NZ245640A

NZ245640A - 7-(5,8-diazabicyclo[4.3.0]non-8-yl) substituted and 7-(2-oxa,-5,8-diazabicyclo[4.3.0]non-8-yl) substituted 6-fluoro-4-oxo quinoline (and naphthyridine)-3-carboxylic acid derivatives and pharmaceutical compositions thereof

Info

Publication number: NZ245640A
Application number: NZ245640A
Authority: NZ
Inventors: Uwe Petersen; Andreas Krebs; Thomas Schenke; Thomas Philipps; Klaus Grohe; Klaus-Dieter Bremm; Rainer Endermann; Karl-Georg Metzger; Ingo Haller
Original assignee: Bayer Ag
Priority date: 1992-01-10
Filing date: 1993-01-08
Publication date: 1995-03-28
Also published as: CN1061351C; CA2086914A1; JPH05271229A; FI104174B; FI990207A; MY115416A; EP0550903A1; NO924978L; SK396692A3; HUT64065A; CN1043142C; FI930049A0; HU9300034D0; JP2003026574A; NO924978D0; SK285223B6; SK2232000A3; SK282971B6; FI104174B1; CN1074218A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £45640 i r . - J .i.V.V??-. Patents Form 5 3P.\V.<=??•, :i: Cl.^s: CP."//+•."? J) 5~!W-}'. .^P.l D"+-F\6f loi+.j, ^'tosv'n.tapfc-. ... Pubiicoiion l;:..s: . ! P.O. Journci, I -o: , 28 MAR 1995 •V s »» V* $ « *i »» ri « (Sfy 21V W 5 ls-% sV «i * NEW ZEALAND N.Z. No. Patents Act 1953 COMPLETE SPECIFICATION OUINOLONE- AND NAPHTHYRIDONE-CARBOXVLIC ACID DERIVATIVES We, BAYER AKTIENGESELLSCHAFT. a Company registered under the laws of the Federal Republic of Germany, of Leverkusen, Germany do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- - 1 - (Followed by 1A) 10 2 4 5 6 4 0 The invention relates to new quinolone- and naphthyridonecarboxylic acid derivatives, processes for their preparation and also antibacterial agents and feed additives containing them. Quinolone- and naphthyridonecarboxylic acids which are substituted in the 7-position by a bicyclic amine radical have already been disclosed in EP-A-0,350,733. The present invention relates to new compounds of the formula (I) COOR2 (I) in which represents CH, CF, CC1, C-OCH3f C-CH3 or N, X1 represents H, halogen, NH2 or CH 3 I 15 represents Ci-Ca-alkyl, FCH2CH2-, cyclopropyl or phenyl which is optionally monosubstituted to trisubstituted by halogen, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3) - iA- R2 represents H, C,-C3-alkyl which is optionally substituted by hydroxyl, halogen or amino or 5-raethyl-2-oxo-1,3-dioxol-4-yl-methyl, and B represents a radical of the formula in which Y represents 0 or CH2, R3 represents C2-C5-oxoalkyl, CH2-CO-C6H5, CH2CH2C02R'/ R' 02C-CH=C-C02R "/ -CH=CH-C02R' or CH2CH2-CN, in which R' and R" each independently denote hydrogen or C|-C,-alkyl, and R4 represents H, C1-C3-alkyl, C2-C5-oxoalkyl, CH2-CO-C6H5/ CH2CH2C02R', R'OjC-CH^-COjR", -CH=CH-C02R' or CH2CH2-CN or represents 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, in which R' and R" each independently denote hydrogen or C,-C3-alkyl; and to pharmaceutical^ utilisable hydrates and acid addition salts thereof as well as the alkali metal, alkaline earth metal, silver and guanidinium salts of the underlying carboxylic acids. These compounds have a high 5 antibacterial activity. The compounds according to the invention are particularly distinguished in that they have a high activity on dormant and resistant microorganisms. Preferred compounds of the formula (I) are those in which 10 A represents CH, CF, CCl, C-OCH3 or N, X1 represents H, F, CI, Br, NH2 or CH3, R1 represents C2H5, cyclopropyl or 2,4-difluorophenyl, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3)-, 15 R2 represents H, CH3, C2HS or 5-methyl-2-oxo-l,3-dioxol- 4-yl-methyl, and b N represents a radical of the formula .3. h r"N y \ / ' in which r4 n n « n n h h \ / y r4n h y h mm...." r n 7 h h n y 4 7" or r n ^ h y - 3 - 24564 Y represents 0 or CH2 , R3 represents CH2-CO-CH3, CH2-CO-CsH5, CH2CH2-CO-CH3, CH2CH2C02R', R'0,C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN, ' 5 in which R' and R" each independently denote C,-Cralkyl, and R4 represents H, C1-C3-al]cyl, 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, CH2-CO-CH3/ CH,-CO-C6H5, CH2CH,-CO-CH3, CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-10 -CN, ' in which R' and R" each independently denote C1-C2-alkyl. Particularly preferred compounds of the formula (I) are those in which 15 A X1 R1 represents CH, CF, CC1, C-OCH3 or N, represents H, F, Cl, Br, NH2 or CH3, represents C2H5, cyclopropyl or 2,4-difluorophenyl, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3)-, - 4 - 245640 R2 represents H, CH3 or C2HS/ and B represents a radical of the formula n n n n \ -h h l-l h h.r^4— h hj-]' h r n y r4n y , rn y or r n y in which Y represents 0 or CH2 , and 5 R4 represents H, C1-C3-alkyl, 5-methyl-2-oxo-l, 3-dioxol-4-yl-methyl, CH2-CO-CH3, CH2-CO-C3Hj, CH2CH2-CO-CH3, CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN, in which 10 R' and R" each independently denote C,-Cj-alkyl. The compounds of the formula (I) in which A, X1, R1 and R2 have the abovementioned meaning, and B represents a radical of the formula - 5 - N R'N y in which R3 and Y have the abovementioned meaning, are obtained by reacting a compound of the formula (II) X1 f (II) in which A, Y, X1, R1 and R2 have the abovementioned meaning, with a compound of the formula (III) R3-X3 (III) 10 in which JT l I flfp - 6 - R3 represents C2-C5-oxoalkyl, CH2-CO-C6H5, CH2CH2-C02R' or CH2CH2-CN, in which R' denotes hydrogen or Ci.-Cj-alkyl, and X3 represents halogen, in particular chlorine, bromine or iodine, if appropriate in the presence of an acid binder. [Method A] Compounds according to the invention of the formula (I) in which A, X1, R1 and R2 have the abovementioned meaning, and B represents a radical of the formula n y -8 MAR 'i994 in which Y has the abovementioned meaning and R represents CH2CH2-CO-CH3, CH2CH2-C02R' 245 6 R'02C-CH=C-C0,R", -CH=CH-C02R' or CH2CH2-CN, in which R' and R" each independently denote hydrogen or Q-Cj-alkyl, and can be obtained 5 by reacting a compound of the formula (II) x1 f (II) with a Michael acceptor such as dialkyl acetylenedi-carboxylate, alkyl propiolate or a compound of the formula (IV) 0 CH2=CH-R5 (IV) in which R5 represents COCH3, C02R' or CN. [Method B] To prepare enantiomerically pure compounds of the formula (I), a compound of the formula (V) - 8 - coor2 (V) in which A, R1, R2 and X1 have the abovementioned meaning and X2 represents halogen, in particular fluorine or chlorine, is reacted with an enantiomerically pure compound of the formula (VI) h h h h n n n n h-—) \ — h h \ h h \ \ -h h» [ \ h (vi) R^N Y , R4N Y R4N Y or R^N Y in which 10 Y represents 0 or CH2 and ' -A R represents H or C:-C3-alkyl, - 9 - ° A R P- k 0 v/ i V if appropriate in the presence of acid scavengers, and the reaction product is optionally further reacted with a compound of the formula (Ilia) R*-X3 (IHa) 5 in which X3 has the abovementioned meaning and R4 represents C2-C5-oxoalkyl, CH2-CO-C6H5, CH2CH2C02R' or CH2CH2-CN, in which 10 R' denotes hydrogen or C1-C3-alkyl, or with a Michael acceptor such as dialkyl acetylene-dicarboxylate, alkyl propiolate or a compound of the formula (IV) CH2=CH-R5 (IV) 15 in which R5 represents C0CH3, C02R' or CN [Method C]. If, for example, 8-chloro-l-cyclopropyl-6,7-difluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and [S,S]—2,8— diazabicyclo[4.3.O]nonane are used as starting compounds, the course of the reaction can be represented by the following reaction scheme: COOH h n h h NH cooh If, for example, 6,8-difluoro-l-(2,4-difluorophenyl)-l,4-dihydro-7-([IS,6R)-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid and diethyl acetylenedicarboxylate are used as starting substances, the course of the reaction can be represented by the following reaction scheme: cooh + c2h502c-c=c-c02c2h5 - 11 - o c2h5o2c-ch= cooh F f The racemic compounds of the formula (II) used as starting compounds are mainly known. Enantiomerically pure compounds of the formula (II) are new and can be obtained in various ways. 1. A racemic intermediate of the formula (II) is reacted with an enantiomerically pure auxiliary reagent, the resulting diastereomers are separated, for example by chromatography and the chiral auxiliary group is removed again from the desired diastereomer. The following reaction may be shown as an example: 0 (r) vv ch- nh-cos ch3 /=x (R) o- ch- nh-co hj~ ^ p . n™ li Diastereomer lUUrt »- separation cooh O cooh HN h /-n" y n f h A h © 2. The bicyclic amines (VI) are, as enantiomerically pure compounds, new. They can be prepared by the following processes: 2.1. The racemic bicyclic amines (a) r4 Nvx> (a) in which R4 represents H or C1-C3-alkylf > tv.i 4***>. $ /x ^ ; . t \ 1" J 4 J 'T U can be reacted with enantiomerically pure acids, for example carboxylic acids or sulphonic acids such as N-acetyl-L-glutaxnic acid, N-benzoyl-L-alanine, 3-bromocamphor-9-sulphonic acid, camphor-3-carboxylic 5 acid, cis-camphoric acid, camphor-10-sulphonic acid, 0,0'-dibenzoyl-tartaric acid, D- or L-tartaric acid, mandelic acid, a-methoxy-phenylacetic acid, 1-phenyl-ethanesulphonic acid or a-phenyl-succinic acid, to give a mixture of the diastereomeric salts, 10 which can be separated by fractional crystallisation to give the diastereomerically pure salts (see P. Newman, Optical Resolution Procedures for Chemical Compounds, Volume 1). The molar ratio between amine and enantiomerically pure acid can be varied in a 15 relatively wide range. By treatment of these salts with alkali metal or alkaline earth metal hydroxides, the enantiomerically pure amines can be liberated. 2.2. In a similar manner, as described in 2.1., 20 resolution of the basic intermediates which occur during the preparation of the racemic bicyclic amines can be carried out using the abovementioned enantiomerically pure acids. Examples of basic intermediates of this type are: - 14 - In the following reaction scheme, the separation of 8-benzyl-cis-2,8-diazabicyclo[4.3.0]nonane into the enantiomers via the tartrates and conversion thereof into the enantiomerically pure cis-2,8-diazabicyclo[4.3.0]nonanes may be shown as an example of a resolution: L(+)-tartaric acid £ 1 1.Crystallisation 2. Crystallisation 1 x recryst. H i N 1) 1 x recrystallisation 2) NaOH H N-CHi-Ph H Mother liquor 1) NaOH 2) D(-)- tartaric acid ^ NaOH N-CH-rPh H,/ Pd-C H,/ Pd-C e.e.> 99 % R.R-Configuration c.c.> 99 % S,S-Configuration 2.3. Both the racemic amines (a) and the basic intermediates (b) - (e) can be separated by chromatography, if appropriate after acylation, by means of chiral support materials (see, for example, G. Blaschke, Angew. Chem. 92, 14[1980]). 2.4. Both the racemic amines (a) and the basic intermediates (b), (c), (e) can be converted by chemical linkage with chiral acyl radicals into diastereomer mixtures which can be separated by distillation, crystallisation or chromatography into the diastereomerically pure acyl derivatives, from which the enantiomerically pure amines can be isolated by hydrolysis. Examples of reagents for linkage to chiral acyl radicals are: a-methoxy-a-trifluoromethyl-phenylacetyl chloride, menthyl isocyanate, D- or L-a-phenyl-ethyl isocyanate, menthyl chloroformate or camphor-10-sulphonyl chloride. 2.5. In the course of the synthesis of the bicyclic amines (a), instead of achiral protective groups chiral protective groups can also be introduced. In this manner, diastereomers are obtained which can be separated. For example, in the synthesis of cis-2,8-diazabicyclof4.3.0]nonane, the benzyl radical can be replaced by the R- or S-a-phenylethyl radical: <,s\ (x n \y V o N Ji . f, i S ^ IP N — CH—<f \ ► f In — CH—" ^ O CH3 C|S £ CH, 2.6. The enantiomerically pure amines (VI) can also be synthesised from enantiomerically pure precursors, such as, for example, [R,R]- or [S,S]-3,4-dihydroxy-pyrrolidine, which should be protected on the nitrogen by a protective group. An example of the synthesis of an enantiomerically pure amine, starting from enantiomerically pure l-benzyl-3,4-dihydroxy-pyrrolidine, which may be given is the following reaction scheme: HO OH HO OH HO OCH.CH^OH c ► ( ) c-d . N N "N' I I I B/.I CO CO R R TosO OCH2CH2OTos N I CO O N-Bzl g.h / \ 0 N-H N N R CO H - 18 - >■ s R = a: b c d e f g h for example, (CH3);C-0, H2, Pd/A-carbon acylation NaH, BrCH2COOC2H5 or c: CH2=CH-CH2Br, NaH, LiBH, d: 02, NaBHi,, tosyl chloride, NEt3, benzylamine, xylene, reflux hydrolysis H2, Pd/A-carbon 10 Examples of compounds of the formula (VI) which may be mentioned are: cis-2,8-diazabicyclo[4.3.0]nonane, cis-2-oxa-5,8-diazabicyclo[4.3.0]nonane, trans-2-oxa-5,8-diazabicyclo[4.3.0]nonane, 15 S,S-2,8-diazabicyclo[4.3.0]nonane, IR,6S-2-oxa-5,8-diazabicyclo[4.3.0 Jnonane, IS,6R-2-oxa-5,8-diazabicyclo[4.3.0]nonane, IR,6R-2-oxa-5,8-diazabicyclo[4.3.0]nonane, IS,6S-2-oxa-5,8-diazabicyclo[4.3.0]nonane, 20 The reaction of (V) with (VI), in which the compounds (VI) can also be employed in the form of their salts, such as, for example, the hydrochlorides, is preferably carried out in a diluent such as dimethyl sulphoxide, N,N-dimethylformamide, N-methylpyrrolidone, hexamethyl-25 phosphoramide, sulpholane, acetonitrile, water, an alcohol such as methanol, ethanol, n-propanol or isopropanol, glycol monomethyl ether or pyridine. Mixtures of these diluents can also be used. - 19 - Acid binders which can be used are all the customary inorganic and organic acid binding agents. These preferably include the alkali metal hydroxides, alkali metal carbonates, organic amines and amidines. Those which may be mentioned specifically as being particularly suitable are: triethylamine, 1,4-diazabicyclo-[2.2.2]octane (DABCO) , 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or excess amine (VI). The reaction temperatures can be varied within a relatively wide range. In general the reaction is carried out between about 20 and 200°C, preferably between 80 and 180 °C. The reaction can be carried out at normal pressure, but also at elevated pressure. In general, it is carried out at pressures between about 1 and 100 bar, preferably between 1 and 10 bar. When carrying out this process, 1 to 15 mol, preferably 1 to 6 mol of the compound (VI) are employed per mol of the compound (V). Examples of compounds of the formula (II) which can be used both as racemates and as enantiomerically pure or diastereomerically pure compounds which may be mentioned are: R1 R2 X1 Y A Cyclopropyl c2h5 h ch2 c-h f-ch2ch2 h h ch2 c-f Cyclopropyl c2h5 h ch2 C-Cl Cyclopropyl h h ch2 c-och Cyclopropyl h h ch2 c-ch3 Cyclopropyl c2h5 h ch2 N Cyclopropyl h Br ch2 c-f Cyclopropyl h ci ch2 c-f Cyclopropyl h ch3 ch2 c-f Cyclopropyl C2H5 nh2 ch2 c-f Cyclopropyl h h 0 c-h Cyclopropyl c2h5 h 0 c-f c2h5 h h 0 C-Cl ch3 h h 0 c-och: Cyclopropyl h h 0 c-ch3 Cyclopropyl h h 0 N Cyclopropyl h Br 0 c-f Cyclopropyl h ci 0 c-f Cyclopropyl h ch3 0 c-f Cyclopropyl h nh2 0 c-f R1 R2 X1 Y A Cyclopropyl ch3 H CH, c-h Cyclopropyl ch,ch,oh H CH, C-F Cyclopropyl ch2ch2oh h CH, C-Cl Cyclopropyl H H ch2 c-och Cyclopropyl H H ch2 c-ch3 Cyclopropyl h h CH, N Cyclopropyl h Br CH, C-F Cyclopropyl H F ch2 C-F Cyclopropyl h ch3 CH, C-F Cyclopropyl H nh2 CH2 C-F Cyclopropyl H h 0 C-H Cyclopropyl ch3 H 0 C-F C2H5 H H 0 C-Cl Cyclopropyl h H 0 c-och Cyclopropyl h H 0 c-ch3 Cyclopropyl H h 0 n Cyclopropyl H Br 0 C-F Cyclopropyl h ci 0 C-F Cyclopropyl H ch3 0 C-F c2h5 H nh2 0 C-F R1 R2 X1 Y A CycIoprop\l h h CH2 C-H Cyclopropyl h h CH2 C-F Cyclopropyl h h ch2 C-Cl Cyclopropyl h h ch2 C-0CH3 Cyclopropyl h h ch2 C-CH3 Cyclopropyl h h ch2 N Cyclopropyl h Br ch2 C-F Cyclopropyl h F ch2 C-F Cyclopropyl h CH, ch2 C-F Cyclopropyl H nh2 ch2 C-F Cyclopropyl H H 0 C-H Cyclopropyl h h 0 C-F Cyclopropyl h h 0 C-Cl Cyclopropyl h h 0 c-ochj Cyclopropyl h h 0 C-CH3 Cyclopropyl h h 0 N Cyclopropyl H Br 0 C-F Cyclopropyl h F 0 c-f Cyclopropyl h CH3 0 c-f Cyclopropyl h nh2 0 c-f R1 R2 X1 Y A Cyclopropyl h h ch; c-h Cyclopropyl h h ch2 C-F Cyclopropyl H h ch2 C-Cl Cyclopropyl h h ch2 c-och3 Cyclopropyl h h ch2 c-ch3 Cyclopropyl H h ch2 N Cyclopropyl H Br ch2 C-F Cyclopropyl H F ch2 C-F Cyclopropyl H ch3 ch2 C-F Cyclopropyl H nh2 ch2 C-F Cyclopropyl h h 0 c-h Cyclopropyl H h 0 C-F Cyclopropyl H H 0 C-Cl Cyclopropyl H H 0 c-ochj Cyclopropyl h H 0 c-ch3 Cyclopropyl h H 0 N Cyclopropyl h Br 0 C-F Cyclopropyl h F 0 C-F Cyclopropyl h ch3 0 C-F Cyclopropyl h nh2 0 C-F R1 R2 X1 Y A 2,4-Dif luorophenylH CI ch2 C-F 2,4-Dif luorophenylH ch3 ch2 C-F 2.4-Dif luorophenylH H ch2 c-ch3 2,4-Dif luorophenylH H 0 C-F 2,4-Dif luorophenylH H 0 C-Cl 4-Fluorophenyl h H 0 ch 2.4 Dif luorophenylH H 0 N 2.4 Dif luorophenylH H 0 C-OCH 2,4-Dif luorophenylH H 0 c-ch3 2,4-Dif luorophenylH H ch2 C-F 2,4-Dif luorophenylH F ch2 C-F 2,4-Dif luorophenyll I h ch2 C-Cl 2.4-DifluorophenylH H 0 C-Cl 2,4- Dif luorophenylH H ch2 n 2,4-Dif luorophenylH H 0 n 2,4-Dif luorophenylH h 0 c-h 2,4-Dif lucrophenylC2H5 h 0 C-F fv / r .■ . s ' , ' , The starting compounds of the structures (III) and (IV) are known. Examples which may be mentioned are: chloroacetone, 4-chloro-2-butanone, 5-chloro-2-pentanone, l-bromo-2-butanone, phenacyl chloride, methyl acrylates, ethyl acrylates, acrylonitrile, methyl vinyl ketone, dimethyl acetylenedicarboxylate, diethyl acetylene-dicarboxylate, methyl propiolate and ethyl propiolate. The reaction of (II) with (III) is preferably carried out in a diluent such as dimethyl sulphoxide, N,N-dimethyl-formamide, N-methylpyrrolidone, hexamethylphosphoramide, sulpholane, acetonitrile, water, an alcohol such as methanol, ethanol, n-propanol or iso: opanol, glycol monomethyl ether or pyridine in the presence of an acid binder. Mixtures of these compounds can also be used. Acid binders which can be used are all the customary inorganic and organic acid binders. These preferably include the alkali metal hydroxides, alkali metal carbonates, organic amines and amidines. Those which may be specifically mentioned as being particularly suitable are: triethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or excess amine (VI). The reaction temperatures can be varied within a relatively wide range. In general the reaction is carried out between about 2 0 and 200°C, preferably between 60 and 130 °C. «*il A IB TPS - 26 - The reaction can be carried out at normal pressure, but also at elevated pressure. In general, it is carried out at pressures between about 1 and 100 bar, preferably between 1 and 10 bar. 5 When carrying out this process, 1 to 15 mol, preferably 1 to 6 mol, of the compound (III) are employed per mol of the compound (II). The reaction of (II) with the Michael acceptors (IV) according to method B is preferably carried out in a 10 diluent such as acetonitrile, dimethyl sulphoxide, N,N-dimethylformamide, an alcohol such as methanol, ethanol, propanol or isopropanol, or glycol monomethyl ether. The reaction temperatures can be varied within a relatively wide range. In general, the reaction is 15 carried out between about 20°C and about 150°C, preferably between 40°C and 100°C. The reaction can be carried out at normal pressure, but also at elevated pressure. In general, the reaction is carried out at pressures between 1 and 100 bar, 20 preferably between 1 and 10 bar. When carrying out the process according to the invention, 1 to 5 mol, preferably 1 to 2 mol, of the compound (IV) are employed per mol of the compound (II). O c f ,> >' - ' * f The preparation of the acid addition salts of the compounds according to the invention is carried out in a customary manner, for example by dissolving the betaine in aqueous acid and precipitating the salt with a water-5 miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equivalent amounts of betaine and acid can also be heated in water or an alcohol such as glycol monomethyl ether and then evaporated to dryness or the precipitated salt filtered off with suction. 10 Pharmaceutically utilisable salts are understood as meaning, for example, the salts of hydrochloric acid, sulphuric acid, acetic acid, glycolic acid, lactic acid, succinic acid, citric acid, tartaric acid, methanesulphonic acid, 4-toluenesulphonic acid, 15 galacturonic acid, gluconic acid, embonic acid, glutamic acid or aspartic acid. The alkali metal or alkaline earth metal salts of the carboxylic acids according to the invention are obtained, for example, by dissolving the betaine in excess alkali 20 metal or alkaline earth metal hydroxide solution, filtering off undissolved betaine and evaporating the filtrate to dryness. Pharmaceutically suitable salts are sodium, potassium or calcium salts. By reacting an alkali metal or alkaline earth metal salt with a suitable silver 25 salt such as silver nitrate, the corresponding silver salts are obtained. Apart from the active substances mentioned in the examples, for example, the compounds listed in the fan it 00 ifllili - 28 - A jJ V following tables (optionally in the cis- or trans-form) can also be prepared by the processes described: r3 x1 a c2h502c-ch2-ch2- h C-F ch3o2c-ch=ch- h C-F nc-ch2-ch2- h C-F 5-Methyl-2-oxo-l,3-dioxol-4-yl-methyl- h C-F ch3-co-ch2- h C-Cl 5-McthyI-2-oxo-l ,3-dioxol-4-yl-meihyl- h C-Cl ch3-co-ch2-ch2- h C-H ch3-co-ch2- h C-H c2h5o2c-ch2-ch2 h C-H c2h5o2c-ch=c-co2c2h5 h c-h ch3o2c-ch=ch- h c-h c2h5o2c-ch=ch- F C-F ch3-co-ch2ch2- nh2 C-F c2h5o2c-ch2ch2- nh2 C-F ch3o2c-ch=c-co2ch3 1 nh2 C-F c2h5o2c-ch=c-co2c2h5 nh2 C-F tov. ) 1 1 '» v.' cooh r3 x1 a c:h502c-ch=ch- nh2 c-f ch3-co-ch2ch2- h n c2h5o2c-ch2-ch2- h n nc-ch2ch2- h n c2h5o2c-ch=c-co2c2h5 h n ch3o2c-ch=ch- h n • ch3-co-ch2ch2- ch3 c-h ch3-co-ch2- ch3 c-h c;h5o2c-ch2ch2- ch3 c-h c;h5o2c-ch=c-co2c2h5 ch3 c-h ch3o2c-ch=c-co2ch3 ch3 c-h c2h502c-ch=ch- ch3 c-h ch3o2c-ch=ch- ch3 c-f c2h5o2c-ch=c-co2c2h5 CHj n in i in lAft - 30 - r3 x1 a ch3-co-ch2ch2- h c-f ch3-co-ch2- h c-f c2h5o2c-ch2ch2- h c-f nc-ch2ch2- h c-f ch3o2c-ch=ch- h c-f ch3o2c-ch=c-co2ch3 1 h c-f c2h5o2c-ch=c-co2c2h5 1 h c-f 5-Methyl-2-oxo-1.3-dioxol-4-yl-methyl - h c-f ch3-co-ch2ch2- h C-Cl ch3-coch2- h c-Cl c2h5o2c-ch2ch2- h c-Cl nc-ch2ch2- h C-Cl ch3o2c-ch=ch- h C-Cl ch3o,c-ch=c-co,ch3 h C-Cl c2h5o2c-ch-c-co2c2h5 i h C-Cl 5-Mcthyl-2-oxo-1,3-dioxol-4-yl-metliyl- h C-Cl 9 k F, Ua t s * r3 x1 a c;h5o:c-ch=c-co2c2h5 i h c-h c\h502c-ch=ch- h c-h ch30:c-ch=ch- f c-f c2h50:c-ch2-ch2- f c-f c2h5o2c-ch=ch- nh2 c-f c2hso2c-ch=c-co2c2hs 1 nh2 c-f chrco-ch2ch2- ch3 c-h c2hso2c-ch=ch- ch3 c-h c2h5o2c-ch=c-co2c2h5 CHj c-h ch3o,c-ch=c-co,c,h5 1 - *• 3 ch3 n 1 ch?-co-ch2ch2- h c-och c2h5o2c-ch=ch- h c-och c2h5o2c-ch=ch h n nc-ch2ch2 h n ch3-co-ch2ch2 h n 25 The compounds according to the invention have potent antibiotic activity and exhibit, together with low toxicity, a broad antibacterial spectrum against gram-positive and gram-negative microorganisms, in particular against enterobacteria; especially even against those which are resistant to various antibiotics, such as, for example, penicillins, cephalosporins, aminoglycosides, sulphonamides and tetracyclines. These useful properties make possible their use as chemotherapeutic active substances in medicine and also as substances for the preservation of inorganic and organic materials, in particular of organic materials of all types, for example polymers, lubricants, dyes, fibres, leather, paper and wood, of foodstuffs and of water. The compounds according to the invention are active against a very broad spectrum of mircoorganisms. With their aid, gram-negative and gram-positive bacteria and bacteria-like microorganisms can be controlled and the diseases produced by these pathogens can be prevented, ameliorated and/or cured. The compounds according to the invention are distinguished by increased activity on dormant and resistant microorganisms. In the case of dormant bacteria, e.g. bacteria which show no detectable growth, the compounds act at concentrations which are far below those of substances known hitherto. This relates not only - 33 - to the amount to be employed, but also to the rate of destruction. It was possible to observe results of this type with gram-positive and gram-negative bacteria, in particular with Staphylococcus aureus, Pseudomonas 5 aeruginosa, Enterococcus faecalis and Escherichia coli. The compounds according to the invention also show surprising increases in activity against bacteria which are classified as less sensitive to comparable substances, in particular resistant Staphylococcus 10 aureus, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. The compounds according to the invention are particularly active against bacteria and bacteria-like microorganisms. They are therefore particularly highly suitable for the 15 prophylaxis and chemotherapy of local and systemic infections in human and veterinary medicine which are caused by these pathogens. The compounds are also suitable for controlling protozoonoses and helminthoses. 20 The compounds according to the invention can be used in various pharmaceutical preparations. Preferred pharmaceutical preparations which may be mentioned are tablets, coated tablets, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, 25 pastes, ointments, gels, creams, lotions, powders and sprays. r\ The table belov; confirms the surprising advantages of the compounds according to the invention compared with ciprofloxacin in the Staphylococcus aureus-infected mouse model: Table: Activity in Staph, aureus infection in the mouse (mg/kg) Substance 10 Ciprofloxacin Example 27 Example 29A Example 31 Example 33 Example 35 p.o 80 10 5 10 10 2.5 s. c. 80 2.5 5 10 5 2.5 15 20 The compounds according to the invention, compared to known structurally similar compounds, show an improved antibacterial action, in particular with anaerobic microorganisms. q COOH Component according to the invention as in Example 2B: A ch3 M R = N , disclosed in EP-A-0,350,733 B Ciprofloxacin Table Compound Species Strain A B C Bacteroides ES 25 0. 25 1 8 fragilis DSM 2151 0. 25 0.5 4 Clostridium perfringens 1024027 0. 125 0.5 0 .5 Bact. thetaiotaomicron DSM 2079 0. 5 2 8 10 (MIC values in pg/ml; agar dilution test in the multipoint inoculator (Denley); isosensitest agar). Preparation of the precursors Example A f S.S1-2,8-Diazabicvclo f 4.3.01nonane 15 H H NH H 1) [S,S]-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane Method I: a) Separation of the diastereomeric salts: «jl 11 IB - 36 - 9 A R /• !t-jsw • 3.0 g (20 nunol) of D-(-)-tartaric acid are dissolved in 10 ml of dimethylformamide by heating to 80"C and the solution is treated with a solution of 2.16 g (10 mmol) of cis-8-benzyl-2,8-diazabicyclo[4.3.0]-nonane in 3 ml of dimethylformamide. The mixture is stirred at 0°C for 1 hour, and the product is filtered off with suction and washed with dimethylformamide and methoxyethanol. Yield: 1.93 g, Melting point: 146-151°C, [ a ]q3 = -19.36 (c = 1, H20). Diastereomerically pure [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D-tartrate is obtained by a single recrystallisation from methoxyethanol. [o]d3 = -22.7° (c = 1, H20). Melting point: 148-154°C. b) Liberation of the base: 40 g of [S,S[-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D-tartrate are dissolved in 250 ml of water and treated with 32 g of 45 % strength sodium hydroxide solution. The precipitated oil is taken up in 150 ml of tert-butyl methyl ether, the aqueous phase is extracted again with 150 ml of tert-butyl methyl ether and the combined organic phases are concentrated after drying over sodium sulphate. The residue is then distilled in vacuo. Yield: 18.5 g of [S,S]-8-Benzyl-2,8-diazabicyclo-[4.3.0]nonane, Boiling point: 107-109°C/0.1 mbar, 5 [a]^4 = 17.3° (undiluted). Method II: 75.0 g (0.5 mol) of L-(+)-tartaric acid are dissolved in 250 ml of dimethylformamide at 80°C and 54.1 g (0.25 mol) of cis-8-benzyl-2,8-diazabicyclo[4.3.0]nonane are added 10 dropwise as a solution in 75 ml of dimethylformamide. The mixture is slowly cooled to 20°C and the crystal suspension is stirred for 1 hour. The crystals ([R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane L-tartrate) are filtered off with suction and the filtrate is 15 concentrated on a rotary evaporator. The residue is dissolved in 500 ml of water and worked up as described in Method I using 63 g of 45 % strength sodium hydroxide solution. Yield: 25.2 g of [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]— 20 nonane; the product contains 3.6 % of the R, R-enantiomer (determined by gas chromatography after derivatisation with menthyl chloroformate). The compound can be reacted with D-(-)-tartaric acid IB 10* - 38 - according to Method I to give diastereomerically pure [S, S ] -8-benzyl-2 ,8-diazabicyclo [4.3.0 ]nonane D-tartrate. Recrystallisation in this case is not necessary. Method III: 73.6 g (0.34 mol) of cis-8-benzyl-2,8-diazabicyclo-[4.3.0 ]nonane are added dropwise at 80 to 90 °C as a solution in 111 ml of dimethylformamide to a solution of 102.9 g (0.685 mol) of L(+)-tartaric acid in 343 ml of dimethylformamide. The mixture is seeded with [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane L-tartrate and slowly cooled to an internal temperature of 18°C. The crystals are filtered off with suction, and the filtrate is seeded with [S,S]-8-benzyl-2,8-diazabicyclo[4 . 