Phenyloxazolidine having a relationship with a 4-8-membered heterocyclic rings

 

(57) Abstract:

The invention relates to new derivatives of phenyloxazolidine that have a relationship with a 4-8-membered heterocyclic rings of formula I and their pharmaceutically acceptable salts, where X represents NR1, S(O)gor Oh, R1represents H, C1-6alkyl, optionally zamesheny one or more CN or halogen, -(CH2)h-phenyl, -COR1-1, -R1-2, -CO-(CH2)h-COR1-1, -SO2- C1-6alkyl or -(CO)i-Het, R2represents H, -CO-(C1-6)alkyl or fluorine, R3and R4are the same or different and represent H or halogen, R5is1-6alkyl and C3-6cycloalkyl, optionally substituted by one or more halogen, g=0, 1, or 2, h=1 or 2, i=0 or 1, m=0, 1, 2, 3, n= 0, 1, 2, 3, provided that m and n taken together, is equal to 1, 2, 3, 4 or 5. The technical result - obtaining new derivatives of phenyloxazolidine that have a relationship with a 4-8-membered heterocyclic rings. 11 C.p. f-crystals, 2 PL.

The invention relates to new and useful N-phenyloxazolidine and their receipt, and, more particularly, to N-phenyloxazolidine in which phenyloxy is oxygen, the nitrogen and sulfur, through a carbon-carbon bond.

The compounds can be used as antimicrobial agents, effective against many pathogens of humans and animals, including gram-positive aerobic bacteria such as multidrug-resistant staphylococci and streptococci, also anaerobic organisms, such as bacteroids and clostridial species, and acid-fast organisms like Mycobacterium tuberculosis and Mycobacterium avium. The compounds are particularly useful because they are effective against newly identified organisms responsible, as it became known, for the disease of AIDS.

SOURCES OF INFORMATION

In a number of patent applications (Derwent Abstracts 61219Y/35, 67436R-B, 84475A/47) described rich heterocycle containing nitrogen, which is connected through the nitrogen atom with phenyloxazolidine radical.

In the French patent (FR2500450 A1 820827) described cyclohexanon, attached in position 3 to phenyloxazolidine.

Other reference materials, including the European patent publication N 0352781A2, U.S. patent N 5130316, U.S. patent N 5254577, U.S. patent N 4948801 and WO 9309103-A1, described fully aromatic heterocycle attached to phenyloxazolidine, whereas in the present invention, the heterocycle yavlyaetsya relates to new compounds of the formula (I)

(I)

or their pharmaceutically acceptable salts,

where X represents NR1, S(O)gor;

R1is

a) H,

b) C1-6alkyl, optionally substituted by one or more radicals HE, CN or halogen,

(C) -(CH2)h-aryl,

d) COR1-1,

e) -COOR1-2,

f) -CO-(CH2)h-COR1-1,

g) -SO2-C1-6alkyl,

h) -SO2(CH2)h-aryl or

i) -(CO)i-Het;

R1-1is

a) H,

b) C1-6alkyl, optionally substituted by one or more radicals HE, CN or halogen,

(C) -(CH2)h-aryl or

d) -(CH2)h-OR1-3;

R1-2is

a) C1-6alkyl, optionally substituted by one or more radicals HE, CN or halogen,

b) -(CH2)h-aryl or

d) -(CH2)h-OR1-3;

R1-3is

a) H,

b) C1-6-alkyl,

(C) -(CH2)h-aryl or

d)- (C1-6alkyl);

R2is

a) H,

b) C1-6-alkyl,

(C) -(CH2)h-aryl or

d) halogen;

R3and R4(same or different) represent

a) H,

C)3-12cycloalkyl,

d) C1-6alkoxy;

d is 0, 1 or 2;

h is 1, 2, 3 or 4;

i is 0 or 1;

m is 0, 1, 2, 3, 4 or 5;

n is 0, 1, 2, 3, 4 or 5;

provided that m and n taken together are equal to 1, 2, 3, 4 or 5.

More specifically the present invention relates to compounds of formula (I), where R1represents H, foradil, tianmei, methylsulphonyl, formyl, hydroxyacetic, acetyl, methoxyacetyl, benzyloxyethyl, acetoxyacetyl, dichloracetyl, methoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, 3-hydroxypropionic, 3-methoxypropyl, 4-oxopentanoic, 2-indolocarbazole, 5 - isoxazolone, 5 - nitro-2-thiazolyl, 4-oxo-2-thiazolyl or 5 - methyl-1,3,4 - thiadiazole-2-yl.

R2represents H, F or CH3;

R3and R4(same or different) are H or F; and

R5represents methyl or methyl substituted by one or more elements of F or Cl.

The present invention relates also to a method of treating microbial infections in patients by introducing the needy in this patient an effective amount of compounds of formula (I). The compound may be administered orally, parenterally or topically in the form of pharmaceutal/day.

DETAILED DESCRIPTION OF THE INVENTION

Applied to the present invention, the term "C1-6alkyl and the term "C1-12alkyl" refers to any unbranched or branched alkyl group having one to six or one to twelve carbon atoms, such as for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, n-heptyl, n-octyl and the like.

The term "C1-6alkylsulfonyl" refers to any unbranched or branched alkyl group with one to six carbon atoms connected to-SO2with the formation of such groups as, for example, methylsulphonyl, ethylsulfonyl-isopropyl sulfonyl and the like.

The term "C3-12cycloalkyl" refers to a three to twelve carbon atoms forming cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

The term "C1-4alkoxy" and the term "C1-6alkoxy" refers to any unbranched or branched group, respectively, with one to four or one to six carbon atoms connected with oxygen atom with the formation of such groups as, for example, methoxy, ethoxy, n-propoxy, ISO is, is texilac and the like.

The term "halogen" refers to fluorine, chlorine, bromine or iodine.

The term "aryl" refers to phenyl, pyridinium or naftalina fragment, which may be optionally substituted by one or more F, Cl, Br, I, CN, IT, SH,1-6alkilani, C1-6alkoxy or C1-6thioalkyl.

The term "Het" means a 5-10 membered jeroticheskie ring containing one or more atoms of oxygen, nitrogen and sulfur with the formation of such groups as, for example, pyridine, thiophene, furan, pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2 - pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4 - pyridazinyl, 3-pyrazinyl, 2-chinolin, 3-chinolin, 1-ethanolic, 3 - ethanolic, 4-ethanolic, 2-hintline, 4-hintline, 2 - honokalani, 1-phthalazine, 4-oxo-2-imidazolyl, 2-imidazolyl, 4 - imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3 - pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 4 - oxo-2-oxazolyl, 5-oxazolyl, 4,5-dihydrooxazolo, 1,2,3-axetil, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4 - oxadiazole, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3 - isothiazol, 4-isothiazol, 5-isothiazol, 2-indolyl, 3-indolyl, 3 - indazole, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, 3-pyrrolyl, 3-isopropyl, 4-isopropyl, 5-isopropyl, 1,2,3-oxadiazol-1 - oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 5-oxo - 1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazole-3-yl, 1,2,4-thiadiazole-5 - yl, 3-oxo-1,2,4-thiadiazole-5-yl, 1,3,4-thiadiazole-5-yl, 2-oxo - 1,3,4-thiadiazole-5-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1-pyrrolyl, 1-pyrazolyl, 1,2,3-triazole-1-yl, 1,2,4-triazole-1-yl, 1-tetrazolyl, 1-indolyl, 1-indazole, 2-isoindolyl, 7-oxo-2-isoindolyl, 1-purinol, 3 - isothiazole, 4-isothiazole and 5-isothiazole, 1,3,4-oxadiazole, 4 - oxo-2 - thiazolyl or 5-methyl-1,3,4-thiadiazole-2-yl, thiazolidin, 1,2,3,4-tetrazol, 1,2,4-dithiazole. Each of these fragments can be in a suitable case replaced.

The term "pharmaceutically acceptable salt" refers to salts useful for administering the compounds of the present invention, and include hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesilate, maleinate, malate, succinate, tartrate, citrate, 2 - hydroxyethylsulphonic, fumarate and the like. These salts may be in hydrated form.

In the structural image of the formula (I) dashed line in the heterocyclic ring means that this connection can be either single or double. In the unleaded version N-phenyloxazolidine of the present invention, the group X preferably represents NR1, SO2or oxygen.

Deputy R1the nitrogen atom can be introduced by methods of synthesis known to the skilled in the art from commercially available reagents.

The preferred substituent R1is H, foradil, tianmei, methylsulphonyl, formyl, hydroxyacetic, acetyl, methoxyacetyl, benzyloxyethyl, acetoxyacetyl, dichloracetyl, methoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, 3-hydroxypropionic, 3-methoxypropyl, 4-oxopentanoic, 2-indolocarbazole, 5-isoxazolone, 5-nitro-2-thiazolyl, 4-oxo-2-thiazolyl or 5 - methyl-1,3,4-thiadiazole-2-yl. The most preferred substituent R1is formyl, methoxycarbonyl or hydroxyacetic.

When the heterocyclic ring is a saturated derivative, the preferred substituent R2is hydrogen, fluorine or methyl.

Preferred substituents R3and R4independently are hydrogen or fluorine.

Preferred substituent R5is stands.

The most preferred compounds in this series receive in the form of optically pure enantiomers, with (S)- configuration in accordance with Sonim of the many methods of asymmetric synthesis. For example, the processing of intermediate compound 12 in SCHEME IN a suitable base followed by addition of (R) - glycidylether gives the corresponding oxazolidinone in optically pure form with the desired (S) - configuration at position 5 oxazolidinone rings. Although (S) - enantiomer of this series of compounds is preferred because it is pharmacologically active as an antimicrobial agent, racemic modification is also useful in this regard as pure (S) - enantiomer, with the only difference that to provide the same antimicrobial effect of racemic substances requires twice.

On the SCHEME AND shows how to obtain the compounds of formula (I) with a heterocycle containing nitrogen. As shown in the DIAGRAM AND the main intermediate compound 1 can be used to obtain derived by carrying out the reactions known to specialists in this field of technology. For example, the acylation gives 2 and 3, the subsequent removal of the protecting y 2 gives 2', alkylation gives 5 substituents, including hydroxy, nitro, halogen, aryl and sulfonyl; structure 5 also covers products that have heteroatomic core), sulfonylamine gives 6 and alkoxysilane gives 4

Enantiomers highly enriched, shown in SCHEME C. the First stage includes the processing patterns 7 ethylcinnamate in the presence of a suitable base such as sodium hydride or potassium carbonate, at a temperature in the range from -10 to 100oC. Subsequent alkylation using alkylhalogenide or tozilaty gives nitrile derivative 8. Nitrile derivative 8 then restore by catalytic hydrogenation in the presence of a suitable catalyst such as palladium on carbon, Raney Nickel W-2 or platinum on carbon, in a suitable solvent, such as ethyl acetate, THF, methanol or combinations thereof, to obtain aminoaniline 9, which after treatment with a suitable base, preferably methyl or ethyl Grignard reagent gives lactam 10. Recovery of lactam 10 using a suitable reducing agent such as LAH (LAG, sociallyengaged) or borane, gives azetidin 11, which when interacting with benzylchloride at a temperature in the range from -10 to 10oC gives the corresponding benzylcarbamoyl derivative 12. Processing benzylcarbamoyl 12 n-butyllithium in a suitable solvent, such as THF, at temperatures ranging from -78 to -40oC followed by the addition pogashenie form in position 5 oxazolidinone rings. As shown in the DIAGRAM, the connection 13 can be converted to the corresponding alkyl - or arylsulfonate 14 by treatment with alkyl - or arylsulfonate in the presence of triethylamine or pyridine (where R' represents a C1-4alkyl or unsubstituted or substituted phenyl). Then the obtained sulfonate 14 is treated with alkali metal azide such as sodium azide or potassium, in an aprotic dipolar solvent such as DMF or N-methylpyrrolidinone (NMP, N), with optional catalysis torus, such as 18-crown-6 at a temperature in the range from 50 to 90oC, resulting in a gain azide derivatives. Azide derivatives can be recovered in the appropriate amine 15 by hydrogenation in the presence of palladium, platinum or Nickel catalyst in a suitable solvent, such as ethyl acetate, THF or methanol. In accordance with another variant Amin 15 can be obtained by treatment of compound 14 with a suitable solvent, such as methanol and/or THF, which is saturated with ammonia, and heating the mixture to 100oC in hermetically sealed tube. The reaction runs for hours, for example 40-70 hours. Then Amin 15 acelerou the acid chloride or acid anhydride in the presence of a base, Tana 16. Finally, catalytic hydrogenation of compound 16 in the presence of a catalyst based on a noble metal, such as palladium on carbon or palladium hydroxide on carbon, gives azetidin 17. Azetidin 17 can be used to obtain derivatives is shown in SCHEME A.

The following compounds of formula (I) having a 4-membered heterocycle containing nitrogen, for example, is obtained directly by the methods shown in SCHEME a and SCHEME B:

(S)-N-[[3-[3-fluoro-4- [1-(carbobenzoxy)- (3-methyl)-3-azetidinol]phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [3 - methyl-3-azetidinol)phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(carboxymethyl)-3- (3 - methyl)-azetidine]phenyl] -2-oxo-5-oxazolidinyl) methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(methoxyacetyl)-3- (3-methyl) -azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(formyl) -3-(3-methyl)-azetidine] phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(dichloroacetyl)-3- (3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(3-methoxypropyl)-3- (3-methyl)azetidine]phenyl] -2-oxo-5 - oxazolidinyl]methyl]-ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(3-hydroxypropyl)-3- (3-l)-azetidine]phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-acetyl-3-(3-methyl) azetidine]- phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(2-foradil)-3- (3-methyl)- azetidine] phenyl]- 2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(lanmeter)-3-(3-methyl) -azetidine] phenyl] - 2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(5-nitro-2-thiazolyl)-3- (3-methyl)azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(methanesulfonyl)-3- (3-methyl)-azetidine] phenyl] -2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(benzyloxyethyl)-3- (3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(hydroxyacetic)-3- (3-methyl)-azetidine] phenyl)-2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide.

The SCHEME shows a second method of obtaining from the intermediate connection 1 connection 4-membered heterocycle containing nitrogen, in which R2represents H, in the form of highly-enriched enantiomers. The first stage includes engagement structure 18 with the protected aniline 19 in the presence of a suitable base, such as second-utility, in a suitable solvent, such as THF, at temperatures ranging from -40 to -78oC, resulting in the / establishment, which upon further interaction with 25-100oC network connection 22. Processing connection 22 excess triethylsilane and triperoxonane acid in a suitable solvent, such as methylene chloride, at a temperature in the range from 10 to 40oC gives compound 23. The remaining stages of the synthesis, leading to the patterns 17, similar to those shown in SCHEME C.

The following compounds of formula (I) having a 4-membered heterocycle containing nitrogen, for example, is obtained directly by the methods shown in SCHEME a and SCHEME WITH:

(S)-N-[[3-[3-fluoro-4- [1-(carbobenzoxy)- 3-azetidinol] -phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [3-azetidinol]phenyl]-2 - oxo-5 - oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- (1-(carboxymethyl)-3-azetidinol] -phenyl] -2-oxo - 5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(formyl)-3-azetidinol] phenyl] -2-oxo-5 - oxazolidinyl] methyl] ndimethylacetamide.

SCHEME D illustrates the method of obtaining of intermediate compound 1, compounds having a 5-membered heterocycle containing nitrogen. As shown in SCHEME D, the first stage is to implement the interaction vinyltrimethylsilane 24 (commercially available) and compound 25. Compound 25 can be obtained in accordance with methods, opiconsivia 26. The reaction is carried out at high temperature for several hours, for example, by heating under reflux for 5-8 hours. Then the connection 26 is treated with a solution of N-benzyl-N- (methoxymethyl)trimethylsilylmethylamine (obtained by known literature methods from commercially available material) and triperoxonane acid in a suitable solvent to obtain compound 27. The reaction is carried out for several hours, for example, 8-17 hours. Then remove the N-benzyl group of compound 27 by catalytic hydrogenation in the presence of a catalyst based on a noble metal, such as palladium on carbon or palladium hydroxide on carbon, with a connection 26. The connection 28 can be used to obtain derivatives is shown in SCHEME A. in a Similar way with minor changes, but with substitution patterns 24 other derivatives vinyltrimethylsilane can be obtained, as shown in example 80, other heterocyclic derivatives connection 26.

SCHEME E shows an alternative way to obtain the intermediate compound 1, compounds having a 5-membered heterocycle containing nitrogen. As shown in SCHEME E, the nucleophilic aromatic the walking solvent, such as THF, at a temperature in the range from -100 to 60oC. Connection 29 easy alkylate by carrying out the reaction, known to experts in the art, to obtain the nitrile 30. Catalytic, reconnecting 30 in the presence of a catalyst based on palladium, platinum or Nickel in a suitable solvent, such as methanol, converts and nitro, and nitrile in amines with concomitant intramolecular cyclization, resulting in a gain lactam 31. Then the covenants 31 decarboxylase getting connection 32, which when restoring a suitable reducing agent, such as sociallyengaged or borane in a suitable solvent, such as THF or ether gives compound 33. The remaining stages of the synthesis, leading to the structure 34, similar to those shown in SCHEME C.

The following compounds of formula (I) having a 5-membered heterocycle containing nitrogen, for example, is obtained directly by the methods shown in SCHEME A, SCHEME D SCHEME E:

(S)-N-[[3-[3-fluoro-4- [1-(hydroxyacetic)-3-pyrrolidinyl] phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- [1-(formyl)-3-pyrrolidinyl] phenyl]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide;

(S)-3-[4-[5- [(acetylamino)met the she method, shown in SCHEME D, to obtain compound 26 with minor changes, but with substitution patterns 24 6-(tributylstannyl)-3,4-dihydro-2H - dihydropyrano receive the following connection:

(S)-N-[[3-[3-fluoro-4- (3,4-dihydro-2H-Piran-6-yl) phenyl] -2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide.

SCHEME F illustrates a method of obtaining compounds of formula (I) having a 5-membered heterocycle containing a sulfur atom, an oxygen atom, a sulfonic group or sulfoxide group, where R3or R4represents halogen, in the form of highly-enriched enantiomers. As shown in SCHEME F, the structure 35 (where X represents O or S) is subjected to interaction with the protected aniline 19 in the presence of a suitable base, such as second-utility, in a suitable solvent, such as THF, at temperatures ranging from -40 to -78oC connection 36. Interaction of compound 36 with benzylchloride when 0-25oC gives compound 37. Subsequent reaction of elimination, known to experts in the art, gives the regioisomers 38 and 39 in the form of a mixture. A common technique shown in the DIAGRAM, network connections 40 and 41 in the form of a mixture. When X represents S, the sulfur group can be oxidized is m as a mixture of water and acetone, or by NaIO4in a suitable solvent such as a mixture of water and methanol, to obtain the corresponding sulfones and sulfoxidov respectively. Optionally, the double bond in the heterocyclic ring can be restored by catalytic hydrogenation in the presence of a suitable catalyst and a suitable solvent. In addition, in the case when X is O, SO or SO2the mixture of regioisomers 40 and 41 can be separated by chromatography, as shown in examples 68 and 69.

The following compounds of formula (I) having a 5-membered heterocycle containing a sulfur atom, an oxygen atom, a sulfonic group or sulfoxide group, for example, is obtained directly by the method shown in SCHEME F:

(S)-(-)-N-([3- [3-fluoro-4-(dehydration-3-yl) phenyl]-2-oxo-5 - oxazolidinyl] methyl] ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4- (2,5-dihydro-1-oxido-3-thienyl) - phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4- (4,5-dihydro-1-oxido-3-thienyl) -phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[(3-[3-fluoro-4- (2,5-dihydro-1,1-dioxido-3-thienyl) phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4- (4,5-dihydro-1,1-dioxido-3-thienyl) phenyl]-2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide.

3or R4represents hydrogen. As shown in SCHEME G, the first stage involves the condensation of the structures 42 and 43 (where X represents O, S or N) to obtain compound 44. When X represents a nitrogen atom, the amino group must be protected with a suitable protecting group, such as carbobenzoxy (CBz). The protective group, although not necessarily, removed after synthesis with the formation of compounds 46 or 47 (where X represents NH), which can be used to obtain derivatives is shown in SCHEME A. the Interaction 42 43 carried out in a suitable solvent, such as THF, at a suitable temperature ranging from -78 to -40oC in the presence of a lithium base such as n-utillity. Subsequent reaction of elimination, well-known specialists in the field of technology, network connection 45. The remaining stages of the synthesis, leading to the connection 46, similar to those shown in SCHEME C. optionally a double bond in the heterocyclic ring may be recovered by obtaining compound 47 by catalytic hydrogenation, and when X represents a sulfur atom, the sulfur group can be oxidized to receive the persons producing compounds having a 6-membered heterocycle where the substituents R3and/or R4represent halogen. As shown in SCHEME H, the structure 48 (X represents O, S or NR, where R represents a suitable protective group) is subjected to interaction with the protected aniline 19 in the presence of a suitable base, such as second-utility, in a suitable solvent, such as THF, at temperatures ranging from -40 to -78oC followed by the addition of zinc chloride and a suitable catalyst, such as tetrakis(triphenylphosphine) palladium, and continuing the reaction by heating under reflux, resulting in a receive connection 49. When X represents a nitrogen compound 49 can be recovered at this point and then to the saturated derivatives or allerban by carrying out the reaction, well-known specialists in the field of technology, with the receiving structure 50. The remaining stages of the synthesis, leading to the connection 51, similar to those shown in SCHEME C. In the case when X is a sulfur atom, a sulfur group structure 51 can be oxidized to the corresponding sulfones and sulfoxidov, as described above. In addition, when X is O, NR or SO2structure 51 mo is a catalyst and a suitable solvent to obtain the saturated derivative 52. As mentioned above, when X represents a nitrogen atom, the amino group in the process of obtaining protects a suitable protecting group. In this case, a suitable protective group is 1,1-dimethylthiocarbamate (BOC). After synthesis, the protective group is removed. The compound obtained can be used to obtain derivatives is shown in SCHEME A.

The following compounds of formula (I) having a 6-membered heterocycle containing a nitrogen atom, a sulfur atom, an oxygen atom, a sulfonic group or sulfoxide group, for example, is obtained directly by the methods shown in the DIAGRAM AND the DIAGRAM G DIAGRAM H:

(S)-(-)-4- [4-[5-[(acetylamino) methyl]-2-oxo-3-oxazolidinyl] phenyl]-3,6-dihydro-1(2H)- pyridineboronic acid fenilmetilovy ether;

(S)-(-)-N-[[2 - oxo-3- [4-(4-piperidinyl)phenyl]-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-[(benzyloxy) acetyl] -4 - piperidinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(hydroxyacetic)-4-piperidinyl]- phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N- [[3-[4-[1- [(benzyloxy)acetyl]-4-piperidinyl]-3-forfinal]- 2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1- (hydroxyacetic)-4 - piperidinyl] -3-forfinal]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide;>/BR>(S)-(-)-N-[[3-[4-[1- (hydroxyacetic)-4-piperidinyl] - 3,5-differenl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(indole-2 - carbonyl)-4 - piperidinyl]-3-forfinal]- 2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(isoxazol-5-carbonyl) -4-piperidinyl]-3 - forfinal]-2-oxo - 5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N-[[3- [4- [1-(methylsulphonyl)-4 - piperidinyl]- 3-forfinal]-2-oxo-5 - oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-4-[4- [5-[(acetylamino)methyl]- 2-oxo-3 - oxazolidinyl]-2-forfinal]-1 - piperidinecarboxylic acid methyl ester;

(S)-(-)-N-[[3- [4-[1-(lanmeter)-4 - piperidinyl] - 3-forfinal]-2 - oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1- (2-foradil)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4 -[1-(formyl)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-4-[4-[5- [[(2,2-dichloroacetyl) amino] methyl]-2-oxo-3-oxazolidinyl] -2-forfinal] -1 - piperidinecarboxylic acid 1,1-dimethylethylene ether;

(S)-(-)-2,2-dichloro-N- [[2-oxo-3-[3-fluoro-4- (4-piperidinyl) phenyl]-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-2,2-dichloro-N- [[2-oxo-3- [3-fluoro-4-[1-[(acetoxy) acetyl]-4 - piperidinyl] phenyl]-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-2,2-dichloro-N- [[2-oxo-3-[3-fluoro-4- [1-(hydroxypiperidine] phenyl]-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-(3,6 -dihydro-2H-Piran-4-yl) -3-forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N-[[3-[4- [tetrahydro-2H-Piran-4-yl] -3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal] -2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3- [3-fluoro-4- (tetrahydro-2H-thiopyran-4 - yl)-phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide S,S - dioxide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-Piran-4-yl) phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-[tetrahydro-2H-Piran-4-yl] phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)- N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide S-oxide;

(S)-(-)-N-[[3- [4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide S-oxide;

(S)-(-)-N-[[3- [4-(tetrahydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3- [4-[1-(4-oxo-2-thiazolyl)- 4-piperidinyl]-3-forfinal] --oxo-5-oxazolidinyl] methyl]- ndimethylacetamide.

