 5.60, 5.85, 6.05, 6.45, a. </ P> Example 25: 7β- [2- (5) <U> amino-l, 2,4-thia </ U> diazole-3-yl) -2-Z-meth <U> oxylminoacetamldo] -3- (l-pivaloyloxymethoxycarbonylmethyltetrazol-5-yl-thiomethyl-3-cephem-4- </ U> carboxylic acid pivaloyloxy <U> methylester </ U> </ P> <p> From 4.8 g (8.28 m mol) of 7/3 [2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- ( 1-carboxymethyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid sodium salt and 3.6 ml (15.44 mmol) of iodomethyl pivalate in 60 ml of Ν, Ν-dimethylformamide are obtained analogously to Example 21, a crude product, after chromatography on silica gel gives the title compound of Rf 0.55 (silica gel, acetone / glacial acetic acid / water / ammonia 20: 8: 5: 1). IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.65 ;. 6.20 ;. 6.50 ^ / U. </ P> <p> Additionally, small amounts of 7β- [2- (5-amino) </ P> <p> 1,2,2-thiadia2ol-3-yl) -2-Z-methoxyiminoacetamido] -3- (1-carboxymethyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester of Rf 0.40 (silica gel, acetone / glacial acetic acid / water / ammonia · 20: 8: 5: 1) and to 7 / 3- [2- (5-amino) </ P> <p> 1,2,4-thiadiazol-3-yl) -2-Z-methoxy-aminoacetinido] -3- (1-pivo- </ P> <p> loyloxymethoxycarbonylmethyl-tetrazol-5-yl-thiomethyl) 3-dephem-4-carboxylic acid of Rf 0.30 (silica gel, acetone / "glacial acetic acid / water / ammonia 20: 8: 5: 1) '. </ P> <P> Example 26: 7β- [2- (5-tert-Butoxycarbonylamino-1, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (1-sulfomethyltetrazol-5-yl-thiomethyl ) -3-cephem-4-carboxylic acid </ U> </ P> <p> 295 mg (0.98 m MoI) of 2- (5-tert-butoxycarbonylamino-1 / 2,4-thiadiazol-3-yl) -2-methoxyiminoacetic acid is added at -5 ° to a stirred suspension of a Vilsmeier Reagenses (prepared from 0.1 ml (1.2 moles) of oxalyl chloride and 0.09 ml of N, N-dimethylformamide in 4 ml of dry ethyl acetate) and the mixture is stirred at this temperature for 30 min (solution 1). On the other hand, 408 mg (1.0 mol) of 7β-amino-3- (1-sulfomethyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid, 0.69 ml of triethylamine and 3 ml of Ν, Ο Stirred bis (trimethylsilyl) acetamide for 30 min at room temperature and then cooled to -15 ° C. (Solution 2) Solution 1 is added to the -15 ° C solution 2 and the mixture is stirred at this temperature for 1 hour. The insoluble constituents are filtered off and the filtrate is treated with diethyl ether / petroleum ether 1: 1 The precipitated solid is filtered off and washed with petroleum ether After preparative Schick Chromatography on silica gel UPC._ with water / acetonitrile 4: 1 gives the uniform title compound of Rf 0.40 (UPC <Sub> 12 </ sub> plates, water / acetonitrile 4: 1). IR spectrum (Nujöl): characteristic absorption bands at 3.10; 5.65; 5.85; 6.05; 6.20; 6.45 <I> μ. </ I>. </ P> <p> - ^ o - </ P> <P> Example 27: 7 / 3- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamidol-3- (1-sulphone </ U> fomethyl-tetrazole <u> -5-yl-thiomethyl) -3-eephem-4-carboxylic acid sodium salt </ U> </ P> <p> A solution of 400 mg (0.58 m mol) <I> ISS </ I> [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (l-sulfomethyl-tetrazol-5-yl-thiomethyl) 3-cephem-4-carboxylic acid in 0.95 ml of methylene chloride is added at room temperature with 4 ml of trifluoroacetic acid and stirred for 30 min. At room temperature, then stirred into 300 ml of diethyl ether / hexane 1: 2. The precipitate is isolated by filtration, dissolved in 8 ml of methanol and adjusted to pH 7.0 with a methanolic 3N sodium 2-ethylhexanoate solution. After addition of 70 ml of ether, the precipitate formed is filtered off with suction and chromatographed (UPC, plates, water / acetonitrile 9: 1). The uniform title compound of Rf value 0.40 (UPC, plates, water / acetonitrile 9: 1) is obtained: mp above 175 ° (dec.). IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.65; 6.20; 6,50 ;, 9,65 ^ p; UV spectrum (methanol):> max (£) 233 (21950) nm. </ P> <P> Example 28: 7g- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (4-Qxo-3,4-dihydro-pyrimidine ~ 2-yl-thiomethyl) -3-cephem-4-carboxylic acid sodium salt </ U> </ P> <p> A suspension of 478 mg (1.0 mol) of 73- [2- (5-amino-1, <I> 2, 4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3-acetoxymethyl-3-cephem-4-carboxylic acid sodium salt and 154 mg (1.2 moles) of 4-OXO-3,4- dihydro-pyrimidin-2-yl-thiol in 5 ml of water is adjusted to pH 6.5 with solid sodium bicarbonate and stirred at this pH for 4 hrs. At 70 °. The solution is brought to pH 7.0 with solid sodium bicarbonate and lyophilized. The residue is purified by preparative layer chromatography on UPC, plates with water / dioxane 98: 2. The uniform title compound of Rf value 0.25 (UPC.sup. </ P> <p> th, water / dioxane 98: 2). IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.65; 6, 15; 9.60 ^ u. </ P> <P> Example 29: 7 / 3- [2- (5-N-Methylamino-1,2,4-thiadiazol-3-yl-2-Z-methoxyiminoacetamido] -S-acetoxymethyl-S-cephem ^ -carbon- </ U> </ P> <P> <U> acid diphenylmethyl </ u> · <i> '. * </ I> </ P> <p> 1.84 g (10.0 mol) of 2- (5-N-methylamino-l, 2,4-thiadiazol-3-yl) -2-methoxyimino-acetic acid and 5 ml of