3 . 0]-nonane L-tartrate and stirred until it has crystallised completely. (After concentration and liberation of the base as described in Method I, [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane D-tartrate can be obtained from the mother liquor by purification with D-tartaric acid). The product is then filtered off with suction, washed with dimethylformamide and isopropanol and dried in air. The crystals are recrystallised from 88 % strength ethanol. 52 g of [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]-nonane L-tartrate trihydrate are obtained. Melting point: 201-204°C, [a]" = +5.2° (c = 1, H20) . The salt can be processed as described in Method I (liberation of the base) to give enantiomerically pure [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane. Method IV: a) Separation of enantiomers of cis-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane to give [lS,6R]-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane. The procedure is analogous to Example B (Method Il/a), using D-(-)-tartaric acid as the chiral auxiliary reagent, or the procedure is as follows: Mother liquor and washing liquor from [lR,6S]-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane L-tartrate (from Example B, Method II/a) are concentrated together, the residue is taken up in water and the solution is extracted three times with toluene. The toluene phases are discarded. The aqueous phase is treated with saturated sodium hydrogen carbonate solution until a pH of 7 to 8 is obtained, then extracted four times with methylene chloride. The combined methylene chloride phases are dried over magnesium sulphate and concentrated. Yield: 14.4 g (60 % of theory of the originally employed racemic cis-8-benzyl-7,9-dioxo-2,8-diazabicyclo [4.3.0]nonane). [a]" = -4.5° (c = 5, ethanol). These 14.4 g (59 nunol) are crystallised from 120 ml of ethanol analogously to Example B (Method Il/a) using 8.6 g (57 mmol) of D-(-)-tartaric acid. Yield: 8.9 g (77 % of theory) of [IS,6R]-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane D-tartrate. [q]^3 = -46.2° (c = 0.5, IN HC1) ; after recrystallisation from an ethanol/glycol monomethyl ether mixture a further purification is carried out: [atf = -59.3° (c = 0.5, IN HCl). 5.0 g (12.7 nunol) of the diastereomerically pure tartrate obtained in this manner were converted, as described in Example B, Method Il/a, into the free amine: Yield: 3.0 g (96 % of theory) of [IS,6R]-8-benzyl- 7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane, Melting point: 60-61°C, [a]" = -22.2° (c = 5, ethanol). An enantiomer excess of 96.6 % ee was determined by gas chromatography after derivatisation with menthyl chloroformate. Reduction of [ IS,6R]-8-benzyl-7,9-dioxo-2,8-diazabicyclo [ 4 . 3 .0 ] nonane to [S,S]-8-benzyl-2,8-diazabicyclo [4.3.0]nonane. The procedure is analogous to Example B (Method II, b), [IS,6R]-8-benzyl-7,9-dioxo-2,8-diazabicyclo-[4.3.0]nonane being, however, employed as the starting material. The crude product obtained after working up proved to be [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane on derivatisation with menthyl chloroformate. Racemisation was thus observed during the reduction. [S,S)-2,8-Diazabicyclo[4.3.0]nonane 28.4 g (0.131 mol) of [S,S]-8-benzyl-2,8-diazabi-cyclo[4.3.0]nonane are hydrogenated at 90°C and 90 bar in the course of 5 hours over 5.8 g of palladium on active carbon (5%) in 190 ml of methanol. The catalyst is then filtered off with suction and washed with methanol, and the filtrate is concentrated on a rotary evaporator. The residue is distilled without fractionation. Yield: 15.0 g (90.5 % of theory) of [S,S]-2,8-diazabicyclo[4.3.0]nonane, Boiling point: 44-59°C/0.18 mbar, [«]? = -2.29° (undiluted), ee > 99 % (determined by gas chromatography after derivatisation with Mosher's reagent). Method V: 3.75 g (25 mmol) of L-(+)-tartaric acid are initially introduced in solution in 50 ml of dimethylformamide at 80°C and 10.82 g (50 mmol) of cis-8-benzyl-2,8-diazabicyclo[4.3.0]nonane are added dropwise as a solution in 15 ml of dimethylformamide. The mixture is seeded with [R/R]-8-benzyl-2,8-diazabicyclo [4. 3. 0] -nonane L-tartrate and stirred for one hour at about 72°C to complete seed crystal formation. This is then slowly cooled to 15°C, and the crystals are filtered off with suction and washed twice with 13 ml of dimethylformamide in each case. The combined filtrates are heated to 80°C and treated with a further 3.75 g (25 mmol) of L-(+)-tartaric acid. The mixture is additionally heated to 119°C until a clear solution is formed, and again slowly cooled to room temperature with seeding with [S,S]-8-benzyl-2,8-diazabicyclo[4 .3.0]-nonane L-tartrate. The crystals are filtered off with suction, washed successively with dimethyl-formamide, 2-methoxy-ethanol and ethanol and dried in air. Yield: 9.59 g Melting point: 188 to 192°C. The crystals are recrystallised from 95 ml of 80 % strength ethanol. 8.00 g of [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonaneL-tartratetrihydrate(76 % of theory) are obtained which melts at 112 to 118°C with foaming, then resolidifies and melts again at 199 to 201°C. [a]" = 4.5° (c = 1, water). ee: 98.0 % (determined by gas chromatography after derivatisation with menthyl chloroformate). Example B f R.R1-2,8-Diazabicvclor 4.3.01nonane 1 ! nh h 1) [ R / R ]-8-Benzyl-2,8-diazabicyclo[4.3.0]nonane 5 Method I: The crystals of [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]— nonane obtained according to Example A, Method II (49.2 g) are washed with dimethylformamide and methoxyethanol and recrystallised from 300 ml of 10 methoxyethanol. 45.6 g of enantiomerically pure [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane L-tartrate are obtained (enantiomer purity determined by gas chromatography after derivatisation with menthyl chloroformate). 15 Melting point: 121-124eC, [a]" = +22.3° (c = 1, H20) . The salt (44.5 g) is converted into the free base as described in Example A, Method lb. 20.2 g of [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane are obtained. 20 Boiling point: 107-111°C/0.04 mbar, A y [a J" = -17.5° (undiluted). Method II a) Separation of enantiomers of cis-8-benzyl-7 ,9-dioxo- 2.8-diazabicyclo[4.3.0]nonane to give [lR,6S]-8-5 benzyl-7,9-dioxo-2, 8-diazabicyclo[4.3.0]nonane 24.1 g (98.8 mmol) of cis-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane are heated to reflux with stirring in a mixture of 410 ml of ethanol and 25 ml ^ of acetonitrile in a three-necked flask. 14.8 g 10 (98.8 mmol) of L-(+)-tartaric acid are then added at once. After all the tartaric acid has completely dissolved, the heating is first turned off, but the flask is left in the oil bath. When the system has cooled until the solution no longer boils, the 15 stirrer is turned off. Crystallisation and addition of seed crystals takes place at a temperature of 50°C. After standing overnight and cooling to room temperature, the precipitated crystals are filtered off with suction and washed with a little 20 ethanol/petroleum ether (1:1) and dried at 80°C for 2 hours. Yield: 9.8 g (50 % of theory) of [IR,6S]-8-benzyl- 7.9-dioxo-2,8-diazabicyclo[4.3.0]nonane L-tartrate, [a]" = +47.7° (c = 0.5, IN HCl). 25 The compound can be further purified by - 45 - A 5 10 15 recrystallising twice from a mixture of ethanol and glycol monomethyl ether: [atf = +58.6° (c = 0.5, IN HC1). ^-NMR (DMSO): 7.22-7.35 (2m, 2H, aryl-H); 4.55 (s, 2H, benzyl-CH2) ; 4.28 (s, 2H, tartaric acid-CH) ; 3.91 (d, 1H, 1-CH); 2.97 (dd, 1H, 6-CH); 2.53-2.66 (m, 2H, 3-cH2) ; 1.78 and 1.68 (2m, 2H, 5-CH2) ; 1.42 and 1.28 ppm (2m, 2H, 4-CH2) . C18H22N208(394) Calculated: C54.4 H5.6 N7.1 0 32.5 Found: C54.7 H5.8 N7.1 0 32.4 The determination of the absolute configuration was carried out by means of an X-ray structural analysis: 3.6 g (9.1 mmol) of the diastereomerically pure tartrate obtained in this manner are dissolved in water to liberate the base and treated with saturated sodium hydrogen carbonate solution until a pH of 7 to 8 is obtained. The aqueous solution is extracted four times with 20 ml of methylene chloride each time. The combined methylene chloride phases are dried over magnesium sulphate and - 46 - I concentrated. Yield 2.2 g (99 % of theory) of [ IR, 6S]-8-benzyl-7, 9-dioxo-2,8-diazabicyclo[4.3.0]nonane Melting point: 60-61°C/ [ct]jj3 = +21.8° (c = 5, ethanol). An enantiomer excess of 93.8 % ee was determined by gas chromatography after derivatisation with menthyl chloroformate. b) Reduction of [IR,6S]-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0Jnonane to [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane In a heated flask, 0.34 g (9 mmol) of lithium aluminium hydride is introduced under N2 in 18 ml of anhydrous tetrahydrofuran and 0.73 g (3 mmol) of [IR,6S]-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]-nonane is added dropwise as a solution in 3 ml of anhydrous tetrahydrofuran. The mixture is then boiled for 16 hours with reflux condensation. Working up is carried out by dropwise edition of 0.34 ml of water in 10 ml of tetrahydrofuran, 0.34 ml of 10 % strength sodium hydroxide solution and 1.02 ml of water. The precipitate is filtered off with suction and washed with tetrahydrofuran, and the filtrate is concentrated. 0.7 g of crude [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane remains (GC purity: 99 %). - 47 - r^ /. n It was not possible to determine any racemisation during the gas chromatographic determination of the enantiomer purity using menthyl chloroformate. 2) [R,R]-2,8-diazabicyclo[4.3.0]nonane 5 19.4 g (0.09 mol) of [R,R]-8-benzyl-2,8-diaza- bicyclo[4.3.0]nonane are hydrogenated according to the procedure of Example A, 2. Yield: 9.61 g (85 % of [R,R]-2,8-diazabicyclo-[4.3.0]nonane, 10 Boiling point: 45-58°C/0.08 mbar, [a]" = +2.30° (undiluted). Example C T S,S1—2 —Methyl—2.8-diazabicyclof 4.3.01nonane ch3 ! h nh h 1) [S ,S]-8-Benzyl-2-methyl-2,8-diazabicyclo[4.3.0] — 15 nonane 43.2 g (0.2 mmol) of [S,S]-8-benzyl-2,8-diazabi-cyclo[4.3.0 ]nonane are treated with 20 ml of 37 % formaldehyde solution, 40 ml of water and 24 g of acetic acid and the mixture is hydrogenated over 1IB A 1U 1W - 48 - 2 g of palladium on active carbon (5 %) at 20°C and 20 bar for 10 hours. The catalyst is then filtered off with suction, the filtrate is rendered alkaline with potassium carbonate and the product is extracted with tert-butyl methyl ether. After drying over sodium sulphate, the mixture is concentrated and the residue is distilled in vacuo. Yield: 14.8 g, Boiling point: 114-124°C/0.14 mbar. [S, S ]-2-Methyl-2,8-diazabicyclo[4.3.0]nonane 12.9 g (56 mmol) of [S,S]-8-benzyl-2-methyl-2,8-diazabicyclo[4.3.0]nonane are hydrogenated over 1.1 g of palladium on active carbon (5 %) at 90°C and 90 bar in 90 ml of methanol. The mixture is then filtered, the filtrate is concentrated on a rotary evaporator and the residue is distilled in vacuo. Yield: 5.5 g of enantiomerically pure [S,S]-2-methyl-2,8-diazabicyclo[4.3.0]nonane (detection by derivatisation with Mosher's reagent), Boiling point: 78-81°C/14 mbar. Example D f R,R1-2-Methyl-2,8-diazabicvclo T 4.3.01nonane ch3 f "PNH h The compound is prepared by the working instructions described in Example C, starting from 43.2 g (0.2 mol) of [R,R]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane. Yield: 4.9 g of [R,R]-2-methyl-2,8-diazabicyclo[4.3.0]- Boiling point: 30-33°C/0.12 mbar. Example E cis-7 ,9-Dioxo-8-( fIS 1-1-phenyl-ethyl ) - 2 . 8-diazabicvclof 4.3.0Inonane O 1) N-([lS]-l-Phenyl-ethyl)pyridine-2,3-dicarboximide 74.5 g (0.5 mol) of pyridine-2,3-dicarboxylic anhydride are initially introduced at 20°C in solution in 500 ml of dioxane and 60.5 g (0.5 mol) nonane. h 24 56 of S-(-)-1-phenyl-ethylamine are added dropwise, whereupon the temperature rises to 33 °C. The xture is stirred for a further 1 hour and then concentrated on a rotary evaporator, and residual solvent is removed at 40°C/0.1 mbar. The residue is taken up in 245 g (2.4 mol) of acetic anhydride, and the solution is treated with 4.9 g (0.06 mol) of anhydrous sodium acetate and stirred at 100 °C for 1 hour. After cooling, the mixture is poured onto 1 1 of ice-water while stirring well, and the precipitate is filtered off with suction, washed with cold water and hexane and dried in air. The crude product (114 g, Melting point: 112-114°C) is recrystallised from 285 ml of methanol. Yield: 96.3 g (76 %), Melting point: 115-117°C, [a]*2 = -46.9° (c = 2, ethanol). 2) cis-7,9-Dioxo-8-([lS]-l-phenyl-ethyl)-2,8-diazabicyclo[4.3.0]nonane 79.7 g (0.316 mol) of N-([IS]-1-phenylethyl)-pyridine-2,3-dicarboximide are hydrogenated over 10 g of palladium on active carbon (5 % strength) at 90°C/100 bar in 600 ml of tetrahydrofuran. The catalyst is filtered off after completion of the absorption of hydrogen and the filtrate is completely concentrated. 83.7 g of a viscose residue are obtained. ? 