SCHEME 1 shows a method of obtaining from the intermediate connection 1 connection with a partially saturated 6-membered heterocycle containing nitrogen, in the form of highly-enriched enantiomers. As shown in figure 1, the first stage is to implement the interaction between the structure 53 and structure 54 with obtaining compounds 55 and 56. Triflate group structure 53 may be located on both sides of the double bond, while both groups are easily obtained from the corresponding commercially available ketones. Structure 54 can be obtained by methods described in PCT/US92/08267 and PCT/US93/09589. The reaction proceeds for a few days, for example 1 to 5 days in the presence of a suitable catalyst, such as Tris(dibenzylideneacetone)dipalladium(0). Aminosidine group connection 55 is removed by treatment with attributively and aminosidine connection group 56 - processing or triperoxonane acid or attributively with obtaining the corresponding compounds 57 and 58. Compounds 57 and 58 can be used to obtain derivatives is shown in SCHEME A.

Following the above General method with minor changes but with the replacement of the 6-membered ring structure 53 on 7 - or 8-membered ring, can Policia obtaining additionally illustrated in the examples 75-79.

The methods shown in SCHEME a and SCHEME I immediately get, for example, the following compounds of formula (I):

(S)-(-)-N-[[3- [4-[1-(4-oxo-2-thiazolyl)-3,6 - dihydro-2H-pyridine-5-yl] -3-forfinal]-2-oxo - 5-oxazolidinyl] methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4- [1-(5-methyl-1,3,4-thiadiazole-2-yl) -3,6-dihydro-2H-pyridine-4-yl] -3-forfinal]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3- [4-(3,6-dihydro-2H-pyridine-4-yl] -3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N- [[2-oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl]-3,6-dihydro-2H - pyridine-4-yl]phenyl] -5-oxazolidinyl] methyl]-ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(hydroxyacetic) -3,6-dihydro - 2H-pyridine-4-yl]-3-forfinal] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4- [1-(formyl)-3,6-dihydro-2H - pyridine-4-yl]-3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-4-[4- [5-[(acetylamino) methyl] -2-oxo - 3-oxazolidinyl] -2-forfinal]-3,6-dihydro-1 (2H)-pyridineboronic acid methyl ester;

(S)-(-)-N- [[2-oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl) -phenyl] - 5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N- [[2-oxo-3-[4- [1-[(acetoxy) acetyl]-3,6-dihydro-2H - pyridine-4-yl] phenyl]-5 - oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N- [[3-[4-[1- (hydroxyacetic)-3,6-dihydro - 2H-pyridine-4-yl] phenyl]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide;
(acetylamino) methyl] -2-oxo-3-oxazolidinyl] phenyl]-3,6-dihydro - 1(2H)-pyridineboronic acid methyl ester;

(S)-N-[[2-oxo-3- [3-fluoro-4-[1- [(acetoxy)acetyl] -5,6-dihydro-2H-pyridine-3-yl]phenyl]-5 - oxazolidinyl]methyl]-ndimethylacetamide;

(S)-N-[[3-[4-[1- (hydroxyacetic)-5,6 - dihydro-2H-pyridine-3-yl] -3-forfinal]-2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[2-oxo-3-[3 - fluoro-4- [1-[(acetoxy)acetyl]-2,3,4,7-tetrahydro - 1H-azepin - 5-yl] phenyl]-5-oxazolidinyl]- methyl] ndimethylacetamide;

(S)-(-)-N- [[3-[4-[1-(hydroxyacetic) -2,3,4,7-tetrahydro-1H-azepin - 5-yl] -3-forfinal] -2-oxo-5-oxazolidinyl] -methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3- [3-fluoro-4-[1-[(acetoxy)acetyl]-2,3,6,7 - tetrahydro-1H-azepin-4-yl] phenyl]-5-oxazolidinyl]- methyl] ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(hydroxyacetic)-2,3,6,7-tetrahydro - 1H-azepin-4-yl]-3-forfinal] -2-oxo-5 - oxazolidinyl]-methyl] ndimethylacetamide;

(5S)-(-)-N-[[3-[4-[1- (hydroxyacetic)hexahydro - 1H-azepin-4-yl] -3-forfinal]-2 - oxo-5-oxazolidinyl] methyl]-ndimethylacetamide.

The second way of obtaining from the intermediate connection 1 connection with a partially saturated 6-membered heterocycle containing nitrogen, in the form of highly-enriched enantiomers, shown in SCHEME J. As shown in SCHEME J, the structure 59 is subjected to interaction with the protected aniline 19, resulting in a gain structure 60. The subsequent acylation reaction network structure 61, which handle the AI, as described in examples 72 and 73 and later. Then remove the protective group by treatment with attributively to obtain the target compounds 64 and 57, which can be used to obtain derivatives is shown in SCHEME A. the Use of 4-ketozole structure 59 is an alternative means of obtaining the 4-isomer, structure 58. In accordance with another variant of the hydroxy-group structure 61 or 4-isomer may be replaced by fluorine atom using a suitable agent, such as diethylaminosulfur, in a suitable solvent, such as methylene chloride. In this case, stage of elimination, shown for patterns 61, not spend. This substitution reaction described in example 74.

The methods shown in SCHEME a and SCHEME J, directly receive, for example, the following compounds of formula (I):

(S)-N-[[2-oxo-3- [3-fluoro-4-[1-[(acetoxy)acetyl]-3,4 - dihydro-2H-pyridine-5-yl] phenyl]-5-oxazolidinyl] methyl]- ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-(hydroxyacetic)-3,4 - dihydro-2H-pyridine-5-yl] -3-forfinal] -2-oxo-5-oxazolidinyl] methyl]- ndimethylacetamide;

(S)-(-)-N-[[3- [4-[1-formyl-4-fluoro-4-piperidinyl] -3 - forfinal]-2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide.

These compounds are useful for treatment of microbial infections is ical composition of the present invention can be obtained by mixing the compounds of formula (I) according to the present invention with a solid or liquid pharmaceutically acceptable carrier and, optionally, with pharmaceutically acceptable excipients and fillers using standard conventional methods. Compositions in the form of solid dosage forms include powders, tablets, dispergirujutsja granules, capsules, pills and suppositories. A solid carrier can be at least one substance, which can also serve as filler, corrigenda, solubilizer, lubricant, suspending substances, binders, powder for tablets and capsulorrhexis substances. Inert solid carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulose materials, viscoplastic wax, cocoa butter and the like. Compositions in the form of liquid dosage forms include solutions, suspensions and emulsions. For example, it is possible to prepare solutions of the compounds of the present invention in water and water-glycol and water-glycol, optionally containing suitable conventional coloring agents, corrigentov, stabilizers and thickeners.

The pharmaceutical composition is preferably made in the traditional ways in view of the same, that is, the compounds of formula (I) according to the present invention.

The number of the active component, i.e. the compounds of formula (I) according to the present invention, in the pharmaceutical composition and its uniform dosage form can widely be changed or adjusted depending on the particular application, the pharmacological effectiveness of specific compounds, the desired concentration. Usually the amount of active component is in the range from 0.5 to 90% by weight of the composition.

In therapeutic use for the treatment or prevention of bacterial infections in warm-blooded animals, the compounds or pharmaceutical compositions are administered orally and/or parenterally at a dose that provides and supports concentration (i.e., the number or the blood level of the active component in the animal undergoing treatment, which is effective against bacteria. Usually, such an antibacterial effective amount of the active component is in the range from about 0.1 to about 100, more preferably from about 3.0 to about 50 mg/kg body weight/day. It should be understood that the dose can be changed depending on the needs Boling is of high value. In addition, you need to understand that the initial injected dose can be increased above the upper level, to quickly attain the required level of concentration in the blood, or the initial dose may be less than optimal, and the daily dose may be gradually increased in the course of treatment, depending on the specific situation. If necessary, the daily dose may be divided into multiple doses for administration, e.g., 2-4 times per day.

The compounds of formula (I) according to the present invention is administered parenterally, i.e., by injection, e.g. intravenous or other parenteral routes of administration. Pharmaceutical compositions for parenteral administration typically contain a pharmaceutically acceptable amount of the compounds of formula (I) or soluble salts (acid-additive or basic salt), dissolved (Oh) in a pharmaceutically acceptable liquid carrier such as water for injection and buffer to obtain an isotonic solution with a suitable buffer, with, for example, a pH of about 3.5-6. Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N - methylglucamine, L(+)-lysine and L(+)-arginine, which are only a few representative is Mr. to ensure pharmaceutically acceptable concentrations of the injected medicinal substance in the range from about 1 mg/ml to about 400 mg/ml. The liquid pharmaceutical composition is administered to provide the above-mentioned antibacterial effective amount. The compounds of formula (I) according to the present invention is suitable to be administered orally in the form of solid and liquid dosage forms.

Test for antimicrobial activity was performed in vivo by the method of Murine (Murine). Groups of mice-females (six mice for 18-20 g each) were administered intraperitoneally injected (intraperitoneally) bacteria that were ottani immediately before use and suspended in the extract of the core brain with 4% indigenous beer yeast (Staphylococcus aureus) or extract the core of the brain (Streptococcus species). Antibiotic treatment with six dose levels for each drug were conducted over one and five hours after infection infection by oral intubation or subcutaneous injection. The survival rate was observed daily for six days. By probit analysis to calculate the values of the ED50on the basis of mortality rates. The proposed compounds were compared with the well-known antimicrobial means vancomycin and U-100592 as a control. See "decision Upjohn Oxazolidinone Antibacterial Agent, ads, data on the 35th IU"ptx2">

To more fully illustrate the nature of the present invention and the method of its implementation, the following experimental examples.

Example 1. (S)-N-[[3-[3-Fluoro-4-[1- (carbobenzoxy]-(3-methyl) 3-azetidinol]phenyl]-2-oxo-5 - oxazolidinyl]methyl]ndimethylacetamide

Stage 1: Ethyl 1-cyano-1-(4-nitro-2-forfinal)propionate

In dried over a flame one litre 3 - necked round bottom flask equipped with a magnetic stir bar and addition funnel, was placed 6,40 g of sodium hydride (0,160 mol, 60% oil dispersion), then washed with pentane (3 x 40 ml) and dried in vacuum. Hydride suspended in 100 ml of tetrahydrofuran, cooled to 0oC and treated with a solution of ethylcinnamate (8.6 ml, 0,080 mol) in 150 ml of THF over 15 minutes, with evolution of gas. The obtained turbid solution enolate was stirred for five minutes, then treated with a solution of 3,4 - deformirovannoe (I) (8,8 ml 0,080 mol) in 150 ml of THF, which was immediately colored in orange. Removed the cooling bath and the reaction mixture was heated to 50oC for 18 hours. Red at this point the suspension was cooled to room temperature and successively treated with 100 g of iodomethane (to 0.72 mol), 33 g of potassium carbonate (0.24 mol) and 100 ml acetol the suspension was cooled to room temperature, was filtered through a layer of Celite and the filtrate was concentrated in vacuum. The obtained residue was diluted with 500 ml of water and was extracted twice with ethyl acetate (500 ml). The combined organic layers were washed once with saturated salt solution (300 ml), dried over MgSO4, filtered and concentrated to obtain 21,39 g of brown oil. This crude material was purified by LC (liquid chromatography) 850 g (230-400 mesh) silica gel with elution with 20% ethyl acetate in hexane to obtain 18,14 g (100%) specified the title compound as a yellow oil which spontaneously crystallized. So pl. 56,0-57,0oC; Rf= 0,34 (20% ethyl acetate/hexane); IR (net) 1752, 1534, 1423, 1355, 1248, 1239, 1213, 1099, 811, 741 cm-1;

1H NMR (300 MHz, CDCl3) is 8.16 (m, 1H, arene.), 8,03 (DD, 1H, J=2.3 Hz, J= 10.4 Hz, arene.), 7,80 (DD, 1H, J=7,6 Hz, J=8.6 Hz, arene.), to 4.33 (m, 2H, O-CH2), 2,04 (s, 3H, CH3), of 1.28 (t, 3H, J=7,2 Hz ). VRMS: vicis. for C12H11N2O4F1+ H1: 267,0781 found: 267,0799.

Step 2: Ethyl 1-aminomethyl-1-(4-amino-2-forfinal)-propionate

A solution of ethyl 1-cyano-1-(4-nitro-2-forfinal)propionate (17.9 g, to 67.3 mmol) in absolute ethanol (500 ml) was treated with Raney Nickel (30,9 g of 50% suspension in water) and subjected to hydrogenation apparatus in actionnow the mixture was filtered through Celite (with repeated washing EtOH) and then concentrated in vacuum, Hairdryer, high vacuum) to produce specified in the connection header in the form of Golden syrup (15.6 g, 97%). This product can be cleaned by chromatography on silica gel using a mixture of 15% methanol/ethyl acetate, but usually it was used in the next stage without additional purification: Rf= 0,32 (15% MeOH/EtOAc);

1H NMR (CDCl3included 7.00 (t, J=8,5, 1H, arene.), of 6.45 (DD, J=8,2, 2,3, 1H, arene. ), 6,36 (DD, J=13,1, 2,4, arene.), 4,18 (KB, J=7,0, 3H ), 3,76 (Shir. s, 2H, NH2), 3,06 (DD, J=18.2, and to 13.8, 2H, CH2N) of 1.52 (s, 3H, CCH3), to 1.21 (t, J= 7,1, 2H ); IR (liquid) 1722, 1634, 1513, 1445, 1305, 1283, 1243, 1172, 1132, 845 cm-1; calc. (C12H17F1N2O2): 240,1274 found: 240,1293.

Stage 3: 3-Methyl-3-(4-amino-2-forfinal)azetidine

A solution of ethyl 1-aminomethyl-1-(4-amino-2-forfinal)propionate (2.1 g, 8,7 mmol) in THF (50 ml) was slowly added with a syringe to a cold solution (0oC) methylacrylamide (15 ml of 3 M solution in ether, 45 mmol, diluted with 100 ml THF). Upon completion of addition, the syringe was rinsed with additional THF (2 x 12 ml). Removed the cooling bath and the solution beige color was allowed to mix at room temperature for three hours, after which it was poured into a saturated solution of ammoniaand (water, bring the tilov ether and the combined organic layers were washed once with water, once saturated salt solution, dried over MgSO4, filtered and concentrated to obtain 1.4 g of a yellow syrup.

Extraction of the aqueous phase with ethyl acetate gave 190 mg of the crude product. Collected in this way the crude products were combined and were chromatographically on silica gel using a mixture of 50% ethyl acetate/hexane, resulting in the received specified in the title compound (1.0 g, 60%) as a pale yellow solid, so pl. 125-127oC; Rf= 0,21 (50% EtOAc/hexane);

1H NMR (CDCl3) 7,46 (t, J=8,3, 1H, arene.), to 6.43 to 6.35 (m, 2H, arene.), 5,77 (Shir. s, 1H, NH), 3,75 (Shir. s, 2H, NH2), of 3.54 (DD, J=5,5, 2,4, 1H, CH2), of 3.45 (d, J=5,5, 1H, CH2), of 1.64 (s, 3H, CH3); IR (pasta) 3439, 3342, 3236, 1738, 1635, 1516, 1441, 1210, 1146, 631 cm-1. Analyte. calc. for C10H11F1N2O2: C, 61,84, H, 5,71, N, 14,43. Found: C, 62,13, H, Of 5.81, N, 14,36.

Stage 4: 3-(4-Amino-2-forfinal)-3-methylaziridine

In dried over a flame two-liter 3-necked round bottom flask equipped with a mechanical stirrer, reflux condenser and addition funnel, were placed 300 ml of tetrahydrofuran and 350 ml of 1 M solution of sociallyengaged (0.35 mol) followed by cooling to 0oC. This solution was treated with RAS is and was observed staining in yellow color. Removed the cooling bath and the reaction mixture was heated under reflux, the result was the rapid formation of a white precipitate. After 20 hours visually unchanged, the reaction mixture was cooled to room temperature and extinguished response sequential addition of 13 ml of water, 12 ml of 5 M sodium hydroxide solution and 47 ml of water. The obtained thick gelatinousness the suspension was diluted with 1 l of ethyl acetate, filtered through a layer of Celite, concentrated and dried under high vacuum to obtain 9,82 g specified in the title compound as a pale orange syrup.

1H NMR (300 MHz, CDCl3) is 6.78 (t, 1H, J=8,5 Hz, arene.), 6,37 (m, 2H, arene. ), 4,06 (d, 2H, J=8,2 Hz, N-CH2as) 3,81 (Shir. s, 3H, NH-s) to 3.58 (d, 2H, J=8,2 Hz, N-CH2bs) of 1.65 (s, 3H, CH3).

Stage 5: N-Carbobenzoxy-3-(N-carbobenzoxy-3 - ftoranila-4-yl)-3-methylaziridine

In a round bottom flask with a capacity of 500 ml, equipped with a magnetic stirrer and addition funnel, was placed 85 ml of water, of 38.4 g of sodium bicarbonate (0.46 mol) and the solution 9,82 g 3-(4 - amino-2-forfinal)-3-methylaziridine (0,051 mol, theoretical quantity) in 165 ml of acetone. Received the orange suspension was cooled to 0oC and was treated with 43 ml of benzylbromide (0.30 mol), prannoy the mixture was stirred at room temperature for 65 hours. TLC (thin layer chromatography) showed incomplete expenditure source aminoaniline, so I added 12.8 g of sodium bicarbonate (0.15 mol) and 14 ml of benzylbromide (0.10 mol), still stood out gas. After two hours the reaction mixture was diluted with 350 ml of saturated sodium bicarbonate solution and was extracted three times with ethyl acetate (300 ml). The combined organic layers were washed once with water (200 ml), once with saturated salt solution (200 ml), dried over MgSO4, filtered and concentrated to obtain 29,86 g light yellow oil. This crude product was purified by LC 850 g (230-400 mesh) silica gel with elution with a mixture of 25% ethyl acetate/hexane, resulting in received 11,67 g (51%) indicated in the title compound as a pale yellow solid. Rf= 0,18 (25% ethyl acetate/hexane); IR (net) 1735, 1707, 1693, 1600, 1534, 1455, 1424, 1414, 1221, 1081 cm-1;

1H NMR (300 MHz, CDCl3) 7,35 (m, 11H, arene.), of 6.96 (m, 3H, arene. and NH), 5,19 (s, 2H, Ph-CH2), 5,09 (s, 2H, Ph-CH2), 4,30 (d, 2H, J=8,2 Hz, N-CH2as) of 4.00 (d, 2H, J=8,4 Hz, N-CH2bs) to 1.59 (s, 3H, CH3);

13With NMR (75 MHz, CDCl3) of 160.4 (d, JCF=245 Hz), of 156.6, 153,0, 138,1 (l, JCF= 11 Hz), 136,5, 135,7, 128,6, 128,4, 128,2, 127,9, 127,8, 127,5, 127,0, 126,9, 113,9, 106,6 (d, JCF= 27 Hz), 67,1, 66,6, 60,8, 60,2 CLASS="ptx2">

Stage 6: (R)-(-)-N-Carbobenzoxy-3-methyl-3-[2-fluoro-4-[5 - hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidin

In a round bottom flask with a capacity of 500 ml, containing 11,48 g N-carbobenzoxy-3- (N-carbobenzoxy-3-ftoranila-4-yl) -3-methylaziridine (25.6 mmol), equipped with a magnetic stirrer, were placed 100 ml of tetrahydrofuran (freshly) and was cooled to -78oC. This light yellow homogeneous solution was treated with 16.6 ml n-utility (to 26.6 mmol), which led to a slight darkening of the color. The carbamate ion was stirred for 30 minutes at the specified low temperature, then treated with 3.8 ml of R-glycidylether (to 26.6 mmol) without visible changes. Removed the cooling bath and the reaction mixture was heated to room temperature for 16 hours. Now orange opaque solution was diluted with 200 ml of saturated solution of ammonium chloride and was extracted twice with ethyl acetate (250 ml), the combined organic layers were washed once with saturated sodium bicarbonate solution (200 ml), once with saturated salt solution (300 ml), dried over MgSO4, filtered and concentrated to obtain 15,72 g specified in the title compound as an orange oil. This crude product was purified by LC 530 g (Ortega solids. Rf= 0,28 (80% ethyl acetate/hexane); []D-35(0,8967, methanol); IR (net) 1754, 1708, 1516, 1454, 1429, 1415, 1358, 1228, 1194, 1076 cm-1;

1H NMR (300 MHz, CDCl3) 7,44 (DD, 1H, J=2.2 Hz, J=13,0 Hz, arene.), 7,33 (m, 5H, arene.), 7,19 (DD, 1H, J=2.2 Hz, J=8,5 Hz, arene.), 7,03 (t, 1H, J= 8.7 Hz, arene.), 5,09 (s, 2H, Ph - CH2), to 4.73 (m, 1H, Metin), 4,30 (d, 2H, J= 8,2 Hz, Ph-C-CH2as) of 3.97 (m, 5H, Ph-C-CH2bs, Ph-N-CH2as, HO-CH2a), to 3.73 (m, 1H, ), 2,80 (t, 1H, J=6.3 Hz, BUT) to 1.60 (s, 3H, CH3);

13With NMR (75 MHz, CDCl3) 160,2 (l, JCF=246 Hz), 156,5, 154,2, 138,0 (l, JCF= 11 Hz), 136,3, 128,2, 128,1, 127,8, 127,7, 126,9 (d, JCF=7 Hz), 113,1 (l, JCF=2 Hz), 106,2 (JCF=27 Hz), 72,6, 66,5, 62,4, 60,1, 46,0, 35,9, 28,0; Molten MES = 3,8% ethyl acetate. Anal. calc. for22H23N2O5F1plus the 3.8% ethyl acetate: C, 63,41; H, 5,73; N, 6,50. Found: C, 63,15; H, 5,52; N, 6,58. VRMS: calculated for C22H23N2O5F1: 415,1169 found 415,1674.