ethyl acetate at -5 ° to a stirred suspension of a ViIsmeier reagent (prepared from 1 ml (1.20 m mol) of oxalyl chloride and 0.9 ml of N, N-dimethylformamide in 30 ml of dry ethyl acetate). The mixture is stirred at 0 ° for 1 hr. And then cooled to -10 °. After addition of 2.75 g (11.0 m mol) of 7ß-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester is stirred for 3 hrs. At 0 °, then diluted with 100 ml of ethyl acetate and successively with aqueous sodium bicarbonate solution and aqueous sodium chloride solution. The organic phase becomes. dried over magnesium sulfate and concentrated in vacuo. The residue is purified by chromatography on silica gel with chloroform. The title compound of Rf 0.35 (silica gel, ethyl acetate) is obtained. IR spectrum (methylene chloride): characteristic absorption bands at 3.0; 5.65 ;. 5.80; 5.90; 6.40 ^ u. , </ P> <p> Example 3p <Sub>; </ Sub> <I> ISS </ I> <U> [2- (5-N-methylamino-l, 2,4-thiadiazol-3-yl) - </ U> <U> .2-Z methoxyiminoacetamidol-3-ac </ U> eto <u> xymethyl-3-cephem-4-carboxylic acid sodium salt </ U> </ P> <p> From 1.0 g (1.57 m mol) of 70- [2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetamido] -3-acetoxymethyl ~ 3 -cephem-4-carboxylic acid diphenylmethyl ester in 1.3 ml of methylene chloride, 2.5 ml of anisole and 10 ml of trifluoroacetic acid are obtained analogously to Example 4, the title compound of Rf value 0.20 ' </ P> <p> (UPC plates, water / acetonitrile 6: 1). F. from 180 ° (dec.). IR spectrum (Nujol):. characteristic absorption bands at 3.0; 5.65; 5.95; 6.25; 6.50; 8.15 ^. ·. " </ P> <P> Beispi <31> 70- [2- (5-tert-Butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxy-imino-acetamido] -3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl </ U> </ P> <p> 1.05 g (3.70 mmol) of 2- (5-tert -butoxycarbonylarnino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetic acid and 0.4 ml of N-methylmorpholine are added -5 ° to a stirred suspension of a Vilsmeier reagent (prepared from 0.031 ml of oxalyl chloride and 0.29 ml of Ν, Ν-dimethylformamide in 10 ml of ethyl acetate). The mixture is stirred for 3o min. At 0 ° and then cooled to -10 °. After addition of 1.357 g (3.1 mmol) of 7j3-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester is stirred for 2.5 hours at 0 °, then diluted with ethyl acetate and washed successively with water, phosphate buffer pH 8.0 and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. A part of the crude product is purified by preparative layer chromatography with ethyl acetate. The uniform title compound of Rf value 0.60 (silica gel, ethyl acetate). IR spectrum (CH-Cl): characteristic absorption bands at 2.95; 3:10; 5.65; 5.80; 5,95 ;, 8,20 <I> μ. </ I> </ P> <P> Example 32: 7/3 [2- (5-Amino-1,2,3,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -S-acetoxymethyl-S-cephem-carboxylic acid sodium salt </ U> </ P> <p> From -519 g (0.68 mmol) <I> ISS </ i> [2- (5-tert-Butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethyl ester in 1.1 ml Methylene chloride, 0.37 ml anisole and </ P> <p> th, .Water / Dioxari 98: 2). IR spectrum (nujol): characteristic absorption bands at 3.0; 5.65; 6.15; 9.60 ^. </ P> <Heading> Example 29: 7g- [2- (5-N-methylamino-1,2,4-thiadiazol-3-yl] </ U> </ Heading> <P> <U> 2-Z-methoxyiminoacetamido] -3-acetoxymethyl-3-cephem-4-carboxylic </ U> <U> acid diphenylfnethylester </ U> &Lt; , <Sup>: </ Sup> <i> '*. </ I> </ P> <p> 1.84 g (10.0 m mol) of 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-methoxy-1-nitroacetic acid and 5 ml of ethyl acetate are added at -5 ° to a stirred suspension of a ViIsmeier reagent (prepared from 1 ml (1.20 m mol) of oxalyl chloride and -0.9 ml of Ν, Ν-dimethylformamide in 30 ml of dry ethyl acetate). The mixture is stirred at 0 ° for 1 h and then cooled to -10 °. After addition of 2.75 g (11.0 mol) of 7ß-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid diphenylmethylester is stirred for 3 hrs. At 0, then diluted with 100 ml of ethyl acetate and successively with aqueous Sodium bicarbonate solution and aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate and concentrated in vacuo. The residue is purified by chromatography on silica gel with chloroform to give the title compound of Rf 0.35 (silica gel, ethyl acetate) IR spectrum (methylene chloride): characteristic Absorption bands at 3.0, 5.65, 5.80, 5.90, 6.40 ^ u. </ P> <P> <u> Example 3q <Sub>: </ Sub> </ U> <I> <U> ISS </ U> </ I> <U> [2- (5-N-methylamino-l </ U> <I> <U> 2, </ U> </ I> <U> 4-thiadiazol-3-yl) - </ u> * <2> Z-methoxyiminoacetamido] -S-acetoxymethyl-S-cephem ^ -carboxylic acid sodium salt </ U> </ P> <p> From 1.0 g (1.57 m mol) of 7/3 [2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetamido] -S-acetoxymethyl -S-cephem ~ 4-carboxylic acid diphenylmethyl ester in 1.3 ml of methylene chloride, 2.5 ml of anisole and 10 ml Triflüoressigsäure obtained analogously to Example 4, the title compound of Rf value 0.20 </ P> <p> brought to pH 7.0 and extracted with ethyl acetate. The aqueous phase is concentrated in vacuo. After chromatography on silica gel "Opti UPC <Sub> 12 </ sub> "(Fa. Antec) with water gives the uniform title compound (1) of Rf value 0.60 (UPC <Sub> 12 </ sub> '- plates, water: acetonitrile .6: 1). IR spectrum (Nuiol): characteristic absorption bands at 3, Oj 5.67; 6.17 yes and the unified title compound (2) of Rf value 0.85 (UPC .