4 ^ fi 4 Purity: 95 % strength, 1H-NMR (CDC13, 200 MHz): 1.4-1.7 (m, 3H); 1.82 and 1.83 (2d, 3H); 1.9-2.05 (m, 1H); 2.28 (broad s, 1H); 2.54-2.86 (m, 3H); 3.77 (d, 1H); 5.39 (q. 1H); 7.24-7.48 ppm (m, 5H) . Example F cis-2-Oxa-5,8-diazabicvclo r 4.3.01nonane H I I I NH 1) trans-l-Benzoyl-3-bromo-4-(2 -hydroxyethoxy)-pyrrolidine 95 g (0.55 mol) of l-benzoyl-3-pyrroline are dissolved in 380 g of ethylene glycol and 101 g (0.57 mol) of N-bromosuccinimide are added in 5 g portions in the course of 2 hours. The mixture is then stirred overnight at room temperature, poured into water and extracted with methylene chloride, and the solution is dried over magnesium sulphate and concentrated. The residue (188 g) was chromatographed on silica gel using ethyl acetate. Yield: 136.5 g (78 % of theory), Purity by GC: 99 %. mr 25 2 ) trans-l-Benzoyl-3-bromo-4-(2-tosyloxyethoxy)-pyrrolidine 92 g (0.239 mol) of trans-l-benzoyl-3-bromo-4-(2-hydroxyethoxy)-pyrrolidine, 32 g (0.316 mol) of triethylamine and 1 g of 4-dimethylaminopyridine are dissolved in 750 ml of toluene and 60 g (0.31 mol) of tosyl chloride in 450 ml of toluene are added dropwise. The mixture is stirred at room temperature for two days, water is added, and the aqueous phase is separated off and extracted with toluene. The toluene solutions are washed with 10 % strength hydrochloric acid, dried over magnesium sulphate and concentrated, the residue is dissolved in ethyl acetate and the solution is filtered through silica gel. The filtrate is concentrated. Yield: 125 g (91 % of theory). The thin layer chromatogram shows a homogeneous compound. 3) cis-8-Benzoyl-5-benzyl-2-oxa-5, 8-diazabi-cyclo[4.3.0]nonane 124 g (0.265 mol) of trans-l-benzoyl-3-bromo-4-(2-tosyloxyethoxy)-pyrrolidine are heated under reflux overnight with 86 g (0.8 mol) of benzylamine in 1.5 1 of xylene, the salts of benzylamine are filtered off with suction and the filtrate is concentrated. *L A 1M IW - 53 - I 245640 Crude yield: 91.2 g. 4) cis-5-Benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane 91 g (0.265 mol) of cis-8-benzoyl-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane are heated under 5 reflux overnight with 200 ml of concentrated hydrochloric acid and 140 ml of water. After cooling, the benzoic acid is filtered off with suction, the filtrate is concentrated to half the volume, the solution is rendered alkaline with 10 potassium carbonte and extracted with chloroform, the extract is dried over potassium carbonate and concentrated, and the residue is distilled. Yield: 30.7 g (48.8 % of theory), Boiling point: 134-142°C/0.6 mbar, 15 Purity by GC: 92 %. 5) cis-2-Oxa-5, 8-diazabicyclo[4.3.0]nonane dihydrochloride 26 g (0.11 mol, 92 % strength) of cis-5-benzyl-2-oxa-5,8~diazabicyclo[4.3.0]nonane in 180 ml of 20 ethanol and 19 ml of concentrated hydrochloric acid are hydrogenated in 3 g of palladium/active carbon (10 % Pd) at 100°C and 100 bar. The catalyst is filtered off with suction, the filtrate is concentrated and the separated crystals are dried in 25 a dessicator over phosphorus pentoxide. Ll ill IP 1AA» - 54 - ? 4 « o 4 0 Yield: 17.1 g (77 % of theory), Melting point: 244-250°C. Example G Separation of enantiomers of cis-5-benzyl-2-oxa-5,8-5 diazabicyclo[4.3.0]nonane 150.1 g (1 mol) of D-(-)-tartaric acid are initially introduced into 700 ml of methanol at 60 to 65°C and 218.3 g (1 mol) of cis-5-benzyl-2-oxa-5,8-diazabicyclo-[ 4.3.0]nonane are added dropwise as a solution in 300 ml 10 of methanol. The mixture is then slowly allowed to cool to about 49°C until the solution becomes cloudy, and is seeded with crystals of IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo [4.3.0]nonane D-tartrate obtained in a prior experiment, stirred for 30 minutes at this temperature for 15 seed crystal formation and then slowly cooled down to 0 to 3°C. After filtering off with suction, the solid is washed with a mixture of 200 ml of ethanol and 100 ml of methanol cooled to 0°C and then 3 times with 300 ml of ethanol in each case and the product is then dried in 20 air. Yield: 160.3 g of IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo-[4.3.0]nonane tartrate (87 % of theory) Melting point: 174.5 to 176.5°C ee > 97 % (after derivatisation with 1-phenyl-ethyl 25 isocyanate and HPLC analysis). - 55 - 6 p 4 5 6 4 0 [q]o3 = +24.0° (c = 1, methanol). 156.9 g of the 1st crystallisate are recrystallised from 1,500 ml of methanol. Yield: 140.0 g (89 % recovered) 5 Melting point: 176 to 177°C [a]» = +25.2° (c = 1, methanol). The methanolic mother liquor from the 1st crystallisation is concentrated on a rotary evaporator. The syrupy residue (236 g) is dissolved in 500 ml of water, adjusted 10 to pH 12 to 13 with 250 ml of 6N sodium hydroxide solution, extracted 3 times with 350 ml of toluene each time, and the extracts are dried over sodium carbonate and concentrated in vacuo. The residue, 113.1 g of a brown oil which, according to gas chromatographic 15 investigation, contains 97 % of cis-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane, is employed without purification for the preparation of the IS,6R-enantiomer. 113.1 g (0.518 mol) of crude concentrated IS,6R-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane are dissolved in 20 155 ml of methanol and added dropwise to a boiling solution of 77.8 g (0.518 mol) of L-(+)-tartaric acid in 363 ml of methanol. A crystal magma is gradually formed during the dropwise addition. The mixture is stirred at 60°C for 1 hour and then slowly cooled to 0°C in the 25 course of 2 hours. The crystals are filtered off with suction and washed with a 2:1 mixture of ethanol and methanol cooled to 0°C and then 3 times with ethanol. The - 56 - product is then dried in air. Yield: 145.5 g of IS,6R-5-benzyl-2-oxa-5,8-diazabicyclo [ 4.3.0]nonane L-tartrate (79 % of theory) Melting point: 174.5 to 176.5°C 5 ee > 97 % (after derivatisation with 1-phenyl-ethyl isocyanate and HPLC analysis) [ a ] q3 = -24.0° (c = 1, methanol). Liberation of the enantiomerically pure bases: 144 g (0.39 mol) of IS,6R-5-benzyl-2-oxa-5,8-diazabi-10 cyclo[4.3.0jnonane tartrate are dissolved in 250 ml of water and 175 ml (1.05 mol) of 6 N sodium hydroxide solution are added. The deposited oil is taken up in 500 ml of toluene, the organic phase is separated off and the aqueous phase is extracted a further 3 times with 250 ml 15 of toluene in each case. The combined organic phases are dried over sodium carbonate, filtered and concentrated on a rotary evaporator. The residue is distilled through a 20 cm Vigreux column under a high vacuum. Yield: 81.6 g (96 % of theory) of IS,6R-5-benzyl-2-oxa-20 5,8-diazabicyclo[4.3.0]nonane Boiling point: 120 to 139°C/0.04 to 0.07 mbar Purity: 100 % determined by gas chromatography Density: 6 = 1.113 g/ml [a]q3 = -60.9° (undiluted). 25 Distillation residue: 0.12 g In the same manner, 76.0 g (93 % of theory) of lR,6S-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane are obtained from 139.2 g (0.376 mol) of IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane tartrate. 7 4 R fi 4 0 runt ' 1-' * u ' [*]? = +61.2° (undiluted). The separation of enantiomers described for cis-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane can also be carried out analogously with trans-5-benzyl-2-oxa-5,8-5 diazabicyclo[4.3.0]nonane to give R;R- and S,S-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane. Example H 1) tert-Butyl 3S,4S-4-allyloxy-3-hydroxypyrrolidine-l-carboxylate 10 16.5 g (0.55 mol) of 80 % strength NaH are initially introduced into 500 ml of absolute dioxane and a solution of 107.5 g (0.53 mol) of tert-butyl S,S-3,4-dihydroxypyrrolidine - 1-carboxy late (DE-A-3,403,194) dissolved hot in absolute dioxane 15 is added dropwise at 60°C. The mixture is stirred at 60°C for 1 hour and 64 g (0.53 mol) of allyl bromide are then added dropwise. The mixture is then stirred at 60°C for three hours. It is concentrated and the residue is dissolved in 200 ml of water and 600 ml 20 of methanol. The solution is extracted three times with 200 ml of pentane each time, the methanol is stripped off on a rotary evaporator, the residue is diluted with 200 ml of water and the mixture is extracted with methylene chloride. The methylene 25 chloride solution is dried over MgS0<, and concentrated, and the residue is dissolved in ?/i kr n tert-butyl methyl ether (200 ml). 9 g of starting material (44 mmol) crystallised out overnight. The ether solution is concentrated and distilled. Yield: 83 g (80 % of theory relative to recovered starting material and diallyl ether) Boiling point: 149°C/0.7 mbar to 159°C/0.9 mbar. The distillate contains 5 % of the starting material and 4 % of diallyl ether. The pentane extract yielded 17 g of a mixture of 15 % desired product and 84 % of diallyl ether, [a]" = -10.5° (c = 1, methanol). 2) tert-Butyl 3S,4S-3-hydroxy-4-(2-hydroxyethoxy)-pyrrolidine-l-carboxylate 64 g (0.24 mol, 91 % strength) of tert-butyl 3S,4S-4-allyloxy-3-hydroxypyrrolidine-l-carboxylate are dissolved in 250 ml of methanol and cooled to 0°C, and ozone is passed through the solution until a washing bottle containing potassium iodide solution and connected in series indicates the emergence of ozone and thus complete reaction. Residues of ozone are carried out by means of a stream of nitrogen, then the resulting ozonide is reduced at 0°C using 18 g of sodium borohydride, which is added in 1 g portions. The mixture is then stirred overnight at room temperature and concentrated, the residue is diluted with water, and the mixture is treated with 2 4 *640 20 g of potassium carbonate and extracted five times with 100 ml of methylene chloride each time. The organic solutions are dried over magnesium sulphate and concentrated. 5 Yield: 65.8 g (100 % of theory) The product is 91 % strength by gas chromatography, [a]" = -15.2° (c = 0.97, methanol). 3) 3S , 4S-l-tert-Butoxycarbonyl-3-tosyloxy-4-(2-tosyloxyethoxy)-pyrrolidine 10 2.7 g (10 mmol, 91 % strength) of tert-butyl 3S,4S- 3-hydroxy-4-(2-hydroxyethoxy)-pyrrolidine-1-carboxylate are initially introduced into 30 ml of methylene chloride, 6 ml of 45 % strength sodium hydroxide solution and 0.1 g of benzyltriethyl-15 ammonium chloride are added and a solution of 2.86 g (20 mmol) of tosyl chloride in 10 ml of methylene chloride are then added dropwise with cooling. The mixture is then stirred for a further hour at room temperature and poured into 20 ml of water, the 20 organic phase is separated off and the aqueous phase is extracted with methylene chloride. The organic phases are dried over magnesium sulphate and concentrated. Yield: 5 g (90 % of theory). 25 The product is homogenous by thin layer chromatography. - 60 - 2 A K (S tert-Butyl IS, 6R-5-benzyl-2-oxa-5,8-diazabicyclo-[4.3.0]nonane-8-carboxylate 87 g (156 mmol) of 3S,4S-l-tert-butoxycarbonyl-3-tosyloxy-4-(2-tosyloxyethoxy)-pyrrolidine are heated under reflux overnight with 58 g (0.54 mol) of benzylamine in 1 1 of xylene. The mixture is cooled, precipitated salts of benzylamine are filtered off with suction and the residue is concentrated. Yield: 43 g (58 % of theory). The product is 67 % strength by gas chromatography. IS,6R-5-Benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane 43 g (90 mmol) of tert-butyl IS,6R-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane-8-carboxylate are heated under reflux in 35 ml of concentrated hydrochloric acid and 35 ml of water until the evolution of carbon dioxide is complete. The mixture is rendered alkaline with potassium carbonate and extracted with chloroform, the organic solutions are dried over MgSO,, and concentrated, and the residue is distilled twice through a 20 cm Vigreux column. Yield: 11.1 g (55 % of theory) Boiling point: 108 - 115°C/0.07 mbar [a]" = -58.3° (undiluted). 7 4 * fi 4 0 &»*n ' iS Example I 1) tert-Butyl 3R,4R-4-allyloxy-3-hydroxypyrrolidine-l-carboxylate The reaction is carried out analogously to Example 5 HI) using tert-butyl R,R-3,4-dihydroxypyrrolidine- l-carboxylate: Boiling point: 145°C/0.1 mbar [a]p3 = +9.5° (c = 1.0/ methanol). The product is 95 % strength by gas chromatography. 10 2) tert-Butyl 3R, 4R-3-hydroxy-4-(2-hydroxyethoxy)-pyrrolidine-1-carboxylate The reaction is carried out analogously to Example H2) using tert-butyl 3R,4R-4-allyloxy-3-hydroxy-pyrrolidine-1-carboxylate: 15 Yield: 99 % of theory (0.175 molar batch) £ce]d° = +16.5° (c = 0.94, methanol). 3) 3R,4R-l-tert-Butoxycarbonyl-3-tosyloxy-4-(2-tosyloxyethoxy)-pyrrolidine The reaction is carried out analogously to Example 20 H3) using tert-butyl 3R,4R-3-hydroxy-4-(2- hydroxyethoxy)-pyrrolidine-1-carboxylate Yield: quantitative (0.11 molar batch). 4) tert-Butyl 1 R , 6 S - 5 - b e n z y 1 - 2 - o x a - 5 , 8 -diazabicyclo[4.3.0]nonane-8-carboxylate flu in 88 - 62 - 0 A £ P, The reaction is carried out analogously to Example H4) using 3R,4R-l-tert-butoxy-carbonyl-3-tosyloxy-4 - ( 2-tosyloxyethoxy)-pyrrolidine s Yield: 40 % of theory (0./1 molar batch). 5 5) IR,6S-5-Benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane The reaction is carried out analogously to Example H5) using tert-butyl IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane-8-carboxylate: Yield: 63 % of theory (40 mmolar batch) 10 Boiling point: 120°C/0.06 mbar The product is 95 % strength by gas chromatography [«]» = +58 . 5° (undiluted). Example J 1) IS,6R-2-Oxa-5,8-diazabicyclo[4.3.0]nonane 15 dihydrochloride 7.5 g (34.4 mmol) of IS,6R-5-benzyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane are hydrogenated at 100°C and 100 bar on 1 g of palladium/active carbon (10 % Pd) in 200 ml of ethanol with the addition of 7 ml 20 of concentrated hydrochloric acid. The catalyst is filtered off with suction and washed several times with water. The aqueous filtrate is concentrated, whereupon the residue crystallises. The crystals are thoroughly saturated with ethanol, filtered off with 25 suction and dried in air. bm in DO 100" - 63 - 0 £ ft /, Yield: 4.6 g (66.5 % of theory) Melting point: 233-235°C. 2) IS,6R-2-Oxa-5,8-diazabicyclo[4.3.0]nonane 59 g (0.27 mol) of IS,6R-5-benzyl-2-oxa-5,8-5 diazabicyclo[4.3.0]nonane are hydrogenated at 120°C and 120 bar on 5 g of palladium/active carbon (10 % Pd) in 500 ml of ethanol. The catalyst is filtered off with suction, the filtrate is concentrated and the residue is distilled. 10 Yield: 32.9 g (95 % of theory) Boiling point: 65°C/0.03 mbar Rotation : [a]c8 = +8.2° (undiluted). ee value: > 99.5 % (by derivatisation with Mosher reagent). 