CA2154024A1 - Benzofuranyl- and benzothienyloxazolidinones - Google Patents

Abstract

The present invention relates to benzofuranyl- and benzothienyloxazolidinones, processes for their preparation and their use as medicaments, in particular as antibacterial medicaments.

Description

215~024 ~n ",~ e RP
Patente Ki)nzem . PB/AB/1088P

~.~r~i- and bellzo~ielyloxazolidinones 5 The present invention relates to benzofuranyl- and l~,~lhienyloxazoli(linon~, processes for their pl~lion and their use as medi~m~nt~, in particular as antibacterial medic~m~nt~.

The publications US 5 254 577, US 4 705 799, EP 311 090, US 4 801 600, US 4 921 869, US 4 965 268, EP 312 000 and C.~ Park et al., J.Med. Chem. 35, 1156 (1992) 10 disclose N-aryloxazoli(1inon~ having ~ntibact~rial action.

The present invention relates to benzofuranyl- and l~l~lhienyloxazoli~inc)n~ of the general formula (I)

2~N O
7 M (I) in which 15 R' represents azido, hydroxyl or a group of the formula -OR2, -O-SO2R3 or -NR4R5, wherein R2 denotes straight-chain or branched acyl having up to 8 carbon atoms or a Le A 30 524 - Foreign countries - hydroxyl protective group, R3 denotes straight-chain or branched alkyl having up to 4 carbon atoms or phenyl which is optionally substituted by a straight-chain or branched alkyl having up to 4 carbon atoms, S R4 and Rs are identical or di~clclll and denote cycloalkyl having 3 to 6 carbon atoms, hydrogen, phenyl or straight-chain or branched alkyl having up to 8 carbon atoms or an amino protective group, or R4 or R5 denotes a group of the formula -C~R6, wherein R6 denotes cycloalkyl having 3 to 6 carbon atoms, straight-chain or branched alkyl or alkoxy in each case having up to 8 carbon atoms, phenyl or hydrogen, A represents an oxygen or sulphur atom, D, E, G, L and M are identical or di~Tcrclll and represent hydrogen, carboxyl, halogen, cyano, nlcl~o~ formyl, trifluoromethyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio or acyl in each case having up to 6 carbon atoms, or straight-chain or branched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to S carbon atoms or by a radical of the formula Le A 30 524 - 2 -215~029 -H3C - CO - NH ~3 0--HO--(CH2)2--N-- ' of by a group of the formula -NR7R8, wherein R7 and R8 are identical or different and S denote hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or phenyl, or together with the nitrogen atom form a 5- to 6-membered, saturated heterocycle optionally containing a further heteroatom from the series N, S
and/or 0, which for its part can optionally also be substituted on a further nitrogen atom by straight-chain or branched alkyl or acyl having up to 3 carbon atoms, and/or optionally represent a group of the formula -NR7R8, wherein R7 and R8 are identical or different and have the meaning of R7 and R8 indicated above and are identical to or different from this, and/or optionally represent (C2-C8)-alkenylphenyl, phenyl or a 5- or 6-membered saturated or unsaturated heterocycle having up to 3 heteroatoms from the series Le A 30 524 - Foreign countries - 3 -- - 215~o2~

- S, N and/or O, which for their part are optionally s~-ksth-lte~l by a group of the formula -Co-NR9RI0, -NR'IR'2-NR~3-So2-R~4, -R'5R'6N-So2- or-R~7-S(O)a-, wherein a denotes a nurnber 0, 1 or 2, S R9, R'0,R~3, R'5 and Rl6 are identical or di~ and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl, Rll and Rl2 are identical or di~ l and have the m~ning of R7 and R8 indicated above and are id~ntic~l to or dil~elcllL from this, Rl4 and R'7 are identical or di~ l and have the m~nin~ of R3 indicated abound are identical to or di~ t from this, and/or for their part are optionally substituted up to 2 tirnes by identical or di~ s~-kstitll~ntc from the series con~ictin~ of carboxyl, halogen, cyano, ~ l~tO, formyl, trifluololll~ l, nitro, phenyl, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio and acyl in each case having up to 6 carbon atoms or straight-chain or branched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 5 carbon atoms or by a group of the formula -NR'3R'9, wherein Rl8 and R'9 have the m.-~ning of R7 and R8 indicated above and are identical to or di~elclll from this, and their salts and S-oxides.

Physiologically acceptable salts of the benzofuranyl- and benzothienyloxazolidinones can be salts of the substances according to the invention with mineral acids, carboxylic LeA30 524 -4 -, 215~o2q acids or sulphonic acids. Particularly ~ lled salts are e.g. those with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, m~th~neslllphonic acid,eth~n~lllphonic acid, toluenesulphonic acid, benzene sulphonic acid, n~phth~lenephonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, 5 fumaric acid, maleic acid or benzoic acid.

Salts which can be mentioned are salts with cl-~t~m~ry bases, such as, for example, alkali metal salts (e.g. sodium or potassium salts), ~lk~line earth metal salts (e.g.
calcium or magnesium salts) or ~mmonium salts derived from ~mm~ni~ or organic amines such as, for example, diethylamine, triethylamine, ethyldiisopropylamine,10 procaine, dibenzylamine, N-methylmorpholine, dihydroabietylamine, l~h~n~min~ or methyl-piperidine.

lhe compounds according to the invention can exist in stereoisol~l~ic forms which either behave as image and mirror image (enantiomers), or which do not behave asimage and mirror image (diastereomers). The invention relates both to the enantiomers 15 and diastel~lllt;l~ or their l~;ti~e mixtures. Like the dia~ om~l~, the racemic forms can also be se~ted into the stereoisomerically uniform con~titll~nt~ in a known manner.

Heterocycle in general represents a 5- to ~membered, saturated or unsaturated ring which as heteroatoms can contain up to 3 oxygen, sulphur and/or nitrogen atoms. The 20 following are mentioned as plc~ell~d: thienyl, furyl, pyrrolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazolyl, oxazolyl, imidazolyl, pyrrolidinyl, piperidinyl or piperazinyl.

These also include N-bonded, 5- to ~membered saturated heterocycles which additionally can contain up to 2 oxygen, sulphur and/or nitrogen atoms as heteroatoms, 25 such as, for example, piperidyl, morpholinyl or pi~l~zillyl or pyrrolidinyl. Piperidyl and pyrrolidinyl are particularly plc~lled.

Hydroxyl protective group in the context of the def~nition indica~ed above in general represents a protective group from the series: trimethylsilyl, triisopropylsilyl, LeA30 524 - 5 .
tert-butyl-dimethylsilyl, benzyl, benzyloxyc~l ollyl, 2-~ ob~l~yl, 4-nitrobenzyl, tert-butyloxycarbonyl, allyloxycarbonyl, 4-methoxybenzyl, 4-methoxybenzyloxycarbonyl,tetrahydropyranyl, formyl, acetyl, trichloroacetyl, 2,2,2-trichloroethoxycarbonyl, methoxyethoxymethyl, [24~ lylsilyl)ethoxy]methyl, benzoyl, 4-methylbenzoyl, S 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlor~b~l~yl or 4-methoxybenzoyl. Acetyl, tert-butyldimethylsilyl and tetrahydropyranyl are plcf~l~ed.

Arnino protective groups in the context of the invention are the c~lon~y amino protective groups used in peptide ~h~ni~try.

These plcf~l~ly include: benzyloxyc~l~llyl, 2,4--lim~oth-xybenzyloxyc~l,ollyl, 10 4-methoxybenzyloxycarbonyl, methoxyc~l,ollyl, ethoxycarbonyl, tert-butoxycarbonyl, allyloxycarbon~l, phthaloyl, 2,2,2-trichloroethoxycarbonyl, fluorenyl-9-methoxycarbonyl, formyl, acetyl, 2-chloroacetyl, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, benzoyl, 4-chlo,ul)el~yl, ~bromob~l~yl, ~nillobel~yl~
phth~limido, isovaleroyl or benzyloxymethylene, ~nitrobenzyl, 2,4-dinitrobenzyl, 15 4-nitrophenyl, 4-methoxyphenyl or lli~h~llylmethyl.

rell~d compounds of the general forrnula (I) are those in which R~ represents azido, hydroxyl or a group of the formula -oR2, -oSo2R3 or -NR4R5, wherein R2 denotes straight-chain or branched acyl having up to 6 carbon atoms or benzyl, R3 denotes straight-chain or branched alkyl having up to 3 carbon atoms, phenyl or toluoyl, R4 and R5 are identical or different and Le A 30 524 - 6 -215402~

denote cyclopropyl, cyclopentyl, cyclohexyl, hydrogen, phenyl or straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms, tert-butoxycarbonyl or benzyloxycarbonyl, or S R4 or R5 denotes a group of the formula -CO-R6, wherein R6 denotes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms, phenyl or hydrogen, 10 A represents an oxygen or sulphur atom, D, E, G, L and M are identical or different and represent hydrogen, carboxyl, fluorine, chlorine, bromine, iodine, cyano, mercapto, trifluoromethyl, formyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio or acyl in each case having up to 4 carbon atoms or lS straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms, by a radical of the formula H3C-Co-NH~3O _ HO--(CH2)2 N-- ' Le A 30 524 - Foreign countries - 7 -215402~
or by a group of the formula -NR7R8, wherein R7 and R8 are identical or di~lc"l and denote hydrogen, straight-chain or branched alkyl having up to 3 carbon S atoms or phenyl, or together with the nitrogen atom form a morpholinyl, pyrrolidinyl, pipcl~lyl or piperidyl ring, each of which is optionally substituted, also via the free N function, by methyl, ethyl or acetyl, and/or optionally represent a group of the formula -NR7R8, wherein R7' and R8' have the m~nin~ of R7 and R8 indicated above and are identical to or di~lclll from this, and/or optionally represent (C2-C4~alkenylphenyl, phenyl, pyridyl or thienyl, which fortheir parts are optionally substituted by a group of the formula -CO-NR9R'0, NR"R'2 -NR'3-So2-R'4, -R'5R'6N-SO2- or -R ~S(O)a~~

wherein a denotes a number 0, 1 or 2, R9 ,R', R'3, Rls and Rl6 are identical or di~erclll and denote hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or phenyl, Le A 30 524 - Forei~n countries - 8 -- 21 5qO2~