Stage 7: Metasemiotic ether (R)-(-)- N-carbobenzoxy-3-methyl-3- [2-fluoro-4-[5 - hydroxymethyl-2-oxo-3-oxazolidinyl] phenyl]azetidine

In a round bottom flask with a capacity of 500 ml, containing 6,55 g of R-(-) -N-carbobenzoxy-3-methyl-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3 - oxazolidinyl] phenyl]azetidine of 15.3 mmol), equipped with a magnetic stirrer, were placed 150 ml of dichloroisatin (23,0 mmol) and 1.4 ml of methanesulfonanilide (18.4 mmol) without visible changes. Removed the cooling bath and the reaction mixture was heated to room temperature within one hour. Visually unchanged, the solution was diluted with 100 ml of 0.5 N. chloroethanol acid was shaken, layers were separated and the acid layer was extracted once with dichloromethane (100 ml). The combined organic layers were washed once with saturated salt solution (75 ml), dried over MgSO4, was filtered and was concentrated with the receipt of 7.68 g (100%) specified the title compound as a pale yellow amorphous solid. Rf= 0,40 (80% ethyl acetate/hexane); IR (pasta) 1758, 1703, 1516, 1418, 1358, 1337, 1230, 1176, 1075, 965 cm-1;

1H NMR (300 MHz, CDCl3) 7,44 (DD, 1H, J=2.2 Hz, J=12,8 Hz, arene.), 7,33 (m, 5H, arene.), 7,17 (DD, 1H, J=2.2 Hz), J=8,5 Hz, arene.), 7,06 (t, 1H, J= 8,5 Hz, arene.), at 5.10 (s, 2H, Ph-CH2), to 4.92 (m, 1H, Metin), 4,50 (DD, 1H, J= 3.6 Hz, J= 11.7 Hz, MsO-CH2a), was 4.42 (DD, 1H, J=4,1 Hz, J=11.7 Hz, MsO-CH2b), or 4.31 (d, 2H, J=8.1 Hz, Ph-C-CH2as) of 4.13 (t, 1H, J=9,2 Hz, Ph-N-CH2a), of 4.00 (d, 1H, J=8.5 Hz, Ph-C-CH2bs) of 3.94 (DD, 1H, J=6.2 Hz, J=9,2 Hz, Ph-N-CH2b), 3,10 (s, 3H, S-CH3), of 1.62 (s, 3H, C-CH3);

13With NMR (75 MHz, CDCl3) to 160.3 (d, JCF=247 Hz), 156,5, 153,3, 137, 6mm (d, JCF=11 Hz), 136,4, 129,0, 128,8, 128,3, 127,9, 127,8, 127,3, 127,2 (d, JCF=6 Hz), 113,3 (l, JCF= 3 Hz), 106,5 (l, JCF=28 Hz), 69,4, 67,8, 66,6, 60,4, 46,2, 37,17; N, 5,61.

Stage 8: (R)-(-)-N-Carbobenzoxy-3-methyl-3-[2-fluoro-4-[5-aminomethyl-2-oxo - 3-oxazolidinyl]phenyl]azetidin

Two kiln dried tubes with airtight stoppers, equipped with magnetic stirrer were placed the same amount of a solution of 7.50 g metaseries ether (R)-(-)-N-carbobenzoxy-3-methyl-3-[2-fluoro-4-[5 - hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine (15,2 mmol) in 75 ml of methanol and 75 ml of tetrahydrofuran (freshly). These light yellow homogeneous solution was saturated with gaseous ammonia for 10 minutes, until they become almost colorless, the test tube was closed with a Teflon prikruchivaem tubes and heated to 100oC for 64 hours. The reaction mixtures were combined and concentrated to obtain specified in the connection header in the form of a crude yellow foamy substance.

Stage 9: (S)-N-[[3-[3-fluoro-4-[1-(carbobenzoxy) -(3-methyl)-3-azetidinol]phenyl]-2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide.

Specified in the title compound was prepared as follows: (R)-(-)-N-carbobenzoxy-3-methyl-3-[2-fluoro-4-[5 - aminomethyl-2-oxo-3-oxazolidinyl] phenyl] azetidin was diluted with 220 ml of dichloromethane, cooled to 0oC and sequentially treated with 3.7 ml pyridinethione the mixture to room temperature for 16 hours. Visually unchanged, the solution was concentrated to a yellow foamy substance was again diluted with 50 ml dichloromethane and filtered to remove any remaining insoluble precipitate. The filtrate was purified by LC on 340 g (230-400 mesh) silica gel with elution with a mixture of 2.5% methanol/ethyl acetate, resulting in received of 5.85 g (84%) of (S) -N-[[3-(3-fluoro-4-[1-(carbobenzoxy)-(3-methyl)-3 - azetidinol]phenyl]-2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide in the form of a colorless glassy substance. Rf= 0,24 (2.5% methanol/ethyl acetate); []D-19(0,9971, methanol); IR (pasta) 1754, 1706, 1676, 1516, 1430, 1415, 1357, 1227, 1194, 1075 cm-1;

1H NMR (300 MHz, CDCl3) 7,42 (DD, 1H, J=2.1 Hz, J=12.9 Hz, arene.), 7,33 (m, 5H, arene.), 7,13 (DD, 1H, J=2.2 Hz, J=8,5 Hz, arene.), ? 7.04 baby mortality (t, 1H, J= 8,5 Hz, arene.), 6,56 (PCs, 1H, J=6.2 Hz, NH), 5,10 (s, 2H, Ph-CH2), 4,79 (m, 1H, Metin), 4,30 (d, 2H, J=8,2 Hz, Pb-C-CH2as) to 4.01 (m, 3H, Ph-C-CH2bs, Ph-N-CH2a), of 3.78 (DD, 1H, J=6,7 Hz, J=9.1 Hz, Ph-N-CH2b), to 3.64 (m, 2H ), 2,02 (s, 3H, O=C-CH3), to 1.60 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 171,2, to 160.3 (d, JCF=246 Hz), of 156.6, 154,2, 137,9 (l, JCF=11 Hz), 136,5, 128,9 (l, JCF=14 Hz), 128,4, 127,9, to 127.2 (d, JCF= 7 Hz), of 113.2 (d, JCF=2 Hz), 106,4 (l, JCF=28 Hz), 72,0, 66,6, 60,7, 60,3, 47,3, 41,7, 36,1, 28,1, 22,9. Anal. calc. for C24H26N3O5F1: C, 63,2 original]methyl]ndimethylacetamide

In a Parr flask with a capacity of 500 ml was placed a solution of 5.83 g (S)-N-[[3-[3-fluoro-4- [1-(carbobenzoxy) -(3-methyl)-3-azetidinol] phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (12.8 mmol) in 100 ml of methanol and of 1.17 g of 10% palladium on carbon. The black suspension was placed in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2) with shaking for four hours, and the pressure is maintained constant at the level of 28 pounds per square inch (1.97 kg/cm2). Took the flask from hydrogenator and the reaction mixture was filtered through a layer of Celite and concentrated with the receipt of 4.05 g (99%) not quite white amorphous solid. Part (1,00 g) of this product was purified by LC on 100 g (230-400 mesh) silica gel with elution with a mixture (2:17: 83) NH4OH/methanol/dichloromethane and the resulting received 776 mg specified in the title compounds as a colorless glassy substance. Rf= 0,26 (2: 17: 83 NH4OH/methanol/dichloromethane); []D-23(0,9015, methanol); IR (pasta) 1752, 1662, 1630, 1554, 1515, 1483, 1435, 1412, 1227, 1194 cm-1;

1H NMR (300 MHz, CDCl3) 7,37 (DD, 1H, J=2.2 Hz, J=12,8 Hz, arene.), for 7.12 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), of 6.99 (t, 1H, J=8.6 Hz, arene.), 6,33 (PCs, 1H, J=6 Hz, O=C-NH), 4,78 (m, 1H, Metin), Android 4.04 (m, 3H, Ph-C-C2as, Ph-N-CH2a), of 3.78 (DD, 1H, J= 6,8 Hz, J=9.1 Hz, Ph-N-CHWith NMR (75 MHz, CDCl3) 171,2, 160,0 (l, JCF=246 Hz), 154,2, 137,3 (l, JCF=11 Hz), 130, 8mm (l, JCF=15 Hz), 126,9 (l, JCF=7 Hz), of 113.2, 106,3 (l, JCF= 27 Hz), 71,9, 58,0, 47,3, 41,7, 40,5, 27,3, 22,9; the water content in K. Fischer = 0,89%. Anal. calc. for C16H20N3O3F1with 0,89% water: C, 59,27; H, 6,32; N, 12,96. Found: C, 59,07; H, 6,45; N, 12,89. VRMS: calc. for C16H20N3O3+H1: 322,1567 found: 322,1569.

Example 3. (S)-N-[[3-[3-Fluoro-4-[1-(carboxymethyl)-3-(3-methyl)- azetidine]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

In kiln dried round bottom flask with a capacity of 25 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N-[[3-[3-fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl] - methyl] ndimethylacetamide(0.75 mmol), 8 ml of dichloromethane and cooled to 0oC. Colourless, but not quite clear solution was treated with 0.16 ml of triethylamine (1.1 mmol) and 70 μl of methylchloroform (0.90 mmol), the resulting reaction mixture became transparent. Remove the cooling bath and the reaction mixture was heated to room temperature within two hours. Visually unchanged, the solution was diluted with 30 ml dichloromethane, washed once with water (20 ml), once with saturated salt solution (15 ml), dried over MgSO4was filtered and 18 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and as a result received 219 mg (77%) indicated in the title compound as a white foamy substance. Rf= 0,30 (5% methanol/dichloromethane); []D-21(1,0194, methanol); IR (pasta) 1755, 1706, 1676, 1631, 1517, 1394, 1227, 1208, 1195, 1076 cm-1;

1H NMR (300 MHz, CDCl3) the 7.43 (DD, 1H, J=2.2 Hz, J=12.9 Hz, arene.), 7,14 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), 7,05 (t, 1H, J=8.6 Hz, arene.), 6.35mm (PCs, 1H, J= 6 Hz, NH), 4,80 (m, 1H, Metin), 4,28 (d, 2H, J=8,2 Hz, CO2-N-CH2as) of 4.04 (t, 1H, J=9.0 Hz, Ph-N-CH2a), of 3.97 (d, 2H, J=8,4 Hz, CO2-N-CH2bs) of 3.77 (DD, 1H, J=6,7 Hz, J=9.1 Hz, Ph-N-CH2b), 3,68 (m, 5H, NH-CH2s, OCH3), 2,03 (s, 3H, O=C-CH3), to 1.61 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) to 170.9, 160,2 (l, JCF=246 Hz), 157,1, 154,0, 137,8 (l, JCF=11 Hz), 128,5 (l, JCF=15 Hz), 127,0 (l, JCF=7 Hz), 113,1 (l, JCF= 3 Hz), 106,3 (l, JCF=27 Hz), 71,8, 60,4, 52,1, 47,2, 41,7, 35,9, 28,0, 22,9; water in K. Fischer = 1,19%. Anal. calc. for C18H22N3O5F1plus 1,19% water: C, 56,31; H, 5,91; N, 10,94. Found: C, 56,27; H, To 5.93; N, Of 10.93.

Example 4 (S)-N-[[3-[3-fluoro-4- [1-(methoxyacetyl)- 3-(3-methyl)-azetidine] phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

In kiln dried round bottom flask with a capacity of 25 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N-[[3- [3-fluoro - 4-[3-methyl-3-azetidinol] phenyl]-2-oxo-5-oxazolidinyl]- methyl] ndimethylacetamide (0.75 mmol), 8 ml of dichloromethane and cooled to 0oC. Colorless, but the non-aligned it stood out a smoke and light haze was observed. Remove the cooling bath and the reaction mixture was heated to room temperature within two hours. Now clear colorless solution was diluted with 25 ml dichloromethane, washed once with water (15 ml), once with saturated salt solution (15 ml), dried over MgSO4, filtered and concentrated to obtain 294 mg of a white foamy substance. This crude product was purified by LC on 27 g (230-400 mesh) silica gel with elution with a mixture of 7% methanol/dichloromethane and the resulting received 240 mg (81%) indicated in the title compound as a white amorphous solid. Rf= 0,23 (7% methanol/dichloromethane); []D-20(0,9736, methanol); IR (pasta) 1754, 1662, 1654, 1632, 1517, 1437, 1412, 1226, 1194, 1122 cm-1;

1H NMR (300 MHz, CDCl3) was 7.45 (DD, 1H, J=2.1 Hz, J=13,0 Hz, arene.), to 7.15 (DD, 1H, J= 2.1 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J=8,5 Hz, arene.), 6,47 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), 4,51 (d, 1H, J=9.0 Hz, Ph-C-CH2a), 4,35 (d, 1H, J=9.7 Hz, Ph-C-CH2b), 4,25 (d, 1H, J=9,2 Hz, Ph-C-CH2a), of 4.05 (m, 4H, O=C-CH2s, Ph-C-CH2bPh-N-CH2a), 3,66 (m, 1H, Ph-N-CH2b), 3,66 (m, 2H, NH-CH2s) 2,03 (s, 3H, O=C-CH3), and 1.63 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 171,2, 169,7, of 160.4 (d, JCF=246 Hz), 154,2, 138,2 (l, JCF= 11 Hz), 128,4 (l, JCF=14 Hz), RUB 127.3 (d, JCF=6 Hz), to 113.4, 10SUB>3O5F1plus 2,03% water: C, 56,83; H, 6,25; N, 10,47. Found: C, 56,99; H, 6,34; N, 10,49. VRMS: calc. for C19H24N3O5F1: 394,1778 found: 394,1784.

Example 5. (S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-(3-methyl)azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

In kiln dried round bottom flask with a capacity of 25 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N-[[3- [3-fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl] -methyl] ndimethylacetamide (0.75 mmol), 8 ml of dichloromethane and cooled to 0oC. Colourless, but not quite clear solution was treated with 0.16 ml of triethylamine (1.1 mmol) and 73 μl ethylformate (0.90 mmol) without visible changes. Remove the cooling bath and the reaction mixture was heated to room temperature for 16 hours. Analysis by TLC (thin layer chromatography) it is now clear solution showed a partial withdrawal (S)-N-[[3-[3-fluoro-4-[3-methyl-3-azetidinol] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

The reaction mixture was treated with another of 0.14 ml ethylformate (1.8 mmol) and 8.0 ml of 1 n sodium hydroxide solution with vigorous stirring for five minutes. The reaction mixture was diluted with 10 ml water and was extracted twice with dichloromethane (25 ml). United SUB>, filtered and concentrated to obtain 253 mg of a white foamy substance. This crude product was purified by LC on 18 g (230-400 mesh) silica gel with elution with a mixture of 6% methanol/dichloromethane and the result was 145 mg (55%) indicated in the title compound as a white amorphous solid. Rf= 0,25 (7% methanol/dichloromethane); []D-20(0,9949, methanol); IR (pasta) 1754, 1666, 1631, 1548, 1516, 1478, 1433, 1414, 1227, 1195 cm-1;

1H NMR (300 MHz, CDCl3) of 8.06 (s, 1H, CHO), 7,47 (DD, 1H, J=2.0 Hz, J= 13,0 Hz, arene.), 7,16 (DD, 1H, J=2.2 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J= 8.6 Hz, arene.), 6,33 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), 4,42 (d, 1H, J= 8,2 Hz, Ph-C-CH2a), 4,30 (d, 1H, J=9.9 Hz, Pb-C-CH2b), is 4.15 (d, 1H, J=8,3 Hz, Ph-C-CH2a), of 4.05 (m, 2H, Ph-C-CH2bPh-N-CH2a), with 3.79 (DD, 1H, J=6,8 Hz, J= 9.1 Hz, Ph-N-CH2b), to 3.67 (m, 2H, NH-CH2s) 2,03 (s, 3H, O=C - CH3), of 1.64 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) RUB 171.1, 162,3, to 160.3 (d, JCF=246 Hz), 154,1, 138,2 (l, JCF= 11 Hz), to 127.9 (d, JCF=14 Hz), 127,1 (l, JCF=6 Hz), 113,3, 106,4 (l, JCF=27 Hz), 71,9, 59,6, 58,2, 47,3, 41,7, 37,6, 28,0, 23,0; VRMS: calc. for C17H20N3O4F1: 349,1438 found: 349,1444.

Example 6 (S)-N-[[3-[3-fluoro-4-[1-(dichloroacetyl)-3-(3-methyl)- azetidine] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

In h is-methyl-3-azetidinol] phenyl] -2-oxo-5 - oxazolidinyl]- methyl] ndimethylacetamide (0.75 mmol), 8 ml of dichloromethane and cooled to 0oC. Colourless, but not quite clear solution was treated with 0.16 ml of triethylamine (1.1 mmol) and 87 μl of dichloroacetylene (0.90 mmol), and there were smoke and observed a light haze. Remove the cooling bath and the reaction mixture was heated to room temperature for three hours. Now clear colorless solution was diluted with 15 ml water and was extracted twice with dichloromethane (25 ml). The combined organic layers were washed once with saturated salt solution (15 ml), dried over MgSO4, filtered and concentrated to obtain 353 mg reddish - brown foamy substance. This crude product was purified by LC on 25 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and the result was 243 mg (75%) indicated in the title compound in the form of not-quite-white amorphous solid. Rf= 0,26 (5% methanol/dichloromethane); []D-18(0,9862, methanol); IR (pasta) 1752, 1666, 1631, 1545, 1517, 1440, 1412, 1288, 1227, 1193 cm-1;

1H NMR (300 MHz, CDCl3) of 7.48 (DD, 1H, J=2.1 Hz, J=13,0 Hz, arene.), to 7.18 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), was 7.08 (t, 1H, J=8.6 Hz, arene.), 6,52 (PCs, 1H, J= 6,1 Hz, NH), to 4.81 (m, 1H, Metin), 4,70 (d, 1H, J=8,9 Hz, Ph-C-CH2a), 4,48 (d, 1H, J=9.1 Hz, Ph-C-CH2b), to 4.41 (Prov. 2b), to 3.67 (m, 2H, NH-CH2s) 2,03 (s, 3H, O-C-CH3), to 1.67 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) is 171.3, to 163.1, to 160.3 (d, JCF=246 Hz), 154,2, 138,4 (l, JCF= 11 Hz), uniforms, 127.6 (d, JCF=15 Hz), 127,1 (l, JCF=6 Hz), to 113.4, 106,6 (l, JCF=27 Hz), 72,1, 64,6, 63,1, 60,3, 47,4, 41,8, 36,9, 28,2, 23,0; water in K. Fischer and 1.3%. Anal. calc. for C18H20N3O4F1Cl2plus the 1.3% water: C, 49,36; H, 4.75 V; N, 9,60. Found: C, 48, 97mm; H, 4,80; N, At 9.53. VRMS: calc. for C18H20N3O4Cl2: 432,0893 found: 432,0900.

Example 7 (S)-N-[[3-[3-Fluoro-4-[1-(3-methoxypropyl)-3-(3 - methyl)azetidine]phenyl]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide

In kiln dried round bottom flask with a capacity of 10 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N-[[3-[3-fluoro-4- [3-methyl-3-azetidinol] phenyl]-2-oxo-5-oxazolidinyl] -methyl] ndimethylacetamide (0.75 mmol), 4 ml of dichloromethane, 81 μl of 3 - methoxypropionate acid (0.83 mmol), 0,13 ml of distilled diethylthiophosphate (0.83 mmol) and cooled to 0oC. the Colorless solution was treated of 0.11 ml of triethylamine (0.78 mmol), the resulting solution became pink. Remove the cooling bath and the reaction mixture was heated to room temperature for 66 hours. Now a reddish - brown solution was diluted with 20 ml of di is literaly and concentrated with getting 297 mg red foamy substance. This crude product was purified by LC on 18 g (230-400 mesh) silica gel with elution with a mixture of 7% methanol/dichloromethane and the result was 216 mg not quite white amorphous solid.1H NMR showed that the product is contaminated with 10% (S)-N-[[3-[3-fluoro-4- [1-(formyl)-3-(3-methyl) azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]acetamide", she was removed by catalytic hydrogenolysis with 22 mg of 10% palladium on carbon in 30 ml of tetrahydrofuran containing 10 drops of concentrated chloroethanol acid. The crude product was again chromatographically 13 g (230-400 mesh) silica gel with elution with a mixture of 7% methanol/dichloromethane and the result was 135 mg (44%) indicated in the title compound in the form of not-quite-white amorphous solid. Rf= 0,23 (7% methanol/dichloromethane); []D-19(0,8324, methanol); IR (pasta) 1755, 1664, 1630, 1548, 1516, 1440, 1410, 1226, 1192, 1115 cm-1;

1H NMR (300 MHz, CDCl3) was 7.45 (DD, 1H, J=2.0 Hz, J=12.9 Hz, arene.), to 7.15 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J=8,5 Hz, arene.), 6,29 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), 4,42 (d, 1H, J=8.0 Hz, Ph-C-CH2a), 4,30 (d, 1H, J=9.6 Hz, Ph-C-CH2b), is 4.15 (d, 1H, J=8,2 Hz, Ph-C-CH2a), Android 4.04 (m, 2H, Ph-C-CH2bPh-N-CH2a), with 3.79 (DD, 1H, J=6,7 Hz, J=9.1 Hz, Ph-N-CH2b), to 3.67 (m, 4H, O-CH3) which is 171,5, RUB 171.1, are 162.5 (d, JCF=246 Hz), 154,2, 138,1 (l, JCF= 11 Hz), 128,5 (l, JCF=15 Hz), RUB 127.3 (d, JCF=6 Hz), to 113.4, 106,5 (l, JCF=28 Hz), 72,0, 68,4, 61,6, 58,9, 47,5, 41,9, 35,6, 32,2, 28,6, 23,1; VRMS: calc. for C20H26N3O5F1: 407,1856 found: 407,1855.

Example 8 (S)-N-[[3-[3-fluoro-4-[1- (3-hydroxypropyl)-3-(3-methyl)azetidine]phenyl] -2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide

In the recovery flask with a capacity of 10 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N-[[3-[3-fluoro-4-[3-methyl-3 - azetidinol]phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (0.75 mmol) and 1.5 ml of water, after which it was cooled to 0oC. Colourless, but not quite clear solution was treated with 52 μl - propiolactone (0.75 mmol) without visible changes. Remove the cooling bath and the reaction mixture was heated to room temperature within two hours. Visually unchanged, the reaction mixture was diluted with 10 ml of saturated salt solution and was extracted twice with dichloromethane (20 ml). The combined organic layers were dried over MgSO4, filtered and concentrated to obtain 232 mg not quite white foamy substance. This crude product was purified by LC on 17 g (230-400 mesh) silica gel with elution with a mixture of 7% methanol/dichloromethane and re is/SUB> = 0,30 (10% methanol/dichloromethane); []D-19(0,9248, methanol); IR (pasta) 3288, 1754, 1630, 1554, 1517, 1436, 1412, 1289, 1227, 1193 cm-1;

1H NMR (300 MHz, CDCl3) 7,46 (DD, 1H, J=2.1 Hz, J=13,0 Hz, arene.), 7,14 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J=8.6 Hz, arene.), 6,55 (PCs, 1H, J=6 Hz, NH), to 4.81 (m, 1H, Metin), to 4.41 (d, 1H, J=8,3, Pb-C-CH2a), 4,32 (d, 1H, J=9.6 Hz, Ph-C-CH2b), of 4.12 (d, 1H, J=8,4 Hz, Ph-C-CH2a), of 4.05 (m, 2H, Pb-C-CH2bPh-N-CH2a), 3,88 (CL, 2H, HO-CH2s) of 3.80 (DD, 1H, J= 6,8 Hz, J=9.1 Hz, Ph-N-CH2b), to 3.67 (m, 2H ), 3.46 in (SHS, 1H, HO), 2,37 (quart., 2H, J=5.6 Hz, BUT-(CH2)-CH2s) 2,03 (s, 3H, O=C-CH3), and 1.63 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) to 172.8, 171,2, to 160.3 (d, JCF=246 Hz), 154,1, 138,1 (l, JCF= 11 Hz), USD 128.0 (d, JCF=14 Hz), 127,1 (l, JCF=6 Hz), 113,3, 106,5 (l, JCF=27 Hz), 72,0, 61,4, 58,8, 58,3, 47,3, 41,8, 35,7, 32,9, 28,2, 23,0; VRMS: calc. for C19H24N3O5F1: 394,1778 found: 394,1788.