15 Example K 1) IR,6S-2-Oxa-5, 8-diazabicyclo[4.3.0]nonane dihydrochloride The reaction is carried out analogously to Example Jl) using IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo-20 [4•3.0]nonane: Yield: 77 % of theory (23.8 mmolar batch) Melting point: 230-232°C. 2) IR,6S-2-Oxa-5, 8-diazabicyclo[4.3.0]nonane - 64 - 2 4 5 6 4 0 The reaction is carried out analogously to Example J2) using IR,6S-5-benzyl-2-oxa-5,8-diazabicyclo-[4.3.0]nonane: Yield: 93.3 % of theory (1.58 molar batch) 5 Boiling point: 63 - 65°C/0.03 mbar Rotation: [a]" = -8.4° (undiluted). ee value: > 99.5 % (by derivatisation with Mosher reagent). IR,6R- or IS,6S-2-Oxa-5,8-diazabicyclo[4.3.0]nonane 10 can be obtained analogously. Example L IR,6S-2-Oxa-5,8-diazabicyclo[4.3. 0 ]nonane dihydro-bromide 1) IR,6S-5-(lR-Phenylethyl)-8-tosyl-2-oxa-5,8-diaza-15 bicyclo[4.3.0]nonane 101.8 g (0.196 mol) of trans-3-brom-l-tosyl-4-(2-tosyloxyethoxy)-pyrrolidine and 72 g (0.584 mol) of R-(+)-1-phenylethylamine in 900 ml of xylene are heated under reflux overnight. The cooled solution 20 is washed with 2N sodium hydroxide solution and dried over potassium carbonate, the drying agent is removed and the solvent is concentrated. On cooling, crystals are deposited from the residue which are filtered off with suction and recrystallised from a 25 mixture of 750 ml of petroleum ether and 200 ml of - 65 - n-butanol. Yield: 15 g (39.6 % of theory of optically pure material. Melting point: 188°C, Rotation : [a]" = +103.7° (c = 1, CHC13). IR,6S-8-Tosyl-2-oxa-5,8-diazabicyclo[4.3.0]nonane 13 g (33.6 mmol) of IR,6S-5-(lR-phenylethyl)-8-tosyl-2-oxa-5,8-diazabicyclo[4 .3.0 ]nonane are hydrogenated at 100 °C and 100 bar on 2.5 g of palladium/ active carbon (10 % Pd) in 200 ml of ethanol. The catalyst is filtered off with suction, the filtrate is concentrated and the residue is recrystallised from 30 ml of toluene. Yield: 7.5 g (79 % of theory), Melting point: 160-161°C, Rotation: [q]d3 = +17.5° (c = 1.21, CHC13) . IR,6S-2-Oxa-5,8-diazabicyclo[4.3.0]nonane dihydro-bromide 7 g (24.8 mmol) of IR,6S-8-tosyl-2-oxa-5,8-diaza-bicyclo[4.3.0]nonane are dissolved in 25 ml of 33 % strength hydrogen bromide solution in glacial acetic acid, 5 g of phenol are added and the mixture is stirred overnight at room temperature. It is diluted with diisopropyl ether, and the crystallised salt is filtered off with suction and dried in air. Yield: 5.5 g. ° A R R /s. Derivatisation with Mosher reagent and gas chromatographic analysis shows only one detectable enantiomer (ee > 99.5 %). Example M 5-Bromo-l-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid Br O 1) 2-Bromo-3,4,5,6-tetrafluoro-benzoyl chloride 365 g (1.33 mol) of 2-bromo-3,4,5,6-tetrafluoro-benzoic acid [Tetrahedron 23., 4719 ( 1967 )] are introduced into 2 1 of thionyl chloride and the mixture is heated under reflux for 11 hours until the evolution of gas stops. Excess thionyl chloride is stripped off in vacuo and the residue is distilled. Yield: 330 g (85 % of theory), Boiling point: 81-85°C/3-5 mbar. 2) Diethyl (2-bromo-3,4,5,6-tetrafluoro-benzoyl)-malonate 15.9 g (0.167 mol) of magnesium chloride are introduced into 150 ml of anhydrous acetonitrile (dried over zeolite) and 26.9 g (0.167 mol) of diethyl malonate are allowed to drop in with cooling. The mixture is cooled to 0°C, 46 ml (33.7 g = 0.33 mol) of triethylamine are added dropwise and the mixture is stirred for 30 minutes. 48.9 g (0.168 mol) of 2-bromo-3/4/5,6-tetrafluoro-benzoyl chloride are then added dropwise, and the mixture is stirred for a further 1 hour at 0°C and brought to room temperature overnight. It is treated with 100 ml of 5 N hydrochloric acid and extracted three times with methylene chloride, and the extracts are dried with Na2S0ll and concentrated in vacuo. Crude yield: 62.7 g. Ethyl (2-bromo-3,4,5,6-tetrafluoro-benzoyl)-acetate 60 g of crude diethyl (2-bromo-3,4,5,6-tetrafluoro-benzoyl ) -malonate are introduced into 150 ml of water and treated with 0.6 g of 4-toluenesulphonic acid, and the mixture is heated under reflux for 6 hours. It is extracted with methylene chloride, and the extract is washed with water, dried with Na2SOA and concentrated. Crude yield: 46 g, Boiling point (sample distillation in a bulb tube): 150-160°C(oven)/3 mbar; Mass spectrum: m/e 342 (M+), 297 (M+-OC2H5), 263 (M+-Br), 257, 255 (M+-CH2C02C2H5) , 235 (263-28). Ethyl 2-(2-bromo-3,4,5,6-tetrafluoro-benzoyl)-3-ethoxy-acrylate 45 g of crude ethyl (2-bromo-3,4,5,6-tetrafluoro-benzoyl ) -acetate are introduced into 32.2 g (0.31 mol) of acetic anhydride and 28.4 g (0.19 mol) of triethyl orthoformate and the mixture is heated under reflux for 2 hours. Excess reagent is first stripped off in vacuo, then under a high vacuum (bath up to 120-130°C) and the crude product is reacted to the next step. Crude yield: 50.7 g Ethyl 2-(2-bromo-3,4,5,6-tetrafluoro-benzoyl)-3-cyclopropylamino-acrylate 50.7 g of crude product from Step 4) are treated dropwise with 8.6 g (0.15 mol) of cyclopropylamine in 90 ml of ethanol with ice-cooling, the mixture is stirred at room temperature, allowed to stand overnight and again well cooled, and the crystallisate is filtered off with suction, washed with cold ethanol and dried. Yield: 29 g (42 % over 4 steps), Melting point: 103-105°C (from ethanol). Ethyl 5-bromo-l-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate 28 g (68 nunol) of ethyl 2-(2-bromo-3,4,5,6-tetrafluoro-benzoyl)-3-cyclopropylaminoacrylate are heated under reflux for 6 hours with 6.9 g (164 mmol) of sodium fluoride in 88 ml of DMF. The mixture is poured into water after cooling, and the deposited precipitate (red) is filtered off with suction, washed with plenty of water and dried at 80°C in a recirculating air oven. Crude yield: 27.3 g, Melting point: 150-175°C; after recrystallisation from glycol monomethyl ether: Melting point: 187-191°C. 5-Bromo-l-cyclopropyl-6,7,8-trif luoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 26.7 g (68 mmol) of crude ethyl 5-bromo-l-cyclopropyl-6,7 , 8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are introduced into a mixture of 165 ml of acetic acid, 110 ml of water and 18 ml of concentrated sulphuric acid and heated under reflux for 2 hours. The cooled reaction mixture is poured into ice-water, and the deposited precipitate is filtered off with suction, washed with plenty of water and dried in a recirculating air oven at 30°C. Yield: 19.7 g (80 % of theory), Melting point: 208-210°C (with decomposition); after recrystallisation from glycol monomethyl ether: Melting point: 212-214°C (with decomposition); NMR *H (DMSO) : 8.73 s (1H at C-2), 4,16 m (1H, cyclopropyl), 1,2 m (4H, cyclopropyl) [ppm]. Mass spectrum: m/e 361 (Mt-H20) , 317 (M-C02), 41 (100 %, C3H5) . Preparation of the final compounds Example 1 A. l-Cvclopropvl-7-f TS,S1-2,8-diazabicvclor4.3.01non-8-vl) -6 .8-difluoro-1,4-dihvdro-4-oxo-3-quinolinecarboxylic acid 141.5 g (0.5 mol) of l-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour with 69.25 g (0.55 mol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane (ee 99.5 %, GC 99.8 % strength) in a mixture of 1500 ml of acetonitrile and 750 ml of dimethylformamide in the presence of 55 g (0.5 mol) of 1,4-diazabicyclo-[2.2.2]octane. The suspension is cooled, and the precipitate is filtered off with suction, washed with water and then additionally stirred with 1 1 of water (pH 7). The product is filtered off with suction and dried at 60°C in a recirculating air 0 A /. E A A 0 '.vt', " ■: \ ? > 5 7 oven. Yield: 163.4 g (84 % of theory), Melting point: 249-251°C (with decomposition) B. (-)-l-Cvclopropvl-7-fr S.S1-2,8-diazabicvclor 4.3.0 lnon-5 8-vl^-6,8-difluoro-l.4-dihvdro-4-oxo-3-ouinoline-carboxvlic acid hydrochloride 6.0 g (15.4 mmol) of l-cyclopropyl-7-([S,S]-2,8-diazabicyclo [ 4.3. 0jnon-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are dissolved in 40 ml of 10 half-concentrated hydrochloric acid at 60 °C and the solution of the hydrochloride is filtered. The filtrate is concentrated to one half, cooled in ice and treated with 40 ml of ethanol. The yellow crystallisate is filtered off with suction, washed with ethanol and dried 15 at 60°C in a high vacuum, where the colour lightens. 5.51 g (84 % of theory) of the hydrochloride are obtained, which is already very pure. For further purification, it is dissolved in 50 ml of water in the presence of heat. The yellow solution is 20 treated with 5 ml of half-concentrated hydrochloric acid and cooled in ice, and the deposited crystallisate is filtered off with suction, washed well with ethanol and dried first at room temperature and then under a high vacuum at 100°C. 25 Yield: 4.64 g (70.8 % of theory), !-> / ^ if f\ Melting point: 324-325°C (with decomposition), TLC (silica gel, dichloromethane/methanol/17 % strength aqueous ammonia = 30:8:1): homogeneous, Rf value: 0.3, [a]": -256° (c = 0.5, H20) , Purity (HPLC): 99.4 % strength, C2oH21F2N303.HC1(425.5) Calculated: C 56.4 H5.2 N 9.9 Cl 8.3 Found: C56.3 H5.4 N 9.8 Cl 8.3 Example 2 10 A; 8-Chloro-l-cvclopropyl-7- (r S. S1 -2 , 8-diazabicvclo- r 4 .3.01non-8-vl)-6-fluoro-1,4-dihvdro-4-oxo-3-quinoline-carboxvlic acid 2 batches of the following size are run in parallel and worked up together: 15 180 g (0.6 mol) of 8-chloro-l-cyclopropyl-6,7-difluoro- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour with 84 g (0.67 mol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane in a mixture of 1.8 1 of acetonitrile/900 ml of dimethylformamide in the - 73 - 25 presence of 99 g (0.88 mol) of 1,4-diazabicyclo[2.2.2]-octane (DABCO) (internal temperature: 90.5°C). The yellow solution is cooled and treated with seed crystals (obtained from a 5 ml sample which was concentrated; residue stirred with acetronitrile) . The mixture is stirred for 2 hours at about 3°C, and the deposited precipitate from both batches is rapidly filtered off with suction, washed with acetronitrile and introduced into 1.5 1 of ice-water. The initially thin, well-stirrable suspension after about 10 minutes becomes a poorly stirrable mass, which is diluted with a further 150 ml of water. The precipitate is filtered off with suction, washed with water and dried at 80 °C in a recirculating air drying oven. Yield: 402 g (82.7 % of theory), faintly yellow product; Melting point: 193-196°C (with decomposition), Rf value (silica gel; methylene chloride/methanol/17 % strength aqueous NH3 = 30:8:1): 0.4. B . 8-Chloro-l-cvclopropyl-7-I f S, S1-2 , 8 - diazabicvclor 4.3.01non-8-vl)-6-fluoro-1,4-dihvdro-4-oxo-3-cruinolinecarboxvlic acid hydrochloride 13.1 g (32 mmol) of 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are suspended in 50 ml of water and brought into solution by addition of 50 ml of half-concentrated hydrochloric acid. The mixture is filtered through a glass frit, the filtrate is m 1u - 74 - concentrated in vacuo and the residue is stirred with about 300 ml of abs. ethanol. The suspension is cooled in ice, the precipitate is filtered off with suction, washed with ethanol and dried first at room temperature and then at 100°C in vacuo. Yield: 13.4 g (93.8 % of theory); Melting point: 328-330°C (with decomposition); Rf value (silica gel, methylene chloride/methanol/17 % strength aqueous NH3 = 30:8:1): 0.4; Purity (HPLC): 99.9 % strength, [a]§': -164.4° (c = 0.45, H20) , C20H21ClFN3O3 .HC1 (442.3) Calculated: C54.3 H5.0 N 9.5 C116.0 Found: C 54.3 H5.0 N 9.5 C116.0 C. The following salts, for example, can also be prepared analogously: 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline carboxylic acid methanesulphonate 8-chloro-l-cyclopropyl-7-([S,S)— 2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid toluenesulphonate 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3- quinoline carboxylic acid sulphate 8-chloro-l-cyclopropyl-7-([S,S]-2 ,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline carboxylic acid acetate 5 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo- [4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline carboxylic acid lactate 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-10 quinoline carboxylic acid citrate 8-chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline carboxylic acid embonate Example 3 15 Analogously to Example 1, the following are obtained with 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid: iiL Ji DO - 76 - A. l-Cyclopropyl-7-([ S,S]-2,8-diazabicyclo[4.3 . O]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid Melting point: 256-258°C (with decomposition). B. l-Cyclopropyl-7-([S, S ]-2,8-diazabicyclo[4.3.0 ]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid hydrochloride, Melting point: > 320°C (with decomposition), A. 6 g (20 mmol) of l-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour with 2.7 g (21.4 mmol) of (+)-[S/S]-2,8-diazabicyclo[4.3.0]nonane in 40 ml of acetonitrile/20 ml of N-methylpyrrolidone in the presence of 2.2 g (20 mmol) of 1,4-diazabicyclo[2.2.2]octane. The suspension obtained is cooled, and the precipitate is filtered off with suction, washed with acetonitrile and dried at 100°C/12 mbar. [a]": -90.6° (c = 0.48, H20) . Example 4 f 0 Yield: 6.7 g (82.3 % of theory) of l-cyclopropyl-7-([ S, S ] -2 , 8-diazabicyclo [4.3.0] non-8-yl) -5,6,8-tri-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic ac id, Melting point: 257-259°C (with decomposition); after recrystallisation from glycol monomethyl ether: Melting point: 260-265°C (with decomposition). B. 1.5 g (3.7 mmol) of the product from Step A are introduced into 6 ml of 1 N hydrochloric acid. After a short time, the hydrochloride deposits, and is filtered off with suction, washed twice with 5 ml of ethanol each time and dried at 100°C/12 mbar. Yield: 1.4 g (85.7 % of theory) of l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-5 , 6 , 8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, Melting point: > 310°C (with decomposition), 5.2 g (13 mmol) of the product from Example 4A are treated with 15 ml of liquid ammonia in 80 ml of pyridine in an autoclave and heated at 130°C for 12 hours. The [a]g6: -272° (c = 