-- plates, water: acetonitrile '6: 1), IR spectrum (nujol): characteristic absorption bands at 3.05; 5.67; 6.15; 8,30 u. </ P> <P> Example 35: 7g- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -3- (1-sulfomethyl-tetrazol-5-y </ U> l <i> thiomethyl) -3-cephem-4-carboxylic acid sodium salt (1) </ u> and </ P> <P> <U> 7ß- [2- (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-hydroxyimino-acetamido] -3- (l-sulfomethyl-tetrazol-5-yl-thiomethyl) -3-cephem-4 </ U> - <u> carboxylic acid sodium salt (2) </ U> </ P> <p> A suspension of 0.306 g (0.5 mmol) of 7g- [2- (5-ammonium-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -S-acetoxymethyl-S- cephem - ^ - carboxylic acid trifluoroacetate, 0.164 g of sodium 1-sulfomethyl-tetrazol-5-yl-thiolate and 2.0 g of sodium iodide in 1.0 ml of aqueous sodium bicarbonate solution, at a pH of 6.5 for 2 hours at 70 ° stirred, then cooled and poured onto 500 ml of ethanol. The resulting precipitate is filtered and washed successively with ethanol and hexane. After chromatography on silica gel Opti UPC <Sub> 12 The uniform title compound (1) of Rf value 0.20 (UPC, -, - plates, water: acetonitrile 98: 2) and the uniform title compound (2) of Rf value 0.65 ( UPC plates, water acetonitrile 98: 2). </ P> <P> 27.11.1980 </ P> <p> AP C 07 D / 222 421 </ P> <p> 57 771/18 </ P> 5 ml of trifluoroacetic acid are obtained analogously to Example 2, the title compound of Rf value 0.40 (UPC <Sub> 12 </ sub> plates, water / acetonitrile 6: 1), IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.67; 6.22; 8.10 / U. </ P> Example 33; 7fi- / 2 ~ (5-amino-i, 2,4-thiadiazol-3-yl) -2-Z-_ <u> me t hy 1 </ u> car bamoy1 ox y iniin ο ac et ami d <U> o7-3 - ( 'i-m </ u> et hy It e t r az ο 1 - <i> 5 - </ i> ^ sodium salt </ P> <p> From 530 mg (1.02 raMql) of 7β ~ / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyl-oxyiminoacetamide q7-3-acetoxymethyl-3-cephem-4 -carbonc <Sup>: </ sup> iure ITatriumsalz and 150 mg '(1,09 mL'Iol) 1-Methyltetrazol ~ 5 ~ ylthiol in 5 »1 ml aqueous sodium bicarbonate solution is obtained analogously to Example 10b) the uniform <Sup> 1 </ sup> Compound of Rf value 0.35 (UPC <Sub> 12 </ sub> plates, Y / ater / acetonitrile 6: 1). IR ~ pectum (nujol): characteristic absorption bands at 3.0; 5.65; 6.20 / ii « </ P> Example 34: 7β - / 2 - (5) <Sup> A </ sup> mino-1,2,4-thiadiazol-3-yl | ~ 2-Z-me t hyjLca rbamoy 1 oxy i min oa cet ami d 0 ^ -3 - (1-c arb oxym et hy 1 -1 etra ζ ο <u> ^ - yl -1 hi on </ u> q tTiy1) -3 - c epliem- · 4-par b on <I> α </ I> <Sup>: </ sup> iur e ITa t r i irosa 1 <I> ζ </ i> (1) 'and. </ P> <P> ' <U> 7.beta. ~ / </ U> 2 - (5 ' <Sup> l </ Sup> -mino-1 <Sub>? </ sub> 2, 4-thiadiazol ~ 3 ~, yl) - 2-Z-hydroxyimino-acetone </ P> <P> ^ <Sub> 1 </ Sub> <U> -carboxylic ' </ U> <I> <U> i </ U> Well <U> tri </ U> to <U> sal </ U> z. (2) </ P> <p> A suspension of 0.260 g (0.5 mmol) of 7β-Z "2 - (5-amino-1,2,4-thiadiazol-3-yl) * -2-Z-methylcarbamoylo5: yiminoacetamido 7 ~ 3 Sodium salt of acetoxymethyl-3-cephem-4-carboxylic acid and 0.08 g of i-carboxymethyl-tetrazol-S-yl-thiol in 2.5 ml of aqueous solution of t-sodium carbonate at pH 6.5 for 3 h <Sup> 0 C. then added with another 0.02 g of 1-carboxymethyl-tetrazol-5-yl-thiol and, after adjusting the pH to 6.5, with solid sodium bicarbonate for an additional hour at 70.degree <Sup> 0 stirred, then with solid sodium bicarbonate </ P> <P> 27.11.1980 </ P> <p> AP C 07 D / 222 </ P> <p> 57 771/18 </ P> A Vilsmeiser reagent (prepared from 1'51.5 mg oxalyl chloride and 0.09 ml!,!, - dimethylformamide in 1 ml <Sup> A </ sup> ethyl acetate). The mixture is at 0 for 45 min <Sup> 0 stirred </ sup> C and then to -10 <Sup> 0 </ sup> C cooled. After addition of 490, 7ß ~ <Sup> A </ sup> Mino-> 3- (i-methyltetrazol-5-yl-thiomethyl) -3 ~ cephem ~ 4-carboxylic acid diphenylmethyl ester is at 0 for 3 h <Sup> 0 stirred, then diluted with ethyl acetate and washed successively with what was ?, phosphate buffer pH 8.0 and aqueous ITatriumchloridlösung, dried over magnesium sulfate and in <Sup> v </ sup> concentrated. The 'J' title compound of Rf value 0.25 (silica gel, toluene / ethyl acetate 1: 1), IR spectrum (CH <Sub> 2 </ sub> CIp): characteristic absorption bands at 3.0; 5.65; 6.45 / U. </ P> Example 39: 7β- / <Sup> r </ sup> 2- (5-1-methylamino-1,2,4-thiadiazol-3-yl) -hoxyiminoacetamide <I> QJ ~ _ </ I> ^ .- ^ Xi ^ methyl t jbra ^ Bo ^ - ^ yl ^^ <U> Mo- </ U> </ P> <P> methyl) -3-cephem-4_-icarbonn <Sub> i </ Sub> <Sup>: </ Sup> i, <Sub> i </ sub> acid_sodium salt </ P> <p> From 4.60 mg (υ, 61 mmol) of 7β - / - - (5-N-methyl-tert-octylcarbonylamino-1,2,4-thiadiazol-3-yl) -2-methoxyiminoacetanido7-3- ( 1-Hiethyltetrazol-5-yl-thiomethyl) -3-cephem-4-carbonoic acid diphenylmethyl ester in 1 ml of methylene chloride, 0.33 ml of anisole and 4.6 ml <Sup> r The title compound of Rf 0.35 (UPC <Sub> 12 </ sub> plates, water / acetonitrile 6: 1), IR spectrum (liujol): characteristic absorption bands at 3.0; 5.65; 6.45 / U. </ P> <P> Be <U> is </ U> pie 40 </ U> <i> 'Jß.