Example 9 (S)-N-[[3-[3-fluoro-4- [1-(4-oxopentanoic)-3-(3 - methyl) azetidine]phenyl] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide

In kiln dried round bottom flask with a capacity of 10 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N- [[3-[3-fluoro - 4-[3-methyl-3-azetidinol] phenyl] -2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide (0.75 mmol), 4 ml of dichloromethane, 100 μl of levulinate acid (0.98 mmol), 216 mg EDCHCl of triethylamine (2.25 mmol), the resulting solution became pale yellow. Remove the cooling bath and the reaction mixture was heated to room temperature for 16 hours. Visually unchanged, the solution was diluted with 20 ml water and was extracted twice with dichloromethane (25 ml). The combined organic layers were washed once with saturated sodium bicarbonate solution (20 ml), saturated salt solution (15 ml), dried over MgSO4, filtered and concentrated to obtain 332 mg light yellow syrup. This crude product was purified by LC on 20 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and the result was 256 mg not quite white amorphous solid.1H NMR showed that the product is contaminated with 8% (S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-(3-methyl)azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she was removed by catalytic hydrogenolysis with 26 mg of 10% palladium on carbon in 30 ml of tetrahydrofuran containing 10 drops of concentrated chloroethanol acid. The crude product was again chromatographically 15 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and the result was 116 mg (37%) indicated in the title compound as a white amorphous) 1754, 1716, 1631, 1548, 1517, 1440, 1411, 1227, 1193, 1166 cm-1;

1H NMR (300 MHz, CDCl3) 7,46 (DD, J=2.1 Hz, J=13,0 Hz, arene.), to 7.15 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J=8,5 Hz, arene.), 6,32 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), to 4.46 (d, 1H, J-8,1, Ph-C-CH2a), 4,27 (d, 1H, J=9.4 Hz, Ph-C-CH2b), 4,19 (d, 1H, J=8,3 Hz, Pb-S-CH2a), to 4.01 (m, 2H, Ph-C-CH2bPh-N-CH2a), with 3.79 (DD, 1H, J=6,8 Hz, J=9.1 Hz, Ph-N-CH2b), 3,68 (m, 2H ), 2,80 (t, 2H, J=6,5 Hz, ), to 2.35 (m, 2H, N-CO-CH2), are 2.19 (s, 3H, (CH2)-CO-CH3), 2,03 (s, 3H, NCO-CH3), and 1.63 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 207,3, 172,0, to 170.9, 160,5 (l, JCF=246 Hz), other 153.9, 137,8 (l, JCF= 11 Hz), 128,2 (l, JCF=14 Hz), 127,0 (l, JCF=6 Hz), 113,1, 106,2 (l, JCF=28 Hz), 71,7, 61,3, 58,6, 47,1, 41,6, 37,6, 35,5, 29,7, 28,0, 24,6, 22,8; water in K. Fischer = 1,67%. Anal. calc. for C21H26N3O5F1plus 1,67% water: C, $ 59.13 USD; H, 6,33; N, 9,85. Found: C, 59,04; H, 6,38; N, 9,80. VRMS: calc. for C21H26N3O5F1: 419,1856. Found: 419,1854.

Example 10 (S)-N-[[3-[3-fluoro-4- [1 - acetyl-3-(3-methyl)azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

In kiln dried round bottom flask with a capacity of 25 ml, equipped with a magnetic stirrer, were placed 75 mg (S)-N-[[3-[3 - fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo - 5-oxazolidinyl] methyl]ndimethylacetamide (0.23 mmol), 5 ml of dichloromethane and okhlazhdaemoi (0.28 mmol), the resulting solution became light yellow. Remove the cooling bath and the reaction mixture was heated to room temperature for three hours. Now clear yellow solution was diluted with 10 ml water and was extracted twice with dichloromethane (20 ml). The combined organic layers were washed once with saturated salt solution (15 ml), dried over MgSO4, filtered and concentrated to obtain 96 mg not quite white foamy substance. This crude product was combined with 28900-RLH-017 and purified by LC on 10 g (230-400 mesh) silica gel with elution with a mixture of 7% methanol/dichloromethane and the result was 143 mg specified in the title compound as a white amorphous solid. Rf= 0,24 (7% methanol/dichloromethane); (0,9238, methanol); IR (pasta) 1754, 1646, 1631, 1552, 1517, 1435, 1413, 1288, 1227, 1193 cm-1;

1H NMR (300 MHz, CDCl3) 7,46 (DD, 1H, J=2.1 Hz, J=13.1 Hz, arene.), 7,14 (DD, 1H, J= 2.2 Hz, J=8.6 Hz, arene.), 7,07 (t, 1H, J=8,5 Hz, arene.), 6,40 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), 4,39 (d, 1H, J=7.9 Hz, Ph-C-CH2a), 4,30 (d, 1H, J=9.5 Hz, Ph-C-CH2b), 4,11 (d, 1H, J=8,2 Hz, Ph-C-CH2a), was 4.02 (m, 2H, Ph-C-CH2bPh-N-CH2a), with 3.79 (DD, 1H, J=6,8 Hz, J=9.1 Hz, Ph-N-CH2b), 3,66 (m, 2H, NH-CH2s) 2,03 (s, 3H ), 1,90 (s, 3H, NCO-CH3), of 1.62 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, 06,3 (l, JCF=27 Hz), 71,8, 61,7, 58,7, 47,3, 41,7, 35,2, 28,1, 22,9, 18,6; water in K. Fischer = 1,83%. Anal. calc. for C18H22N3O4F1plus 1,83% water: C, 58,41; H, 6,20; N, 11,35. Found: C, 58,43; H, 6,45; N, 11,27. VRMS: calc. for C18H22N3O4F1: 363,1594 found: 363,1585.

Example 11. (S)-N-[[3-[3-fluoro-4-[1-(2-foradil)-3-(3-methyl)- azetidine] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

In kiln dried recovery flask with a capacity of 10 ml, equipped with a magnetic stirrer and reflux condenser, was placed 262 mg of 2 - fluoro-1-tilateral (1.2 mmol), 321 mg (S)-N-[[3-[3-fluoro-4- [3-methyl-3-azetidinol] phenyl]-2-oxo - 5-oxazolidinyl] methyl]ndimethylacetamide (1.0 mmol), 7,0 ml of acetonitrile and 415 mg of powdered potassium carbonate (3.0 mmol). The obtained white suspension was heated under reflux for 16 hours. Visually unchanged, the reaction mixture was cooled to room temperature, removed in vacuum, volatile substances and the resulting residue was diluted with 20 ml water and was extracted twice with dichloromethane (20 ml). The combined organic layers were washed once with saturated salt solution (20 ml), dried over MgSO4, filtered and concentrated to obtain 394 mg of a light brown syrup. This crude product is 260 mg (71%) indicated in the title compound as a pale peach amorphous solids. Rf= 0,30 (7% methanol/dichloromethane); []D-21(0,95445, methanol); IR (pasta) 1753, 1660, 1630, 1550, 1515, 1481, 1435, 1411, 1225, 1195 cm-1;

1H NMR (300 MHz, CDCl3) of 7.36 (DD, 1H, J=2.2 Hz, J=a 12.7 Hz, arene.), 7,11 (DD, 1H, J= 2.3 Hz, J=8,5 Hz, arene.), 6,98 (t, 1H, J=8.6 Hz, arene.), 6,23 (PCs, 1H, J=6 Hz, NH), 4,79 (m, 1H, Metin), 4,47 (dt, 2H, J=4,8 Hz, JHF= 47,4 Hz, F-CH2), Android 4.04 (t, 1H, J=9.0 Hz, Ph-N-CH2a), of 3.77 (DD, 1H, J=6,8 Hz, J= 9,2 Hz, Ph-N-CH2b), 3,66 (m, 4H, NH-CH2-s, N-CH2as) to 3.34 (d, 2H, J=7.2 Hz, N-CH2bs) of 2.75 (dt, 2H, J=4.9 Hz, JHF=28,2 Hz ), 2,03 (s,3H, O=C-CH3), of 1.64 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 170,8, 159,9 (l, JCF=245 Hz), other 153.9, 137,0 (l, JCF= 11 Hz), RB 131.1 (d, JCF=16 Hz), 127,0 (l, JCF=7 Hz), of 113.2 (d, JCF=3 Hz), 106,2 (l, JCF=28 Hz), 82,6 (l, JCF=166 Hz), 71,7, 66,0, 58,5 (l, JCF=19 Hz), 47,2, 41,6,

36,8, 27,1, 22,8; water K. Fisher = 1,05%; Anal. calc. for C18H3N3O3F2plus 1,66% water: C, 57,87; H, to 6.39; N, 11,25. Found: C, 57,67; H, To 6.43; N, 11,18. VRMS: calc. for C18H3N3ABOUT3F5: 368,1786 found: 368,1789.

Example 12. (S)-N-[[3- [3-fluoro-4-[1-(lanmeter)-3-(3-methyl)-azetidine] phenyl]-2-oxo - 5-oxazolidinyl]methyl]ndimethylacetamide

In kiln dried recovery flask with a capacity of 10 ml, equipped with a magnetic stirrer and a reverse holomon), 7,0 ml of acetonitrile, 76 μl of chloroacetonitrile and 415 mg of powdered potassium carbonate (3.0 mmol). The obtained white suspension was heated under reflux, causing it to quickly darkened to a reddish-brown color. After 20 minutes, TLC showed almost total expenditure (S)-N-[[3-[3-fluoro-4-[3-methyl-3-azetidinol] - phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide, after which the reaction mixture was stirred at room temperature for 16 hours. Visually unchanged, the reaction mixture was cooled to room temperature, removed in vacuum volatiles, the resulting residue was diluted with 20 ml water and was extracted twice with dichloromethane (20 ml). The combined organic layers were washed once with saturated salt solution (20 ml), dried over MgSO4, filtered and concentrated to obtain 340 mg of a yellow foamy substance. This crude product was purified by LC on 24 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and the result was 271 mg (75%) indicated in the title compound as a white amorphous solid. Rf= 0,30 (5% methanol/dichloromethane); []D-22(0,9252, methanol); IR (pasta) 1752, 1661, 1631, 1546, 1516, 1480, 1434, 1412, 1227, 1195 cm-1;
2a), of 3.77 (DD, 1H, J=6,8 Hz, J=9.1 Hz, Ph-N-CH2b), 3,66 (m, 2H, NH-CH2s) 3,55 (s, 4H, N-CH2s) to 3.49 (s, 2H, NC-CH2), 2,02 (s, 3H, O=C-CH3), of 1.64 (s, 3H, Ph - C-CH3);

13With NMR (75 MHz, CDCl3) RUB 171.1, 159,9 (l, JCF=246 Hz), 154,1, 137,4 (l, JCF= 11 Hz), 129,7 (l, JCF=15 Hz), 126,9 (l, JCF=7 Hz), 114,8, 113,3, 106,2 (l, JCF= 28 Hz), 71,8, 63,3, 47,2, 43,9, 41,6, 36,5, 26,9, 22,8; water in K. Fischer = 1,42%; Anal. calc. for C18H21N4O3F1plus 1,42% water: C, 59,14: H, 5,95: N, 15,33. Found: C, 58,96, H, 5,88; N, 15,33. VRMS: calc. for C18H21N4O3F1: 360,1598 found: 360,1610.

Example 13. (S)-N-[[3-[3-Fluoro-4-[1-(5-nitro-2-thiazolyl)-3-(3 - methyl)azetidine]phenyl]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide

In kiln dried round bottom flask with a capacity of 10 ml, equipped with a magnetic stirrer, were placed 241 mg (S)-N- [[3-[3 - fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (0.75 mmol), 4 ml of dimethyl sulfoxide and 188 mg of 2-bromo-5-nitrothiazole. Golden homogeneous solution was treated with 207 mg of powdered potassium carbonate (1.5 mmol) and stirred at room temperature for 16 hours. Dark brown now, the suspension was diluted in 40 ml of dichloromethane and washed in what rucenim 280 mg orange foamy substance. This crude product was purified by LC on 18 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/dichloromethane and the result was 191 mg (56%) indicated in the title compound as a yellow solid. This product was recrystallized from a mixture of ethyl acetate/hexane to obtain 88 mg of yellow solid. So pl. 182-185oC (Razlog.); Rf= 0,29 (5% methanol/dichloromethane); []D-20(0,4062, DMSO); IR (pasta) 1747, 1771, 1572, 1517, 1498, 1475, 1439, 1282, 1228, 1199 cm-1;

1H NMR (300 MHz, CDCl3) to 7.50 (DD, 1H, J=2.1 Hz, J=13.1 Hz, arene.), then 7.20 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), for 7.12 (t, 1H, J=8,5 Hz, arene.), rate 4.79 (m, 1H, Metin), 4,51 (d, 2H, J=8,9, Ph-C-CH2s), 4,24 (d, 2H, J=9.4 Hz, Ph-C-CH2s) 4,07 (t, 1H, J=9.0 Hz, Ph-N-CH2a), with 3.79 (DD, 1H, J=7,0 Hz, J= 9.5 Hz, Ph-N-CH2b), 3,62 (m, 2H, ), a 2.01 (s, 3H, O=C-CH3), a 1.75 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 201,0, 171,9, 171,8, 160,1 (l, JCF=247 Hz), 154, 6mm, 145,5, 138,4 (l, JCF=11 Hz), 127,1, 126,9 (l, JCF=6 Hz), 113,5, 106,5 (l, JCF=27 Hz), 72,2, 64,0, 47,4, 41,7, 38,1, 28,0, 22,4; water in K. Fischer = 0,59%; Anal. calc. for C19H20N5O5F1S1plus 0,59% water: C, 50,48; H, a 4.53; N, 15,49. Found: C, 50,26; H, 4,69; N, 15,29.

Example 14. (S)-N-[[3-[3-Fluoro-4- [1-(methanesulfonyl)-3- (3-methyl)azetidine] phenyl]-2-oxo-5-oxazolidinyl] methyl]-the 241 mg (S)-N-[[3-[3-fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo - 5-oxazolidinyl] methyl]ndimethylacetamide (0.75 mmol), 8 ml of dichloromethane and cooled to 0oC. Colourless, but not quite clear solution was treated with 0.16 ml of triethylamine (1.1 mmol) and 70 μl of methanesulfonanilide (0.90 mmol) without visible changes. Remove the cooling bath and the reaction mixture was heated to room temperature for three hours. Now clear solution was concentrated to a colorless syrup. This crude product was purified by LC on 18 g (230-400 mesh) silica gel with elution with a mixture of 5% methanol/ethyl acetate and the result was 234 mg (78%) indicated in the title compound as a white foamy substance. Rf= 0,30 (5% methanol/ethyl acetate); []D-9(C 0,9701, methanol); IR (pasta) 1753, 1664, 1631, 1517, 1436, 1412, 1333, 1228, 1194, 1151 cm-1;

1H NMR (300 MHz, CDCl3) 7,44 (DD, 1H, J=2.2 Hz, J=13,0 Hz, arene.), 7,16 (m, 1H, arene.), of 7.00 (t, 1H, J=8.6 Hz, arene.), 6,30 (PCs, 1H, J= 6 Hz, NH), 4,80 (m, 1H, Metin), 4,24 (d, 2H, J=7,4 Hz, Ms-N-CH2as) of 4.05 (t, 1H, J= 9.0 Hz, Ph-N-CH2a), 3,88 (d, 2H, J=7,6 Hz, Ms-N-CH2bs), with 3.79 (m, 1H, Ph-N-CH2b), 3,66 (m, 2H ), 2,87 (c, 3H, S-CH3), 2,03 (s, 3H,=C-CH3), by 1.68 (s, 3H, Ph-C-CH3);

13With NMR (75 MHz, CDCl3) 171,2, 160,2 (l, JCF=246 Hz), 154,2, 138,3 (l, JCF= 11 Hz), 128,2 (l, JCF=15 Hz), 126,9 (l, JCF=6 Hz), 113,5 (dCF=3 Hz), 106,5 (l, JCF= 28 Hz), 72,0, 60,8, 47,4 SUB>N3ABOUT5F1S1plus 0,3% ethyl acetate and 1.05% water: C, 50,59; H, 5,62; N, 10,38. Found: C, 50,50; H, Of 5.81; N, 10,29. VRMS: calc. for C17H22N3O5F1S1: 400,1342 found: 400,1352.

Example 15. (S)-N-[[3-[3-fluoro-4-[1-(benzyloxyethyl)-3- (3 - methyl) azetidine]phenyl]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide

In kiln dried round bottom flask with a capacity of 25 ml, equipped with a magnetic stirrer, were placed 313 mg (S)-N-[[3- [3-fluoro-4- [3-methyl-3-azetidinol] phenyl] -2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide (0.97 mmol), 10 ml dichloromethane and cooled to 0oC. Colourless, but not quite clear solution was treated with 0.27 ml of triethylamine (2.0 mmol) and 0.23 ml of benzyloxyacetaldehyde (1.5 mmol), the resulting reaction mixture was transparent and had a pale yellow color. Remove the cooling bath and the reaction mixture was heated to room temperature for 16 hours. Visually unchanged, the solution was diluted with 15 ml saturated sodium bicarbonate solution and was extracted twice with dichloromethane (20 ml). The combined organic layers were washed once with 15 ml of saturated salt solution, dried over MgSO4, filtered and concentrated to obtain 521 mg light yellow foamy veshestvah and the result was 370 mg (81%) indicated in the title compound as a white foamy substance. Rf= 0,29 (10% methanol/ethyl acetate); []D-17(0,9516, methanol); IR (pasta) 1754, 1654, 1631, 1548, 1516, 1438, 1411, 1226, 1193, 1122 cm-1;

1H NMR (300 MHz, CDCl3) was 7.45 (DD, 1H, J=2.2 Hz, J=13,0 Hz, arene.), 7,33 (m, 5H, arene.), to 7.15 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), ? 7.04 baby mortality (t, 1H, J= 8.6 Hz, arene.), 6.42 per (PCs, 1H, J=6 Hz, NH), 4,79 (m, 1H, Metin), of 4.57 (s, 2H, Ph-CH2), 4,50 (d, 1H, J=9.0 Hz, Ph-C-CH2a), to 4.33 (d, 1H, J=9.7 Hz, Ph-C-CH2b), to 4.23 (d, 1H, J=9,2 Hz, Ph-C-CH2b), Android 4.04 (m, 4H, Ph-C-CH2a, O-CH2Ph-N-CH2a), with 3.79 (DD, 1H, J=6,8 Hz, J=9.0 Hz, Ph - N-CH2b), 3,66 (m, 2H, NH-CH2), 2,02 (s, 3H, O=C-CH3), to 1.61 (s, 3H, Ph-C-Snz);

13C NMR (75 MHz, CDCl3) RUB 171.1, 169,6, to 160.3 (d, JCF=246 Hz), 154,1, 138,1 (l, JCF= 11 Hz), 137,0, 128,4, 128,2, 128,0, 127,9, 127,2 (d, JCF=6 Hz), 113,3, 106,5 (l, JCF=26 Hz), 73,3, 71,9, 69,0, 62,4, 59,4, 47,4, 41,8, 37,7, 28,2, 23,0; BPMC: calc. for C25H28N3O5F1: 470,2091 found: 470,2101.

Example 16. (S)-N-[[3-[3-Fluoro-4- [1-(hydroxyacetic)-3-(3 - methyl)azetidine]phenyl)-2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide

In a Parr flask with a capacity of 250 ml was placed 310 mg of (S)-N-[[3- [3-fluoro-4-[1- (benzyloxyethyl)-3-(3-methyl) azetidine] -phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (0.66 mmol) in 30 ml of methanol and 31 mg of 10% palladium on carbon. The black suspension was placed in an atmosphere of hydrogen at a pressure of 40 pounds per square had ontrolirovat by TLC analysis with the addition of several equivalents of 10% palladium on carbon (total 300 mg) and increasing time (five days) until complete consumption of (S)-N-[[3-[3-fluoro-4-[1- (benzyloxyethyl)-3-(3-methyl)azetidine] phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide. The reaction mixture was filtered through a layer of Celite and concentrated to obtain 221 mg (88%) indicated in the title compound in the form of not-quite-white amorphous solid. Rf= 0,21 (15% methanol/ethyl acetate); []D-20(0,9432, methanol); IR (pasta) 1754, 1655, 1632, 1552, 1517, 1481, 1435, 1412, 1227, 1192 cm-1;

1H NMR (300 MHz, CDCl3) 7,47 (DD, 1H, J=2.1 Hz, J=13,0 Hz, arene.), to 7.15 (DD, 1H, J= 2.2 Hz, J=8,5 Hz, arene.), 7,07 (t, 1H, J=8.6 Hz, arene.), 6,37 (PCs, 1H, J=6 Hz, NH), 4,80 (m, 1H, Metin), to 4.38 (m, 2H, Ph-C-CH2aand2b), to 4.01 (m, 5H, Ph - C-CH2aand2b, , Ph-N-CH2a), with 3.79 (DD, 1H, J=6,8 Hz, J= 9.1 Hz, Ph-N-CH2b), 3,68 (m, 2H ), 2,03 (s, 3H, O=C-CH3), of 1.65 (s, 3H, Ph-C-CH);

13C NMR (75 MHz, CDCl3) is 171.3, to 170.9, 160,1 (l, JCF=246 Hz), other 153.9, 138,1 (l, JCF= 11 Hz), uniforms, 127.6 (d, JCF=14 Hz), 126,9 (l, JCF=6 Hz), 113,1, 106,3 (l, JCF=28 Hz), 71,8, 60,1, 59,3, 58,5, 47,1, 41,6, 37,0, 28,0, 22,8; VRMS: calc. for C18H22N3ABOUT5F1: 379,1543 found: 379,1542.

Example 17. (S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)phenyl]-5-oxazolidinyl] methyl] ndimethylacetamide

Stage 1: 4-Hydroxy-4-[4-[[(phenylmethoxy)carbonyl]- amino] phenyl]-1-piperidinecarboxylic acid fenilmetilovy ether

To a solution of N-(carbobenzoxy)-4-bromoaniline (5,00 g) in dry tetrahydrofuran (80 ml) at -78oC in Aty the solution was stirred at -78oC for 30 minutes and then treated with a solution of N-(carbobenzoxy)-4-piperidone (3,99 g) in dry tetrahydrofuran (17 ml). The reaction mixture was stirred for three hours while allowing the temperature of the reaction mixture to rise to 0oC, and abruptly stopped the reaction by adding saturated aqueous solution of ammonium chloride (30 ml). Then the mixture was diluted with water (100 ml), layers were separated, the aqueous phase was extracted with diethyl ether and the combined organic phase was washed with saturated salt solution (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (230-400 mesh mesh, 350 g) with elution with a mixture of ethyl acetate/hexane (25/75) and the fraction with Rf= 0,38 according to TLC (ethyl acetate/hexane, 50/50) was collected and concentrated under reduced pressure to obtain specified in the connection header, so pl. 156-158oC.

Stage 2: 3,6-Distro-4-[4- [[(phenylmethoxy) carbonyl]-amino] phenyl]-1(2H)- pyridineboronic acid fenilmetilovy ether

The solution phenylmethylene ester 4 - hydroxy-4- [4-[[(phenylmethoxy) carbonyl] amino] phenyl]-1 - piperidinecarboxylic acid (example 17, step 1, 2.50 g) in dry methylene chloride in an atmosphere of N2processed Terrassen aqueous solution of potassium carbonate (25 ml) to neutralize excess triperoxonane acid and the layers were separated. The organic phase is washed with water (20 ml) and saturated salt solution (20 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue chromatography was carried out on silica gel (230-400 mesh mesh, 300 g) with elution with a gradient mixture of ethyl acetate/hexane (20/80-50/50). Collecting fractions with Rf= 0,69 according to TLC (ethyl acetate/hexane, 50/50) and removing under reduced pressure the solvent has been specified in the header of the connection, so pl. 146-148oC.

Stage 3: (R)-(-)-3,6-Distro-4-[4-[5-(hydroxymethyl)- 2-oxo-3-oxazolidinyl]phenyl]-1(2H)-pyridineboronic acid fenilmetilovy ether

The solution phenylmethylene ester of 3,6-dihydro-4- [4-[[phenylmethoxy)carbonyl] amino] phenyl] -1(2H) - pyridineboronic acid (example 17, step 2, 0,500 g) in dry THF (5.7 ml) at -78oC in an atmosphere of N2processed by adding n-utility (0,73 ml, 1.6 M in hexane) dropwise over five minutes. The resulting mixture was stirred at -78oC for 45 minutes and then treated by adding dropwise (R)-(-)- glycidylether. The resulting solution was allowed to warm to ambient temperature for about 45 minutes and stirred it for another 20 hours, then abruptly stopped the reaction of saturated aqueous hlushkou phase was washed with saturated salt solution (10 ml), was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (230-400 mesh mesh, 40 g) with elution with a mixture of methanol/methylene chloride (1/99). Pooling and concentration of fractions with Rf=0,37 according to TLC (methanol/chloroform, 5/95) gave specified in the title compound, I. 131, 5mm square-133,5oC.