0.5, H20) . Example 5 NH2 0 mixture is then cooled, the autoclave is let down, the mixture is concentrated and the residue is treated with acetonitrile in an ultrasonic bath. The undissolved precipitate is filtered off with suction, the residue is dissolved in about 150 ml of water in the presence of heat, the solution is filtered and the hydrochloride is precipitated using 10 ml of half-concentrated hydrochloric acid, filtered off with suction and dried at 100°C in a recirculating air drying oven. The product obtained is suspended in 100 ml of glycol monomethyl ether at 110-115°C and brought into solution by addition of 38 ml of half-concentrated hydrochloric acid. The solution is filtered hot through a glass frit, cooled and the cooled yellow crystallisate is filtered off with suction, washed with ethanol and dried at 120°C/12 mbar. Yield: 2.5 g (44 % of theory) of 5-amino-l-cyclopropyl-7 -( [S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, Melting point: > 335°C (with decomposition; dark colouring already below 335°C), [q]d8: -280.8° (c = 0.53, H20) . Example 6 O 1.4 g (5 nunol) of 7-chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid are stirred at room temperature for 1 hour with 1.3 g (10.3 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane with exclusion of water in 15 ml of acetonitrile. After standing overnight, the precipitate is filtered off with suction, washed with acetonitrile and chromatographed on silica gel for purification (eluent: methylene chloride/-methanol/17 % strength aqueous ammonia 30:8:1; Rf value: 0.4). The l-cyclopropyl-7-([S,S]-diazabicyclo[4.3.0]non-8-yl) -6-fluoro-1,4-dihydro-4-oxo-l, 8-naphthyridine-3-carboxylic acid obtained is dissolved in 15 ml of half-concentrated hydrochloric acid, the solution is evaporated and the residue is stirred with ethanol. The precipitate is filtered off with suction, washed with ethanol and dried at 120°C/12 mbar. Yield: 960 mg (47 % of theory) of l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride Melting point: 345-346°C (with decomposition), [q ]d°: +5.4° (c = 0.5, H20) . Example 7 fa— - 80 - Analogously to Example 1, the following are obtained using-(-)-[R,R]-2,8-diazabicyclo[4.3.0]nonane: A. l-Cyclopropyl-7-([R,R]-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid Melting point: 247-249°C (with decomposition). B. l-Cyclopropyl-7 - ( [R,R]-2, 8-diazabicyclo[4 . 3 .0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid hydrochloride, Melting point: 322-326°C (with decomposition), Purity (HPLC): 99.4 % strength, ee: 98.6 %, [a]": +250° (c = 0.5, H20). Example 8 Analogously to Example 2, the following are obtained using (-)-[R,R]-2,8-diazabicyclo[4.3.0]nonane: A. 8-Chloro-l-cyclopropyl-7-([R,R]-2,8-diazabicyclo-[4.3.Q]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-quinolinecarboxylic acid, O Melting point: 192-195°C (with decomposition). B. 8-Chloro-l-cyclopropyl-7-([R,R]-2,8-diazabicyclo-[4.3.0] non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-quinolinecarboxylic acid hydrochloride, Melting point: 323-324°C (with decomposition). Purity (HPLC): 99.9 % strength, [o]"s +164.5° (c = 0.53, H20). C20H21ClFN3O3.HC1 ( 442 . 3) Calculated: C54.3 H5.0 N 9.5 Cl 16.0 Found: C54.2 H5.0 N9.5 C116.1 Example 9 Analogously to Example 1, the following are obtained from 1-cyclopropy1-6,7-difluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and (-)-[R,R]-2,8-diazabicyclo-[4.3.0]nonane: A. l-Cyclopropyl-7-([R,R]-2,8-diazabicyclo[4.3.0]non-8-yl)-6 -fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: 254-258°C (with decomposition). 0 B. l-Cyclopropyl-7 - ( [R, R ] -2 , 8-diazabicyclo [4.3.0 ]non-8-yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: decomposition above 320°C, [o]d4: +92.5° (c = 0.53, H20) . Example 10 A. l-Cyclopropyl-6,8-difluoro-1,4-dihydro-7- (cis-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinoline-carboxylic acid: 10 1.43 g (5 mmol) of l-cyclopropyl-6,7,8-trifluoro- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour with 0.74 g (5.4 mmol) of 93 % strength cis-2-oxa-5,8-diaza-bicyclo[4.3.0]nonane in the presence of 0.67 g (6 15 mmol) of 1,4-diazabicyclo[2.2.2]octane in a mixture of 15 ml of acetonitrile/75 ml of dimethylformamide. The suspension is concentrated, the residue is stirred with water, and the precipitate is filtered off with suction and dried in vacuo at 80°C. 20 Yield: 1.67 g (85.4 % of theory), Melting point: 210-212°C (with decomposition). - 83 - rv * •.* ■' ■ " B. l-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride: 1.6 g (4 mmol) of the product from Step A are dissolved in 120 ml of half-concentrated hydrochloric acid at 60°C, the solution is concentrated, the residue is stirred with ethanol and the precipitate is filtered off with suction and dried at 90°C in vacuo. Yield: 1.57 g, Melting point: 300-303°C (with decomposition), Purity (HPLC): 97 % strength. C. Analogously to Example 10A, l-cyclopropyl-6,8-difluoro-1 ,4-dihydro-7-( IR,6S-2-oxa-5,8 -diazabicyclo[4 .3 .0 ]non-8-yl)-4-oxo-3-quinolinecarboxylic acid of melting point 204-206°C (with decomposition) is obtained using IR,6S-2-oxa-5,8-diazabicyclo[4.3.0]nonane. D. Analogously to Example 10B, l-cyclopropyl-6,8-difluoro-1 , 4-dihydro-7-(IR,6S-2-oxa-5,8 -diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride of melting point 324-325°C (with decomposition) is obtained using the betaine from Example 10C. [q]": -241° (c = 0.59, H20) . 15 o / " •' f" A E. Analogously to Example 10A, l-cyclopropyl-6,8-difluoro-l,4-dihydro-7-(lS,6R-2-oxa-5,8-diazabicyclo[4.3 .0 ]non-8-yl)-4-oxo-3-quinolinecarboxylic acid of melting point 204-206°C (with decomposition) is obtained using lS,6R-2-oxa-5,8-diazabicyclo[4.3.0]nonane. [a]": +248° (c = 0.57, DMF). F. Analagously to Example 10B, l-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(IS,6R-2-oxa-5,8 -diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride of melting point 323"C (with decomposition) is obtained using betaine from Example 10E. [q]c6: +238° (c = 0.5, H20) . Example 11 0 Analogously to Example 10, the following are obtained using 8-chloro-l-cyclopropyl-6,7-difluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid: fia ft 81 mUi&m - 85 - I 8-Chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-7-(cis 2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl-4-oxo-3 quinolinecarboxylic acid, Melting point: 180-185°C (with decomposition). 8-Chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-7-(cis 2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3 qpjinolinecarboxylic acid hydrochloride, Melting point: 227-232"C (with decomposition). 8-Chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-7 (IR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo 3-quinolinecarboxylic acid, Melting point: 186-188°C (with decomposition). [o]d6: -269° (c = 0.5, DMF) . 8-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-7 (IR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo 3-quinolinecarboxylic acid hydrochloride Melting point: 278-280°C (with decomposition). [o]g*: -208° (c = 0.5, H20) . 8-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-7 (IS, 6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo 3-quinolinecarboxylic acid Melting point: 188-190°C (with decomposition), [a]": +270° (c = 0.5, DMF). F. 8-Chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-7-(IS, 6R-2-oxa-5,8-diazabicyclo [4.3. 0]non-8-yl) -4-oxo-3-quinolinecarboxylic acid hydrochloride, Melting point: 292-294°C (with decomposition). [q]d7: +193° (c = 0.5, H20) . Example 12 Analogously to Example 10A, the following are obtained using l-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid: A. l-Cyclopropyl-6-f luoro-1,4-dihydro-7- (cis-2-oxa-5,8-diazabicyclo[4.3.0] non-8-yl) -4-oxo-3-quinolinecarboxylic acid, Melting point: 246-249°C (with decomposition) (from glycol monomethyl ether). B. l-Cyclopropyl-6-fluoro-1, 4-dihydro-7- (IR, 6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 243-245°C (with decomposition) 0 C • l-Cyclopropyl-6-f luoro-1,4-dihydro-7- (IR, 6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride, Melting point: 300°C (decomposition) [a]": -99° (c = 0.5, H20) . Example 13 Analogously to Example 10A, the following are obtained using l-cyclopropyl-5,6,7,8-tetrafluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid: A. 1-Cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 210-216°C (with decomposition). B. 1-Cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(IR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 234-237°C (with decomposition), [a]": -287° (c = 0.5, DMF). F 0 COOH - 88 - 20 O f. / " .• ,-n C. l-Cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(IS,6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 236-237°C (with decomposition), [a]": +282° (c = 0.5, DMF). Example 14 NH2 O A. 4.1 g (10 mmol) of the product from Example 13A are treated with 5 ml of liquid ammonia in 40 ml of pyridine and heated at 130°C for 10 hours in an autoclave. After cooling, the precipitate is filtered off with suction, washed with water and dried at 100°C in a recirculating air drying oven. The crude product (2 g) is purified by recrystallisation from glycol monomethyl ether: yellow crystallisate. Yield: 1.3 g (31 % of theory) of 5-amino-l-cyclopropyl-6 , 8-dif luoro-1,4-dihydro-7 - (cis-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinoline-carboxylic acid, Melting point: 233-240°C (with decomposition). fl 00 - 89 - B. 5-Amino-l-cyclopropyl-6,8-difluoro-1,4-dihydro-7-{IR, 6S-2-oxa-5,8-diazabicyclo[4 .3. Q)non-8-yl) -4-oxo-3-quinolinecarboxylic acid is obtained analogously using the product from Example 13C, Melting point: 212-214°C (with decomposition), [a]": -260° (c = 0.5, DMF). C. 5-Amino-l-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(IS, 6R-2-oxa-5,8-diazabicyclo [4.3.0] non-8-yl) -4-oxo-3-quinolinecarboxylic acid is obtained analogously using the product from Example 13C, Melting point: 213-215°C (with decomposition), [a]": +261° (c = 0.5, DMF). Mass spectrum: m/e 406 (MT,95 %), 346, 249, 98, 41, 28 ( 100 %) . Example 15 0 (S) COO- CIV CH- CH2- CH3 I CH, H xCF3COOH A. 7- (2-tert-Butoxycarbonyl-2,8-diazabicyclo [4.3.0] non-8-yl)-l-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 7.8 g (20 mmol) of l-cyclopropyl-7-(2,8-diazabicyclo [4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are dissolved in a mixture of 60 ml of dioxane/water (2:1) and 20 ml of 5 IN sodium hydroxide solution and the mixture is treated with ice-cooling and stirring with 5.24 g (24 mmol) of di-tert-butyl pyro-carbonate. The mixture is stirred at room temperature for 1 hour and allowed to stand overnight. The deposited 10 precipitate is filtered off with suction, washed with 250 ml of water and dried overnight at 50°C in a recirculating air drying oven. Yield: 9.34 g (95.5 % of theory), Melting point; 216-219°C (with decomposition). 15 B. 2S-Methyl-l-butyl 7-(2-tert-butoxycarbonyl-2,8-diazabicyclo[4.3.0] non-8-yl) - l-cyclopropyl-6 , 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate 2.15 g (4.4 nunol) of the product from Step A are suspended in 60 ml of tetrahydrofuran/water (1:1) at 20 room temperature and 1.65 g (5 mmol) of cesium carbonate are added. The mixture is allowed to react at about 40°C in an ultrasonic bath for 20 minutes, about 40 ml of the solvent are distilled off at 40°C/12 mbar) and the solution which remains is 25 lyophilised, the slightly soluble crude caesium salt being obtained. 3.3 g of this crude salt are dissolved in 40 ml of dimethylformamide and treated with 1.4 g of S(+)-l-bromo-2-methyl-butane and - 91 - ? A R 6 A 0 reacted overnight in the ultrasonic bath at 40-50°C. The suspension obtained is concentrated, and the residue is treated with water and extracted with methylene chloride. After drying with sodium 5 sulphate, the solution is concentrated and the residue is purified by chromatography (silica gel, eluent: methylene chloride/methanol 95:5). Yield: 950 mg (38 % of theory), Melting point: 72-83°C (with decomposition). 10 C. 2S-Methyl-1-butyl l-cyclopropyl-7-(2,8-diazabicyclo-[4.3.0 ]non-8-yl) -6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate trifluoroacetate 570 mg (1 mmol) of the product of Step B are dissolved in 3 ml of trifluoroacetic acid at room 15 temperature and the solution is concentrated at 60°C/12 mk.r. The viscous oil obtained is stirred with 5 ml of ether, a solid product being obtained. This is filtered off with suction, washed with ether and dried at 80°C in a high vacuum. 20 Yield: 450 mg (78 % of theory), Melting point: 214-216°C (with decomposition), [a]": +2.8° (c = 0.5, DMF). Example 16 v X (R) ■ch I ch ch— nh- co i ~N JL 18 - 92 - 390 mg (1 mmol) of l-cyclopropyl-7-(2,8-diazabicyclo-[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are dissolved in a solution of 4 0 mg of sodium hydroxide in 3 ml of water at room temperature in an ultrasonic bath and the solution is treated with ice-cooling with a solution of 160 mg (1.1 mmol) of R-( + )_Q-methyl-benzyl isocyanate. The deposited precipitate is filtered off with suction, washed with dioxane and dried at 100°C in a high vacuum. Yield: 530 mg (99 % of theory) of l-cyclopropyl-6,8-dif luoro-1,4-dihydro-4-oxo-7- (2- [ lR-phenyl-ethyl-amino-carbonyl]-2,8-diazabicyclo[4.3.0]non-8-yl)-3-quinolinecarboxyl ate, Melting point: 208-210°C (with decomposition), [a]": -23.2° (c - 0.5, DMF). The reaction product can be separated into the diastereomers by chromatography and the carbamoyl radical removed again by acidic hydrolysis, the compounds of Examples 1 and 7 being obtained. Example 17 O 9 A R , u i : • 1.52 g (5 mmol) of ethyl l-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are reacted with 550 mg (5 mmol) of l,4-diazabicyclo[2.2.2joctane and 760 mg (6 mmol) of (+)-[S,S]-2,8-diazabicyclo-[4.3.0]nonane in 30 ml of acetonitrile for 2 hours at 50 °C and for 2 hours at 60°C. After cooling, the suspension obtained is filtered off with suction, and the precipitate is washed with water and dried at 90°C in vacuo. Yield: 0.99 g (47.5 % of theory) of ethyl 1-cyclopropyl-7 -( [S ,S]-2, 8-diazabicyclo[4 .3 . 