R~ and Rl2 are identical or diff~ l and have the m~ning of R7 and R8 indicated above and are identical to or difr~lclll from this, R~4 and R~7 are identical or diff~lcllt and have the m~ning of R3 indicated above and are identical to or difr~lclll from this, and/or for their part are optionally substituted up to 2 times by identical or - dirfelcnl~ substit~l~nt~ from the series cm~ "g of carboxyl, fluorine, chlorine, bromine, iodine, cyano, llæ~o, trifluoromethyl, formyl, nitro, phenyl, straight-chain or branched alkoxy, alkoxyc~l,ollyl, alkylthio and acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substit~ 1 by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms or by a group of the formula -NR'8R'9, wherein Rl8 and R~9 have the m~ning of R7 and R8 indicated above and are identical to or diffe~clll from this, and their salts and S-oxides.

Particularly plcfellcd compounds of the general formula (I) are those in which R' represents azido, hydroxyl or a group of the formula -oR2, -oSo2R3 or -NR4Rs, wherein R2 denotes a straight-chain or branched acyl having up to 6 carbon atoms, R3 denotes methyl, ethyl, phenyl or toluoyl, Le A 30 524 - 9 -215~02~
R4 and R5 are identical or different and denote cyclopropyl, cyclopentyl, cyclohexyl, hydrogen, phenyl or straight-chain or branched alkyl having up to 5 carbon atoms, or R4 or R5 denotes a group of the formula -CO-R6, wherein R6 denotes cyclopropyl, cyclopentyl, cyclohexyl or straight-chain or branched alkyl or alkoxy in each case having up to 4 carbon atoms, hydrogen or phenyl, 10 A represents an oxygen or sulphur atom, D, E, G, L and M are identical or different and represent hydrogen, carboxyl, fluorine, chlorine, bromine, iodine, cyano, formyl, trifluoromethyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl or acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substituted byhydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms, by a radical of the formula H3C- CO - NH ~3 0-- ~

HO--(CH2)2--N-- ' or Le A 30 524 - Foreign countries - 10 -- - 2I5~02~

or by a group of the formula -NR7R8, wherein R7 and R8 are identical or di~lclll and denote hydrogen or methyl, or together with the nitrogen atom form a morpholinyl, pyrrolidinyl, ~i~ucl~yl or piperidyl ring, each of which is optionally substi also via the free N function, by methyl, ethyl or acetyl, and/or optionally represent a group of the formula -NR7R8, whereln R7 and R8 have the m~ning of R7 and R8 indicated above and are identical to or di~lclll from this, and/or optionally represent 2-phenylvinyl, phenyl, pyridyl or thienyl, which for their parts are optionally substituted by a group of the formula -C~NR9RI0 or -NRI IRI2, wherein R9 and R' are identical or di~e~clll and denote hydrogen or methyl, R'l and Rl2 are identical or di~lclll and have the mP~ning of R7 and R8 indicated above and are identical to or di~elclll from this, and/or for their part are optionally substituted up to 2 times by identical or different substituents from the series co~ g of carboxyl, fluorine, chlorine, bromine, iodine, cyano, formyl, trifluoromethyl, nitro, phenyl, straight-chain or branched alkoxy, alkoxycarbonyl and acyl in each case having up to 4 carbon LeA30 524 -11-21$~ 02 1 atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms or by a group of the formula -NR'8R'9, wherein Rl8 and R~9 have the m~ning of R7 and R8 indicated above and are identical to or di~ from this, and their salts and S-oxides.

Very particularly l)le~l~d compounds of the general formula (T~ are those 10 in which G, L and M represent hydrogen and the oxæolidinone radical is bonded to the phenyl ring in position 5 or 6.

Processes for the plel,al~lion of the compounds of the general formula (I) according to the invention have additionally been found, characterized in that 15 [A] compounds of the general formula (II) or (III) E G L E G L
D ~ N=C=O (II) or ~ CO2-N3 (III) M M

in which A, D, E, G, L and M have the m~-~nin~ indicated above, LeA30 524 -12-215~o2~
are reacted with lithium bromide/(C4~)3 P(O) and epoxides ofthe general formula (IV) *
(rv in which T represents Cl-C6-acyloxy, S in inert solvents, if a~lu~liate in the presence of a base, and if Rl = OH the hydroxyl function is liberated by a typical ester hydrolysis or by a typical l~ ~l~irlcation, or [B] cornpounds of the general formula (V) E G L
D ~NH-CO2-V

M

in which A, D, E, G, L and M have the m.q~ning indicated above and V represents a typical protective group, preferably benzyl, 15 are reacted in inert solvents and in the presence of a base, for example lithium alkyls LeA30524 - 13-215402~

or lithium-N-alkyl- or lithium-N-silylalkylamides, l~rer~.~ly N-butyllithium, with epoxides of the general formula (IV), or [C] if R' = OH, f~rst compounds of the general formula (III) are converted by el;",;"~lion of nitrogen in alcohol to the compounds ofthe general forrnula (Va) E G L
D ~ NH-CO2-X
M (Va) in which A, D, E, G, L and M have the m~ning in~ t~1 above and 10 X represents straight-chain or branched C2-C6-alkyl, pl~r~l~bly n-butyl, and in a second step reacted as described under [A] in inert solvents and in thepresence of a base, pl~r~l~bly lithium-N-alkyl- or N-silylalkylamides or n-butyllithium and epoxides of the general formula (IV), or 15 [D] compounds of the general formula (VI) LeA30 524 -14-215402~

D~ ) M (VI) in which A, D, E, G, L and M have the m~ning indicated above, are either reacted directly with acids and diethyl carbonate, S or f~t, by reaction of the compounds of the general formula (VI) with acids, the com~ounds of the ~eral formula (VII) E G L OH
D ~ ~, OH
<~ ~ NH CH2 M (VII) in which A, D, E, G, L and M have the m~ning indicated above, 10 are prepared, and then cyclized in inert solvents in the presence of an auxiliary, or LeA30 524 -15 -[E] first compounds of the general formula (Ia) E G L O
~,~N O

(Ia) in which A, D, E, G, L and M have the m~ning indicated above, S are converted by reaction with (C~-C4~alkyl- or phenylsulfonyl chlorides in inert solvents and in the presence of a base to the corresponding compounds of the general forrnula (Ib) E G L O
D ~ N O
M oso2R3 ~Ib) in which 10 A, D, E, G, L, M and R3 have the mt~nin~ indicated above, then, with sodium azide in inert solvents, the azides of the general formula (Ic) E G L O
D ~ N O

3 (Ic) in which LeA30524 - 16-215~02~1 A, D, E, G, L and M have the m~ning indicated above, are prepared, in a further step the products are converted by reaction with (Cl-C4-0)3-P or Ph3P, ~ler~lably (CH30)3P, in inert solvents and with acids to the amines of the general S formula (Id) E G L o D ~ N O
M N H2 (Id) in which A, D, E, G, L and M have the m~nin~ indicated above, and by reaction with acetic anhydride or other acylating agents of the general formula 10 (VIII) Y-C0-R6 ~I) in which R6 has the meaning indicated above and 15 Y represents halogen, preferably chlorine or the radical -OCOR6, in inert solvents the compounds of the general formula (Ie) LeA30 524 -17-- 215~02~

E G L O

~,~ N 0 6 M NH-CO-R ~Ie in which A, D, E, G, L, M and R6 have the m~ning indicated above, are ylc~alc;d, 5 or [F] compounds of the general formula (Ie) are converted by a halogenation, if a~ in the presence of a silver catalyst, to the com~ounds of the general formula (If) E' G L O
D'~NJ~O
M NH-CO-R6 ~If) 10 in which D' or E' represents halogen, ~l~rel~ly bromine or iodine, and A, G, L M and R6 have the m~ning indicated above, or 15 [G] compounds of the general formula (If) are reacted with compounds of the LeA30524 - 18-- general formula (IX) E" G' L' D~ R20 M' in which A hæ the m~ning indicated above 5 and D", E", G', L' and/or ~ represent one of the optionally substituted, monocyclic heterocycles mentioned above under D, E, G, L and M, phenyl or (C2-C8}
alkenylphenyl, and 10 R20 represents the boronic acid radical -B(OH)2 or represents an organotin radical of the formula -SnR2'R22R23, wherein R2~, R22 and R23 are identical or di~e~ and denote C,-C4-alkyl, in inert solvents and in the presence of a palladium catalyst, 15 or [~ if A=O
compounds of the formula (~) LeA30524 - 19-o - ,~3 N o (X) HO ~, NH - CO - CH3 are cyclized by reaction with ~lv~ar~yl alcohol in inert solvents and in the system Pd(P(C6H5)3)2(OAc)2/CuI, NaOAc, and in the case of the S-oxides an oxidation is carried out, and if Ri, R5, R9, Rl, R~, Rl2, Rl3, Rl5, Rl6, Rl8 and R~9 ~ H an alkylation is carried out by cl-~tom~ry methods, and if al~ro~l,ate further sl-kstih~ntc or functional groups which are already present are introduced or derivatized by cu!i~o~ y mrth~l~, such as, for example, redox reactions, substitution reactions andlor hydrolysis or incol~lalion and dec~lmrosition of protective groups.