Stage 4: (R)-(-)-3,6-Distro-4-[4-[5- [[(methylsulphonyl)-oxy] methyl]-2-oxo-3-oxazolidinyl] phenyl] -1 (2H) -pyridineboronic acid fenilmetilovy ether

The solution phenylmethylene ether (R)-(-)-3,6-dihydro-4-[4-[5- (hydroxymethyl)-2-oxo-3-oxazolidinyl]phenyl]-1(2H)- pyridineboronic acid (example 17, step 3, 970 mg) and triethylamine (0,50 ml) in dry methylene chloride (9.5 ml) atoC in an atmosphere of N2handled methanesulfonanilide (0,20 ml), adding it dropwise. The resulting mixture was stirred at 0oC for one hour, diluted with methylene chloride (40 ml), washed with water (10 ml), saturated aqueous sodium bicarbonate (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header, so pl. 166-168oC.

Stage 6: (S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl) phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide

The mixture phenylmethylene ether (S)-(-)-4-[4-[5-[(acetylamino)- methyl]-2-oxo-3-oxazolidinyl] phenyl] -3,6-dihydro-1(2H) -pyridineboronic acid (example 17, step 5, 625 mg) and 10% palladium on carbon (300 mg) in methanol (100 ml) was shaken in a Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2within one hour and at a pressure of 20 psig (1.4 kg/cm2) for 16 hours, the catalyst was removed by filtration through Celite and the filtrate was concentrated under reduced pressure to obtain specified in the connection header, so pl. 169-171oC.

Example 18. (S)-(-)-N-[[3-[4- [1-[(Benzyloxy) acetyl]-4-piperidinyl] phenyl]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide

A mixture of (S)-(-)-N- [[2-oxo-3-[4- (4-piperidinyl) phenyl]-5-oxazolidinyl] methyl] ndimethylacetamide (example 17, 300 mg) and triethylamine (0,20 ml) in dry methylene chloride (19 ml) at 0oC in an atmosphere of N2handled benzyloxyacetaldehyde (of 0.18 ml) and the resulting solution was stirred at 0oC for water (2 x 10 ml), saturated aqueous sodium bicarbonate (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (230-400 mesh mesh, 45 g) with elution by a gradient of methanol/methylene chloride (1/99-2/98). Pooling and concentration of fractions with Rf= 0,28 according to TLC (methanol/chloroform, 5/95) gave specified in the title compound, NMR (CDCl3, 400 MHz) 7,45, 7,35, 7,18, 6,26, 4,75, 4,63, 4,22, 4,04, 3,78, 3,70, 3,60, 3,09, 2,70, 2,02, 1,85, 1,60.

Example 19. (S)-(-)-N-[[3-[4-[1-(Hydroxyacetic)-4-piperidinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide

A mixture of (S)-(-)- N-[[3-[4-[1-[(benzyloxy)acetyl]-4-piperidinyl]phenyl]-2 - oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 18, 207 mg) and 10% palladium on carbon (100 mg) in methanol (9 ml) was shaken in a Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2within 20 hours, the catalyst was removed by filtration through Celite and the filtrate was concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (230-400 mesh mesh, 20 g) with elution by a gradient of methanol/methylene chloride (5/95-10/90). Unification and the end is lorid/diethyl ether gave specified in the title compound, so pl. 155-157oC.

Example 20. (S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)-3-forfinal]-5 - oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 1-(3-Forfinal)-of 2.2.5.5-tetramethyl-1-Aza-2,5 - disilacyclobutane

A solution of freshly Diisopropylamine (22.9 ml) in dry tetrahydrofuran (175 ml) at -78oC in an atmosphere of N2was treated with n-butyllithium (1.6 M in hexane, 109 ml) dropwise over 15 minutes and the resulting mixture was stirred at -78oC for 45 minutes and then was added over ten minutes via cannula to a solution of 3-foronline (8,00 ml) in dry tetrahydrofuran (166 ml) at -78oC in an atmosphere of N2. The resulting reaction mixture was stirred at -78oC for 50 minutes and then treated with a solution of 1,1,4,4-tetramethyl-1,4 - DICHLOROSILANE (18.3 g) in dry tetrahydrofuran (85 ml). The mixture was let to slowly warm to ambient temperature for four hours under stirring and then washed with water (2 x 200 ml) and saturated salt solution (100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the title compound, NMR (CDCl3400 MHz) 7,12, 6,65, 6,58, 0,86, 0,24.

Stage 2: 3,6 - Distro-4-[[(trifluoromethyl) sulfonyl]oxy]- 1(2H)-the feast of the Hom tetrahydrofuran (133 ml) at - 78oC in an atmosphere of N2was treated with n-butyllithium (1.6 M in hexane of 41.5 ml) dropwise over ten minutes and the resulting mixture was stirred at -78oC for one hour and then treated dropwise within 10 minutes with a solution of 1-(1,1 - dimethylethoxysilane)-4-piperidone (12.0 g) in dry tetrahydrofuran (120 ml). The resulting mixture was stirred at -78oC for 40 minutes and then treated with a solution of N - phenyltrichlorosilane (22,0 g) in dry tetrahydrofuran (62 ml) for five minutes. The reaction mixture was stirred at -78oC for 10 minutes and at 0oC for four hours and then the reaction abruptly stopped by the addition of water (200 ml). Separated the layers, the aqueous phase was extracted with diethyl ether (100 ml) and the combined organic phase was washed with saturated salt solution (50 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain specified in the title compound, NMR (CDCl3, 400 MHz) 5,77, 4,05, 3,64, 2,45, 1,48 .

Stage 3: 3,6-Distro-4-[4-amino-2-forfinal] -1(2H)-pyridineboronic acid 1,1-dimethylethylene ether

A solution of 1-(3-forfinal)-of 2.2.5.5-tetramethyl-1-Aza-2,5 - disilacyclobutane (example 20, step 1, of 19.1 g) in dry tetrahydrofuran within ten minutes and the resulting mixture was stirred at -78oC for 2.25 hours. Then was added over 15 minutes a solution of zinc chloride (0.5 M in tetrahydrofuran (THF, 150 ml) and gave the mixture to warm to ambient temperature over one hour with stirring. Was added a solution of 1,1-dimethylethylene ester of 3,6-dihydro-4- [[(trifluoromethyl) sulfonyl] oxy] -1(2H)- pyridineboronic acid (example 20, step 2, to 20.8 g) in dry tetrahydrofuran (63 ml) and tetrakis(triphenylphosphine)-palladium(0) (1.45 g) and the mixture was degirolami, was heated to boiling and boiled under reflux for five minutes, cooled to ambient temperature and stirred for 12 hours. Then the mixture was diluted with water (150 ml), layers were separated, the aqueous phase was extracted with diethyl ether (2 x 100 ml) and the combined organic phase was washed with water (100 ml) and saturated salt solution (100 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. After that, the residue was dissolved in methanol (630 ml) and treated with anhydrous potassium carbonate (17.3 g) and the mixture was stirred at ambient temperature for 40 minutes, concentrated under reduced pressure, diluted with water (100 ml) and was extracted with diethyl ether (2 x 150 ml). The combined organic phase was washed eigendom the pressure to get the crude product, which was chromatographically on silica gel (230-400 mesh mesh, 1 kg) with elution with a gradient mixture of ethyl acetate/hexane (15/85 - 50/50). Pooling and concentration of fractions with Rf=0,17 according to TLC (ethyl acetate/hexane, 25/75) were specified in the title compound, so pl. 123-125oC.

Stage 4: 4-[4- [[Phenylmethoxy) carbonyl] amino-2-forfinal] -1-piperidinecarboxylic acid 1,1-dimethylethylene ether

A mixture of 1,1-dimethylethylene ester of 3,6-dihydro-4- [4-amino-2-forfinal] -1(2H)- pyridineboronic acid (example 20, step 3, 11,44 g) and 10% palladium on carbon (4 g) in methanol (400 ml) in four flasks Parra was shaken on the Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2), the catalyst was removed by filtration through Celite and the filtrate was concentrated under reduced pressure to obtain the intermediate 1,1-dimethylethylene ester 4-[4-amino-2-forfinal] -1 - piperidinecarboxylic acid. A mixture of this intermediate (11,17 g) and sodium bicarbonate (to 6.57 g) in dry tetrahydrofuran (390 ml) was treated with benzylchloride (5,86 ml) and the resulting mixture was stirred at ambient temperature for 15 hours and washed with water (200 ml). The aqueous phase was extracted with methylthio the sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (70-230 mesh, 800 g) with elution with a gradient mixture of ethyl acetate/hexane (15/85-25/75). Pooling and concentration of fractions with Rf=0,38 according to TLC (ethyl acetate/hexane, 25/75) were specified in the title compound, so pl. 96-98oC.

Stage 5: (R)-(-)-4-[4-[5- (Hydroxymethyl)-2-oxo-3 - oxazolidinyl]-2-forfinal] -1 - piperidinecarboxylic acid 1,1-dimethylethylene ether

A solution of 4-[4-[[phenylmethoxy) carbonyl] amino-2-forfinal] -1 - piperidinecarboxylic acid 1,1-dimethylethylene ester (example 20, step 4, 0,500 g) in dry tetrahydrofuran (5.7 ml) at -78oC in an atmosphere of N2was treated with n - butyllithium (0,73 ml, 1.6 M in hexane) dropwise over five minutes. The resulting mixture was stirred at -78oC for 45 minutes and then treated dropwise (R)-(-)-glycidylether. The resulting solution was allowed to warm to ambient temperature for about 45 minutes and was stirred for another 20 hours after which the reaction abruptly stopped by adding a saturated aqueous solution of ammonium chloride (10 ml), the reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (2 x 15 ml). The combined organic phase was washed with saturated salt solution (10 ml), dried over b is that was chromatographically on silica gel (230-400 mesh mesh, 40 g) with elution with a mixture of methanol/methylene chloride (1/99). Pooling and concentration of fractions with Rf=0,37 according to TLC (methanol/chloroform, 5/95) gave specified in the title compound, so pl. 120-122oC.

Stage 6: (R)-(-)-4-[4-[5- [[(Methylsulphonyl)oxy]methyl]-2-oxo-3-oxazolidinyl]-2 - forfinal]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

A solution of (R)-(-)-4-[4-[5 (hydroxymethyl) 2-oxo-3 - oxazolidinyl]-2-forfinal]-1-piperidinecarboxylic acid 1,1 - dimethylethylene ester (example 20, step 5, 970 mg) and triethylamine (0,50 ml) in dry methylene chloride (9.5 ml) atoC in an atmosphere of N2handled methanesulfonanilide (0,20 ml) dropwise. The resulting mixture was stirred at 0oC for one hour, diluted with methylene chloride (40 ml), washed with water (10 ml), saturated aqueous sodium bicarbonate (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header, so pl. 163-165oC.

Stage 7: (R)-(-)-4-[4-[5-(Azidomethyl)-2-oxo-3-oxazolidinyl] - 2-forfinal]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

A mixture of (R)-(-)-4-[4-[5-[[(methylsulphonyl)oxy] methyl] -2 - oxo-3-occasionally (a 7.62 g) in dry dimethylformamide (117 ml) in an atmosphere of N2was stirred at 60oC for five hours and at ambient temperature for 16 hours. Then the mixture was diluted with ethyl acetate (200 ml), washed with water (8 × 100 ml) and saturated salt solution (100 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain specified in the connection header, so pl. 109-110oC.

Step 8: (S)-(-)-4-[4-[5-(Aminomethyl)-2-oxo-3-oxazolidinyl] -2-forfinal]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

A solution of (R)-(-)-4-[4-[5-(azidomethyl)-2-oxo-3-oxazolidinyl] -2-forfinal] -1-piperidinecarboxylic acid 1,1-dimethylethylene ester (example 20, step 7, a 12.05 g) in dry tetrahydrofuran (96 ml) in an atmosphere of N2was treated with triphenylphosphine (8,29 g) for five minutes and the resulting mixture was stirred at ambient temperature for two hours. Then the mixture was treated with water (3.1 ml), was heated to 40oC, stirred at 40oC for five hours and at ambient temperature for 12 hours, then concentrated under reduced pressure to obtain a viscous oil, which was chromatographically on silica gel (70-230 mesh, 500 g) with elution by a gradient of methanol/methylene chloride (2,5/97,5 - 1 header connection so pl. 136-137oC.

Stage 9: (S)-(-)-4-[4-[5-[(Acetylamino)methyl]-2-oxo - 3-oxazolidinyl] -2-forfinal]-1 - piperidinecarboxylic acid 1,1-dimethylethylene ether

Solution (S)-(-)-4-[4-[5-(aminomethyl)-2-oxo-3-oxazolidinyl] - 2-forfinal] -1-piperidinecarboxylic acid 1,1-dimethylethylene ester (example 20, step 8, to 9.45 g) in dry methylene chloride (96 ml) in an atmosphere of N2was treated with pyridine (of 5.82 ml) and acetic anhydride (3,40 ml) and the resulting mixture was stirred at ambient temperature for 4 hours, diluted with methylene chloride (25 ml), washed with water (25 ml), saturated aqueous sodium bicarbonate (25 ml) and saturated salt solution (25 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (230-400 mesh mesh, 350 g) with elution by a gradient of methanol/methylene chloride(2,5/97,5- 7,5/92,5). Pooling and concentration of fractions with Rf=0,51 according to TLC (methanol/chloroform, 10/90) were specified in the title compound, so pl. 144-146oC.

Stage 10: (S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl]-3 - forfinal]-5-oxazolidinyl]methyl] ndimethylacetamide

Solution (S)-(-)-4-[4-[5-[(acetylamino)methyl]-2-oxo-3 - oxazolidinyl]-2-de (100 ml) at 0oC in an atmosphere of N2, worked triperoxonane acid (24,0 ml) for one minute and the resulting mixture was stirred at 0oC for 1.75 hours, concentrated under reduced pressure, diluted with water (100 ml), cooled in an ice bath, brought to pH 11 with saturated aqueous potassium carbonate solution and was extracted with a mixture of methanol/methylene chloride (5/95,6 x 100 ml). The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header, so pl. 163-164oC.

Example 21. (S)-(-)-N-[[3-[4-[1-[(Benzyloxy) acetyl]-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide

Following the General method of example 18, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl] phenyl-5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-)-N- [[2-oxo-3-[4-(4-piperidinyl]-3-forfinal]-5-oxazolidinyl]- methyl]the ndimethylacetamide and purification of the crude product by trituration with a mixture of chloroform/diethyl ether and filtration, has been specified in the header of the connection, so pl. 147-149oC.

Example 22. (S)-(-)-N-[[3-[4-[1-(Hydroxyacetic)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (S)-(-)-N-[[3-[4-[1-�XID palladium on carbon (2,80 g) in methanol (500 ml) was stirred in hydrogen atmosphere (balloon) for four hours, remove the catalyst by filtration through Celite and the filtrate was concentrated under reduced pressure, triturated with a mixture of methylene chloride/diethyl ether and filtered, resulting in the specified header connection, so pl. 182-183oC.

Example 23. (S)-(-)-N-[[3-[4-[1-(Indole-2-carbonyl)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A solution of indole-2-carboxylic acid (79 mg) and 1,1'-carbonyldiimidazole (80 mg) in dry tetrahydrofuran (2.0 ml) was stirred at ambient temperature for one hour and was added a solution of (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl] -3-forfinal] -5-oxazolidinyl]- methyl] ndimethylacetamide (example 20, 150 mg) in dry tetrahydrofuran (6.0 ml). Then the mixture was stirred at ambient temperature for 19 hours, concentrated under reduced pressure, diluted with methylene chloride (20 ml), washed with saturated aqueous sodium bicarbonate (10 ml), water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (70-230 mesh, 10 g) with elution with a mixture of methanol/methylene chloride (7,5/92,5). Association and kontsentriruemoy ether gave specified in the title compound, so pl. 223-225oC.

Example 24. (S)-(-)-N-[[3-[4-[1-(Isoxazol-5-carbonyl)- 4-piperidinyl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide

The solution isoxazol-5-carboxylic acid (79 mg) and 1,1'- carbonyldiimidazole (80 mg) in dry tetrahydrofuran (2.0 ml) was stirred at ambient temperature for one hour and was added a solution of (S)-(-)-N- [[2-oxo-3- [4-(4 - piperidinyl] -3-forfinal] -5-oxazolidinyl] methyl]-ndimethylacetamide (example 20, 150 mg) in dry tetrahydrofuran (6.0 ml). Then the mixture was stirred at ambient temperature for 19 hours, concentrated under reduced pressure, diluted with methylene chloride (20 ml), washed with saturated aqueous sodium bicarbonate (10 ml), water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (70-230 mesh, 10 g) with elution with a mixture of methanol/methylene chloride (7,5/92,5). Pooling and concentration of fractions with Rf=0,67 according to TLC (methanol/chloroform, 10/90) and recrystallization from a mixture of chloroform/diethyl ether gave specified in the title compound, so pl. 290-292oC.

Example 25. (S)-(-)-N-[[3-[4-[1-(Methyl is original]-3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 125 mg) and pyridine (60 μl) in dry methylene chloride (1.9 ml) at 0oC were treated with methanesulfonamide (32 μl) and the resulting mixture was stirred at 0oC for one hour and at ambient temperature for 16 hours. Then the reaction mixture was diluted with methylene chloride (30 ml), washed with water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure and the residue was recrystallized from a mixture of methylene chloride/diethyl ether to obtain specified in the connection header, so pl. 240-242oC.

Example 26. (S)-(-)-4-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl] -2-forfinal]-1-piperidinecarboxylic acid methyl ester

A mixture of (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 150 mg) and sodium bicarbonate (75 mg) in dry tetrahydrofuran (6.0 ml) at 0oC in an atmosphere of N2handled methylchloroform (38 μl) and the resulting mixture was stirred at 0oC for one hour. Then the reaction mixture was diluted with ethyl acetate (20 ml), washed with water (10 ml) and saturated salt solution (10 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure and odinani, so pl. 165-166oC.

Example 27. (S)-(-)-N-[[3-[4-[1-(Lanmeter)-4-piperidinyl]-3 - forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 150 mg), chloroacetonitrile (31 μl) and anhydrous potassium carbonate (124 mg) in dry acetonitrile (4 ml) in an atmosphere of N2was stirred at ambient temperature for 20 hours, diluted with methylene chloride (20 ml), washed with water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure and the residue was recrystallized from a mixture of methylene chloride/diethyl ether to obtain specified in the connection header, so pl. 165-167oC.

Example 28. (S)-(-)-N-[[3-[4-[1-(2-Foradil)-4-piperidinyl]-3 - forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method of example 27 with minor changes but with the replacement of chloroacetonitrile on the complex 2-perately ether 4-toluensulfonate acid and purification of the crude product by chromatography on silica gel (70-230 mesh, 30 g) with elution with a mixture of methanol/methylene chloride, got mentioned in the title compound, so pl. 155-157oC.

Example 29. (S)-(-)-N-[[3-[4 shall dinyl)-3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 150 mg), 1- (3-dimethylaminopropyl) -3 - ethylcarbodiimide (171 mg) and formic acid (34 μl) in dry tetrahydrofuran (6 ml) was stirred at ambient temperature for one hour, diluted with methylene chloride (10 ml), washed with water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure and the residue was recrystallized from a mixture of methylene chloride/diethyl ether to obtain specified in the connection header, so pl. 186-187oC.

Example 30. (S)-(-)-4-[4-[5- [[(2,2-Dichloroacetyl)amino] methyl]- 2-oxo-3-oxazolidinyl] -2-forfinal]-1 - piperidinecarboxylic acid 1,1-dimethylethylene ether

Solution (S)-(-)-4-[4- [5-(aminomethyl)-2-oxo-3-oxazolidinyl]- 2-forfinal] -1 - piperidinecarboxylic acid 1,1 - dimethylethylene ester (example 20, step 8, 400 mg) in dry methylene chloride (4,1 ml) at 0oC in an atmosphere of N2was treated with triethylamine (of 0.21 ml) and dichloroacetylene (0,11 ml) and the resulting mixture was stirred at 0oC for three hours, diluted with methylene chloride (10 ml), washed with water (10 ml), saturated aqueous sodium bicarbonate (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and Cockerel (70-230 mesh, 50 g) with elution with a mixture of methanol/chloroform (5/95). Pooling and concentration of fractions with Rf=0,53 according to TLC (methanol/chloroform, 10/90), rubbing with a mixture of methylene chloride/diethyl ether and filtration gave specified in the title compound, so pl. 168-170oC.

Example 31. (S)-(-)-2,2-Dichloro-N-[[2-oxo-3-[3-fluoro-4-(4 - piperidinyl)phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General methodology of stage 10 of example 20, with minor changes but with the replacement phenylmethylene ether (S)-(-)-4-[4- [5-[(acetylamino)methyl]-2-oxo - 3-oxazolidinyl] -2-forfinal]-1 - piperidinecarboxylic acid 1,1 - dimethylethylene ether (S)-(-)-4- [4-[5-[[(2,2-dichloroacetyl) -amino] methyl]-2-oxo-3 - oxazolidinyl]-2-forfinal] -1-piperidinylcarbonyl acid (example 30), have been specified in the title compound, NMR (CDCl3, 400 MHz) 7,37, 7,22, 7,10, 5,99, 5,29, 4,83, 4,07, 3,78, 3,71, 3,30, 2,98, 2,83, 2,09, 1,81.

Example 32 (S)-(-)-2,2-Dichloro-N- [[2-oxo-3-[3-fluoro-4- [1-[(acetoxy) acetyl] -4-piperidinyl] phenyl]-5-oxazolidinyl] -methyl]ndimethylacetamide

Following the General method of example 18, with minor changes, but replacing (S)-(-)-3-N-[4-(4-piperidinyl)phenyl] -5-atsetamidometil-2-oxazolidinone (S)-(-)-2,2-dichloro-N- [[2-oxo-3-[3-fluoro-4- (4-piperidinyl) phenyl] -5-oxazolidinyl] -methyl] ndimethylacetamide (Cl3, 400 MHz) 7,42, 7,15, 6,24, 4,77, 4,04, 3,77, 3,68, 3,20, 3,07, 2,71, 2,20, 2,02, 1,88, 1,68.

Example 33. (S)-(-)-2,2-Dichloro-N-[[2-oxo-3-[3-fluoro-4-[1- (hydroxyacetic)-4-piperidinyl]phenyl] 5-oxazolidinyl]-methyl] ndimethylacetamide

A mixture of (S)-(-)-2,2-dichloro-N-[[2-oxo-3-[3-fluoro-4-[1- [(acetoxy)acetyl] -4-piperidinyl]phenyl]-5-oxazolidinyl]-methyl] ndimethylacetamide (example 32, 110 mg) and anhydrous potassium carbonate (60 mg) in methanol (8,8 ml) was stirred in an atmosphere of N2at ambient temperature for one hour and then concentrated under reduced pressure and was chromatographically on silica gel (70-230 mesh, 10 g) with elution with a mixture of methanol/chloroform (10/90). Pooling and concentration of fractions with Rf=0,41 according to TLC (methanol/chloroform, 10/90), re-purification by radial chromatography (silikagelevye vinyl 2000 MK) with elution with a mixture of methanol/methylene chloride and rubbing with a mixture of chloroform/diethyl ether gave specified in the title compound, NMR (CDCl3, 400 MHz) 7,46, 7,39, 7,15, 5,99, 4,84, 4,74, 4,22, 4,09, 3,77, 3,61, 3,10, 2,79, 1,89, 1,65.

Example 34. (S)-(-)-N-[[2-Oxo-3- [3-fluoro-4-[1-[(acetoxy) acetyl]-4-piperidinyl] phenyl]-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 18, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)cetamide (example 20) and benzyloxyacetaldehyde on acetoxyacetyl, got mentioned in the title compound, NMR (CDCl3, 400 MHz) 7,42, 7,15, 6,24, 4,77, 4,04, 3,77, 3,68, 3,20, 3,07, 2,71, 2,20, 2,02, 1,88, 1,68.