0]non-8-yl)-6, 8-dif luoro-1,4-dihydro-4-oxo-3-guinolinecarboxylate, Melting point: 194-195°C (from acetonitrile), [a]": -188.9° (c = 0.51, CHC13) . Example 18 1.4 g (5 mmol) of 9 ,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[ 1, 2 ,3-de] [1,4]-benzoxacine-6-carboxylic acid are reacted with 0.85 g (7.7 mmol) of 1,4-diazabicyclo[2.2 .2]octane and 0.7 g (5.6 mmol) of ( + )-[S,S]-2,8-diazabicyclo[4.3.0]nonane in 15 ml of acetonitrile/7.5 ml of dimethylformamide analogously to Example 1. Yield: 1.24 g (64 % of theory) of 10-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-9-fluoro-2,3-dihydro-3- 0 2/ r- r* f 4 ? ! : • : ; methyl-7 -oxo-7H-pyr ido [l,2,3-de][l,4]benzoxacine-6-carboxylic acid, Melting point: 265-268°C (with decomposition), [a]D: -232,2° (c = 0.58, CHC13) 3S-10-([S,S]-2 , 8-Diazabicyclo[4 .. 0 ]non-8-yl) - 9-f luoro-2 , 3-dihydro-3-methyl-7-oxo-7H-pyrido[1 ,2,3-de][1,4]benzoxacine-6-carboxylic acid is also obtained analogously. Example 19 H. COOH 10 l-Cyclopropyl-6 , 7-difluoro-l, 4-dihydro-8-methoxy-4-oxo- 3-quinolinecarboxylic acid is reacted analogously to Example 1 and the reaction product is purified by chromatography (silica gel, eluent: methylene chloride/methanol/17 % strength aqueous ammonia = 15 30:8:1). 20 l-Cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1 , 4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid of melting point 203-208°C (with decomposition) is obtained. ["] 23, -193° (c = 0.4, CHC13) . - 95 - Example 20 O COOH The reaction is carried out analogously to Example 1A using l-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and l-ethyl-7-([S,S]-2,8-diazabicyclo[4.3.0] -non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of melting point 236-239°C (with decomposition) is obtained (recrystallised from glycol monomethyl ether); [a]": -186.3° (c = 0.3, CHC13) . Example 21 A. Ethyl 7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-1-(2,4-dif luorophenyl) -6-f luoro-1,4-dihydro-4-oxo-l, 8-naphthyridine-3-carboxylate O x HCI F 1.9 g (5 mmol) of ethyl 7-chloro-l-(2,4-difluorophenyl )-6-fluoro-1,4-dihydro-4-oxo-l,8 -naphthyridine-3-carboxylate are stirred at 10°C for 245640 3 hours with 680 mg (5.4 mmol) of [S,S]-2,8-diazabicyclo[4.3.0]nonane in the presence of 560 mg (5 mmol) of 1,4-diazabicyclo[2.2.2]octane in 20 ml of acetonitrile. The suspension is filtered off with suction, washed with water and dried. 0.35 g of product is obtained. By concentrating the mother liquors, stirring the residue with water, isolating the undissolved product and purifing by chromatography (silica gel, eluent: dichloro-methane/methanol/17 % strength aqueous ammonia), a further 0.7 g of product is isolated. Total yield: 1.05 g (44 % of theory), Melting point: 184-185°C (with decomposition) [q]d3: +6.8° (c = 0.46, CHC13) . B. 7-([S,S]-2,8-Diazabicyclo[4.3. 0]non-8-yl) -1-(2,4-dif luorophenyl) -6 -f luoro-1, 4-dihydro-4-oxo -1, S-naphthyridine-3-carboxylic acid hydrochloride 0.8 g (1.7 mmol) of the product from Step A are heated under reflux for 4 hours in a mixture of 10 ml of acetic acid and 8 ml of half-diluted hydrochloric acid. The mixture is concentrated, the residue is stirred with a little water, and the precipitate is filtered off with suction, washed with ice-cold ethanol and dried. Yield: 0.67 g (83 % of theory), Melting point: 324-326°C (with decomposition), [a]": +10.8° (c = 0.37, DMF). Example 22 CH3 O COOH 0.56 g (2 mmol) of l-cyclopropyl-6,7-difluoro-l,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylate are heated at 120°C for 2 hours with 0.38 g (3 mmol) of [S,S]-2,8-diazabicyclo[4.3.0]nonane and 0.45 g (4 mmol) of l,4-diazabicyclo[2.2.2]octane in 3.5 ml of dimethyl sulphoxide. After cooling, the solvent is removed in a high vacuum. The residue is taken up with acetonitrile. The solid is separated off, washed with acetonitrile and dried at 60 to 80°C. Yield: 0.5 g (65 % of theory) of l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylate Melting point: 217-219°C (with decomposition), [a]D: -119° (c = 0.5, DMF) Example 23 CH3 O H!^ A. 837 mg (3 mmol) of l-cyclopropyl-6,7-difluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 2 hours with 1.1 g (10 mmol) of 1,4-diazabicyclo[2.2.2]octane and 665 mg (3.3 mmol) of IR,6S-2-oxa-5,8-diazabi-cyclo[4.3.0]nonane-dihydrochloride in a mixture of 10 ml of acetonitrile and 5 ml of dimethylformamide. The mixture is evaporated, the residue is stirred with 30 ml of water, and the precipitate is filtered off with suction and dried at 80°C in vacuo. Yield: 400 mg (34 % of theory of l-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-7-(lR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 213-214°C (with decomposition). B. 0.4 g of the betaine from Step A is dissolved in 5 ml of half-concentrated hydrochloric acid at room temperature, the solution is concentrated and the residue is stirred with about 3 ml of ethanol. The precipitate is filtered off with suction and dried at 80°C/12 mbar. Yield: 290 mg (66 % of theory) of l-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-7-(lR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride, Melting point: 305-308°C (with decomposition), [a]": -79° (c = 0.52, H20) 9 /* r> / fx f"< r * t Example 24 COOH 362 mg (1 mmol) of 5-bromo-l-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1.5 hours with 220 mg (2 mmol) of 1,4-5 diazabicyclo[2.2.2]octane and 220 mg (1.1 mmol) of 1S,6R-2-oxa-5,8-diazabicyclo[4.3.0]nonane dihydrochloride in a mixture of 3 ml of acetonitrile and 1.5 ml of dimethylformamide. The suspension is cooled, and the precipitate is filtered off with suction, stirred with 30 ml of water 10 and dried at 90°C in a high vacuum. Yield: 320 mg (68 % of theory) of 5-bromo-l-cyclopropyl-6,8-difluoro-l,4-dihydro-7-(lS,6R-2-oxa-5,8-diaza-bicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, Melting point: 263-264"C (with decomposition), 15 [q]d°: +251° (c = 0.3, CH2C1 Example 25 2 J i— - 100 - Analogously to Example 1, the following are obtained using [S,S]-2-methyl-2,8-diazobicyclo[4.3.0]nonanes A: l-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-([S,S]-2-methyl-2,8-diazobicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, melting point: 230-233°C (with decomposition) (recrystallised from glycol monomethyl ether); B. l-Cyclopropyl-6,8-difluoro-l,4-dihydro-7-([S,S]-2-methy1-2,8-diazobicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid hydrochloride, melting point: 258-260°C (with decomposition), [a]oS: -216.3° (c = l, H20) . Example 26 Analogously to Example 1, the following are obtained using [R,R]-2-methyl-2,8-diazabicyclo[4.3.0]nonane: A: l-Cycopropyl-6,8-difluoro-1,4-dihydro-7-([R,R]-2-methyl-2,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid, melting point: 228-230°C (with decomposition) (recrystallised from glycol monomethyl ether): B: l-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-( [R,R]-2-methyl-2,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3- 0 2 4 £ A quinolinecarboxylic acid hydrochloride, melting point: 258-260°C (with decomposition), [a]": +213.8° (c = l, H20) . Example 27 0 CH3-CO-CH:CH2 COOH 5 1.95 g (5 mmol) of the product from Example 1A are heated under reflux for 4 hours with 2.1 g (30 mmol) of methyl vinyl ketone in 50 ml of ethanol. The mixture is concentrated, the residue is stirred with water, and the precipitate is filtered off with suction, washed with 10 ethanol and dried at 100°C/12 mbar. Yield: 2.1 g (91.5 % of theory) of l-cyclopropyl-6,8-difluoro-l,4-dihydro-oxo-7-([S,S]-2-[3-oxo-l-butyl]-2,8-diazabicyclo[4.3.0]non-8-yl)-3-quinolinecarboxylic acid, Melting point: 181-183°C (with decomposition) 15 (recrystallised from glycol monomethyl ether, [a]Di,:-120.7° (c = 0.57, CH2C12) £4 r;> Example 28 0 CH3-CO-CH2 COOH 1.95 g (5 mmol) of the product from Example 1A are heated at 50-80°C for 3 hours with 1.0 g (10.8 mmol) of chloroacetone and 1.3 g (13 mmol) of triethylamine in 30 ml of dimethylformamide. The solution is concentrated, the residue is stirred with water (pH 6), and the undissolved precipitate is filtered off with suction, washed with water and dried at 100°C in a recirculating air drying oven (crude yield: 1.3 g) and recrystallised from glycol monomethyl ether: Yield: 1.12 g (50 % of theory) of l-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-([S,S]-2-[2-oxopropyl]-2,8-diazabicyclo[4.3.0]]non-8-yl)-3-quinolinecarboxylic acid, Melting point: 181-184°C (with decomposition), [ a ]q3 : -72 0 (c = 0. 55, CHC13) . Example 29 O CH3-CO-CH2CH COOH ') / r* ^ k 4 r n A. The product from Example 2A is reacted analogously to Example 27 and 8-chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-([S,S]-2-[3-oxo-1-butyl]-2,8-diazabicyclo[ 4.3. 0 ]non-8-yl) -3-quinolinecarboxylic 5 acid of melting point 107-109°C is obtained. [q]": -53° (c = 0.67, CHC13) , Purity: 99.2 % strength (HPLC). B. Rac . 8-chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-cis-2-[3-oxo-l-butyl]-2,8-diazabicyclo[4.3.0]-10 non-8-yl)-3-quinolinecarboxylic acid of melting point 124-1256C is obtained analogously using 8-chloro-l-cyclopropyl-7-(cis-2,8-diazabicyclo[4.3.0J-non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid. 15 Example 30 CH3-CO-CH2 N COOH 1.56 g (4 mmol) of the product from Example 10A are treated with 0.82 g (8.8 mol) of chloroacetone and 1.05 g (10.4 mmol) of triethylamine in 30 ml of dimethylformamide and the mixture is heated at 50-80 °C for 20 3 hours. The yellow solution obtained is concentrated at r*'. 80°C/15 mbar, and the oily residue is stirred with water until it solidifies. The solid product is filtered off with suction, washed with water and recrystallised from glycol monomethyl ether. Yield: 830 mg (47 % of theory) of l-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(cis-5-[2-oxopropyl]-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-3-quinolinecarboxylic acid, Melting point: 192-193°C (with decomposition). r\ 10 Example 31 CH3-CO-CH2CH, 1.56 g (4 mmol) of the product from Example 10A are heated under reflux for 3 hours with 1.8 g (25.6 mmol) of methyl vinyl ketone in 50 ml of ethanol. The suspension is concentrated at 70°C/12 mbar, and the residue is 15 stirred with water and recrystallised from glycol monomethyl ether. Yield: 1.33 g (72 % of theory) of l-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(cis-5-[3-oxo-l-butyl]-2- - 105 - / oxa-5 , 8-diazabicyclo[4 . 3 .0 ]non-8-yl) - 3 -guinolinecarboxylic acid, Melting point: 188-189°C (with decomposition). Example 32 1.95 g (4.8 mmol) of the product from Example 2A are heated under reflux for 2 hours with 3 g (30 nunol) of ethyl acrylate in 30 ml of glycol monomethyl ether. The mixture is evaporated, the residue is stirred with water, and the precipitate is filtered off with suction, dried (Crude yield: 1.9 g) and recrystallised from glycol monomethyl ether. Yield: 1.45 g (60 % of theory) of 8-chloro-l-cyclopropyl-7 -( f S ,S]-2-[2-ethoxy-carbonyl-ethyl ]-2 , 8 -diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-guinolinecarboxylic acid, Melting point: 117-118°C (with decomposition), [q]d6: -103.5° (c = 0.49, DMF), Purity: 99.6 % strength (HPLC). O c2h5o;c-ch2-ch cooh 9 /j r r- A Example 33 H /~~lN,T NC-CH2-CH2 s^x^J Cl H 1.95 g (4.8 nunol) of the product from Example 2A are heated under reflux for 5 hours with 0.8 g (15 mmol) of acrylonitrile in 30 ml of ethanol. The mixture is 5 evaporated, and the residue is stirred with water, dried (crude yield: 1.9 g) and recrystallised from glycol monomethyl ether. Yield: 1.6 g (73 % of theory of 8-chloro-7-([S,S]-2-[2-cyanoethyl]-2,8-diazabicyclo[4.3.0]non-8-yl)-l-10 cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: 153-155°C (with decomposition), [a]": -98.6° (C = 0.53, DMF), Purity: 96 % strength (HPLC), 15 Mass spectrum: m/e 458 (M+), 250, 149 (100 %, C9H13N2) , 110, 49. Am - 107 - Example 34 0 1.95 g (5 nunol) of the product from Example 1A are heated under reflux for 2 hours with 1.2 g (8 mmol) of dimethyl acetylenedicarboxylate in 60 ml of ethanol. The 5 suspension is concentrated, the residue is stirred with water, and the precipitate is filtered off with suction and dried. The crude product (2.3 g) is recrystallised from glycol monomethyl ether/dimethylformamide. Yield: 2 g (74 % of theory) of l-cyclopropyl-7-[2-(1,2-10 methoxycarbonyl-vinyl)-IS,6S-2,8-diazabicyclo[4.3.0]non-8-yl]-6,8-difluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: 262-264"C (with decomposition); [o]jj*: +28.8° (c = 0.24, CH2C12) . 15 Example 35 f> /; r n A fi The product from Example 2A is reacted with dimethyl acetylenedicarboxylate analogously to Example 34. 8-Chloro-l-cyclopropyl-7-[2 - (1, 2-bis-methoxycarbonyl-vinyl) - IS, 6S-2 , 8-diazabicyclo[4 . 