- £ 2- </ i> (5- ° tert, butqxycarbonylamino-J <I> <Sub> f </ Sub> </ I> 2 <Sub>? </ Sub> 4 <U> -thi </ U> adiazol-3 ~ vl) - <U> 2-Z-- </ U> 2-te <U> rtob </ U> utoxycarbonylproO-2-yloxyamino) - </ P> <p> A suspension of 15 ml of methylene chloride abs ,, 0.3 ml of dimethylformamide and 0.33 ml (7.84 mmol) of oxalic acid dichloride is stirred at -10 C for 30 minutes under nitrogen. Then </ P> <P> Example 36: 7g- [2- (5-Amino-1,2,3,4-thiadiazol-3-yl) -2-Z] </ U> methyl <u> carbamoyloxyiminoacetamidoj-3- (1-methyltetrazol-5-yl-thiomethyl) -S-cephem ^ -carboxylic acid pivaloyloxymethyl ester </ u> * </ P> <p> From 2.30 g (4.0 mmol) of 7/3 [2- (5-amino-1 / 2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] .- 3- ( 1-methyltetrazol-5-yl-thiomet'hyl) -3-cephem-4-carboxylic acid sodium salt, and 0.9 ml (3.85 mmol) of iodomethyl pivalate in 20 ml of N, N-dimethylformamide is obtained analogously to Example 21, the title compound of Rf value 0.85 (silica gel, acetone / glacial acetic acid / water / ammonia .20: 8: 5: 1). IR spectrum (Nujo'l); characteristic absorption bands at 2.95; 5.63; 5.93 ;. 6.45 u. </ P> <P> Example 37; 7 / 3- [2- (5-N-Methylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (1-carboxymethyltetrazol-5-ylthiomethyl) -3-cephem- 4-carboxylic acid sodium salt </ U> </ P> <p> From 350 mg (0.71 mmol) of 73- [2- (5-methylamino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3-acetoxymethyl-3-cephem 4-carboxylic acid sodium salt and 136 mg of 1-carboxymethyl-tetrazol-5-ylthiol in 3 ml of aqueous sodium bicarbonate are obtained analogously to Example 10b), the title compound of Rf 0.70 (UPC <Sub> 12 </ Sub> plates ,. Water / acetonitrile 9: 1). IR spectrum (Nujol): characteristic absorption bands at 3.0; 5.65; 6.25; 6.45 ρ. </ P> <P> <u> Example 38: 7 / 3- [2- (5-N-methyl-tert-butoxycarbonylaminol, 2,4-thiadiazol-3-yl) -2-methoxyirrine-aminoacetamido] -3- (1-methyltetrazole-5-yl) yl-thiomethyl) -3-cephem-4-carboxylic acid "diphenylmethyl ester </ U> </ P> <p> '316 mg (i / o mmol) of 2- (5-N-methyl-tert.butpxycarbonylamino-1, 2, 4-thiadiazol-3-yl) -2-methoxyiminoacetic acid and 5 ml of ethyl acetate are added at - 5 ° to a stirred suspension </ P> <P>. 27.11.1980 </ P> <p> AP C 07 D / 222 421 57 771/18 </ P> <p> Example 4: 4.2 <I> TßrCZ- </ i>. (5-1 e.rt.But oxycarbqny! amino-1 <Sub>? </ sub> 2.4-t hia ~ </ P> <p> ^ " </ P> <P> -i <sup> e Ξ </ sup> ^ ' <sup> e r </ Sup> </ P> <p> A solution of 15 ml of methylene chloride, 0.094 ml (0.854 mmol) of ΪΤ-methylraorpholine and 0.35 g (0.814 mmol) of 7β- / 2- (5-tert.-butoxycarbonylamino-1,2,4-thiadiazole-3 -yl) ~ 2 ~ Z- (2-tert-butoxycarbonylprop-2-yloxyimino) acetic acid becomes -10 <Sup> 0 cooled, treated with 0.11 ml (0.854 ml) of butyl chloroformate and stirred for 45 min. After addition of 0.422 g (0.854 mLiol.) Of 7β- <Sup> A </ sup>> Mino-3- (1-methyltetrazol-5-ylthiomethyl) -3-cephera-4-carboxylic acid diphenylmethyl ester, the solution is stirred for 5 h at room temperature. 3Jas reaction mixture is in vacuo at 35 <Sup> 0 The residue is taken up in ethyl acetate and washed successively with dilute sodium bicarbonate solution, water, 1H hydrochloric acid and saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo, the residue is applied to thick-layer plates The compound is of 'Rf value 0.49 (silica gel, 1'-toluene / ethyl acetate 1: 1). IR spectrum (Nujol): characteristic absorption bands at 5 <Sub> f </ Sub> 58; 5.82; 6.17; 6.44 / U. </ P> <P> .43 ,; , .7ß- / 2- (5- * tmino-1,2,4-thiadiazol-3-yl) "2-Z- (2 ~ </ P> <P> y <U> lt </ U> hiomethyl) -3 ~ cephem-4 ~ <U> carbon </ U> ^ acid inatii.umsalz </ P> <p> A solution of 100 mg (0.11 mmol) of 713- / 2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -2 »Z- (2-tert-butoxycarbon) ylprop-2-yloxyimino) acetamido-7-3- (1-methyltetrazol-5-ylthioinethyl) -3-cephem-4-carboxylic acid dipheny! methyl ester in 5 ml (65.33 mmol) of frifluoroacetic acid and 1 ml (3 <Sub> S </ sub> 18 mmol) <Sup> A </ sup> nisol is stirred at room temperature for 3 h. The </ P> <P> 27.11.1980 </ P> <p> AP C 07 D / 222 </ P> <p> 57 771/18 </ P> <p> 1.3 g (3.01 mmol) of 7β- / "2- (5-tert-tocycarbonylamino" -1,2,4-thiadiazol-3-yl) -2-Z- (2-tert-butoxycarbonylprop ~ 2 ~ yloxyimino) acetic acid is added to the suspension, the resulting clear solution is 30 Md.n &Lt; > at 0 to 5 <Sup> 0 </ sup> G stirred under nitrogen. To this solution is added dropwise a freshly prepared solution of 0.87 g (3.19 mmol) of 7ß-Aminocephalosporansäure in 18 ml of "methylene chloride abs" and 3 ml of IT, O-Bistrimethylsilylacetamid and stirred at a temperature of 0 to 5 <Sup> 0 </ sup> C, under nitrogen '16 h. Piezification solution is washed successively with water and saturated sodium chloride solution, dried over magnesium sulphate and dried in vacuo <Sup> ö The mixture is then reduced to Rf 0.43 (silica gel, ethyl acetate / acetic acid 9: 1). IR spectrum (Nujol): characteristic absorption bands at 5.6; 5.82; 6.04 / U · </ P> <p> Example 4I; 7ß- / £ ~ (5-amino-1,2,4 ~ th: lad <U> iazo </ U> l ~ 3-yl) -2-Z- <U> <Sub> i </ Sub> (2 ~ carboxy </ U> prop-2-yloxyiirii <U> no) acet </ U> airiido / -3-acetoxyme1; hyl - 3 ·. , cephem-4 <U> -carb </ u> onic acid dinatr <U> iumsalz </ U> </ P> <p> A solution of 2.3 g (3.35 mmol) of 7β ~ / 2- (5-tert-utoxycarbonylamine O "1,2,4-thiadiazol-3-yl) -2-Z- (2 tert-butoxycarbonylprop-2-yloxyimino) acetamide-q / ~ 3-acetoxymethyl-3-cephem-4-carboxylic acid in 12.54 ml (16.38%) <Sup> IJ </ sup> - 'r: L fluoroacetic acid and 2.10 ml (19.28 mmol) of anisole are stirred at room temperature for 1 h. The reaction mixture is evaporated at 30 G bath temperature in vacuo to dryness, the residue stirred with ether and'das product filtered off. Then the product is dissolved in 28 ml of methanol and treated with sodium ethylhexanoate. The solution is stirred in 50 ml of ethyl acetate. The precipitated product is filtered off and dried under high vacuum. The compound with the Rf value 0.78 (UPC.p plates, Y / ater / acetonitrile 4: 1) "IR spectrum Hujol) j characteristic absorption bands at 3.04; 5, t >8;6.24; 6.57 / u · </ P> <P> <u> Example 45: 7) 3- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -acetamido] -3-acetoxymethyl-3-cephem-4-carboxylic acid (sodium salt) </ U> </ P> <p> From 1.0 g (1.47 mmol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) acetamido] -S-acetoxymethyl-S-cephem-4 carboxylic acid diphenylmethyl ester. 2.4 ml of methylene chloride, 0.8 ml of anisole and 11.2 ml of trifluoroacetic acid are obtained analogously to Example 2, the title compound of Rf 0.35 (UPC ^ plates, water / acetonitrile 6: 1) , UV spectrum (methanol): Λ max U): 246 (8100). </ P> <P> Example 46; 7j3- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -acetamido] -3- (1-methyltetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid </ u> j <U> Sodium salt </ U>) </ P> From 0.70 g (0.95 mmol) of 7β- [2- (5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl) -acetamido] -3- (1-methyltetrazole-5 -yl-thiomethyl) -3-cephem-4-carboxylic acid diphenylmethyl ester in 1.5 ml of methylene chloride, 0.5 ml of anisole and 7.2 ml of trifluoroacetic acid are obtained analogously to Example 2, the title compound of Rf 0.35 (UPC <Sub> 12 </ sub> plates, water / acetonitrile 4: 1). UV spectrum (methanol): λ max (Π: 244 (13240). </ P> <P> <u> Example 47: In a manner analogous to the above examples, starting from corresponding starting materials, the following compounds are obtained: </ P> <P> 7.beta. ~ [2- (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (2-methyl-l, 3,4-thiadiazol-5- yl-thiomethyl) -3-cephem-4-carboxylic acid, </ P> <p> 7/3 [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- [1- (2-sulfoethyl) -H-tetrazole] 5-yl-thiomethyl] -3-cephem-4-carboxylic acid. </ P> <P> - <i> ΛΙΑ - </ I> </ P> <p> ι? </ P> <P> 7β- [2- (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-hydroxyiminoacetamido] -S-acetoxymethyl-p-cephemM-carboxylic acid. </ P> <p> 7β- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (3-hydroxypyridazin-6-yl-thiomethyl) -S-cephem - ^ carboxylic acid. =. , </ P> <p> 7 / 3- [2- (5-Anilino-l, 2,4-thiadiazol-3-yl) -2-Z- (2-carboxymethoxyimino) acetamido] -3-acetoxymethyl-3-cephem-4 carboxylic acid <Sub> / </ Sub> </ P> <p> 7β - "[2- (5-amino-1,2,3,4-thiadiazol-3-yl) -2-Z-carbamoyloxyimino-acetamido] r3-ac" etoxymethyl-3-cephem-4-carboxylic acid, </ P> <p> 7j3- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z- (1-carboxycyclopropyloxyimino) acetamido] -3- (1-methyltetrazol-5-ylthiomethyl) - ~ 3-cephem 4-carboxylic acid, </ P> <p> 7 / 3- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -3- [1- (2-sulfoethyl) -tetrazole-5- ylthiomethyl] -3 "cephem-4-carboxylic acid, </ P> <P> 7ß- [2- (5-amino-l, 2,4 "thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -3- [1- (2-carboxyethyl) tetrazole-5-ylthiomethyl] 3-cephem-4-carboxylic acid, </ P> <P> 7β- [2- (5-amino-l, 2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido] -3- (l-carboxymethyltetrazol-5-ylthiomethyl) -S-cephem ^ - carboxylic acid pivaloyloxymethyl ester, </ P> <p> 73- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamodo] -3- (• 1-dimethylaminomethyltetrazol-5-yithiomethyl-3-cephem-4 carboxylic acid-pivaloyloxymethy! ester </ P> <P> 27.11.1S80 </ P> <p> AP C 07 D / 222 421 </ P> <p> 57 771/18 </ P> <P> -1.2 <Sub>) </ Sub> 4-thiadiazol-3-yl) -2-Z-methylcar <Sup> 1 </ Sup> bamoyloxyiminoacetamido7-3-carbamoyloxymethyl ~ 3 ~ cephera-4-car'bonsäure, </ P> <p> ~ 1,2,4-thiadiazol-3-yl) -2-Z-ethyl-carbaraoyloxyiminoacetamido-7-3 / i - (2-dimethylaminoethyl) -t-etrazol-5-ylthiomethyl-2-cephem-4-carboxylic acid, </ P> ~ 1,2,4 thiadiazol-3-yl) -2-Z-carbamoyloxyiminoacetamido / -3 ~ (1-me-thyltetrazol-5-ylthior <p> <Sub> l </ Sub> iethyl-3-cephem-4 </ P> <P> carboxylic acid, </ P> <p> 7β- / 2- (5-rino-1-j2,4-thiadiazol-3-yl) -2-Z-carbamoyloxyimino-acetamido-7,3-carboxymethyl-tetrazole-5-rylthiomethyl-3-cephera-4-carboxylic acid ; lure, </ P> <P> 7.beta. ~ / 2 ~ (5-amino-1, .2,4-thiadiazol-3-yl) -2-Z-carbamoyloxyiminoacetamido7-3- (1-sulforaethyl "tetrazol-5 ~ ylthioraetiiyI) ~ 3- </ P> <P> cephem-4-carboxylic acid, </ P> <P> 7.beta. ~ / 2- (5-Aniino-1,2,4 ~ thiadiaz ol-3-yl) -2-Z ~ carbamoyloxyiminoacetaftiido7'-3- (i-diraeohylaminomethyltGtrazolr5 ~ yl'thiomethyl) -3-ceph .EM ~ 4-carboxylic acid, </ P> <p> 7β- / 2 .