Example 35. (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)-3,5 - differenl]-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 1-(3,5-Differenl)-of 2.2.5.5-tetramethyl-1-Aza-2,5 - disilacyclobutane

Following the General methodology stage 1 of example 20, with minor changes, but replacing 3-foronline 3.5-diptiranjan got mentioned in the title compound, NMR (CDCl3, 400 MHz) 6,38, 6,31, 0,87, 0,17.

Stage 2: 3,6-Dihydro-4-[4-amino-2,6-differenl] -1(2H)-pyridineboronic acid 1,1-dimethylethylene ether

Following the General method of stage 3 of example 20, with minor changes, but replacing 1-(3-forfinal)-of 2.2.5.5-tetramethyl-1-Aza - 2,5-disilacyclobutane 1-(3,5-differenl)-of 2.2.5.5-tetramethyl-1-Aza - 2,5-disilacyclobutane

(example 35, step 1) has been specified in the header of the connection, so pl. 134-135oC.

Stage 3: 4-[4-[[(Phenylmethoxy)carbonyl]amino]-2,6 - differenl]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

Following the General method of stage 4 of example 20, with minor changes, but replacing 1,1-dimethylethylene ester of 3,6-dihydro-4- [4-amino-2-forfinal] -1(2H)-pyridineboronic acid nogo product by trituration with a mixture of ethyl acetate/hexane and filtration, got mentioned in the title compound, so pl. 153 to 155oC.

Stage 4: (R)-(-)-4-[4-[5-(Hydroxymethyl)-2-oxo-3-oxazolidinyl] -2,6-differenl]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid 4-[4-[[(phenylmethoxy)-carbonyl]amino-2,6-differenl] -1-piperidinecarboxylic acid 1,1-dimethylethylene ester (example 35, step 3) has been specified in the title compound, NMR (CDCl3, 400 MHz) 7,11, 4,75, 4,22, 3,96, 3,75, 3,06, 2,76, 2,50, 1,98, 1,65, 1,48.

Stage 5: (R)-(-)-4-[4-[5- [[(Methylsulphonyl)oxy] methyl]-2 - oxo-3-oxazolidinyl] -2,6 - differenl]-1 - piperidinecarboxylic acid 1,1-dimethylethylene ether

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-(hydroxymethyl) -2-oxo-3-oxazolidinyl] phenyl] -1(2H)- pyridineboronic acid 1,1-dimethylethylene ether (R)-(-)-4-[4- [5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl]-2,6 - differenl]-1 - piperidinecarboxylic acid, has been specified in the header of the connection, so pl. 125-126oC.

Stage 6: (R)-(-)-4-[4-[/BR> Following the General method stage 7 of example 20, with minor changes, but replacing 1,1-dimethylethylene ether (R)-(-)-4-[4-[5- [[(methylsulphonyl)oxy] methyl]-2-oxo-3-oxazolidinyl]-2 - forfinal]-1 - piperidinecarboxylic acid 1,1-dimethylethylene ether (R)-(-)-4- [4-[5-[[(methylsulphonyl) oxy] methyl] -2-oxo-3 - oxazolidinyl] -2,6-differenl] -1-piperidinecarboxylic acid, has been specified in the header of the connection, so pl. 125-127oC.

Stage 7: (S)-(-)-4-[4-[5-[(Acetylamino)methyl]-2-oxo - 3-oxazolidinyl] -2,6-differenl]-1-piperidinecarboxylic acid 1,1-dimethylethylene ether

A mixture of (R)-(-)-4-[4-[5-(azidomethyl)-2-oxo-3-oxazolidinyl] - 2,6-differenl] -1-piperidinecarboxylic acid 1,1-dimethylethylene ester (example 35, step 6, 1.51 g) and 10% palladium on carbon (367 mg) in methanol (35 ml) was stirred in hydrogen atmosphere (balloon) for 18 hours, remove the catalyst by filtration through Celite and the filtrate was concentrated under reduced pressure to obtain the intermediate compound 5-aminomethyl-2-oxazolidinone (Rf=0,10 according to TLC, methanol/chloroform, 5/95). The solution of this intermediate compound (1.28 g) and pyridine (of 2.51 ml) in dry methylene chloride (31 ml) at 0oC in an atmosphere of N2was treated with acetic, angiari the s 1.5 hours. Then the mixture was diluted with methylene chloride (15 ml), washed with water (10 ml), saturated aqueous sodium bicarbonate (2 x 10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (70-230 mesh, 150 g) with elution by a gradient of methanol/methylene chloride (1/99 - 4/96). Pooling and concentration of fractions with Rf=0,31 according to TLC (methanol/chloroform, 5/95) gave specified in the title compound, NMR (CDCl3, 400 MHz) 7,06, 6,56, 4,78, 4,22, 4,00, 3,74, 3,65, 3,05, 2,75, 2,02, 1,96, 1,64, 1,47.

Step 8: (S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)-3,5-differenl] -5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (S)-(-)-4-[4-[5-[(acetylamino)methyl] -2-oxo-3 - oxazolidinyl]-2,6-differenl] -1-piperidinecarboxylic acid 1,1-dimethylethylene ester (example 35, step 7, 847 mg) and triperoxonane acid (12 ml) at 0oC in an atmosphere of N2was stirred for two hours and then concentrated under reduced pressure to remove excess triperoxonane acid. The residue was diluted with saturated aqueous potassium carbonate (70 ml) and methylene chloride (50 ml) and layers were separated. The aqueous phase was extracted with methylene chloride (2 x 50 ml of the tion, triturated with diethyl ether and recrystallized from ethyl acetate to obtain specified in the connection header,

NMR (CDCl3, 400 MHz) 7,08, 6,10, 4,78, 4,00, 3,74, 3,64, 3,19, 3,07, 2,72, 2,03, 1,99, 1,68.

Example 36. (S)-(-)-N-[[3-[4-[1-[(Benzyloxy)acetyl] -4 - piperidinyl]-3,5-differenl]-2-oxo-5-oxazolidinyl]- methyl] ndimethylacetamide

Following the General method of example 18, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl) phenyl] -5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-)-N-[[2-oxo - 3-[4-(4-piperidinyl)-3,5-differenl] -5-oxazolidinyl] - methyl]acetamide", she got mentioned in the title compound, so pl. 169-171oC.

Example 37. (S)-(-)-N-[[3-[4-[1-(Hydroxyacetic)-4 - piperidinyl]-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide

A mixture of (S)-(-)-N-[[3-[4-[1-[(benzyloxy)acetyl]-4 - piperidinyl]-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide (example 36, 207 mg) and 10% palladium on carbon (100 mg) in methanol (9 ml) was shaken on the Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2within 20 hours, the catalyst was removed by filtration through Celite and the filtrate was concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (2 who shares with Rf=0,26 according to TLC (methanol/chloroform, 10/90) and recrystallization from a mixture of methylene chloride/diethyl ether gave specified in the title compound, NMR (CDCl3, 400 MHz) 7,07, 6,80, 4,78, 4,69, 4,18, 3,99, 3,74, 3,63, 3,60, 3,16, 3,06, 2,90, 2,72, 2,00, 1,97, 1,75.

Example 38. (S)-(-)-]-N-[[2-Oxo-3-[4-(3,6-dihydro-2H-pyridine - 4-yl]-3-forfinal]-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: (S)-(-)-4-[4-[5- [(Acetylamino)methyl]-2-oxo - 3 - oxazolidinyl]-2-forfinal] -3,6-dihydro-1(2H)-pyridineboronic acid 1,1-dimethylethylene ether

A mixture of (S)-(-)-N- [[3-[4-tributylstannyl-3-forfinal] -2 - oxo-5-oxazolidinyl] methyl]ndimethylacetamide (690 mg), 3,6-dihydro-4- [[(trifluoromethyl) sulfonyl] oxy] -1(2H)-pyridineboronic acid 1,1-dimethylethylene ether (stage 2 of example 20, 500 mg), Tris(dibenzylideneacetone)diplegia(0) (14 mg) and triphenylarsine (37 mg) in N-methyl-2-pyrrolidinone (7.5 ml) was degirolami, was stirred in an atmosphere of N2at ambient temperature for 4.5 days, diluted with ethyl acetate, washed with water (3 x 40 ml) and saturated salt solution (20 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (230-400 mesh mesh, 120 g) with elution by a gradient of methanol/methylene chloride (1/99-2/98) and the fraction with Rf1H NMR (CDCl3, 400 MHz) 7,39, 7,22, 7,13, 7,01, 5,92, 4,82, 4,06, 3,80, 3,67, 3,61, 2,47, 2,03, 1,49.

Stage 2: (S)-(-)-N-[[2-Oxo-3-[4-(3,6-dihydro-2H-pyridine - 4-yl] -3-forfinal]-5-oxazolidinyl]methyl]ndimethylacetamide

Solution (S)-(-)-4-[4-[5- [(acetylamino)methyl]-2-oxo-3 - oxazolidinyl] -2-forfinal] -3,6-dihydro - 1(2H)-pyridineboronic acid 1,1-dimethylethylene ester (example 38, step 1, and 1.00 g) in dry methylene chloride (9,2 ml) at 0oC in an atmosphere of N2processed triperoxonane acid (2.3 ml) for one minute and the resulting mixture was stirred at 0oC for three hours and was slowly added to a saturated aqueous solution of potassium carbonate (30 ml) to neutralize excess triperoxonane acid. The resulting suspension was filtered and the precipitate was chromatographically on silica gel (70-230 mesh, 60 g) with elution by the mixture of ammonium hydroxide/methanol/methylene chloride (0,25/19, 75/80). Fractions with Rf=0,08 according to TLC (methanol/chloroform, 20/80), were combined and concentrated under reduced pressure to obtain specified in the connection header,1H NMR (MeOH-d4, 400 MHz) 7,47, 7,33, 7,25, 6,02, 4,80, 4,15, 3,83, 3,58, 3,47, 3,04, 2,46, 1,98.

Example 39. (S)-(-)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl] -3,6-dihydro-2H-pyridine-4-yl]phenyl]-5-oxazolidinyl]-methyl] ndimethylacetamide
< a phenyl]-5-oxazolidinyl]methyl] ndimethylacetamide (S)-(-)-N-[[2-oxo-3- [4-(3,6-dihydro-2H-pyridine-4-yl)-3-forfinal] -5 - oxazolidinyl] methyl] ndimethylacetamide and benzyloxyacetaldehyde on acetoxyacetyl, got mentioned in the title compound, so pl. 188-191oC.

Example 40. (S)-(-)-N- [[3-[4-[1-(Hydroxyacetic) -3,6-dihydro - 2H-pyridine-4-yl] -3-forfinal] -2-oxo-5-oxazolidinyl] methyl]- ndimethylacetamide

A mixture of (S)-(-)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl]-3,6-dihydro-2H-pyridine-4-yl] phenyl]-5-oxazolidinyl]- methyl]ndimethylacetamide (example 39, 475 mg) and anhydrous potassium carbonate (303 mg) in methanol (44 ml) was stirred in an atmosphere of N2at ambient temperature for 1.5 hours and then brought to pH 7 water chloroethanol acid (1M) and concentrated under reduced pressure. The residue was chromatographically on silica gel (230-400 mesh mesh, 40 g) with elution by a gradient of methanol/chloroform (5/95-10/90) and the fraction with Rf= 0,21 according to TLC (methanol/chloroform, 10/90) were combined and concentrated under reduced pressure. Then the obtained foamy substance was rubbed with a mixture of methylene chloride/diethyl ether and the precipitate was filtered to obtain specified in the connection header. Anal. calc. for C19H22N3O5F: C, 58,31; H, 5,67; N, A 10.74. Found: C, 58,15; H, 5,64; N, Of 10.72.

Example 41. (5S)-N-[[3-[3-Fluoro-4-[1-(phenylmethyl)-3-pyrrolidinyl] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: (S)-N-[[3-[4-Ethynyl-3-forfinal]-MIDA (of 5.45 g), vinyltrimethylsilane (5,48 g) and bis(triphenylphosphine)palladium(II)chloride (303 mg) in 1,4-dioxane (72 ml) in an atmosphere of N2was degirolami, was heated to boiling and boiled under reflux for seven hours, cooled to ambient temperature and stirred for 12 hours. Then the mixture was diluted with ethyl acetate (40 ml) and water (50 ml) and layers were separated. The aqueous phase was extracted with ethyl acetate (2 x 30 ml) and the combined organic phase was washed with saturated salt solution (40 ml), dried over anhydrous magnesium sulfate, concentrated under reduced pressure and triturated with diethyl ether. The precipitation was filtered to obtain specified in the connection header, so pl. 165-166oC.

Stage 2: (5S)-N-[[3-[3-Fluoro-4-[1-(phenylmethyl)-3-pyrrolidinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A solution of (S)-(-)-N-[[3-[4-vinyl-3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 41, step 1, 3.50 g) and triperoxonane acid (0,23 ml) in dry methylene chloride in an atmosphere of N2was treated with a solution of N-benzyl-N-(methoxymethyl) trimethylsilylmethylamine (6,10 g) in dry methylene chloride (50 ml) dropwise over 4.5 hours and the resulting solution was stirred at ambient temperature for 17 hours. Satm salt solution (30 ml), was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain residue, which was chromatographically on silica gel (230-400 mesh mesh, 350 g) with elution by a gradient of methanol/methylene chloride (1/99 - 10/90). Pooling and concentration of fractions with Rf=0,19 according to TLC (methanol/chloroform, 10/90) and rubbing with a mixture of methanol/diethyl ether gave specified in the title compound,1H NMR (CDCl3, 400 MHz) 7,35, 7,25, 7,13, 6,08, 4,78, 4,03, 3,76, 3,69, 3,62, 2,97, 2,78, 2,56, 2,33, 2,02, 1,85.

Example 42. (5S)-N-[[3-[3-Fluoro-4-(3-pyrrolidinyl)phenyl]-2 - oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (5S)-N-[[3-[3-fluoro-4-[1-(phenylmethyl)-3-pyrrolidinyl] phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 41, of 1.09 g) and 20% palladium hydroxide on carbon (545 mg) in methanol (30 ml) was shaken on the Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2) for 1.5 hours and 10 psig (0.7 kg/cm2) for 18 hours. Remove the catalyst by filtration through Celite and the filtrate was concentrated under reduced pressure to obtain specified in the connection header,1H NMR (CDCl3, 400 MHz) 7,39, 7,24, 7,11, 6,35, 4,78, 4,04, 3,77, 3,67, 3,44, 3,37, 3,18, 3,11, 2,88, 2,21, 2,02, 1,86.

Example 43. (5S)-N- [[3-[3-Fluoro-4-[1-(bener 18 with minor changes, but replacing (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl) phenyl]-5-oxazolidinyl]methyl] ndimethylacetamide (5S)-N- [[3-[3-fluoro-4- (3-pyrrolidinyl) phenyl]-2-oxo - 5-oxazolidinyl] methyl] -ndimethylacetamide (example 42), have been specified in the title compound, VRMS: calculated for C25H28N3O5F: 470,2091; found: 470,2106.

Example 44. (5S)-N-[[3-[3-Fluoro-4-[1-(hydroxyacetic)-3-pyrrolidinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method of example 22, with minor changes, but replacing (S)-(-)-N-[[3- [4-[1-(benzyloxy) acetyl]-4 - piperidinyl]-3-forfinal] -2-oxo-5-oxazolidinyl] methyl] - ndimethylacetamide (5S)-N-[[3-[3-fluoro-4- [1-(benzyloxy)acetyl] -3 - pyrrolidinyl] phenyl]-2-oxo-5-oxazolidinyl ]methyl] ndimethylacetamide (example 43), have been specified in the title compound, FAB-VRMS: calculated for C18H22N3O5F+H: 380,1622; found: 380,1625.

Example 45. (5S)-N-[[3-[3-Fluoro-4-[1-(formyl)-3-pyrrolidinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method of example 29 with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl)-3 - forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (5S)-N-[[3-[3 - fluoro-4- (3-pyrrolidinyl) phenyl] -2-oxo-5-oxazolidinyl] -methyl] ndimethylacetamide (example 44), have been specified in the header�)-3-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl]-2-forfinal]-1-pyrrolidinecarboxylic acid methyl ester.

Following the General method of example 26, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl) -3-forfinal]-5-oxazolidinyl] methyl]ndimethylacetamide (5S)-N-[[3-[3 - fluoro-4-(3-pyrrolidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide (example 44), have been specified in the title compound, VRMS: calculated for C18H22FN3O5: 379,1543; found: 379,1546.

Example 47. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-Piran-4-yl)-3 - forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: an ester of 3,6-dihydro-2H-Piran-4 - intraformational acid

Following the General methodology step 2 of example 20, with minor changes, but replacing 1-(1,1-dimethylethoxysilane)-4 - piperidone on tetrahydropyran-4-he got mentioned in the title compound, 1H NMR (CDCl3, 400 MHz) 5,82, 4,27, 3,90, 2,47 .

Stage 2: 3-Fluoro-4-(3,6-dihydro-2H-Piran-4-yl)benzolamide

Following the General method of stage 3 of example 20, with minor changes, but replacing 1,1-dimethylethylene ester of 3,6-dihydro - 4-[[(trifluoromethyl)sulfonyl] oxy] -1(2H)-pyridineboronic acid ester of 3,6-dihydro - 2H-Piran-4 - intraformational acid (example 47, step 1) has been specified in the header of the connection, so square 86-88oC.

the-(3,6-dihydro-2H-Piran-4-yl)benzenamine (example 47, stage 2, 2.28 g) and sodium bicarbonate (1.98 g) in THF (59 ml), was treated with benzylchloride (of 1.85 ml) and the resulting suspension was stirred at ambient temperature for six hours. The mixture is then washed with water (50 ml), the aqueous phase was extracted with methylene chloride (50 ml) and the combined organic phase was washed with saturated salt solution (25 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (70-230 mesh, 80 g) with elution with a mixture of ethyl acetate/hexane (15/85) and the fraction with Rf=0,45 according to TLC (ethyl acetate/hexane, 25/75) were combined and concentrated to obtain specified in the connection header, so pl. 75-76oC.

Stage 4: (R)-(-)-3-[3-Fluoro-4-(3,6-dihydro-2H-Piran-4-yl) phenyl] -5-hydroxymethyl-2-oxazolidinone

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid fenilmetilovy ether 3-fluoro-4-(3,6-dihydro-2H-Piran-4-yl) benzilnikotinova acid (example 47, step 3) has been specified in the header of the connection, so pl. 127-130oC.

Stage 5: (R)-(-)-3-[3-Fluoro-4-(3,6-dihydro-2H-Piran-4-yl) what additional changes, but with the replacement phenylmethylene ether (R)-(-)-3, 6-dihydro-4-[4-[5-(hydroxymethyl)-2-oxo-3-oxazolidinyl] phenyl]-1(2H)-pyridineboronic acid (R)-(-)-3- [3-fluoro-4- (3,6-dihydro-2H-Piran-4-yl) phenyl]-5 - hydroxymethyl-2-oxazolidinone, has been specified in the title compound, so pl. 166-169oC (Razlog.).

Stage 6: (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)-3 - forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method stage 5 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-[[(methylsulphonyl) oxy] methyl] -2 - oxo-3-oxazolidinyl] phenyl]-1(2H)- pyridineboronic acid (R)-(-)-3-[3-fluoro-4-(3,6-dihydro-2H-Piran-4-yl) phenyl] -5 [[(methylsulphonyl)oxy] methyl]-2-oxazolidinone (example 47, step 5) has been specified in the header of the connection, so pl. 148-151oC.

Example 48. (S)-(-)-N-[[3-[4-[Tetrahydro-2H-Piran-4-yl]- 3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)-3 - forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 47, of 1.00 g) and 10% palladium on carbon (637 mg) in methanol (60 ml) was shaken on the Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2within three hours, the catalyst was removed by filtrowanie, so pl. 191-192oC.

Example 49. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- 3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: an ester of 3,6-dihydro-2H-thiopyran-4 - intraformational acid

Following the General methodology step 2 of example 20, with minor changes, but replacing 1-(1,1-dimethylethoxysilane)-4 - piperidone on tetrahydrothiopyran-4-he got mentioned in the title compound, NMR (CDCl3, 400 MHz) 6,01, 3,30, 2,86, 2,62.

Stage 2: 3-Fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)benzolamide

Following the General method of stage 3 of example 20, with minor changes, but replacing 1,1-dimethylethylene ester of 3,6-dihydro - 4-[[(trifluoromethyl) sulfonyl] oxy] -1(2H)- pyridineboronic acid ester of 3,6-dihydro-2H-thiopyran-4 - intraformational acid (example 49, step 1) has been specified in the title compound,1H NMR (CDCl3, 400 MHz) 6,98, 6,40, 6,35, 5,94, 3,73, 3,31, 2,84, 2,62.

Stage 3: 3-Fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl) benzylisoquinoline acid fenilmetilovy ether

Following the General method of stage 3 of example 47 with minor changes, but replacing 3-fluoro-4-(3,6-dihydro-2H - Piran-4-yl)benzoylamino 3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl) benzolamide (example 49, step 2), the Iran-4-yl) phenyl]-5-hydroxymethyl-2-oxazolidinone

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid fenilmetilovy ether 3-fluoro-4-(3,6-dihydro-2H-thiopyran-4 - yl)benzylisoquinoline acid (example 49, step 3) has been specified in the header of the connection, so pl. 119-122oC.

Stage 5: (R)-(-)-3-[3-Fluoro-4- (3,6-dihydro-2H-thiopyran-4 - yl) phenyl]-5-[[(methylsulphonyl) oxy]methyl]-2-oxazolidinone

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl] phenyl] -1(2H)- pyridineboronic acid (R)-(-)-3-[3-fluoro-4- (3,6-dihydro-2H-thiopyran-4-yl) phenyl]-5-hydroxymethyl-2 - oxazolidinone (example 49, step 4) has been specified in the header of the connection, so pl. 138-141oC.

Stage 6: (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method stage 5 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6-dihydro-4-[4- [5-[[(methylsulphonyl)oxy] methyl] -2 - oxo-3-oxazolidinyl] phenyl]-1(2H)- pyridineboronic acid (R)-(-)-3-[3-fluoro-4- (3,6-this in the title compound, so pl. 187-189oC.

Example 50. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- 3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S - dioxide

A solution of (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 49, 300 mg) in a mixture of water/acetone (25%, 17 ml) was treated with N - oxide N-methylmorpholine (301 mg), followed by osmium tetroxide (2.5 wt.% in tert-butanol, 0.54 ml) and the resulting mixture was stirred at ambient temperature overnight. Then the reaction mixture was rapidly cooled by the addition of saturated aqueous solution of sodium bisulfite (10 ml) and was extracted with methylene chloride (2 x 20 ml). The combined organic phase was washed with saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (70-230 mesh, 30 g) with elution by a gradient of methanol/methylene chloride (3/97-5/95). Combining fractions with Rf=0,49 according to TLC (methanol/chloroform, 10/90) and rubbing with a mixture of methylene chloride/diethyl ether gave specified in the title compound, so pl. 181-182oC.

Example 51. (S)-(-)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran - 4-yl) phenyl] -2-oxo-5-oxazolidin the Noi (S)-(-)-N-[[3-[4- (3,6-dihydro-2H-Piran-4-yl) -3-forfinal]-2-oxo-5-oxazolidinyl] methyl] -ndimethylacetamide (S)-(-)-N-[[3-[4- (3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide S,S-dioxide (example 50) and recrystallization of the product from a mixture of methylene chloride/diethyl ether, got mentioned in the title compound, so pl. 199-200oC.

Example 52. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-Piran - 4-yl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 4-[4-(Hydroxy)-tetrahydro-2H-Piran-4-yl]- benzylisoquinoline acid fenilmetilovy ether

Following the General methodology stage 1 of example 17 with minor changes, but replacing N-(carbobenzoxy)-4-piperidone on tetrahydropyran-4-one, has been specified in the header of the connection, so pl. 143-145oC.