3 .0]non-8-yl]-6-fluoro-5 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of melting point 210-212°C (with decomposition) is obtained in 87 % yield; [a]§*: +16.6° (c = 0.5, DMF) . Example 36 O 10 780 mg (2 mmol) of l-cyclopropyl-7-(cis-2,8-diazabicyclo-[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour with 500 mg (5 mmol) of ethyl propiolate in 15 ml of ethanol. The suspension is cooled, and the precipitate is 15 filtered off with suction, washed with 25 ml of ethanol and dried at 80°C in a high vacuum. Yield: 880 mg (90 % of theory) of l-cyclopropyl-7-[2-(trans-2-ethoxycarbony1vinyl)-cis-2,8-diazabicyclo-[4.3.0]non-8-yl]-6,8-difluoro-l,4-dihydro-4-oxo-3-20 quinolinecarboxylic acid, Melting point: 244-246°C. Analogously to Example 36, the following are obtained from the corresponding starting materials: c2h5o2c 11 \ /11 c = c / II n Example 37 38 39 40 41 42 43 44 Starting material A example) 2A x1 22 3 A 5 6 19 13c 1A cc1 ch Cl I cf n c-och;, Cl7 cf 11 cll3 h nh2 h II F ii *)not recrystallised COO 11 Y ch. 4. cll2 Cl 12 cll2 cll2 ci i, o cii2 Melting point [*C] 211-213 199-201 284-286 246-248 219-221 232-233 225-227 l«]r +6,3° (c=0,5, CIICI3) -205° (c=0,5, CIICI3) -231° (c=0,5, CHCl,) -14° (c=0,5, CHCI3) -162° (c=0,25t CI ICI3) -23° (c=0.25, CHCI3 +8° (c=0,5, CHCI3) Analogously to Example 10, the following are obtained from the corresponding intermediate products: M Starting material m Example •° (example) A X1 Y Melting point [*C] [a]D ' 45 10C CF H O 208-209 +24° (c=0,5, CHC13) 46 11C CC1 11 O l'W-199 -46° (c=0,5, CMCI3) 47 13B CF F 0 230-232 -5° (c=0,25, CIICI3) ro CJl C3> a r- / r- ^ / a A ' j ! ' ' i '.V Example 48 CH302C COOH 8-Chloro-l-cyclopropyl-7-( [ S , S ] - 2 , 8 -diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-guinolinecarboxylic acid is reacted with methyl 5 propiolate in ethanol or methanol analogously to Example 36 and 8-chloro-l-cyclopropyl-6-fluoro-1,4-dihydro-7-[2-(trans -2-methoxycarbonyl-vinyl) - [ S, S ] -2, 8-diazabicyclo-[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid of melting point 220-222°C (with decomposition) is obtained, 0 [a]": +8.2° (c = 0.5, CHC13) . Example 49 O CH302C \ C = H COOH 407.5 g (1 mmol) of 8-chloro-l-cyclopropyl-6-fluoro-l,4-dihydro-7-(IS,6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)- - 113 - 245640 4-oxo-3-quinolinecarboxylic acid (from Example HE) are heated under reflux for 1 hour with 210 mg (2.5 mmol) of methyl propiolate in 10 ml of methanol. The mixture is concentrated and the isolated crude product (450 mg) is 5 recrystallised from 4 ml of acetonitrile. Yield: 8-Chloro-l-cyclopropyl-6-fluoro-l,4-dihydro-7-[ 5-(trans-2-methoxycarbonyl-vinyl)-lS,6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl]-4-oxo-3-quinolinecarboxylic acid, 10 Melting point: 153-156°C (with decomposition), [q]d8: +36° (c = 0.5, CHC13) . Example 50 F O F JL JL COOH Reaction with the compound of Example 13A is carried out analogously to Example 49 and l-cyclopropyl-5,6,8-15 trifluoro-1,4-dihydro-7-[5-(trans-2-methoxycarbonyl-vinyl)-cis-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl ] -4-oxo-3-quinolinecarboxylic acid of melting point 169-170°C (with decomposition) is obtained (from glycol monomethyl ether). Z 4 5 6 4 0 Example 51 CH302C COOH Reaction is carried out with the compound from Example 10E analogously to Example 49 and l-cyclopropyl-6,8-difluoro-1,4-dihydro-7-[5-(trans-2-methoxycarbonyl-vinyl)-IS,6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl]-4-oxo-3-quinolinecarboxylic acid of melting point 230-234 °C (with decomposition) is obtained (from glycol monomethyl ether); [a]§8: -27° (c = 0.5, CHC13) . 10 Example 52 CH30;C Br 0 Reaction is carried out with the compound from Example 24 analogously to Example 49 and 5-bromo-1-cyclopropyl-6, 8-dif luoro-1,4-dihydro-7 - [ 5- (trans-2-methoxycarbonyl- - 115 - 24 5 6 4 vinyl)-IS,6R-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl] -4-oxo-3-quinolinecarboxylic acid of melting point 158-160°C (with decomposition) is obtained (from isopropanol): [a]": +8° (c = 0.27, CHC13) . Reaction is carried out with the compound from Example 17 analogously to Example 36 and methyl l-cyclopropyl-7-[ 2-(trans-2-ethoxycarbonyl-vinyl)-IS,6S-2,8 -diazabicyclo[4.3.0]non-8-yl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate of melting point 168-169°C is obtained. Example 54 5 Example 53 0 F 0 C2H502C — CH= C COOH 2 4 5 6 4 818 mg (2 mmol) of l-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(IR,6S-2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid (from Example 13B) are treated with 680 mg (4 mmol) of diethyl acetylene-5 dicarboxylate in 15 ml of ethanol and the mixture is treated in an ultrasonic bath at 30°C for 1 hour. The suspension is filtered off with suction, and the precipitate is washed with ethanol and dried at 70°C in a high vacuum. 10 Yield: 890 mg (77 % of theory) of l-cyclopropyl-7-[ 5-(1,2-bis-ethoxycarbonyl-vinyl)-IR,6S-2-oxa-5,8-diazabicyclo[4 .3. 0]non-8-yl]-5,6,8-trif luoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: 220-222°C (with decomposition) (from 15 glycol monomethyl ether) [a]f: -57° (c = 0 . 5 , CHC13) . Example 55 c2h5o2c cooh 20 The reaction is carried out with l-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(trans-2-oxa-5,8-diaza[4.3.0]non-8-yl)-4-oxo-3-quinolinecarboxylic acid analogously to </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 7 4 : : c ei U Example 36 and l-cyclopropyl-7-[5-(trans-2-ethoxy-carbonyl-vinyl]-trans-2-oxa-5, 8-diaza[4.3.0]non-8-yl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is obtained. Melting point: 266-268°C (with decomposition) (from glycol monomethyl ether). Example 56 CH-iOOC COOH l-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-(trans-2-oxa-5, 8-diaza [4.3. 0 ]non-8-yl) -4 -oxo-3-quinolinecarboxylic acid is reacted with methyl propiolate analogously to Example 36 and l-cyclopropyl-7-[5-(trans-2-methoxy-carbonyl-vinyl)-trans-2-oxa-5,8-diaza[4.3.0]non-8-yl]-',8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is obtained. Melting point: 275-277°C (with decomposition). - 118 - WHAT WE CLAIM IS; 1. A quinolone- or naphthyridone-carboxylic acid derivative of the formula (I) in which A represents CH, CF, CC1, C-OCH3, C-CH3 or N, X1 represents H, halogen, NH2 or CH3, R1 represents C1-C3-alkyl, FCH2CH2-, cyclopropyl or phenyl which is optionally monosubstituted to trisubstituted by halogen, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3)-, R2 represents H, C1-C3-alkyl which is optionally substituted by hydroxyl, halogen or amino or 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, and B represents a radical of the formula -• -i . < v C ( - 119 - 245640 n- n n* n n RJN^ Y t R"N^ Y f R"N^ Y f R'N^ Y or R'N^ Y in which Y represents 0 or CH2 , R3 represents C2-C3-oxoalkyl, CH2-CO-C5H3, CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN, 5 in which R' and R" each independently denote hydrogen or C,-Cj-alkyl, and R4 represents H, C:-C3-alkyl, 5-methyl-2-oxo-1,3-dioxol-4-yl-methyl, C2-C3-oxoalkyl, CHj-CO-CsHj, 10 CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN, in which r ' and R " each independently denote hydrogen or CpQ-alkyl and pharmaceutically utilisable hydrates and acid 15 addition salts thereof and the alkali metal, alkaline earth metal, silver and guanidinium salts of any underlying carboxylic acids. h- ^ ^—■ h h- \ h ^—h h-, ) \ h ■X*'0 c> ..." \ \ - 120 - % n 245640 2. A quinolone- or naphthyridone-carboxvlic acid derivative of the formula (I) according to Claim 1, in which A represents CH, CF, CC1, C-OCH3 or N, 5 X1 represents H, F, Cl, Br, NH2 or CH3, R1 represents CZH5, cyclopropyl or 2,4-difluorophenyl, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3)-, R2 represents H, CH3, C2H5 or 5-methyl-2-oxo-l,3-10 dioxol-4-yl-methyl, and B represents a radical of the formula iii! n n n n Hrr-V-H V H HT^rX~H HrU K R'N Y R Y , RN Y , RN^ Y orR N Y in which Y represents 0 or CH2 , R3 represents CH2-CO-CH3, CH2-C0-C8H5, CH2CH2-CO-CH3, 15 CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN, in which R' and R" each independently denote hydrogen or C,-ChalkyI, and - 121 - 245640 R* represents H, Ci-Cj-alkyl, 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, CH2-C0-CH3/ CH2-CO-C6H5/ CH2CH2-CO-CH3, CH2CH2C02R' , R' 02C-CH=C -C02R ", -CH=CH-C02R' or CH2CH2-CN, ' in which R' and R"each independently denote C,-C2-alkyl, and phaxmaceutically utilisable hydrates and acid addition salts thereof and the alkali metal, alkaline earth metal, silver and guanidinium salts of any underlying carboxylic acids. A quinolone- or naphthyridone-carboxylic acid derivative of the formula (I) according to Claim 1, * in which A represents CH, CF, CCl, C-OCH3 or N, X1 represents H, F, Cl, Br, NH2 or CH3, R1 represents C2H5, cyclopropyl or 2,4-difluorophenyl, or A and R1 together can denote a bridge of the structure C-0-CH2-CH(CH3)-, R2 represents H, CH3/ C2Hj or 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, and B represents a radical of the formula 122 24 5 6 4 0 N N N N h h V r4n y " h 5 10 in which Y represents 0 or CH2, and r4 represents CH2-CO-CH3, CH2-CO-CsH5, CH2CH2-C0-CH3/ CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or ch2ch2-cn, in which R' and R" each independently denote Cj-C2-alkyl, and pharmaceutically utilisable hydrates and acid addition salts thereof and the alkali metal, alkaline earth metal, silver and guanidinium salts of any underlying carboxylic acids. 4. 8-Chloro-l-cyclopropyl-7-([S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and pharmaceutically utilisable hydrates and acid addition salts thereof and the alkali metal, alkaline earth metal, silver and guanidinium salts of the underlying carboxylic acid. i; w - 123 - 245640 q • 5. A quinolonecarboxylic acid selected from the group consisting of l-cyclopropyl-7-([S,S ] -2,8-diazabicyclo[4.3.0]non-8-yl ) - 6 , 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxyiic acid, l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl ) - 6- f luoro - 1 , 4- dihydro- 4-oxo- 3 quinolinecarboxylic acid, and l-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-5,6,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid , and pharmaceutically utilisable hydrates and acid addition salts thereof and alkali metal; alkaline earth metal, silver and guanidinium salts of any underlying carboxylic acids. 6- A process for the preparation of a quinolone- or naphthyridone-carboxylic acid derivative according to claim 1 of the formula (I) in which A represents CK, CF, CCl, C-OCH3, C-CH, or N, X1 represents H, halogen, NH, or CH3, R1 represents C,-C3-alkyl, FCH2CH2-, cyclopropyl or phenyl which is optionally monosubstituted to trisubstituted by halogen, or A and R' together 124 can denote a bridge of the structure C-0-CH2-CH(CH3)-, R2 represents H, C:-C3-alkyl which is optionally substituted by hydroxyl, halogen or amino or 5 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, and B represents a radical of the formula N .« R N Y in which Y represents 0 or CH2 and R3 represents C2-C5-oxoalkyl, CH2-CO-C6H5, CH2CH2-C02R' 10 or CH2CH2-CN, in which R' denotes hydrogen or C1-C3-alkyl, - 125 - 24564 in which A, Y, X1, and R2 have the abovementioned meaning, is reacted with a compound of the formula (III) R3-X3 (III) in which R3 has the abovementioned meaning, and X3 represents halogen, if appropriate in the presence of an acid binder. 10 7 . A process for the preparation of a quinolone- or naphthyridone-carboxylic acid derivative according to claim 1 of the formula (I) in which A represents CH, CF, CC1, C-OCH3/ C-CH3 or N, 15 X1 represents H, halogen, NH2 or CH3/ R1 represents C1-C3-alkyl, FCH2CH2-, cyclopropyl or phenyl which is optionally monosubstituted to trisubstituted by halogen, or A and R1 together can denote a bridge of the structure 2456 C-0-CH2-CH(CH3)-, R represents H, Cx-C3-alkyl which is optionally substituted by hydroxyl, halogen or amino or 5-methyl-2-oxo-1,3-dioxol-4-yl-methyl, and B represents a radical of the formula N in which R lNl ? Y represents 0 or CH2 and R3 represents CH2CH2-CO-CH3, CH2CH2-C02R' , R' 02C-CH=C-C02R-CH=CH-C02R' or CH2CH2-CN, in which R' and R" each independently denote hydrogen or C,-Cj-alkyl, characterised in that a compound of the formula (II) NAN HN Y R1 in which y 245640 A, Y, X1, R1 and R2 have the abovementioned meaning, is reacted with a suitable Michael acceptor. 8. A process for the preparation of a quinolone- or naphthyridone-carboxylic acid derivative according to any one of Claims 1 to 3 of the formula (I) in which A represents CH, CF, CC1, C-OCH3, C-CH3 or N, X1 represents H, halogen, NH2 or CH3 , R1 represents C1-C3-alkyl, FCH2CH2-, cyclopropyl or phenyl which is optionally monosubstituted to •trisubstituted by halogen, or A and Rl together can denote a bridge of the structure C-0-CH2-CH(CH3)-, R2 represents H, Cx-C3-alkyl which is optionally substituted by hydroxyl, halogen or amino or 5-methyl-2-oxo-l,3-dioxol-4-yl-methyl, and B represents a radical of the formula, I I I I m n n n h ■ h h w""~}— h h -j—■* h h ■* j h ^ r4n y , r4n y r4n y , rn y -44 v_y or in which Y represents 0 or CH2 , and R* represents H, Cx-C3-alJcyl, C2-C3-oxoalkyl, CH2-CO-C6Hj, CH2CH2C02R', R'02C-CH=C-C02R", -CH=CH-C02R' or CH2CH2-CN or represents 5-methyl-2-oxo-1,3-dioxol-4-yl-methyl, in which - 128 - 2456 R' and R" each independently denote hydrogen or C,-C3-aIkyl, characterised in that a compound of the formula (V) vi A 0 U COOR2 (V) in which A, R1, R2 and X1 have the abovementioned meaning and X2 represents halogen, is reacted with an enantiomerically pure compound of the formula (VI) H H H H N N N N H- ) \ — H H )—(" H H \ ( ■■ H H—7—^ H (VI) R4N Y R4N Y R4N Y rtY. R4N Y \. / t \ / \ / or \ / in which Y represents 0 or CH2, and R* represents H or Ci-Cj-alkyl, if appropriate in the presence of an acid scavenger, and the reaction product is optionally further reacted with a compound of the formula (Ilia) R*-X3 (IHa) - 129 - 245640 in which X3 represents halogen, and R* represents C2-C3-oxoalkyl, CH2-C0-C6H«, CH2CH,C02R' or CH2CH2-CN, in which R' denotes hydrogen or Cx-C3-alkyl, or with a suitable Michael acceptor. 9. A process for the preparation of a quinolone- or naphthyridone-carboxylic acid derivative according to Claim 7 or 8, wherein the Michael acceptor is dialkyl acetylenedicarboxylate, alkyl propiolate or a compound of the formula (IV) CH2=CH-R5 CW) in which R5 represents COCH3, C02R' or CN, wherein R' denotes hydrogen or C,-C3-alkyl. 10. A quinolone- or naphthyridone-carboxylic acid derivative according to any one of Claims 1 to 5 for controlling diseases. 11. A quinolone- or naphthyridone-carboxylic acid derivative according to any one of Claims 1 to 5 for controlling infectious diseases. 12. A medicament containing a quinolone- or naphthyridonecarboxylic acid derivative according to any one of Claims 1 to 5. - 130 - n A : ' 13. An antibacterial agent containing a quinolone- or naphthyridone-carboxylic acid derivative according to any one of Claims 1 to 5. 14. Use of a quinolone- or naphthyridone-carboxylic acid derivative according to any one of Claims 1 to 5 in the production of a medicament for the control of an infectious disease. 15. A quinolone- or naphthyridone-carboxylic acid derivative according Claim 1 substantially as herein described or exemplified. 16. A process according to any one of Claims 6-9, substantially as herein described or exemplified. •' v 131 </div>