Ihe processes according to the invention can be illustrated by way of ~ lc by the following reaction srllrrnrs:

- Le A 30 524 - 20 -[A] ~3~N=CX-LiBr, Bu3P=O, NEt3 (CH2)2-CH3 Xylene, reflux O

MeOH N~o ~ (CH2)2-cH3 LeA30 524 - 21 -.
[A] ~ N3 LiBr, Bu3P=O

O ~ (CH2)z-CH3 Xylene. reflux. -N2 O
~ (CH2)2-CH3 Cs2C03 0 MeOH

~ ~ OH

[B] 1. n-BuLi THF

~3 NH~ o ~J~l 3 NH4CI

OH

Le A 30 524 - 22 -21540~
- [C] <~¢ N3 r~BuOH, reflux - N2 1. LiNlSiMe3~2. THF
O O
,(CH2)3-CH3 2 ~ Ob~(CH2)2-CH3 -70C -> RT
3. NH4CI

~OH

[D]
0~ H+
~NH~ ~TsOH/CH30H

~N~ 1 C l,u ;'' i~ ol /CH Cl S OH 2. (EtO)2CO, refl~

~ ~OH

Le A 30 524 - 23 -215~029 [E]

~N OHCISO2CH3, NEt3, CH2C12 N~ NaN3, DMF, 70C

~ N~ (MeO)3P, 1 ,2-DME, 90C
S--W ~N3 6N, HCI, 90C

N~ AcCI, THF
Et3N, -5C

~ \~ NH~ CH3 Le A 30 524 - 24 -- 21S~o~4 [F]

~N O

Br~ Ll~_ NH-CO-CH3 [G]
CH O

Br~ NH CH
~ 3 (65%) W~B(OH)2, [Ph3P]4Pd, THF, reflux ~ H CH

Le A 30 524 - 25 -215402~

[H]

H~\ ~ HC--CH2--OH
N O Pd (PPh3)2 (OAC)2 ~NH-CO-CH3 CUI, NaOAc, DMF

J~N

Dep~n~ing on the individual process steps, suitable solvents are the c~ )",i1.y solvents which do not change under the reaction conditions. Ihese ~l~r~l~bly include alcohols 5 such æ m~h~m)l, ethanol, propanol or iso~ ol, or ethers such æ diethyl ether, dioYane, 1,2--lim~th~xyethane, tetrahydrofuran, glycol dimethyl ether or tert-butyl methyl ether, or k~ton~ such æ acetone or b~non~, or amides such æ dimethyl formamide or hexamethylphosphoramide, or hydrocarbons such æ h~Y~n~., bcn7~n~, dichlorobenzene, xylene or toluene, or dimethyl sulphoxide, a~lo~ ile, ethyl acetate 10 or halogenohydrocarbons such æ methylene chloride, chlol~ofollll or carbon tetrachloride, or pyridine, picoline or N-methylpiperidine. Mixtures of the solvents mentioned can also be used.

Depending on the individual process steps, suitable bæes are the c~lctom~ry inorganic or organic bases. These pl~r~l~bly include allcali metal hydroxides such æ, for 15 example, sodium or potæsium hydroxide, or alkali metal carbonates such æ sodium or potæsium carbonate, or alkali metal alkoxides such æ, for ~ l4,1c, sodium or po~sillm methoxide, or sodium or potæsium ethoxide, or organic amines such æ
ethyldiisopropylamine, triethylamine, picoline, pyridine or N-methylpiperidine, or amides such æ sodium amide or lithium diisopropylamide, or lithium 20 N-silylalkylamides, such æ, for example, lithium N-(bis)triphenylsilylamide or lithium alkyls such as n-butyllithium.

The base is employed in an amount from 1 mol to 10 mol, preferably from 1 mol to3 mol, relative to 1 mol of the compounds of the general formulae (II), (III), (IV) Le A 30 524 - 26 -215 102~
- and (Va).

All reactions are in general carried out at normal, elevated or reduced pressure(e.g. 0.5 to 5 bar). In general the reactions are carried out at normal pressure.

Process [A] is pler~lably carried out in xylene or dichlorob~n7~e, if a~ liate in the 5 presence of triethylamine under reflux.

The base-catalysed tr~t~rification is carried out using one of the abovementioned alcohols, pler~ ,~bly methanol, in a tempe~n~ range from -10C to +40C, ~ler~.~ly at room temperature.

Suitable bases are in general sodiurn hydrogen carbonate, sodium methoxide, hydrazine 10 hydrate, potassiurn C~bO1~ or c~illm c~uboll~. C5~ rn ~U~ k; iS ~l~r~;llCd.

Process [B] is carried out in one of the abovementioned ethers using lithium alkyl compounds or lithium N-silylamides, sueh as, for ex~ )le n-butyllithillm, lithium diisopropylamide or lithium bis-L,illlelhylsilylamide, plerel~bly in tetrahydrofuran and lithium bis-trimethylsilylamide or n-butyllithium, in a tell~e~ re range from -100C
to +20C, pler~l~bly from -75C to -40C.

For process [C], suitable alcohols for the 1st step are pl~f~.~ly those mentioned above, in the case of subsequent cycli~tion tetrahydrofuran.

Suitable bases for the cyclization are pler~l~bly the abovementioned lithium N-silylalkyl compounds or n-butyllithium. n-Butyllithium is partieularly pler~lled.

20 Ihe first reaction step is carried out at the boiling point of the ~llcs~ lding alcohol and the cyclisation in a tel~ lure range from -70C to room temperature.

The cyclisation [D] is carried out in the presence of an auxiliary and/or in the presence of an acid.

Le A 30 524 - 27 -215gO2~
Suitable acids are in general inorganic acids such as, for exarnple, hydrochloric acid or sulphuric acid, or organic carboxylic acids having 1~ C atoms, optionally substituted by fluorine, chlorine and/or bromine, such as, for exarnple, acetic acid, trifluoroacetic acid, trichloroacetic acid or propionic acid, or slllphonic acids cn,~ g C~-C4-alkyl 5 radicals or aryl radicals, such as, for exarnple, m~.th~n~slllrhonic acid, eth~n~ lrh-nnic acid, b~n7PnP~ulphonic acid or tolll~n~lllph-)nic acid. Hydrochloric acid is particularly ~l~r~ d.

The acid is employed in an amount from 1 mol to 10 mol, pl~r~l~ly from 1 mol to 2 mol, based on 1 mol of the compounds of the general formula (VI).

10 Suitable auxiliaries are the clutom~ry reagents such as phos~n~., carbonyldiimidazole, or diethyl carbonate or trichlolvnl~lhyl chlol~folll~. Carbonyltliim;~7~1e, diethyl carbonate or trichlol~nlc~lyl chlol~r~ e is ~lef~

Suitable solvents are the abovementioned halogenohydrocarbons. Methylene chloride is plcr~ll~d.

The cyclisations are in general carried out in a te"4~l~ re range from -20C to 100C, plerelably at -20C to room tell4~~ re.

The acylation [E] is in general carried out in one of the abovementioned ethers or halogenohydrocarbons, plcrel~ly tetrahydrofuran or methylene chloride, in a temperature range from -30C to 50C, pl~rel~bly from -10C to room temperature.
20 The coupling reaction [G] with the boronic acid and aryl tin compounds is likewise carried out in one of the abovementioned ethers or hydrocarbons, pl~r~l~bly tetrahydrofuran or toluene, and in the presence of a palladium complex.

Suitable palladium complexes are, for example, Pd[P(C6H5)3]4, [(C6H5)3P]2PdC12 or (C6H5CN)2PdC12 [(c6H5)3p]4pd is pler~lled.

25 The reaction is carried out in a temperature range from room temperature to 150C, Le A 30 524 - 28 -2l5~D2~ ' fel~l)ly at the boiling point of the respective solvent.

Ihe reductions are in general carried out using hydrides in inert solvents or using boranes, diboranes or their complex compounds.

~fel~ly, the reductions are carried out using hydrides, such as complex borohydrides 5 or aluminium hydrides and also boranes. Sodium borohydride, lithium borohydride, sodium cyanoborohydride, lithium alllminillm hydride, sodium bis-(2-methoxyethoxy}
aluminium hydride or borane-tetrahydrofuran are particularly l"~f~l~ly employed in this case.

The reduction is in general carried out in a l~ lure range from -50C up to the 10 respective boiling point of the solvent, pl~f~.~ly from -20C to +90C.

The reductions can in general be carried out by hydrogen in water or in inert organic solvents such as alcohols, ethers or halogenohydrocarbons, or their mixtures, using catalysts such as Raney nickel, palladium, palladium on animal carbon or pl~tinl]rn, or using hydrides or boranes in inert solvents, if ~,o~,iate in the presence of a catalyst.