- (5-Methylamino-1,2,4-thiadiazol-3-yl) r2-Z-methoxyiminoacetamide Q7-3- (1-sulforaethyltetrazol-5-ylthiomethyl) - </ P> <p> 3 ~ cephera-4-carboxylic acid, </ P> <P> 7ß- / 2- (5-methylamino-1,2,4-thiadiazol-3-yl) -2-Z-me-fchoxyiminoacetamido7-3 ~ / <Sup> i </ sup> I- (2-di-tiethylaminoethyl) tetrazol-3-yl-yl methyl 7-3-CGphera-4-carboxylic acid </ P> <P> 7ß- / 2- (5-Methylämino-1 <Sub> t 2,4-thiadiazol-3-yl) -2.-Z-methoxy-irineaacetamido7-3- (1-metyl-tetrazol-5-ylthiomethyl) -3- </ P> <P> cepliem ~ 4-carboiißäure p: ivaloyloxymethylester, </ P> <p> 73- [2- (5-Methylamino-l, 2,4-thiadiazol-3-yl) -2-Z-methoxyimino-acetamido] -3- (1-carboxymethyltetrazol-S-ylthiomethyl) -3-caphem-4 carboxylic acid pivaloyloxymethyl ester, </ P> <p> 70- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-hydroxyiminoaceto, amido] -3- [1- (2-dimethylaminoethyl) tetrazol-5-yl thiomethyl] -3-cephem-4-carboxylic acid, </ P> <p> 70- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -2-hydroxyiminoacetamido] -3- (1-methyltetrazol-5-ylthiomethyl) -3-cephem-4-. carboxylic acid pivaloyloxymethyl ester, </ P> <p> 7β- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -acetamido] -3- (1-carboxymethyltetrazol-5-ylthiomethyl) -3-cephem-4-carboxylic acid . </ P> <p> 70- [2- (5-Amino-1, 2,4-thiadiazol-3-yl) -acetamido] -3- (1-sulfo-methyl-tetrazol-5-yl-thiomethyl) -3-cephem-4-carboxylic acid . </ P> <P> 7ß- [2- (5-amino-l, 2,4-thiadiazol-3-yl) acetamido] -3- [1- (2 <Sub> r </ Sub> dimethylaminoäthyltetrazol-5-ylthiomethyl] -3-cephera-4-carboxylic acid, </ P> <p> the sodium salts and disodium salts of those compounds containing one or two acidic groups μηα the hydrochlorides of those compounds containing a basic group. </ P> <P> <Sup> 3 </ sup> PJlLIB 'dry ampoules or vials containing 0.5 g of active substance, <I> e.g. la- </ I> [2- (5-amino-l, 2,4-thiadiazol »3-yl) -2-Z-methoxyiminpacefamido] -3- (l-methyltetrazol-5-yl-thiomethyl) -3-cephem- 4-Carboxylic acid (sodium salt) are prepared as follows. ''. </ P> <P> <U> Composition </ u> (for 1 ampoule or vial) </ P> <p> active substance "0.5 g mannitol 0.05 g </ P> A sterile, aqueous solution of the active substance and mannitol is sealed and tested under aseptic conditions in 5 ml. or 5 ml. vials. </ P> <P> ' Example 49; Dry ampoules or vials containing 0.25 g of active substance, e.g. 7β- [2- (5-Amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido] -3- (1-methyltetrazol-5-ylthiomethyl) -3-cephem-4-carboxylic acid ( Sodium salt) are prepared as follows: </ P> <P> <U> Zusammenset </ u> (for 1-ampoule or vial) </ P> <p> Active substance 0.25 g </ P> <p> mannitol 0.03 g </ P> A sterile, aqueous solution of the active substance and mannitol is sealed and tested under aseptic conditions in 5 ml. or 5 ml. vials. </ P>

Claims (7)

27.11.1980 AP C 07 D / 222 421 57 771/18 - * 9 ' Brfinaungsanspruch Process for the preparation of 7β-aminothiadiazolylacetainido-3-cephera-4-carboxylic acid compounds of the formula ur - »- c-coHH-l S \ Arn, 1, H J_ B J-CH ₂ -R ₃ OR ₁ O f ι '' wherein Am represents an optionally protected amino group, R _{1 is} hydrogen, optionally substituted lower alkyl or cycloalkyl, or optionally H-substituted carbamoyl, R _{2 is} hydrogen or lower alkoxy, R-, is hydrogen, acyl oxy or Heterocyclylthio, and R is represents an optionally protected carboxyl group, and salts of such compounds *, which have a salt-forming group, characterized in that. - a) in a compound of the formula
_ R ₀ H I VS I IT i-CH _? -R _o (II), wherein R ₂ , R 1 and R ₂ have the meanings given above, and wherein the 7β-minmino group is optionally substituted by an acylating group, the 7β-amino group is treated by treating with an acyl radical of a carboxylic acid of the formula H ^ _ o C-COOH it Ii it Am- I H H. (III) introducing acylating agent / wherein Am and R- have the meanings indicated above, acylated "or _Ä b) a compound of the formula _N. -C-CONH-j-, \ ^ (IV) wherein Am, R_, R_ and R have the meanings given above, with a hydroxylamine of the formula H-N-O-R, (V), wherein R, has the meaning given above, pder c) a 2-cephem compound of the formula ? 2 w-s- · -C-CONH · · ·, · wherein Am, R ₁ , R ₂ , R, and R have the meanings given above, isomerized, or d) for the preparation of a compound of formula (I) wherein Am represents a primary or secondary amino group, a compound of formula • ·? 2 : A -conh- · 7 · ¹ ° "X- ^ ³ wherein X is halogen or hydroxy and R ₁ , R ^, R and R. JL ** · «j H ⁵ have the meanings given above, is treated with a salt of thiocyanic acid, or with a Isorhodanwasserstoffsäure-ester, or a compound of formula (VII) wherein X is hydrogen with thiocyanate, or , e) for the preparation of a compound of formula (I) wherein R _{1 is} hydrogen and wherein Am ,. R-, R ₃ and R _{4 have} the meanings given above, a compound of Formula '* .'