Stage 2: 4-(3,6-Dihydro-2H-Piran-4-yl)benzylisoquinoline acid fenilmetilovy ether

Following the General methodology step 2 of example 17 with minor changes but with the replacement phenylmethylene ester 4-hydroxy-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl]-1-piperidinecarboxylic acid fenilmetilovy ester 4-[4-(Hydroxy)tetrahydro-2H-Piran - 4-yl]benzylisoquinoline acid (example 52, step 1) and recrystallization of the crude product from a mixture of ethyl acetate/hexane, got mentioned in the title compound, so pl. 145-148oC.

Stage 3: (R)-(-)-3-[4-(3,6-Dihydro-2H-Piran-4-yl)-phenyl] -5-hydroxymethyl-2-oxazolidinone

Following the General method of stage 3 of example 17 with minor changes but with the replacement of phenylmethyl the new ester of 4-(3,6-dihydro-2H-Piran-4-yl) benzylisoquinoline acid (example 52, stage 2) and grinding of the crude product with a mixture of ethyl acetate/hexane (50/50) has been specified in the header connection. Anal. calc. for C15H17NO4: C, 65,44; H, TO 6.22; N, 5,09. Found: C, 65,05; H, 6,04; N, 4,91.

Stage 4: (R)-(-)-3-[4-(3,6-Dihydro-2H-Piran-4-yl)-phenyl]-5- [[(methylsulphonyl)oxy]methyl]-2-oxazolidinone

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6-dihydro-4- [4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl] phenyl] -1(2H)- pyridineboronic acid (R)-(-)-3-[4- (3,6-dihydro-2H-Piran-4-yl) phenyl]-5-hydroxymethyl - 2-oxazolidinone (example 52, stage 3) has been specified in the header of the connection, so pl. 182-184oC.

Stage 5: (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following the General method stage 5 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-[[(methylsulphonyl) oxy] -methyl]-2-oxo-3 - oxazolidinyl]phenyl] -1(2H)-pyridineboronic acid (R)-(-)-3-[4-(3,6-dihydro-2H-Piran-4-yl)phenyl-1-5- [[(methylsulphonyl)oxy] methyl] -2-oxazolidinone (example 52, step 4) has been specified in the title compound, NMR (CDCl3, 400 MHz) 7,45, 7,36, 6,83, 6,09, 4,77, 4,31, 4,05, 3,92, 3,80, 3,65, 2,48 Following the General method of example 48 with minor changes, but replacing (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran - 4-yl)-3-forfinal]-2-oxo-5-oxazolidinyl] methyl] -ndimethylacetamide (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)-phenyl] -2-oxo-5 - oxazolidinyl]methyl]the ndimethylacetamide (example 52), have been specified in the header of the connection, so pl. 185-187oC.

Example 54. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 4-[4-(Hydroxy)tetrahydro-2H-thiopyran-4-yl]- benzylisoquinoline acid fenilmetilovy ether

Following the General methodology stage 1 of example 17 with minor changes, but replacing N-(carbobenzoxy)-4-piperidone on tetrahydrothiopyran-4-one and recrystallization of the product from a mixture of ethyl acetate/hexane, got mentioned in the title compound, so pl. 152-154oC.

Stage 2: 4-(3,6-Dihydro-2H-thiopyran-4-yl)benzylisoquinoline acid fenilmetilovy ether

Following the General methodology step 2 of example 17 with minor changes but with the replacement phenylmethylene ester 4-hydroxy-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl]-1-piperidinecarboxylic acid fenilmetilovy ester 4-[4-(hydroxy)tetrahydrothiopyran - 4-yl]benzylisoquinoline acid (example 54, step 1) and grinding of the crude product with diethyl ether or Perek="ptx2">

Stage 3: (R)-(-)-3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- phenyl]-5-hydroxymethyl-2-oxazolidinone

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid fenilmetilovy ester of 4-(3,6-dihydro-2H-thiopyran-4-yl) benzylisoquinoline acid (example 54, step 2) and grinding of the crude product with a mixture of methanol/methylene chloride, got mentioned in the title compound, so pl. 182-184oC (Razlog.).

Stage 4: (R)-(-)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-phenyl] -5-[[(methylsulphonyl)oxy]methyl]-2-oxazolidinone

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl] phenyl] -1(2H)- pyridineboronic acid (R)-(-)-3-[4- (3,6- dihydro-2H-thiopyran-4-yl) phenyl]-5-hydroxymethyl - 2-oxazolidinone (example 54, stage 3) and grinding of the crude product with a mixture of methylene chloride/diethyl ether (25/75) has been specified in the header connection. so pl. 171-174oC (Razlog.).

Stage 5: (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Following hydro- 4-[4-[5- [[(methylsulphonyl) oxy] methyl]-2 - oxo-3-oxazolidinyl] phenyl]-1(2H)- pyridineboronic acid (R)-(-)-3- [4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl] -5- [[(methylsulphonyl) oxy]methyl] -2-oxazolidinone (example 54, stage 4) and ISO-propanol in acetonitrile has been specified in the header of the connection, so pl. 169-173oC (Razlog.).

Example 55. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide

Following the General method of example 50, with minor changes, but replacing (S)-(-)-N-[[3-[4-(3,6-dihydro-2H - thiopyran-4-yl)-3-forfinal] -2 - oxo-5-oxazolidinyl] methyl] - ndimethylacetamide (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (example 54) and rubbing the product with a mixture of ethyl acetate/methylene chloride, got mentioned in the title compound, so pl. 185-187oC.

Example 56. (S)-(-)-N-[[3-[4- [1-(Formyl)-3,6-dihydro-2H - pyridine - 4-yl] -3-forfinal] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide

Following the General method of example 29 with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl)- 3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-)- N-[[2-oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl) -3-forfinal] -5 - oxazolidinyl]methyl] the ndimethylacetamide (example 38), have been specified in the header of the connection, so pl. 148-151oC.

Example 57. (S)-(-)-4- [4-[5-[(Acetylamino) methyl] -2-oxo-3 - oxazolidinyl] -2-forfinal] -3,6-dihydro-1(2H)- pyridineboronic acid methyl ester

Ledpanel] -5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-)- N-[[2-oxo-3-(4-(3,6-dihydro-2H-pyridine-4-yl)-3-forfinal]- 5-oxazolidinyl]methyl]ndimethylacetamide (example 38), got mentioned in the title compound, NMR (CDCl3, 400 MHz) 7,35, 7,18, 7,10, 6,85, 5,89, 4,78, 4,08, 4,02, 3,78, 3,71, 3,64, 2,45, 2,00.

Example 58. (S)-(-)-N-[[2-Oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl) phenyl] -5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: (S)-(-)-4-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl] phenyl]-3,6-dihydro-1(2H)-pyridineboronic acid 1,1-dimethylethylene ether

Following the General methodology stage 1 of example 38 with minor changes, but replacing (S)-(-)-N- [(3-(4-(tributylstannyl) -3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-) -N-[[3-[4- (tributylstannyl) phenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide", she got mentioned in the title compound, NMR (CDCl3, 400 MHz) 7,45, 7,35, 6,55, 6,00, 4,77, 4,05, 3,80, 3,63, 2,49, 2,01, 1,48.

Stage 2: (S)-(-)-N-[[2-Oxo-3-[4-(3,6-dihydro-2H - pyridine-4-yl)phenyl] -5-oxazolidinyl]methyl]ndimethylacetamide

Solution (S)-(-)-4-[4-[5-[(acetylamino)methyl-2-oxo-3 - oxazolidinyl]phenyl] -3,6-dihydro-1(2H)-pyridineboronic acid 1,1-dimethylethylene ester (example 58, step 1, to 0.92 g) in dry methylene chloride (8,8 ml) at 0oC in an atmosphere of N2processed triperoxonane acid (2.2 ml) for one minute, and the resulting mixture was stirred at 0oC for four hours and was slowly added to saturated aq the mixture was diluted with water (50 ml) and saturated salt solution (50 ml), were extracted with a mixture of methanol/methylene chloride (3 x 150 ml, 25/75) and the combined organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain specified in the connection header, so pl. 164-166oC (Razlog.).

Example 59. (S)-(-)-N-[[2-Oxo-3-[4-[1-[(acetoxy)acetyl]- 3,6-dihydro-2H-pyridine-4-yl]phenyl]-5-oxazolidinyl]methyl]- ndimethylacetamide

Following the General method of example 18, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl) phenyl)-5-oxazolidinyl]methyl)ndimethylacetamide (S)-(-)-N-[[2 - oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl)phenyl] -5-oxazolidinyl] methyl] the ndimethylacetamide and benzyloxyacetaldehyde on acetoxyacetyl (example 58), has been indicated in the title compound, VRMS: calc. for C21H25N3O6: 415,1743; found: 415,1752.

Example 60. (S)-(-)-N- [[3-[4-[1-(Hydroxyacetic) -3,6-dihydro - 2H-pyridine-4-yl] phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide

Following the General method of example 40, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [3-fluoro-4-[1- [(acetoxy) acetyl)-3,6-dihydro-2H - pyridine-4-yl] phenyl]-5 - oxazolidinyl] methyl] ndimethylacetamide (S)-(-)-N-[[2-oxo-3-[4-[1- [(acetoxy) acetyl]-3,6-dihydro-2H-pyridine-4-yl] phenyl] -5 - oxazolidinyl] methyl] ndimethylacetamide (example ideno: 374,1713.

Example 61. (S)-(-)-N-[[3-[4-[1-(Formyl)-3,6-dihydro-2H - pyridine-4-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide

Following the General method of example 29 with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl) -3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (S)-(-)-N- [[2-oxo-3- [4-(3,6-dihydro-2H-pyridine-4-yl) phenyl] -5-oxazolidinyl) methyl] ndimethylacetamide (example 58)got mentioned in the title compound, so pl. 149-152oC.

Example 62. (S)-(-)-4-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl] phenyl]-3,6-dihydro-1(2H)-pyridineboronic acid methyl ester

Following the General method of example 26, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl)-3-forfinal] -5-oxazolidinyl] methyl]ndimethylacetamide (S)-(-)-N- [[2-oxo-3-[4- (3,6-dihydro-2H-pyridine-4-yl) phenyl]-5-oxazolidinyl] methyl]ndimethylacetamide (example 58)got mentioned in the title compound, so pl. 142-145oC.

Example 63. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl) -3 - forfinal]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide S-oxide

The solution periodate sodium (192 mg) in water at 0oC was treated with a suspension of (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran - 4-yl)-3-forfinal)-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 49, 300 mg) in methanol (10 ml) and the resulting mixture on the second night. The mixture is then concentrated to remove methanol, diluted with water (20 ml) and was extracted with a mixture of methanol/chloroform (3 x 30 ml, 5/95). The combined organic phase was washed with saturated salt solution (20 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (30 g, 70-230 mesh) by elution with a mixture of methanol/methylene chloride (5/95). Fractions with Rf=0,39 according to TLC (methanol/chloroform, 10/90) were combined and concentrated and the residue was recrystallized from a mixture of methylene chloride/diethyl ether to obtain specified in the connection header, so pl. 150-151oC.

Example 64. (S)-(-)-N-[[3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S-oxide

Following the General method of example 63, with minor changes, but replacing (S)-(-)-N-([3-[4-(3,6-dihydro-2H - thiopyran-4-yl)-3-forfinal]-2-oxo-5-oxazolidinyl)methyl] - ndimethylacetamide (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 54), have been specified in the header of the connection, so pl. 158-162oC (Razlog.).

Example 65. (S)-(-)-N-[[3-[4-[Tetrahydro-2H-thiopyran-4-yl] - phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (example 55, 75 mg) and 10% palladium on carbon (44 mg) in tetrahydrofuran (20 ml) was stirred in hydrogen atmosphere (balloon) for one hour, the catalyst was removed by filtration through Celite, the filtrate was concentrated under reduced pressure and the residue was recrystallized from a mixture of methylene chloride/diethyl ether to obtain specified in the connection header, so pl. 190-192oC (Razlog.).

Example 66. 3-(4-Amino-2-forfinal)pyrrolidin

Stage 1: 2-(2-Fluoro-4-nitrophenyl)diethylmalonate

In dried over a flame round bottom flask with a capacity of 500 ml, equipped with a magnetic stirrer and addition funnel, was placed sodium hydride (4.0 g, 0.10 mol). This oil dispersion was washed three times with pentane (30 ml), dried by vacuum, diluted with 50 ml of fresh tetrahydrofuran and cooled to 0oC. Gray suspension was treated dropwise with a solution of diethylmalonate (5.7 ml, 50 mmol) in 100 ml of THF, while abundantly stood out gas. The obtained thick suspension was treated with a solution of 3,4-deformirovannoe in 100 ml of THF, which was quickly acquired a Golden color, and was heated to 50oC for 16 hours.

Then the homogeneous solution is dark red was cooled to room temperature the current was extracted three times with ethyl acetate (200 ml) and the combined organic layers were washed once with saturated salt solution (200 ml), dried over MgSO4was filtered and concentrated, resulting in of 13.58 g of brown solid. This product is triturated with a mixture of ethyl acetate/hexane/dichloromethane with the receipt of 7.60 g specified in the title compound as a pale yellow solid. The filtrate was concentrated and purified by HPLC (Prep 500) on a single cartridge with silica gel with elution with a mixture of 25% ethyl acetate/hexane, resulting in received 3,95 g specified in the connection header. The total yield was or 10.60 g (78%). So pl. 108-109oC; Rf= 0,38 (25% ethyl acetate/hexane); IR (pasta) 1744, 1736, 1532, 1438, 1357, 1345, 1273, 1243, 1232, 812 cm-1;

1H NMR (300 MHz, CDCl3) of 8.09 (dt, 1H, J=2.2 and 7.8 Hz, arene.), to 7.99 (DDD, 1H, J=2.3 and 9.4 Hz, arene.), 7,74 (DD, 1H, J=7,l and 8.6 Hz, arene.), to 5.08 (s, 1H, Metin), 3,81 (s, 6H, mately). Anal. calc. for C11H10N1O6F1: C, 48,74; H, AND 3.72; N, 5,17. Found: C, 48,74; H, A-3.84; N, 5,14.

Stage 2: 2-(2-Fluoro-4-nitrophenyl)-2-(lanmeter)diethylmalonate

In kiln dried round bottom flask with a capacity of 100 ml equipped with a stirrer and reflux condenser, was placed 2-(2 - fluoro-4-nitrophenyl)diethylmalonate (example 66, step 1, 3.25 g, 12,0 mmol) and 60 ml of acetone. This yellow homogeneous solution was treated with a single dose powder is alali bromoacetonitrile (1.3 ml, 18 mmol) and it was heated under reflux for 16 hours. At the end of this time, brown is now the suspension was cooled to room temperature, diluted with 100 ml of 1M chloroethanol acid and was extracted twice with ethyl acetate (150 ml). The combined organics were washed once with saturated salt solution (100 ml), dried over MgSO4, filtered and concentrated to obtain 4,10 g of crude brown foamy substance. This product was purified by HPLC (Prep 500) on a single cartridge with silica gel with elution with a mixture of 30% ethyl acetate/hexane, resulting in received of 3.60 g not quite white solid. This product was recrystallized from a mixture of ethyl acetate/hexane to obtain 3,14 g (84%) indicated in the title compound as white needle crystals. So pl. 137-138oC; Rf= 0,26 (30% ethyl acetate/hexane); IR (pasta) 1749, 1730, 1527, 1355, 1290, 1276, 1262, 1234, 812, 739 cm-1;

1H NMR (300 MHz, CDCl3) to 8.12 (DDD, 1H, JHF=0,8, J=2,2, J=8.6 Hz, arene. ), 8,01 (DD, 1H, J= 2,3 and 10.8 Hz, arene.), of 7.48 (DD, 1H, J=7.5 and 8.7 Hz, arene.), to 3.92 (s, 6H, mately), to 3.34 (s, 2H, Metin);

13C NMR (75 MHz, CDCl3) KZT 166.5, 159,5 (JCF=253 Hz), 148, 7mm, 130,2 (JCF=3 Hz), 129, 9mm (JCF= 13 Hz), 119,4 (JCF=3 Hz), 111,9 (JCF=28 Hz), 58,0, 54,1, 24,2. �>Stage 3: 2-(4-Amino-2-forfinal)-2-carbomethoxyamino

In a Parr flask with a capacity of 500 ml was placed a solution of 2-(2-fluoro-4 - nitrophenyl)-2-(lanmeter)diethylmalonate (example 66, step 2, 1,236 g, 4.0 mmol) in 100 ml of methanol and of 1.17 g of 10% palladium on carbon. The black suspension was placed in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2) with shaking for 64 hours. Took the flask from hydrogenator, the reaction mixture was filtered through a layer of Celite and concentrated with the receipt of 1.02 g of a white foamy substance. This product was purified by LC on 70 g (230-400 mesh) silica gel with elution by ethyl acetate and the resulting received 824 mg (82%) of compound as a white amorphous solid. Rf= 0,20 (75% ethyl acetate/hexane); IR (pasta) 3359, 3233, 1738, 1695, 1694, 1634, 1515, 1254, 1276, 1128 cm-1;

1H NMR (300 MHz, CDCl3) to 7.15 (t, 1H, J=9,0 Hz, arene.), 6,58 (SHS, 1H, O= C-NH), 6,41 (m, 2H, arene.), 3,80 (CL, 2H, NH2), of 3.77 (s, 3H, CH3), to 3.49 (m, 1H, N-CH2a) at 3.25 (m, 2H, C-CH2s) of 2.28 (m, 1H, N-CH2b);

13C NMR (75 MHz, CDCl3) 173,6, TO 170.9, 161,4 (JCF=245 Hz), a 147.7 (JCF=11 Hz), 128,9 (JCF= 5 Hz), 115, 7mm (JCF=14 Hz), 110,2, 102,5 (JCF=25 Hz), 56,9, 53,2, 39,4, 34,3; water in K. Fischer = 0,87%. Anal. calc. for C12H13N2O3F10,,0910. Found: 252,0902.

Stage 4: 2-(4-Amino-2-forfinal)-2-carbomethoxyamino

In the recovery flask with a capacity of 100 ml, containing 2- (4-amino-2-forfinal)-2-carbomethoxyamino (example 66, step 3, 930 mg, 3.7 mmol), was placed 26 ml of DMSO and sodium cyanide (542 mg, 11.1 mmol). This pink suspension was heated to 150oC for 30 minutes, and as a result she became reddish-brown with some gas evolution. Then the reaction mixture was cooled to room temperature, removed under reduced pressure (approximately 60oC, 0.1 mm RT. Art.) DMSO and the resulting residue was diluted with 30 ml of brine and was extracted three times with dichloromethane (30 ml). The combined organic layers were washed once with saturated salt solution (15 ml), dried over MgSO4, filtered and concentrated to obtain 521 mg red-brown oil. TLC showed the presence of the remaining product in the layers of brine and they were United and were extracted three times with ethyl acetate (30 ml). These combined organic layers were washed once with saturated salt solution (15 ml), dried over MgSO4was filtered and concentrated, resulting in another 230 mg of a red-brown oil. These crude extracts were purified by LC frame in the title compound as a pale yellow solid. So pl. 157-160oC; Rf= 0,24 (ethyl acetate); IR (pasta) 3465, 3363, 1680, 1630, 1614, 1515, 1447, 1285, 830, 828 cm-1;

1H NMR (300 MHz, CDCl3) 7,73 (SHS, 1H, O=C-NH), 6,85 (t, 1H, J=8,4 Hz, arene. ), of 6.31 (m, 2H, arene.), 5,28 (CL, 2H, NH2), of 3.48 (t, 1H, J=9.4 Hz, Ph-CH), 3,24 (m, 2H, C-CH2s) to 2.35 (m, 1H, N-CH2a), of 1.95 (m, 1H, N-CH2b);

13C NMR (75 MHz, CDCl3) 178,8, 161,9 (JCF=244 Hz), 147,5 (JCF=11 Hz), 130,4 (JCF= 6 Hz), 115, 7mm (JCF=15 Hz), 111,1 (JCF=2 Hz), to 102.3 (JCF=25 Hz), 41,5, 40,5, 30,1; VRMS: calc. for C10H11N2O1F1+H: 195,0134. Found: 195,0937.

Stage 5: 3-(4-Amino-2-forfinal)pyrrolidin

In a round bottom flask with a capacity of 100 ml equipped with a stirrer and reflux condenser, was placed 2-(4-amino-2-forfinal)-2 - carbomethoxyamino (example 66, step 4, 430 mg, 2.2 mmol) and 22 ml of fresh THF and then cooled to 0oC. This light yellow homogeneous solution was treated with 1M solution of sociallyengaged (11 ml, 11 mmol), the resulting solution immediately became opaque and bought a light pink color and there was a rapid evolution of gas. The reaction mixture was heated to room temperature and then was heated to boiling under reflux with the formation of a gelatinous precipitate. 5 N. solution of sodium hydroxide and 1.5 ml of water. Received a thick gelatinous suspension was diluted with ethyl acetate, filtered through a layer of Celite and concentrated with getting 392 mg of yellow oil. This product was purified by LC on 25 g (230-400 mesh) silica gel with elution with a mixture (2/17/81) saturated NH4OH/methanol/dichloromethane and the result was 295 mg (74%) indicated in the title compound as a pale yellow oil. This product was dissolved in a mixture of methanol/ethyl acetate and treated with gaseous HCl without visible changes. This solution was concentrated to obtain foamy substance peach color, which unsuccessfully tried to recrystallized from many different combinations of solvents. Rf= 0,20 (2/17/81, us. NH4OH/methanol/dichloromethane); IR (pasta) 3139, 3042, 3016, 2766, 2562, 1514, 1485, 1444, 1266, 1108 cm-1;

1H NMR (300 MHz, CDCl3) of 6.99 (t, 1H, J=8,2 Hz, arene.), to 6.39 (m, 2H, arene. ), 3,70 (CL, 2H, Ph-NH2s) of 3.27 (m, 2H, Metin, ), 3,11 (m, 2H, CH2), 2,80 (DD, 1H, J=6,2 and 8.9 Hz ), 2,30 (SHS, 1H, NH), and 2.14 (m, 1H, ), 1.81 (m, 1H, N-CH2-CH2b);

13C NMR (75 MHz, CDCl3) 161,4 (JCF=243 Hz), 146,0 (JCF=11 Hz), 128,4 (JCF= 7 Hz), 119,9 (JCF=152 Hz), 110,5 (JCF=2 Hz), 102,1 (JCF=26 Hz), 56,3, 47,0, 38,1, 32,9. Anal. calc. for C10H13
180,1063. Found: 180,1060.

Example 67. (S)-(-)-N-[[3-[3-Fluoro-4-(dehydration-3-yl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 3-Fluoro-4-[3-(hydroxy)tetrahydrothiophene-3-yl] - benzylisoquinoline acid fenilmetilovy ether

A solution of 1-(3-forfinal)-of 2.2.5.5-tetramethyl-1-Aza-2,5 - disilacyclobutane (example 20, step 1, and 1.00 g) in dry tetrahydrofuran (16 ml) at -78oC in an atmosphere of N2processed second-butyllithium (1.3 M in cyclohexane, 3,30 ml) dropwise over 2 minutes and the resulting mixture was stirred at -78oC for 2 hours. Then the mixture was treated with a solution of tetrahydrothiophene-3-one (423 mg) in dry tetrahydrofuran (4,1 ml) dropwise over 2 minutes and stirred at -78oC, allowing the cooling bath is allowed to drain for 4 hours. The mixture is then extinguished saturated aqueous ammonium chloride (25 ml), diluted with water (25 ml), the layers were separated and the combined organic phase was washed with saturated salt solution (20 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol (16 ml) and treated with anhydrous potassium carbonate (1,09 g) and the resulting mixture was stirred at ambient temperature for 30 minutes, concentrated Ave is practical phase was washed with saturated salt solution (10 ml), was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the crude intermediate product - 3-fluoro-4-[3- (hydroxy)tetrahydrothiophene-3-yl]benzenamine (Rf= 0,37 according to TLC, ethyl acetate/hexane (50/50)). Then a solution of this intermediate in tetrahydrofuran (16 ml) and water (8 ml) was treated with sodium bicarbonate (662 mg) and benzylchloride high (0.56 ml) and the resulting mixture was stirred at ambient temperature for 4 hours, diluted with water (8 ml), layers were separated and the organic phase is washed with saturated salt solution (10 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (230-400 mesh mesh, 150 g) with elution with a mixture of ethyl acetate/hexane (25/75) and the fraction with Rf=0,19 according to TLC (ethyl acetate/hexane, 25/75) were combined and concentrated to obtain specified in the connection header, so pl. 134-135oC.