15 The reaction is ~lcr~,~bly carried out using hydrides, such as complex borohydrides or aluminium hydrides. Sodium borohydride, lithium al~uni~ l hydride or sodium cyanoborohydride are particularly ~lcf~l~ly employed in this case.

Suitable solvents in this case are all inert organic solvents which do not change under the reaction conditions. These p,~re,ably include alcohols such as m~th~nol, ethanol, 20 propanol or isopr~lol, or ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether or amides such as hexamethylphosphorarnide or dimethylf~nll~nide, or acetic acid. It is also possible to use mixtures of the solvents mentioned.

The oxidation to the N-oxide is in general carried out in one of the abovementioned 25 solvents, preferably in methylene chloride, using oxidizing agents such as, for example, metachloroperbenzoic acid, hydrogen peroxide or peracetic acid, plef~l~bly using Le A 30 524 - 29 -- ' - 215qO24 - m~qt~r~llor~,lenzoic acid in a ~ lure range from 0C to 80C, preferably from 0C to 40C.

The removal of the hydroxyl protective groups is in general carried out according to a customa~y method, for exarnple by hydrogenolytic cleavage of the benzyl ethers in the abovementioned inert solvents in the presence of a catalyst using hydrogen gas.

The amino protective group is in general likewise removed by c~ lo" ~ methods, to be specific pler~,~bly Boc using hydrochloric acid in dioxane, Fmoc using piperidine and Z using HBr/HOAc or by hydrogenolysis.

The abovementioned other derivatization reactions are in general carried out acco~ g to the methods published in Com~n~ m of Organic Synthetic Methods, T.T.Harrison and S.Harrison, Urlley Interscience.

Redox reactions, reductive amination, tr~n~t~rification and the halogenation of methyl groups using N-bromosl~ccinimide (NBS) or N-chlorosuccil~imide (NCS) are ~ r~ l~bly mentioned, which are illustrated by way of example in the following.

Suitable solvents for the alkylation are customaty organic solvents which do not change under the reaction conditions. These pler~l~bly include ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons such æ bPn7Pn~,toluene, xylene, hexane, cyclohexane or petroleum fractions, or halogenohydrocarbons such as dichlolu~ hane, trichlolu,~ "~, tetrachloromethane, dichloroethylene, trichloroethylene or chlorob~n7~ne, or ethyl acetate, or triethylamine, pyridine, dimethyl sulphoxide, dimethylr()lma nide, acetonitrile, acetone or l~il~ n~ It is also possible to use mixtures of the solvents mentioned. Dichlorom~.t~n~, dimethyl sulphoxide and dimethylrc,llllal1~ide are pl~r~ d.

The alkylation is carried out at norrnal pressure in the abovementioned solvents at temperatures from 0C to +150C, ~ r~l~ly at room temp~ re to +100C.

The amidation and the sulphoamidation are in general carned out in inert solvents in Le A 30 524 - 30 -- - 215402~
.
- the presence of a base and of a dehydrating agent.

Suitable solvents in this case are inert organic solvents which do not change under the reaction conditions. lhese include halogenohydrocarbons such as dichloromtth~nt,trichlorometh~ne, tetrachloromethane, 1,2-dichloroethane, trichloroethane, tetrachloroethane, 1,2-dichloroethane or trichloroethylene, hydrocarbons such asbenzene, xylene, toluene, hexane, cyclohexane or petroleum fractions, niLIo~ h~
dimethylr.lll~ ide, acet-nittile or tetrahydrofuran. It is also possible to employ mixtures of the solvents. Dichlo~ h~n~ and tetrahydrofuran and particularly ~cr~llcd.

Suitable bases for the amidation and the s~llpho~rnidation are the customary basic compounds. Ihese preferably include allcali metal and ~lk~lin~ earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or barium hydroxide, alkali metal hydrides such æ sodium hydride, allcali metal or ~lk~lin~ earth metal carbonates such as sodium carbonate or potassium C~ , or alkali metal alkoxides such as, for example, sodium methoxide or ethoxide, potassium methoxide or ethoxide or pol~iiulll tert-butoxide, or organic amines such as benzyl~ lcthyl~mmonium hydroxide, tetrabutyl~mmonium hydroxide, pyridine, triethylamine or N-methylpiperidine.

Ihe amidation and the snlrho~midation are in general carried out in a telll~,~ure range from 0C to 150C, pl~rel~bly at 25C to 40C.

Ihe amidation and the sulI h-~midation are in general carried out at normal pressure.
However, it is also possible to carry out the process at reduced pressure or at elevated pressure (e.g. in a range from 0.5 to 5 bar).

When carrying out the amidation and the sulphoamidation, the base is in general employed in an amount from 1 to 3 mol, preferably from 1 to 1.5 mol, relative to 1 mol of the respective carboxylic acid.

Suitable dehydrating reagents are carbodiimides such as, for example, Le A 30 524 - 31 -diisopropylcarbodiimide, dicyclohexylcarbodiimide or N{3-dimethylaminopropyl~N'-ethylcarbodiimide hydrochloride or carb~nyl compounds such æ carbonyldiimidazoleor 1,2-oxazolium compounds such as 2-ethyl-5-phenyl-1,2-oxazolium-3-sulphonate or prop~n~hosph-nic anhydride or isobutyl chloroformate or be~ iazolyloxy-tris-5 (dimethylamino)phosphonium hexafluororhosph~te or diphenyl phosphc)ramidate ormethançsulphonyl chloride, if al)~r~ iate in the presence of bases such as triethylamine or N-ethylmorpholine or N-methylpiperidine or ~dimethylaminopyridine.

Suitable bases for the hydrolysis are the cuetom~ry inorganic bases. Ihese ~l~f~.~ly include alkali metal hydroxides or ~lk~lin~ earth metal hydroxides such as, for example, 10 sodiurn hydroxide, pot~ lm hydroxide or barium hydroxide, or allcali metal carbonates such as sodium or pot~ lrn carbonate or sodium hydrogen C~ . Sodium hydroxide or pot~sil-rn hydroxide is particularly ~l~r~l~bly employed.

Suitable solvents for the hydrolysis are water or the organic solvents cu~ y forhydrolysis. These ~l~f~ bly include alcohols such as ",~h~-ol, ethanol, propanol, 15 isol~r~pallol or butanol, or ethers such as tetrahydrofuran or dioxane, or dimethyl ro""~"~ide or dimethyl sulphoxide. Alcohols such as ",~lh~ ethanol, propanol or iso~ lol are particularly pl~r~l~ly used. It is also possible to employ mixtures of the solvents mentioned.

lhe hydrolysis is in general carried out in a tel~ lure range from 0C to +100C, 20 plcr~l~bly from +20C to +80C.

In general, the hydrolysis is carried out at normal pressure. However, it is also possible to work at reduced pressure or at elevated pressure (e.g. from 0.5 to 5 bar).

When carrying out the hydrolysis the bæe is in general employed in an amount from 1 to 3 mol, plcf~l~ly from 1 to 1.5 mol, relative to 1 mol of the ester. Molar amounts 25 of the re;~ct~ntc are particularly plcrel~bly used.

Ihe esterification is in general carried out using the a~)prul)liate alcohols in the presence of acids, pl~rel~bly sulphuric acid, in a ten~ lure range from 0C to 150C, Le A 30 524 - 32 -215~02q p,er~ lably from 50C to 100C, and at normal pressure.

Ihe compounds of the general forrnulae (IV), (VIII) and (IX) are known or can beprepared by customary methods.

The compounds of the general forrnula (VII) are in the main new and can be prepared, 5 for example, as described above.

lhe compounds of the general formula (II) are known in some cases or are new andcan then be ~ aled, for exarnple, by reacting the a~ o~liate amines with trichloroethyl chlorof .""~l~s in one ofthe abovementioned solvents, ~l~,f~bly xylene, at reflux ten~at~l~.

10 Ihe compounds of the general formula (IlI) are known in some cases or are new and can then be plc~ed, for example, starting from the a~ liate carboxylic acids, byreacting either wi~ isobutyl chlol~r(,lll~1etacet)n~., sodiurn azide/water or with diphenylphosphoryl azidettetrahydrofuran or with xylene or methylene chloride in the presence of one of the bases indicated above, l~f~r~ly triethylamine, at -10C to 15 room ten~ ure.

Ihe compounds of the general fonn~ (V) and (Va) are known in some cases or are new and can be ~lc~d either by removal of nitrogen from the coll~l~ding carboxylic acid azides and reaction with the a~ liate alcohols or by reaction of the corresponding amines with chloroformic acid esters, ~ r~l~ly benzyl chlor~fcll,~l~, 20 in one of the abovementioned solvents, ~lcr. .~bly tetrahydrofuran or dioxane, in a telll~;l~ure range from -10C to 200C, plcrel~bly from 0C to 150C.

The compounds of the general formula (VII) are in the main new and can be prepared as described above.

Ihe compounds of the general formula (Ia) are new and can be prepared, for exarnple, 25 as described under [A], [B], [D] or [E].

Le A 30 524 . - 33 -215~02~

- The compounds of the general form~ e (Ib), (Ic), (Id), (Ie) and (If) are new and can be ~l~aled as described above.