>> * - "2 * C * ss. μ «-CH - CCNH · ··· Air »- · N · N _v , - -Ci -'- R-, (VIII), ' ^R 4 wherein Am, R-, R ₃ and R have the meanings given above, treated with a nitrosating agent, or f). for preparing a compound of formula I wherein R 1 represents optionally substituted lower alkyl or cycle alkyl, or optionally N-substituted carbamoyl, and wherein Am, R-, R "and R have the meaning given above, in a compound of formula / ^S \ wherein Am, R, R and R have the meanings given above,. the hydroxyimino group is treated with a radical R introducing agent, or g) for the preparation of a compound of formula (I) wherein R is lower alkoxy, and wherein Am, -R ₁ , R ₃ and R ₄ are as defined above, in a compound of formula -CONE- -T T Arn · , - ^N S OR. wherein Am, R, / R- and R _{4 have} the meanings given above, wherein functionally »groups are in protected form, in α-position introduces a lower alkoxy group, or ff. h) for the preparation of a compound of the formula (I) in which R ^ is heterocyclicthio and in which Am, R, R and R _{4 have} the meanings given above, a "" compound of the formula N · -C-CONK · · · S OR ₁ 0 · "4 wherein Am, R ^, R ₂ and R _{4 have} the meanings given above, and R ° denotes a residue which can be replaced by a heterocyclylthio radical R, is treated with a mercaptan HR ₃ , or Preparation of a compound of formula (I) wherein R _{3 is} acyloxy and wherein Am, R ₁ ; R ₂ and R _{4 have} the meanings given, a compound of formula * C-CCNH- · · al wherein Am, R ,, R and R _{4 have} the meanings given above, treated with an Acylieruhgsmittel, or j) for the preparation of a compound of the formula (I) in which R _{4 is} free carboxyl and in which Am, R 1, R ₂ and R ₂ have the meanings given above, in a compound of the formula -C-CONK- · · · · · · § I -jI, .1-CK ₇ -R, (Ij), wherein Am, R ,, R and R _{3 have} the meanings given above, and R represents a protected carboxyl group, the carboxyl protecting group is removed and replaced by hydrogen, or k) for the preparation of a compound of the formula (I) in which R _{4 represents} an esterified carboxyl group and in which Am, R _1, R ₃ and R _{3 have} the meanings given above, a compound of the formula ^R 2 if-Γ-ί-^ς0ΚΗ-Γ-(^ l (Ro, COOH wherein Am, R ^, R ₂ and R ^ have the meanings given above, the 4-carboxyl group esterified, or 27.11.1980 AP C 07 D / 222 57 771/18 1) for the preparation of compounds of formula (I), v / orin Am is a primary, secondary or tertiary amino group, a compound of formula U - β - C - COHTH "* β - 6» Il II / til y- ⁸ . N Ii ^ -N'-CHOREOR ₁ ; ^R 4 v / orin y is halogen and R, Rp, R and R have the meanings given above, with ammonia or a primary or secondary amine Am-H, or a metal amide thereof, and, vexixi necessary, in cleaving unsolicited protecting groups from an obtained compound, and / or, if desired, converting a resulting compound having a salt-forming group into a salt, or a salt obtained, into a free compound or another salt. Process according to item 1 for the preparation of compounds of formula (i), characterized in that Amino or methylamino, R ^ is hydrogen, methyl, 2 ~ carboxy-2-propyl or 1-carboxy-1-cyclopropyl, R _{2 is} hydrogen or methoxy , Ro acetoxy, carbamoyloxy, optionally substituted by IJiederalkyl or carboxy lower alkyl substituted Triazolyl'thio, such as 4 ^ü arboxymethyl-1,2,4-triazolylthio, optionally substituted by Hiederälkyl, Carboxiliederalkyl, SuIfoniedefalkyl or Diniederalkylaminoniederalkyl substituted tetrazolylthio, such as 1-methyl ~ 1H-tetrazole -5-ylthio, 1-sulfomethyl-1H-tetrazol-5-ylthio- _f 1- (2-sulfoethyl) -1H-tetrazol-5-ylthio, 1 ~ carboxyniethyl-1IT-tetraal ~ 5-yl-triol, 1- (2- Dimethylaminoethyl) -1H-tetrazol-5-ylthio, optionally substituted by thio-alkyl substituted thiadiazolylthio, such as 2-methyl-1, 3-thiadiazol-3-ylthio or 3-methyl-1,2,4- 27.11.1980 AP C 07 D / 222 421 57 771/18 thiadiazol-5-ylthio, optionally substituted by hydroxy pyridazinylthio, such as 3-hydroxy-pyridazin-6-ylthio, optionally substituted by hydroxy pyrimidinylthio, v / ie _a 4 ~ hydroxy-2-pyrimidinyl or this tautomere 4 ~ ^Cteo-3) 4-dihydro ~ 2-pyrimidinylthio, or by lower alkyl and two hydroxy substituted ifriazinylthiOj such as 2-lower alkyl-5,6-dihydroxy-1,2,4-triazin-3-ylthio, and R. carboxyl or in physiologically cleavable form, it esterifies carboxyl, e.g. B, Privaloyl- 'oxymethoxycarbonyl, or Phthalidyloxycarbonyl, as well as pharmaceutically acceptable ^ alze of such compounds, A method according to item 1, characterized in that 7ß- / 2- (5- ^A Niino ~ 1,2,4-thiadiazol-3 ~ yl) -2-methoxyimino Z ~ ~ ~ acetaraido_7-3 (1,2,5, 6-t-etrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl-thiomethyl) -3-cephem-4-carbonone ^; iure, and pharmaceutically acceptable S _a i _Z e prepared therefrom v / ground. Process according to item 1, characterized in that 7β- / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-hydroxyiminoacetamido7-3- (methyltetrazol-5-yl-thiomethyl) 3-cephem-4-carboxylic acid, and pharmaceutically acceptable salts thereof are prepared. Process according to item 1, characterized in that 7β ~ / 2 ~ (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamide / -: 3 ~ ac et oxymethyl-3 ~ c ephern ~ 4-carboxylic acid