Ihe compounds of the general formula (VI) are in the main known or are new and can be ~Ic~ed, for cxall~le, starting from the free amines (Ia), by reacting either with the 5 acetonide of glyceraldehyde in methanol and in the ~lcsel~ce of sodium acetate/sodium cyanoborohydride or of sodium borohydride and m~th~nol in a te~ re range from -20C to +40C, plcr~ly from -10C to 20C, and at normal pressure.

Ihe introduction of the halogen atom Y (compounds of the general formula (If)) is carried out in the case of broll~ille and iodine either using el~m~nt~l bromine or iodine, 10 or in the case of bromine or iodine in the ~ s~lce of a silver salt, in one of the abovementioned solvents, p,~f~l~bly methylene chloride, ~c~lo~ ile or chlolvfc,~ , in a lel~ re range from -30C to +60C, ~,~,f. l~bly from 0C to +30C, and at normal pressure.

Suitable silver salts are, for example, silver tetrafluoroborate, silver 15 trifluor ~mPth~nesulphonate or silver trifluoro~cet~te Ihe compound of the formula (~) is covered by the scope of mP~ning of the publication, but as a species is new and can be plc~cd, starting from the known 3-methoxy-substituted phenyl-2-oxazolidinone, by carrying out an iodination with I2 in the presence of Ag(OAc) in ~cetonitrile and chloroform and then liberating the 20 hydroxyl function using BBr3 in dichloromethane.

Process [~ is carried out in one of the abovementioned solvents, preferably dimethylro""~nide, in a tem~erature range from 40C to 80C, p,~ rel~bly 60C, and at normal pressure.

The minimllrn inhibitory concentrations (MIC) were det~mined by serial dilution 25 methods on Iso-Sensitest agar (Oxoid). For each test substance, a number of agar plates were prepared which contained a decreasing concentration of the active compound on double dilution in each case. The agar plates were inoculated with a multipoint Le A 30 524 - 34 -inoculator (Denley). For inoculation, overnight cultures of the bacilli were used which were previously diluted such that each inoculation point contained about 104 colony-forming particles. Ihe inoculated agar plates were incllb~t~ at 37C, and the bacterial growth was read off after about 20 hours. lhe M~C value (~lg/ml) indicates the lowest S active cornpound c~ n~nlration at which no growth could be detect~d using the naked eye.

Ihe M~C values were det~nined in BH medium with the aid of the microdilution method. Each test substance was dissolved in the nutrient medium. A concentration series of the test sllbstances was ~ )al~l in the microtitre plates by serial dilution. For 10 inoculation, overnight cultures of the bacilli were used which had previously been diluted 1:250 in the nutrient m~lillm 100 ,ul each of inoall~ti~n solution were added to 100 ~11 of the diluted, active col~ d~ nutrient solutions.
The rnicrotiter plates were ;I~ b~1~1 at 37C and read off after about 20 hours. Ihe MlC value (,ug/ml) indicates the lowest active compound cc,llc~ lion at which no15 growth could be detecte~l Le A 30 524 - 35 -MlC values (~yml) ~ Ex. No. S~h 133 S~h 48N S~pb 25701 Sb~h 91rV E coli Neunn mn kDebs. 57 USA P~dnL Bonn o 9 4 4 2 2 ~64 >64 >64 16 1 1 1 0.5 >64 >64 >64 27 16 16 16 8 >64 >64 >64 o 215402~

Compounds of the general f~rm~ e a), (Ia), ab), ac), ad), ae) and afl according to the invention have a broad antibacterial spectrum combined with low tox1City, especially against grarn-positive bacteria as well as mycobacteria, coIynPb~ct~ria, Haemophilus influenzae and anaerobic micro-or~ i"-c. These ~ulu~llies make S possible their use as chemotherapeutic active compounds in hum~n and v~leli-l~y medicine.

The compounds according to the invention are active against a broad spectmm of micro-or~ni~m~ th their aid, gram-positive b~ct~i~ and b~ct~ri~-like micro-or~ni~m~, such as mycoplasma, can be controlled and the ~ s produced by these 10 pathogens can be prevented, ameliorated and/or cured.

The compounds according to the invention are particularly active against b~ct~ and bacteria-like micro-o~ ."~. They are l~lc~cr~n~ particularly well suited for theprophylaxis and ~llPm~lh~.~y of local and systemic infections in human and V~ ~ymedicine which are caused by such pathogens.

15 The present invention includes ph~rm~celltical p~ lions which, in addition to non-toxic, inert ph~rm~ce~ltically suitable excipients, contain one or more compounds according to the invention or which consist of one or more active compounds according to the invention, and processes for the production of these plcl)al~lions.

The active compound or compounds can optionally also be present in one or more of 20 the excipients indicated above in micro-encapsulated form.

The therapeutically active compounds should be present in the abovementioned ph~ Rutical pl~ions in a concentration of about 0.1 to 99.5, pl~r~lal)ly of about 0.5 to 95, % by weight of the total mixture.

In addition to the compounds according to the invention, the abovementioned 25 pharm~Rl-tical p~ lions can also contain further ph~ R.lltical active compounds.

In general, it has proven advantageous both in human and in veterinary medicine to Le A 30 524 - 37 -.

administer tlle active compound or compounds according to the Inverltion in total amoullts of about 0.5 to 500, preferahly 5 to 100, my/kg of body weight every 24 hours, if appropriate in the form of several individllal doses, to achieve the desired results. An individual dose contains the active compound or compoullds according to the invention preferahly in amounts from about 1 to 80, in particular 3 to 30, mg/kg of body W~ i gh1 .

1~ The new compouncls can be combined in tlle customary con-centxations and ureuarat;ions together Witll the feed or lactamase inhibitc\rs, e.g. with penicillins which are par-ticularly resistant to penicillinase and clavu]anic acid.
comhinatiol-l of this ty~e would be e.g. that with oxacillin or dicloxacillin.

For the purpose of wideniny -the spectrum of actioll and in order to a(llieve an increase in actiol-l, the compounds according to the invelltiorl can also be combined with other arltihiotics.

The inventiorl also extends to a commercial package containing a compound of tlle invention, together with instructions for lts use as an antibacterial agent.

- - - 215402~
Anpendix to the experimental section List of the eluent mixtures used for cLAull~lo~hy:

Dichloromloth~n~: m~th~nol II Toluene: ethyl acetate S III Acetonitrile: water IV Ethyl acetate V Petroleum ether: ethyl acetate Vl Dichlc,lu",r~hil.,e: ethanol VII Toluene: ethanol o vm Toluene: ~c~cn~

Abbreviations:

Z Benzyloxycarbonyl Boc tert-Butylox~c~l~"~l DMF Dimethylrc-""~.,.;de 15 Ph Phenyl Me Methyl THF Tetrahydrofi~ran CDI Carbonyldiimidazole DCE Dichloroethane Le A 30 524 --39 -215402~

S~ffir~ compolmds e I

5-Benzyloxycarbonylamino-benzo[b]thiophene H !3 ~3~N~O

5 44 ml (294 mmol) of benzyl chlo~f()~ are slowly added dropwise to a solution of 40 g (268 mmol) of 5-amino-b~zo[b]thiophene (Synthetic C~ mmlmir~tions, pp.959-964 (1991)) in 410 ml of T~DF, 530 ml of water and 530 ml of satd. NaHCO3solution. Ihe mixture is allowed to come to RT overnight with stirring, the T~ is evaporated in vacuo, and the aqueous phase is extracted 3 times with CH2Cl2, dried 10 with Na2SO4 and collc~ led. Ihe residue is taken up in a little CH2Cl2, and the solution is diluted with ether (about 200 ml) and mixed slowly with stirnng with 1 l of low-boiling petroleum ether. Ihe plcci~ d solid is filtered offwith suction and dried at 50C overnight.
Yield: 58.10 g (76.5%) Mp.: 110C
H-NMR (D6-DMSO, TMS): 9.88 (s, lH); 8.09 (d, J = 1 ~ lH); 7.9 (d, J = 9 1~; 7.73 (d, J = 6 H~ lH); 7.3 - 7.5 (m, 7H~; 5.2 (s,2H~.

The compounds shown in Table I are ple~cd in analogy to the procedure of ExampleI:

LeA30 524 -40 -2lsg o29 - Table I:
- H

R24 ~~

E~ No. R~4 Yield M~: R, Elue~ mix~re /3 (o~ (~) II CH3 98 111 0.5 (1/1) V

III ~ 55 0.84 (100/5) I

IV HOOC~ 98 205 wi~ 0.3 (100/5) I

H3C~ 82 108 C 0.68 (5/1) V

Le A 30 524 - 41 -Ekample VI

tert-Butyl 5-ben~yloxycarbonylamino-benzo[b]thiophene-2 carboxylate OOC ~ NHZ

A solution of 25 g (76.4 mmol) of the compound from Example IV, 16.5 g (229 mmol) of t-BuOH and 1.67 g (15.27 mmol) of 4-dimethylaminopyridine in 150 ml of CH2Cl2is cooled to -10C, treated with 16.10 g (84 mmol) of 1-ethyl-3-[3-(dimethylamino)propyl]car~odiimide hydr~hkni~le and brought to RT overnight withstilring The solution is diluted with 200 ml of CH2Cl2, washed once each with dilute H2SO4, satd NaHCO3 and satd. NaCl solution, dried and c~n~ d Ihe crude product thus obtained is ~ ~lographed on silica gel (PE/EA 1:1).
Yield: 7.5 g (26%) ~H-NMR (D6-DMSO, TMS): 10.0 (s, lH); 8.2 (d, J = 2 Hz, lH); 8.06 (s,lH); 7.93 (d, J = 8 Hz, lH); 7.58 (dd, J = 8 ~, J = 2 Hz, lH); 7.32 - 7.5 (m, 5~; 5.20 (s, 2H);
1.55 (s, 9H).

F~m~e VII

(5S}(3-Methoxy4-iodophenyl)-5-acetyl~minnm~tl~yl-2-oxazolidinone H3CO ~ N O

254 mg (1.0 mmol) of iodine in 25 ml of dichloromethane are added to a suspension of 264 mg (1.0 mmol) of(5S)-(3-methoxyphenyl}5-acetylaminomethyl-2-oxazolidinone LeA30 524 -42-- - 215~024 - (J. Med. Chem. 35 (1992) 1156-1165), 250 mg (1.5 mmol) of silver acetate, 30 ml of dichlolo",~h~n~ and 20 ml of ~cetonitrile. After 16 h, the mixture is treated with water and dichlor~m~qth~n~, the aqueous phase is extracted with dichloromethane, the combined organic phases are washed with satd. NaCI solution and dried over MgSO45 and the solvents are stripped off in vacuo.
Yield: 370 mg (95/O) ~H-NMR (D~CDCl3, TMS): 7.70 (d, 1H), 7.42 (d, 1~, 6.60 (dd, lH), 6.25 (bt, 1H),

4.78 (m, lH), 4.05 (7, lH), 3.89 (s, 3H), 3.50-3.85 (m, 3H), 2.00 (s, 3H).

le VII~

10 (SSH3-Hydroxy~iodophenyl~5-acetylaminomethyl-2-oxazolidinone H~ N O

~f o 77 ml (77 mmol) of a 1.0 M BBr3 solution in dichloro,n~ Ihi~ are added dropwise at -78C to a solution of 10.0 g (25.6 mmol) of the compound from Exarnple VII in 100 ml of dichlorom~lh~ne. lhe mixture is allowed to come to room temp=~, and 15 is stirred for a further 3 h, cooled to -10C and treated with water. The mi~ure is treated with ethyl acetate, and the precipitate which is deposited is filtered off with suction and dried.
Yield: 8.0 g (83%) Rf= 0.34 (toluene/acetone 1:1) M p.: 227-230C
MS (DCI/NH3): 377 (M+ + H) [a]2=-18.76 (DMSO, c=1.0) 'H-NMR (D6-DMSO, TMS): 10.5 (bs, lH), 8.25 (bt, lH), 7.62 (d, lH), 7.30 (d, lH~,6.68 (dd, lH), 4.70 (m, lH), 4.05 (t, lH), 3.70 (dd, lH), 3.40 (t, lH), 1.80 (s, 3H).

LeA30524 -43 -Ple~on F:Y~es (SR)-3 -[5-Benzo~b]-thiophenyl]-S-hydroxyrnethyl-oAazolidine-2-one 56.55 g aoo mmol) of the compound from Example I are dissolved in 600 ml of THF,treated with 10 mg of 1,10-rh~ ll,.oline hydrate and cooled to -70C. About 80 ml of 2.5 N n-butyllitl~ rn solution in hexane are then slowly added dropwise until the colour ~h~n~ to red. 28 ml (200 mmol) of (R~glycidyl butyrate are then added dropwiæ. The mixture is allowed to come to RT, treated with saturated ~.",.,. ,~chloride solution, the organic phase is se~led offand the aqueous phase is ~A~ ed twice with ethyl acetate. The ~ ed organic phaæs are dried (Na2SO4) and concentrated. The residue is stirred in 1 l of ether, filtered off with suction and dried.
Yield: 43.4 g (87.05%) Mp.: 141C
lS [a]2=-58.9 (DMSO, c= 1.0) MS (EI): 249 (M+, 100%) ~H-NMR (D6-DMSO, TMS): 7.95 - 8.07 (m, 2H); 7.8 (d, J = S Hz, lH); 7.7 (dd, J =
10 Hz, J = 2 Hz, lH); 7.45 (d, J = 5 Hz, lH); 5.23 (t, J = 6 Hz, 1H); 4.67 - 4.8 (m, lH);4.15(t,J=9Hz, 1H);3.92(dd,J=9Hz,J=5Hz, lH);3.52-3.78(m,2H).

Le A 30 524 - 44 -215402~

o o ~ o o o ~~D ~ O ~D
- .~
~o ~
o C~

.

O
~s =(o~

;~I I
O
~O~

LeA30 524 -45 -21~4 02 ample 6 (5R~3-[5-Benzo[b]-thiophenyl]-S-mPth~n~s-llphonylmethyl-oxazolidine-2-one ~ \~ OSO2CH,3 A solution of 42.4 g (170 mmol) of the compound from Exarnple 1 and S9 ml (425 mmol) of triethylamine in 2 1 of THF is cooled to -10C and slowly treated with 29 ml (374 mmol) of ,~ 1rh(myl chloride. The mixture is stirred at -10C for 2 h, solid is filtered offwith suction and the residue is washed 3 to 4 times with CH2Cl2.
Aflcer the solvent mi~ure has been stripped off on a rotary e~ l(,l, the residue is dissolved in CH2Ck and washed once each with satd. NaHCO3, dil. H2SO4 and dil.
NaCl solution. After drying (Na2SO4) and con~ g, the product is obtained sufficiently pure for further reactions.
Yield: 55.6 g (100%) E~ample 7 (SR~3-[S-Benzo[b]thiophenyl]-S-azidomethyl-oxazolidin-2-one N~N3 55 g (168 mmol) of the compound from Exarnple 6 are dissolved in 390 ml of DMF
and treated with 12 g (185 mmol) of sodiurn azide. The reaction mixture thus obtained is stirred at 70C for 14 h. It is allowed to cool to RT and is poured into 3 l of ice-water. The precipitated solid is filtered off with suction, washed with water and Le A 30 524 - 46 -215402~
`
petroleum ether and dried in air.
Yield: 43 g (93/O) Mp.: 108C
[a]2=-144.7 (DMSO, c= 1.0) MS: 275 (M++l, 100%) ~H-NMR (D6-DMSO, T~): 7.98 - 8.08 (m, 2H); 7.8 (d, J = 5 Hz, lH); 7.68 (dd, J =
10 Hz, J = 2 Hz, lH); 7.45 (d, J = S Hz, lH); 4.85 - S.0 (m, lH); 4.21 (t, J = 9 Hz, lH~; 3.86 (dd, J = 9 Hz, J = S Hz, lH); 3.75 (t, J = 6 Hz, 2~.

FY~le 8 (SR~3-[S-Benzo[b]-thiophenyl]-S-~minom~thyl-oxazolidin-2~ne hydrochloride ~ \~ NH2 x HCI

43 g (157 mmol) of the compound from Example 7 are dissolved in 110 ml of ethylene glycol dimethyl ether and the solution is heated to 50C. 22.2 ml (188 mmol) of trimethyl phosphite are slowly added dropwise (evolution of gas), and the mixture is lS heated to 90C after addition is complete and stirred at 90C for S h. 30 ml(180 mrnol) of 6 N HCI are then added dropwise and the mixture is again stirred at 90C for 5 h. It is allowed to cool to RT, and the precipitate which is deposited is filtered off with suction, stirred in 1 l of ether for 1 h, filtered off with suction again and dried at 50C.
Yield: 44g (98%) Mp.: 195C
MS (DCI): 249 (M+ + 1, 100%) Le A 30 524 - 47 -2ISg~2~
- E~ca~e 9 (SS~3-[5-Benzo[b]thiophenyl]5-acetylamino-methyl-oxazolidin-2-one ~ \~NH~CH, 43 g (151 mrnol) of the compound from Example 8 are treated with 320 ml of CH2CkS and 54 ml (407 mmol) of triethylamine. The reaction solution ~us obtained is cooled to 0C with stirring and slowly treated with 16.5 ml (233 mmol) of acetyl chloride.
The mi~ure is suksequ~ntly stirred at 0C for Sh and is diluted with 400 ml of water and 300 ml of CH2Cl1. The organic phase is separated off and washed once each with dilute H2SO4, satd. NaHCO3 and satd. NaCl solution. A~er dlying (Na2SO4) and 10 conc~ ling, CU~ ~1 product is obtained which is cl~ ~ographed on silica gel (methylene chloride: mP.th~nol 100: 2).
Yield: 32.5 g (74.2%) Rf = 0.26 (CH2Cl2/CH30H = 100/5) Mp.: 160C
~H-NMR (D6-DMSO): 8.28 (t, J = 7 Hz, lH); 7.95 - 8.05 (m, 2H); 7.8 (d, J = S Hz,1H~;7.69 (dd, J = 10 Hz, J = 2 Hz, lH); 7.45 (d, J = S Hz, lH); 4.7 - 4.83(m, lH~; 4.2 (t, J = 9 Hz, lH); 3.85 (dd, J = 9 ~, J = S ~, lH); 3.45 (t, J = 6 Hz, 2H); 1.85 (s, 3H).

The compounds shown in Table 2 are prepared in analogy to the procedures of 20 Examples S to 9:

Le A 30 524 - 48 -.~

~o ~Z ~ ~ ~ ~

~ o~

0~ 0~ 0~ 0~

o=( Z

LeA30 524 -49 -- - - ' 2I5gO24 ~ æ_ ~.