pivaloyloxymethyl esters, and pharmaceutically acceptable salts thereof are prepared _o ''. " '-Ml- 27.11.1980 AP C 07 D / 222 57 771/18 β »Procedure according to item 1 ,. characterized in that 7ß- / 2- ^(5-A mino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido7-3-carbamoyloxymethyl-3-cephera-4-car'bonsäurepivaloyloxymethylester, .and pharmaceutically acceptable ^ü Alze thereof produced v / ground, Process according to item 1, characterized in that 78- / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido-7-3- (1-methyltetrazol-5-yl thiomethyl) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester, and pharmaceutically acceptable ester thereof ^ä Alze v / earth * 8 »The method of item 1, characterized in that 7.beta. ~ / 2- ^(5-A mino-1, 2,4-thiadiazol-3-yl) -2-methoxyiminoacetamido ~ Z? ~ 3 £ 1 -Z" 2- (H, lT-dimethylaraino) äthyi7-1H-1etrazol-5-yl-thiomethylJj 3-cephem-4-carboxylic acid pivaloyloxymethyl ester, and pharmaceutically acceptable salts thereof are prepared » 9, method according to item 1, characterized in that 7β- / 2- (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamide Qj ^ -3- (1 ~ pivaloyloxyraethoxycarbonylmethyltetrazole- 5-yl-thiomethyl-3-cephem-4-carboxylic acid ~ pivaloyloxymethyl ester, and pharmaceutically acceptable salts thereof. 10 »Process according to item 1, characterized in that 7β-ε ~~ (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetanido-3- (4-0X0-3, 4-dihydro-pyrimidin-2-yl-thiomethyl) .3-cephem-4-carboxylic acid, and pharmaceutically acceptable. '° alze of which are produced,'. · ' 27.11.1980 AP C 07 D / 222 421 * * * *, 57 771/18 11, method according to item 1, characterized in that 7ß- / 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-Z-metho. "Xyiminoacetaniido7-3-acetoxymethyl-3 cephine-4-carboxylic acid, and pharmaceutically acceptable products thereof, 12, "^" erfaliren according to item 1, characterized in that 7.beta. ~ / "2 -" (5 ^"Ä Niino-4, 2,4'-thiadia2iol ~ 3 ~ yl) -2-Z-methylcar'bamoyloxyiminoacetamido7-3 ~ acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable amounts thereof. 13 »Method according to item 1, characterized in that 7β- / 2 ~ (5-amino-1,2,4-thiadiazol-3-yl) -2-Z-methylcarbamoyloxyiminoacetamido7-3- (1-methyltetrasol-5-yl ~ thiomethyl) ~ 3-cephem-4-carboxylic acid and pharmaceutically acceptable ^u alse be made of it. 14c method according to item 1, characterized in that 7 ^ - / 2- _(? ^5-A mino-1 2,4-thiadiazol'-3 ™ yl) -2-Z-methylcarbaraoyloxyiminoacetamido7-3 ~ (1 ~ carboxymethyl-tetrazole -5-yl-thiomethyl) -3-cephem ~ 4-carboiacid and pharmaceutically-mediable salts thereof are prepared » 15, method according to item 1, characterized in that • 7ß- / 2- ^(5-A mino-1,2,4-tliiadiazol-3-yl) -2-Z-hydroxylminoacetamido7-3- (1-carboxymethyl-tetrazol-5-yl ~ ± th Omethyl) -3 cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof are prepared '27.11.1980 07 C 07 D / 222. , 57 471/18 16. The method of item 1, characterized in that 7ß- / 2- ^(5-A mino-1,2,4-thiadiazol-3-yl) -2 ~ Z-methylcarbamoyl oxyiminoacetamido7-3 ~ (1-t -sulfomethyl tetrazol-5-yl-thio-methyl) -3-cephera-4-carboxylic acid and pharmaceutically acceptable salts thereof. 17 · The method of item 1, characterized in that 7ß- / 2- ^(5-A mino-1,2,4-thiadiazol ~ 3 ~ yl) ~ 2 ~ Z ~ hydroxyiminoacetamido_7-3- (1-sulfomethyltetrazol ~ 5- yl-thiomethyl) -3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof are prepared » 18 »Method according to item 1, characterized in that 7β ~ / 2 ~ (5- ^ 1-thiol-1,2- _i- 4-thiadiazol-3-yl) -2-ZZ-2-methylcarbamoyl oxyiminoacetarnide4-3- (1-methyl te trazol-5-yl-thi-omethyl) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester and pharmaceutically acceptable salts thereof. Process according to item 1, characterized in that 7β- / 2- (5-N-methylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxyiminoacetamido7,3- (1-carboxymethyltetrazole-5 -ylthiomethyl) -3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof. Method according to item 1, characterized in that , 7β- / 2- (5-H-Methylamino-1,2,4-thiadiazol-3-yl) -2-Z-methoxy-iminoacetamido-7α- (1-methyltetrazol-5-yl-thiomethyl) -3-cephem 4-carboxylic acid and pharmaceutically acceptable salts thereof are prepared, 21. The method according to item 1, characterized in that 7ß- / 2- (5-tert-utoxycarbonylamino-1,2 ₅ 4 ~ thiadiazol-3 · yl) -2-Z- (2'-carboxyprop-2-yloxyiinino ) acetamido / -3-acetoxy fea 27/11/1900 AP C 07 D / 222 57 771/18 methyl "-3" cephem "4" carboxylic acids and pharmaceutically acceptable salts thereof, 22 «A method according to item 1, characterized in that 7.beta. - /" 2 -. ^(5-A mino-1,2,4-thiadiaa-ol-3-yl) -2-Z- (2-carboxyprop-2 ~ yloxyimino) acetamido7--3 ~ (1 ~ methyltetrGzol-5-ylthiomethylD-3 ~ cephera-4 ~ carboxylic acid and pharmaceutically _Toggle: '^ nelmibare aize thereof are prepared.. 23c method according to item 1, characterized in that 7ß- ^ 2- (5- ^J Wno-1,2,4-thiadiaz ol ~ l ^r 3-3) "2-Z- (2-carboxyprop-2-yloxyimino) acetoinidyl-3,7- (2-11, IT-di-ethylamino-ethyl) 1-tetrasol-5-ylthiomethyl-3-cephem 4-carboxylic acid and pharmaceutically acceptable salts thereof. ...'-....