~ O ~

O
0~ 0~ 0~

Le A 30 524 - 50 -21 S ~ 02~

Ekan~e 17 (5S~3-[5-(2-Bromo-benzo[b]thiophenyl)]-5-acetylamino-methyl-oxazolidin-2-one Br ~ O

S g (17.2 mmol) of the compound from Example 9 are dissolved in 55 ml of chloroform and 35 ml of ~c~lo,.il,ile and cooled to 0C. A solution of 0.88 ml (17.2 mmol) of bromine in 10 ml of chlol~f~ is then slowly added dropwise and the mi~ure is stirred at RT for 72 h. The ~ which is d~osiled is filtered offwith suction and stirred for 16 h with 100 ml of satd. NaHCO3 solution. The pleCi~ e iS
filtered off with suction, washed well with water and ether and dried at 50C.
Yield: 4.01 g (63%) Mp.: 132C
IH-NMR (D6-DMSO): 8.28 (t, J = 7 Hz, lH~; 8.1 (d, J = 10 Hz, lH); 8.07 (s, lH);
7.92 (d, J = 2 Hz, lH); 7.7 (dd, J = 10 ~, J = 2 Hz, lH); 4.72 - 4.82 (m, 1H); 4.26 (t, J = 9 Hz, lH); 3.90 (dd, J = 9 Hz, J = S Hz, 1H); 3.47 (t, J = 6 Hz, 2H); 1.83 (s, 3H).

The compounds shown in Table 3 are prepared in analogy to the procedure of Example 17:

LeA30 524 - 51 -oO ~
~ ~ ~
L~ _ O O

o _ o m L~A30 524 - 52 -(SS)-3-[S-(2-Phenyl-3-methyl-benzo[b]thiophenyl)]-5-acetyl~rnin-)m~tllyloxazolidin-2-one ~ \~NH~CH, 383 mg (lmmol) of the compound from Example 18 and 159 mg (1.3 mmol) of phenylboronic acid are dissolved in 8 ml of THF, treated with 34 mg (0.029 mmol) of Pd(P(C6Hs)3)4 and the solution is boiled under reflux for 1 h. 1.4 ml of 2 M Na2CO3 solution are added and ~e mixture is boiled under reflux for 16 h, cooled to RT and concentrated and the residue is cl~ graphed on silica gel (CH2Cl2/CH30H 100:1).Yield: 336 mg (88%) Mp.: 205C
Rf=0.22 (CH2CI2/CH30H 100/5) MS: 380 (M+, 100%) 'H-NMR (D6-DMSO, TMS): 8.28 (t, J = 7 Hz, lH); 7.98 (d, J = 10 Hz, lH); 7.88 (d, J=2Hz, lH);7.7(dd,J=2Hz~J=lOHz, 1~;7.4-7.62(m,5H);4.7-4.85(m, lH); 4.28 (t, J = 9 Hz, lH); 3.89 (dd, J = 9 Hz, J = S Hz, lH); 3.45 (t, J = 6 Hz, 2H);
2.42 (s, 3H); 1.85 (s, 3H).

The compounds shown in Table 4 are prepared in analogy to the procedure of Example 20:

Le A 30 524 - 53 -T~e 4:
O
O RZ4--N J~O
r \~ NH~ CH3 Ex. No. F~ Yield MP~ rhlc~d fnDm F~ E~uent (% of ~heo~y) (C~ E~L No. (ratio) 21 CH3 90 191 18 0.28 (100/5) I
OHC ~
r 22 o~c~ 89 122 17 0.24(100/5)1 r~

23 ~ 83 215 vnih d 17 0.24 (100/5) 1 o 24 F ~ 86 187 17 0.44 (100/5) 1 ~ 59 167n.Z. 17 0.14(100/5)1 x HCI

- 215402~

e 26 (SS)-3-~5-[(2-Bromo-1,1-dioxo-3-methyl)benzo[b]thiophenyl]}-5-acetylaminomethyloxazolidine-2-one 0// \\ ~NHIl~CH3 O O

192 mg (0.5 mmol) of the c~ oulld from Example 18 and 344 mg (1.2 rnmol) of meta-chlo~ ~ic acid are dissolved in 2.5 ml of CH2CI2 and the rnixture is stirred at RT for 48 h. Ihe batch is diluted with 20 ml of e~er and 10 ml of satd. NaHCO3 solution and the mixture is stirred at RT for 1 h. The p~ which is deposited is filtered off with suction, washed with ether and dried at 50C.
Yleld: 146 mg (71%) Rf= 0.17 (CH2Cl2/CH3OH 100/3) MP.: 243C
MS (FAB): 415 (M+, 100%) IH-NMR (D6-DMSO, TMS): 8.25 (t, J = 7 ~, lH); 8.0 (d, J = 10 Hz, lH); 7.85 (d, J= 2 Hz, lH); 7.73 (dd, J = 10 Hz, J = 2 Hz, lH); 4.75 - 4.88 (m, lH); 4.23 (t, J = 9 Hz, lH); 3.84 (dd, J = 9 Hz, J = S Hz, lH); 3.46 (t, J = 6 Hz, 2H); 2.28 (s, 3H);
1.83 (s, 3H).

The compounds shown in Table 5 are prepared in analogy to the procedure of Example 26:

Le A 30 524 - 55 -215~02~

.~

o z o ~)C=O
o~i ~//
~1 ~ \0 V~ O
,~ t Le A 30 524 - 56 -(SSH2-Hydroxymethyl-benzofuran-6-yl}S-acetylaminomethyl-2-oxæolidinone HO~ N )~
ll~ NH~ CH3 A mixture of 100 mg (0.27 mmol) of the compound from Example VIII, 55 mg (0.66 mmol) of sodium acetate, 30 mg (0.54 mmol) of ~ yl alcohol, 40 mg (0.05 mmol) of bis(triphenylrhosphino)~~ rn(II) acetate and 20 mg (0.1 mmol) of copperiodide in 2 ml of DMF is stirred at 60C for 14 h. The batch is added to ice-water and extracted with ethyl acetate, the co~ ed organic phases are dried over Na2SO4, the solvents are stripped off in vacuo and the residue is purified by ~ ography 10 (toluene/ac~to~e) and reclyst~lli7~tion.
Yleld: 40 mg (58%) Rf = 0.25 (toluene/acetone 1/1) MP.: 142-144C
MS (EI): 304 (M+) IH-~vMR (D6-DMSO, T~S): 8.25 Cbt, lH), 7.75 (s, lH), 7.57 (d, lH~, 7.40 (dd, lH), 6.70 (s, lH~,5.45 (t, lH),4.70 (n4 lH),4.55 (d, 2H),4.20 (t, lH~, 3.75 (dd, lH),3.45 (m, 2H), 1.85 (s,3H).

The compounds shown in Table 6 are prepared in analogy to the procedure of Example 28:

L~ A 30 524 - 57 -., - 215gO2~

Table 6:

DJ~N
1~, NH~CH3 Ex. No. D Yield Rf MS
(%of (Eluent (DCI, M~+H) theoIy) mi~) ratio 29 CH3 71 0.38 (Vm) 1:1 376 ~olo~

C6Hs 28 0.38 (VIII) 1:1 424 HO /\~ N ~

34 ~ 36 0.19 (VII) 1:1 438 H3C NH~O

Le A 30 524 - 58 -

Claims (20)

Claims:

1. Oxazolidinones of the general formula (I) (I) in which R1 azido, hydroxyl or a group of the formula -OR2, -O-SO2R3 or -NR4R5, wherein R2 denotes straight-chain or branched acyl having up to 8 carbon atoms or a hydroxyl protective group, R3 denotes straight-chain or branched alkyl having up to 4 carbon atoms or phenyl which is optionally substituted by a straight-chain or branched alkyl having up to 4 carbon atoms, R4 and R5 are identical or different and denote cycloalkyl having 3 to 6 carbon atoms, hydrogen, phenyl or straight-chain or branched alkyl having up to 8 carbon atoms or an amino protective group, or R4 or R5 denotes a group of the formula -CO-R6, wherein R6 denotes cycloalkyl having 3 to 6 carbon atoms, straight-chain or branched alkyl or alkoxy in each case having up to 8 carbon atoms, phenyl or hydrogen, A represents an oxygen or sulphur atom, D, E, G, L and M are identical or different and represent hydrogen, carboxyl, halogen, cyano, mercapto, formyl, trifluoromethyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio or acyl in each case having up to 6 carbon atoms, or straight-chain or branched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 5 carbon atoms or by a radical of the formula , , or by a group of the formula -NR7R8, wherein R7 and R8 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or phenyl, or together with the nitrogen atom form a 5- to 6-membered, saturated heterocycle optionally containing a further heteroatom from the series N, S

and/or O, which for its part can optionally also be substantial on a further nitrogen atom by straight-chain or branched alkyl or acyl having up to 3 carbon atoms, and/or optionally represent a group of the formula -NR7R8, wherein R7 and R8 are identical or different and have the meaning of R7 and R8 indicated above and are identical to or different from this, and/or optionally represent (C2-C8)alkenylphenyl, phenyl or a 5- or 6-membered saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N and/or O, which for their part are optionally substituted by a group of the formula -CO-NR9R10, -NR11R12, -NR13-SO2-R14, R15R16N-SO2- or-R17-S(O)a-, wherein a denotes a number 0, 1 or 2, R9 , R10, R13, R15 and R16 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl, R11 and R12 are identical or different and have the meaning of R7 and R8 indicated above and are identical to or different from this, R14 and R17 are identical or different and have the meaning of R3 indicated above and are identical to or different from this, and/or for their part are optionally substituted up to 2 times by identical or different substituents from the series consisting of carboxyl, halogen, cyano, mercapto, formyl, trifluoromethyl, nitro, phenyl, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio and acyl in each case having up to 6 carbon atoms or straight-chain orbranched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 5 carbon atoms or by a group of the formula -NR18R19, wherein R18 and R19 have the meaning of R7 and R8 indicated above and are identical to or different from this, and their salts and S-oxides.

2. Oxazolidinones according to Claim 1, wherein R1 azido, hydroxyl or a group of the formula -OR2, -OSO2R3 or -NR4R5, wherein R2 denotes straight-chain or branched acyl having up to 6 carbon atoms or benzyl, R3 denotes straight-chain or branched alkyl having up to 3 carbon atoms, phenyl or toluoyl, R4 and R5 are identical or different and denote cyclopropyl, cyclopentyl, cyclohexyl, hydrogen, phenyl or straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms, tert-butoxycarbonyl or benzyloxycarbonyl, or R4 or R5 denotes a group of the formula -CO-R6, wherein R6 denotes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms, phenyl or hydrogen, A represents an oxygen or sulphur atom, D, E, G, L and M are identical or different and represent hydrogen, carboxyl, fluorine, chlorine, bromine, iodine, cyano, mercapto, trifluoromethyl, formyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio or acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally besubstituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms, by a radical of the formula , , or by a group of the formula -NR7R8, wherein R7 and R8 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 3 carbon atoms or phenyl, or together with the nitrogen atom form a morpholinyl, pyrrolidinyl, piperazinyl or piperidyl ring, each of which is optionally substituted also via the free N function, by methyl, ethyl or acetyl, and/or optionally represent a group of the formula -NR7R8, wherein R7' and R8' have the meaning of R7 and R8 indicated above and are identical to or different from this, and/or optionally represent (C2-C4)alkenylphenyl, phenyl, pyridyl or thienyl which for their parts are optionally substituted by a group of the formula -CO-NR9R10, -NR11R12, -NR13-SO2-R14, -R15R16N-SO2- or -R17-S(O)a-, wherein a denotes a number 0, 1 or 2, R9, R10, R13, R15 and R16 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or phenyl, R11 and R12 are identical or different and have the meaning of R7 and R8 indicated above and are identical to or different from this, R14 and R17 are identical or different and have the meaning of R3 indicated above and are identical to or different from this, and/or for their part are optionally substituted up to 2 times by identical or different substituents from the series consisting of carboxyl, fluorine, chlorine, bromine, iodine, cyano, mercapto, trifluoromethyl, formyl, nitro, phenyl, straight-chain or branched alkoxy, alkoxycarbonyl, alkylthio and acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms or by a group of the formula -NR18R19, wherein R18 and R19 have the meaning of R7 and R8 indicated above and are identical to or different from this, and their salts and S-oxides.

3. Oxazolidinones according to Claim 1, wherein R1 represents azido, hydroxyl or a group of the formula -OR2, -OSO2R3 or -NR4R5, wherein R2 denotes a straight-chain or branched acyl having up to 6 carbon atoms, R3 denotes methyl, ethyl, phenyl or toluoyl, R4 and R5 are identical or different and denote cyclopropyl, cyclopentyl, cyclohexyl, hydrogen, phenyl or straight-chain or branched alkyl having up to 5 carbon atoms, or R4 or R5 denotes a group of the formula -CO-R6, wherein R6 denotes cyclopropyl, cyclopentyl, cyclohexyl or straight-chain or branched alkyl or alkoxy in each case having up to 4 carbon atoms, hydrogen or phenyl, A represents an oxygen or sulphur atom, D, E, G, L and M are identical or different and represent hydrogen, carboxyl, fluorine, chlorine, bromine, iodine, cyano, formyl, trifluoromethyl, nitro, straight-chain or branched alkoxy, alkoxycarbonyl or acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally be substituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms, by a radical of the formula , , or by a group of the formula -NR7R8, wherein R7 and R8 are identical or different and denote hydrogen or methyl, or together with the nitrogen atom form a morpholinyl, pyrrolidinyl, piperazinylor piperidyl ring, each of which is optionally substituted, also via the free N
function, by methyl, ethyl or acetyl, and/or optionally represent a group of the formula -NR7R8, wherein R7 and R8 have the meaning of R7 and R8 indicated above and are identical to or different from this, and/or optionally represent 2-phenylvinyl, phenyl, pyridyl or thienyl, which for their parts are optionally substituted by a group of the formula -CO-NR9R10 or -NR11R12, wherein R9 and R10 are identical or different and denote hydrogen or methyl, R11 and R12 are identical or different and have the meaning of R7 and R8 indicated above and are identical to or different from this, and/or for their parts are optionally substituted up to 2 times by identical or different substituents from the series consisting of carboxyl, fluorine, chlorine, bromine, iodine, cyano, formyl, trifluoromethyl, nitro, phenyl, straight-chain or branched alkoxy, alkoxycarbonyl and acyl in each case having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which for its part can optionally besubstituted by hydroxyl, by straight-chain or branched alkoxy or acyl having up to 4 carbon atoms or by a group of the formula -NR18R19, wherein R18 and R19 have the meaning of R7 and R8 indicated above and are identical to or different from this, and their salts and S-oxides.

4. Oxazolidinones according to Claim 1, in which G,L
and M represent hydrogen and the oxazolidinone radical is bonded to the phenyl ring in position 5 or 6.

5. Oxazolidinones according to Claim 1,2,3 or 4 wherein R1 represents a hydroxyl group.

6. Oxazolidinones according to Claim 1,2,3 or 4 wherein R1 represents a group of formula OSO1R3 wherein R3 is as defined in Claim 1,2 or 3.

7. Oxazolidinones according to Claim 1,2,3 or 4 wherein R1 represents an azido group.

8. Oxazolidinones according to Claim 1,2,3 or 4 wherein R1 represents an amino group.

9. Oxazolidinones according to Claim 1,2,3 or 4 wherein R1 represents a group of formula NH-CO-R6 wherein R6 is as defined in Claim 1,2 or 3.

10. Oxazolidinones according to Claim 9 wherein D or E
represents halogen or both D and E represent halogen.

11. The compound (5S)-3-[5-benzo[b]thiophenyl]-5-acetylaminomethyl-oxazolidin-2-one or a salt or S-oxide thereof.

12. The compound (5S)-3-(2-methyl-benzofuran-5-yl)-5-acetylamidinomethyl-2-oxazolidinone or a salt thereof.

13. The compound (5S)-3-(benzo[b]thiophen-5-yl)-5-acetylaminomethyl-2-oxazolidinolle-S,S-dioxide or a salt thereof .

14. A process for preparing an oxazolidinone of the general formula (I) according to Claim 1, or a salt or S-oxide thereof, which process comprises [A] reacting a compound of the formula II

( I I ) or formula (III) ( I I I ) wherein A, D, E, G, L, M are as defined in Claim 1, is reacted with an epoxide of general formula (IV) ( I V ) wherein T represents a C1-C6-acyloxy group, followed, if required, by hydrolysis to obtain a compound in which R1 is OH, or by transesterification;

[B] reacting a compound of the general formula (V) ( V ) wherein A, D, E, G, L, M are as defined in Claim 1 and V
represents a leaving group, with an epoxide of formula (IV) above, [C] reacting a compound of the general formula (Va) ( V a ) wherein A, D, E, G, L and M are as defined in Claim 1 and X
represents straight-chain or branched C1-C6 alkyl with an epoxide of formula (IV) above;
[D] cyclizing a compound of the general formula (VII) (VII) wherein A, D, E, G, L and M are as defined in Claim 1, followed, if required, by converting an obtained compound of the general formula (I) into a salt or an S-oxide thereof.

15. A process according to Claim 14 wherein reaction [A]
is carried out in the presence of lithium bromide/(C4H9)3 P(O).

16. A pharmaceutical composition which comprises an oxazolidinone of the general formula (I) according to any one of Claims 1 to 4 and 10 to 13 or A pharmaceutically ac-ceptable salt or S-oxide thereof together with a suitable diluent or carrier.

17. A process for preparing a pharmaceutical composition for combating bacteria which process comprises admixing all oxazolidinone of the general formula (I) according to any one of Claims 1 to 4 and 10 to 13 or a pharmaceutically accept-acceptable salt or S-oxide thereof with a suitable diluent or carrier.

19. Oxazolidinones of the general formula (I) according to any one of Claims 1 to 4 and 10 to 13 and pharmaceutically acceptable salts and S-oxides thereof for use as anti-bacterial agents.

19. Use of an oxazolidinone of the general formula (I) according to any one of Claims 1 to 4 and 10 to 13 or a pharmaceutically acceptable salt or S-oxide thereof as an antibacterial agent.

20. A commercial package containing, as an active pharm-aceutical ingredient an oxazolidinone of the general formula (I) according to any one of Claims 1 to 4 and 10 to 13 or a pharmaceutically acceptable salt or S-oxide thereof together with instructions for its use as an antibacterial agent.