Stage 2: 3-Fluoro-4-(dehydration-3-yl)benzylisoquinoline acid fenilmetilovy ether

Following the General methodology step 2 of example 17 with minor changes but with the replacement phenylmethylene ester 4 - hydroxy-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl]-1-piperidinecarbonitrile the EP 67, stage 1) has been specified in the title compound in the form of a mixture of 2,5 - and 4,5-dihydro of regioisomers. NMR (CDCl3, 400 MHz) 7,40, 7,21, 7,14, 7,02, 6,73, 6,69, 6,31, 5,21, 4,10, 3,94, 3,33 and 3.15.

Stage 3: (R)-3-[3-Fluoro-4-(dehydration-3-yl)phenyl]-5 - hydroxymethyl-2-oxazolidinone

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid fenilmetilovy ether 3-fluoro-4-(dehydration-3 - yl)benzylisoquinoline acid (example 67, step 2, a mixture of 2,5 - and 4,5-dihydro of regioisomers), have been specified in the title compound in the form of a mixture of 2,5 - and 4,5-dihydro of regioisomers. VRMS: calculated for C14H14N1F1O3S1: 295,0678; found: 295,0676.

Stage 4: (R)-3-[3-Fluoro-4-(dehydration-3-yl)phenyl]-5- [[(methylsulphonyl)oxy]methyl]-2-oxazolidinone

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6-dihydro-4- [4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl) phenyl] -1(2H)- pyridineboronic acid (R)-3-[3-fluoro-4- (dehydration-3-yl)phenyl] -5 - hydroxymethyl-2 - oxazolidinone (example 67, step 3, a mixture of 2,5 - and 4,5-dihydro of regioisomers), received from the SUB>N1F1O5S2: 373,0454; found: 373,0440.

Stage 5: (S)-N-[[3-[3-Fluoro-4-(dehydration-3-yl)phenyl]- 2-oxo-3-oxazolidinyl]methyl]ndimethylacetamide

Following the General method stage 5 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6-dihydro-4-[4- [5-[[(methylsulphonyl)oxy] methyl] -2-oxo-3 - oxazolidinyl] phenyl]-1(2H)- pyridineboronic acid (R)-3-[3-fluoro-4- (dehydration-3-yl) phenyl]-5- [[(methylsulphonyl) oxy] methyl]-2 - oxazolidinone (example 67, step 4, a mixture of 2,5 - and 4,5-dihydro of regioisomers), have been specified in the title compound in the form of a mixture of 2,5 - and 4,5-dihydro of regioisomers. Anal. calculated for C16H17F1N2O3S1: C, 57,13; H, 5,09; N, with 8.33; found: C, 56,89; H, 5,18; N, 8,24.

Example 68. (5S)-N-[[3-[3-Fluoro-4-(2,5-dihydro-1-oxido-3-thienyl) phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide (68a) and (5S)-N- [[3-[3-Fluoro-4-(4,5-dihydro-1-oxido-3-thienyl)-phenyl] -2-oxo - 5-oxazolidinyl] methyl] ndimethylacetamide (68b)

Following the General method of example 63, with minor changes, but replacing (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl) -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide (S)-N-[[3-[3-fluoro-4- (dehydration-3-yl) phenyl] -2 - oxo-5-oxazolidinyl] methyl] the ndimethylacetamide (example 67, step 5, a mixture of 2,5 - and 4,5-dihydr the reed (4/96)), got listed in the connection header, so square (68a) 208-210oC (Razlog. ). NMR (68b) (CDCl3, 400 MHz) 7,55, 7,46, 7,27, 7,13, 6,11, 4,82, 4,07, 3,82-3,62, 3,43, 3,23, 3,10 and 2.03.

Example 69. (S)-N-[[3-[3-Fluoro-4-(2,5-dihydro-1,1-dioxido-3 - thienyl)phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (69a) and (S) -N-[[3-[3-Fluoro-4-(4,5-dihydro-1,1-dioxido-3-thienyl)-phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide (69b)

Following the General method of example 50, with minor changes, but replacing (S)-(-)-N-[[3-[4-(3,6-dihydro-2H - thiopyran-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide (S)-N-[[3-[3-fluoro-4-(dehydration-3-yl)phenyl] -2 - oxo-5-oxazolidinyl]methyl]the ndimethylacetamide (example 67, step 5, a mixture of 2,5 - and 4,5-dihydro of regioisomers) and separation of the regioisomers by HPLC (Chirapaq AD, 10% isopropanol/methanol (0.05% diethylamine), 0.5 ml/min) has been specified in the connection header, so square (69a) 183-185oC (Razlog.); (69b) 238-239oC (Razlog.).

Example 70. (S)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] - 5,6-dihydro-2H-pyridine-3-yl]phenyl]-5-oxazolidinyl]methyl]- ndimethylacetamide

Step 1: 5,6-Dihydro-3-[[(trifluoromethyl)sulfonyl]oxy]- 1(2H)-pyridineboronic acid 1,1-dimethylethylene ether

Following the General method of example 20 (stage 2), with minor changes, but replacing 1-(1,1-dimitratos is matography on silica gel (70-230 mesh, the ethyl acetate/hexane (10/90) has been specified in the title compound, NMR (CDCl3, 400 MHz) of 5.92, Android 4.04, 3,49, 2,30 and 1.47.

Stage 2: (S)-3-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl]-2-forfinal] -5,6-dihydro-1(2H)-pyridine-1 - carboxylic acid 1,1-dimethylethylene ether

Following the General method of example 38 (stage 1), with minor changes but with the replacement of 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl] oxy]-1(2H)-pyridineboronic acid 1,1-dimethylethylene ether on 5,6-dihydro-3-[[(trifluoromethyl)-sulfonyl]oxy]-1(2H)- pyridineboronic acid 1,1-dimethylethylene ester (example 70 stage 1) has been specified in the title compound, NMR (CDCl3, 400 MHz) 7,41, 7,25, 7,17, 6,06, 4,79, 4,19, 4,06, 3,78, 3,75-3,59, 3,57, 2,32, 2,03 and 1,49.

Stage 3: (S)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl] -5,6-dihydro-2H-pyridine-3-yl]phenyl]-5-oxazolidinyl]-methyl] ndimethylacetamide

Solution (S)-3-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] -2-forfinal] -5,6-dihydro-1(2H)-pyridineboronic acid 1,1-dimethylethylene ester (example 70, step 2, 158 mg) in dry acetonitrile in the atmosphere N2handled attributively (62 μl) dropwise and the resulting solution was stirred at ambient temperature for 50 minutes, during which added additional iodimetric the reduced pressure to obtain an intermediate connection with the remote protection. A mixture of this intermediate compound and triethylamine (0,122 ml) in dry methylene chloride (3.6 ml) at 0oC in an atmosphere of N2handled acetoacetanilide (47 μl) and the resulting mixture was stirred at 0oC for 2 hours and at ambient temperature for 2 hours and then was diluted with methylene chloride (20 ml), washed with water (10 ml), saturated aqueous sodium bicarbonate (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (70-230 mesh, 15 g) with elution with a mixture of methanol/methylene chloride (5/95) and the fraction with Rf= 0,5 according to TLC (methanol/chloroform, 10/90) were combined and concentrated to obtain specified in the connection header, VRMS: calculated for C21H24N3F1O6+ H1: 434,1727; found: 434,1741.

Example 71. (S)-N-[[3-[4-[1-(Hydroxyacetic)-5,6 - dihydro-2H-pyridine-3-yl]-3-forfinal]-2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide

A mixture of (S)-N-[[2-oxo-3- [3-fluoro-4-[1-[(acetoxy) acetyl]-5,6 - dihydro-2H-pyridine-3-yl] phenyl]-5-oxazolidinyl] methyl]-ndimethylacetamide (example 70, step 3, 105 mg) and anhydrous potassium carbonate (67 mg) in methanol (4.8 ml) was stirred in an atmosphere of N2f=0,30 according to TLC (methanol/chloroform, 10/90) were specified in the title compound, so pl. 188-190oC.

Example 72. (S)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -3,4-dihydro-2H-pyridine-5-yl]phenyl]-5-oxazolidinyl]methyl]- ndimethylacetamide

Stage 1: 3-Hydroxy-3-[4-[[(phenylmethoxy)carbonyl]- amino]-2-forfinal] -1-piperidinecarboxylic acid fenilmetilovy ether

Following the General method of example 67 (stage 1), with minor changes but with the replacement of the tetrahydrothiophene-3-one N-(carbobenzoxy)-3-piperidin got mentioned in the title compound, so pl. 137-139oC.

Stage 2: 3,4-Dihydro-5-[4-[[(phenylmethoxy)carbonyl]- amino]-2-forfinal]-1(2H)-pyridineboronic acid fenilmetilovy ether

Following the General methodology step 2 of example 17 with minor changes but with the replacement phenylmethylene ester 4-hydroxy-4-[4- [[(phenylmethoxy)carbonyl]amino]phenyl]-1-piperidine eingabedatei acid (example 72, stage 1) has been specified in the header of the connection, so pl. 138-139oC.

Stage 3: (R)-3,4-Dihydro-5-[4-[5-(hydroxymethyl)-2 - oxo-3-oxazolidinyl]-2-forfinal]-1(2H)-pyridineboronic acid fenilmetilovy ether

Following the General method of stage 3 of example 17 with minor changes but with the replacement phenylmethylene ester of 3,6-dihydro-4-[4- [[(phenylmethoxy)carbonyl] amino] phenyl] -1(2H)-pyridineboronic acid fenilmetilovy ester of 3,4-dihydro-5-[4-[[(phenylmethoxy) carbonyl]amino]-2-forfinal] -1(2H)-pyridineboronic acid (example 72, step 2) has been specified in the title compound, VRMS: calculated for C23H23N2F1O5: 426,1591; found: 426,1594.

Stage 4: (R)-3,4-Dihydro-5-[4-[5-[[(methylsulphonyl)-oxy] methyl]-2-oxo-3-oxazolidinyl] -2-forfinal] -1(2H)- pyridineboronic acid fenilmetilovy ether

Following the General method of stage 4 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-(hydroxymethyl)- 2-oxo-3-oxazolidinyl] phenyl)-1 (2H)-pyridineboronic acid fenilmetilovy ether (R)-3,4 - dihydro-5- [4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl] -2-forfinal] -1(2H)pyridineboronic acid (example 72, step 3) has been specified in reception is ethylamino)methyl]-2-oxo-3 - oxazolidinyl] -2-forfinal-3,4-dihydro-1(2H)-pyridineboronic acid fenilmetilovy ether

Following the General method stage 5 of example 17 with minor changes but with the replacement phenylmethylene ether (R)-(-)-3,6 - dihydro-4- [4-[5-[[(methylsulphonyl) oxy] methyl]-2 - oxo-3-oxazolidinyl] phenyl]-1(2H)- pyridineboronic acid fenilmetilovy ether (R)-3,4-dihydro-5- [4-[5-[[(methylsulphonyl) oxy] methyl] -2-oxo-3-oxazolidinyl] -2-forfinal] - 1(2H)-pyridineboronic acid (example 72, step 4) has been specified in the title compound, VRMS: calculated for C25H26F1N3O5: 467,1856; found: 467,1862.

Stage 6: (S)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl]-3,4-dihydro-2H-pyridine-5-yl]phenyl]-5-oxazolidinyl]- methyl]ndimethylacetamide

Following the General method of stage 3 of example 70, with minor changes, but replacing 1,1-dimethylethylene ether (S)-(-)-5- [4-[5-[(acetylamino) methyl] -2-oxo-3-oxazolidinyl] - 2-forfinal] -5,6 - dihydro-1(2H)-pyridineboronic acid fenilmetilovy ether (S)-(-)-5-[4-[5- [(acetylamino) methyl] -2-oxo-3 - oxazolidinyl] -2-forfinal]-3,4-dihydro - 1(2H)- pyridineboronic acid (example 72, step 5) has been specified in the header of the connection, so pl. 146-148oC.

Example 73. (S)-(-)-N-[[3- [4-[1-(Hydroxyacetic)-3,4 - dihydro-2H - pyridine-5-yl] -3-forfinal] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide

Smimer 72, stage 6, 238 mg) and anhydrous potassium carbonate (151 mg) in methanol (27 ml) was stirred in an atmosphere of N2at ambient temperature for 2 hours and then neutralized chloroethanol acid (1M) and concentrated under reduced pressure. The residue was diluted with methylene chloride (100 ml) and saturated salt solution (50 ml) and the resulting insoluble product was separated by filtration and dried under reduced pressure. Separated the layers in the filtrate and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain additional quantities specified in the connection header, so pl. 171-173oC.

Example 74. (S)-(-)-N-[[3-[4-[1-Formyl-4-fluoro-4-piperidinyl]- 3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 4-Hydroxy-4-[2-fluoro-4-[[(phenylmethoxy)-carbonyl] amino]phenyl] -1-piperidinecarboxylic acid fenilmetilovy ether

A solution of 1-(3-forfinal)-of 2.2.5.5-tetramethyl-1-Aza-2,5 - disilacyclobutane (example 20, step 1, and 1.00 g) in dry tetrahydrofuran (9.8 ml) at -78oC in an atmosphere of N2processed second-butyllithium (1.3 M in cyclohexane, to 3.64 ml) dropwise over 3 minutes and the resulting mixture was stirred at -78oC for 2 hours. Then with the for 2 minutes and stirred at -78oC for 2 hours. Then the mixture was allowed to warm to -20oC for 1 hour and extinguished saturated aqueous ammonium chloride (5 ml), diluted with water (20 ml), layers were separated, the aqueous phase was extracted with diethyl ether (20 ml) and the combined organic phase was washed with saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol (15 ml) and treated with anhydrous potassium carbonate (544 mg, of 3.94 mmol) and the resulting mixture was stirred at ambient temperature for 30 minutes, concentrated under reduced pressure, diluted with diethyl ether (30 ml), washed with water (20 ml) and saturated salt solution (10 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the crude intermediate product 4-(hydroxy)piperidinylmethyl (Rf=0,25 according to TLC, ethyl acetate/hexane (50/50)). A mixture of this intermediate product and N,N-dimethylaniline (1,00 ml) in tetrahydrofuran (20 ml) was cooled to -20oC and treated with benzylchloride (0,59 ml) and the resulting mixture was stirred at -20oC for 1 hour. Then the mixture was diluted with saturated aqueous carbonate kalyanam salt solution (20 ml), was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographically on silica gel (230-400 mesh mesh, 150 g) with elution with a gradient mixture of ethyl acetate/hexane (25/75-50/50) and the fraction with Rf=0,47 according to TLC (ethyl acetate/hexane, 50/50) were combined and concentrated to obtain specified in the title compound, NMR (400 MHz, CDCl3) 7,35, 7,00, 6,92, 5,20, 5,16, 4,10, 3,32, 2,15 and 1.79. Anal. calculated for C27H27FN2O5: C, 67,77; H, 5,69; N, 5,85. Found: C, 67,44; H, Of 5.83; N, 5,65.

Stage 2: 4-Fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino]-2 - forfinal]-1-piperidinecarboxylic acid fenilmetilovy ether

To a solution of diethylaminoethyl TRIFLUORIDE (DAST, will GIVE, of 0.65 ml) in dry methylene chloride (49 ml) at -78oC in an atmosphere of N2was added a solution of 4-hydroxy-4-[4-[[(phenylmethoxy)carbonyl] amino] -2-forfinal]-1-piperidinecarboxylic acid phenylmethylene ester (example 74, step 1, 2.25 g) in dry methylene chloride (47 ml) for 2 minutes. The resulting mixture was stirred at -78oC for 1 hour and at ambient temperature for 30 minutes and then brought to pH 8 with saturated aqueous sodium bicarbonate solution (50 ml), diluted with water (50 ml) and layers were separated. The organic phase is washed with water (25 is the pressure and the residue was chromatographically on silica gel (230-400 mesh mesh, 150 g) with elution with a mixture of methanol/methylene chloride (0.5 in/99,5). Fractions with Rf=0,27 according to TLC (ethyl acetate/hexane, 25/75) were combined and concentrated to obtain specified in the connection header (with an admixture of about 15% by-product elimination). An analytical sample is prepared by radial chromatography (saikaley rotor 1000 μm, ethyl acetate/hexane (20/80) as eluent), so pl. 116-118oC.

Stage 3: (R)-4-Fluoro-4-[4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl]-2-forfinal]-1-piperidinecarboxylic acid fenilmetilovy ether

A solution of 4-fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino] -2-forfinal]-1-piperidinecarboxylic acid phenylmethylene ester (example 74, step 2, 2,03 g, mixed with by-product elimination) in dry tetrahydrofuran (21 ml) at -78oC in an atmosphere of N2, was treated with n-butyllithium (2,80 ml of 1.6 M solution in hexane) dropwise over 5 minutes. The resulting mixture was stirred at -78oC for 1.25 hours and then was treated with (R)-(-)-glycidylether (0.63 ml) dropwise. The resulting solution was stirred at -78oC for 1 hour, warmed to ambient temperature and was stirred for another 20 hours after which the reaction mixture was suppressed by the addition of nasionale saturated salt solution (10 ml), was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to get crude product, which was chromatographically on silica gel (230-400 mesh mesh, 250 g) with elution with a mixture of methanol/methylene chloride (3/97). Pooling and concentration of fractions with Rf=0,51 according to TLC (methanol/chloroform (10/90) and re-purification by chromatography on silica gel (230-400 mesh mesh, 100 g, a mixture of methanol/methylene chloride (4/96) as eluent) gave specified in the title compound, mixed with a by-product of the elimination of the original product). An analytical sample is prepared by radial chromatography (saikaley rotor 2000 μm, ethyl acetate/hexane (60/40) as the eluent), NMR (400 MHz, CDCl3) 7,45, 7,34, 7,18, 5,16, 4,74, 4,17, 3,97, 3,72, 3,22, 2,25 and 1,90 and BPMC: calculated for C23H24F2N2O5: 446,1653; found: 446,1660.

Stage 4: (R)-4-Fluoro-4-[4-[5- [[(methylsulphonyl) oxy]- methyl]-2-oxo-3-oxazolidinyl] -2-forfinal]-1 - piperidinecarboxylic acid fenilmetilovy ether

A solution of (R)-4-fluoro-4-[4-[5-(hydroxymethyl)-2-oxo-3 - oxazolidinyl]-2-forfinal] -1-piperidinecarboxylic acid phenylmethylene ester (example 74, step 3, 0.17 g) and triethylamine (0,080 ml) in dry methylene chloride (2 ml) at 0oC in the atmosphere the/SUP>C for 12 hours and at ambient temperature for 1.5 hours, diluted with methylene chloride (10 ml), washed with water (5 ml), saturated aqueous sodium bicarbonate (5 ml) and saturated salt solution (5 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header, VRMS: calculated for C24H26F2N2O7S+H1: 525,1507; found: 525,1522.

Stage 5: (S)-N-[[2-oxo-3-[4-(4-fluoro-4-piperidinyl)-3 - forfinal]-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (R)-4-fluoro-4-[4-[5-[[(methylsulphonyl)oxy] methyl]- 2-oxo-3-oxazolidinyl] -2-forfinal]-1-piperidinecarboxylic acid phenylmethylene ester (example 74, step 4, 0,190 g) and concentrated aqueous ammonium hydroxide (2 ml) in isopropanol (1 ml) and acetonitrile (2 ml) were placed in a hermetically closed tube and immersed in a closed test tube in an oil bath, the temperature of which was maintained at a level of 95oC for 18 hours. Then the mixture was diluted with methylene chloride (20 ml), washed with water (10 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude intermediate which mediate the connection and pyridine (0,088 ml) in dry methylene chloride (3.6 ml) in an atmosphere of N2was treated with acetic anhydride (0,051 ml) and the resulting solution was stirred at ambient temperature for 18 hours. Then the mixture was diluted with methylene chloride (10 ml), washed with water (5 ml), saturated aqueous sodium bicarbonate (5 ml) and saturated salt solution (5 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude intermediate ndimethylacetamide, which after merging with about 1.5 g of the crude product of the previous series, the reaction was chromatographically on silica gel (230-400 mesh mesh, 150 g) with elution by a gradient of methanol/methylene chloride (1/99 - 2/98). Pooling and concentration of fractions with Rf=0,18 according to TLC (methanol/chloroform, 5/95) gave 0,80 g (approximately 70% of the nelfinavir) product (impurity a by-product elimination) as a white amorphous solid, which was used without further purification. A mixture of this intermediate product (0.75 g) and 20% palladium hydroxide on carbon (200 mg) in methanol (30 ml) was shaken on the Parr apparatus in an atmosphere of hydrogen at a pressure of 40 psig (2.8 kg/cm2) for 1 hour, the catalyst was removed by filtration through Celite and the filtrate conc entom mixture of triethylamine/methanol/methylene chloride (1/9/90-1/4/95) and the fraction with Rf=0,19 according to TLC (triethylamine/methanol/chloroform, 1/9/90) were combined and concentrated to obtain specified in the connection header, so pl. 163-165oC.

Stage 6: (S)-(-)-N-[[3-[4-[1-Formyl-4-fluoro-4-piperidinyl]-3 - forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A mixture of (S)-3-N-[[2-oxo-3-[4-(4-fluoro-4-piperidinyl)-3 - forfinal]-5-oxazolidinyl)methyl] ndimethylacetamide (example 74, step 5, 205 mg), 1-(3-dimethylaminopropyl)-3 - ethylcarbodiimide (145 mg) and formic acid (28 μl) in dry tetrahydrofuran (11,6 ml) was diluted with water to dissolve all reagents and stirred at ambient temperature for 6 hours. Then the reaction mixture was diluted with methylene chloride (30 ml), washed with water (20 ml) and saturated salt solution (20 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure and the residue was chromatographically on silica gel (230-400 mesh mesh, 40 g) with elution by a gradient of methanol/methylene chloride (3/97-5/95). Fractions with Rf=0,40 according to TLC (methanol/chloroform, 10/90) were combined and concentrated and the residue was recrystallized from a mixture of chloroform/diethyl ether to obtain specified in the connection header, so pl. 180-181oC (Razlog.).

Example 75. (S)-N-[[2-Oxo-3-[3-f is,7-Tetrahydro-5-[[(trifluoromethyl)sulfonyl] oxy] -1H - azepin-1-carboxylic acid 1,1-dimethylethylene ether (a) and 2,3,6,7-tetrahydro-4-[[(trifluoromethyl)sulfonyl] oxy] -1H - azepin-1-carboxylic acid 1,1-dimethylethylene ether (b)

Following the General method of example 20 (stage 2), with minor changes, but replacing 1-(1,1 - dimethylethoxysilane)-4-piperidone 1-(1,1-dimethylethoxysilane)- 1,2,3,5,6,7-hexahydroazepin-4-one and allocation of regioisomers by chromatography on silica gel (230-400 mesh mesh, ethyl acetate/hexane (5/95) as eluent) has been specified in the title compound, (a) NMR (CDCl3, 400 MHz) 5,87, 3,95, 3,55, 2,57, 1,95 1,46 and (b) NMR (CDCl3, 400 MHz) 5,90, 3,54, 2,69, 2,35 and 1.47.

Stage 2: (S)-5-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl]-2-forfinal] -2,3,4,7-tetradehydro-1H - aspengrove acid 1,1-dimethylethylene ether

Following the General method of example 38 (stage 1), with minor changes but with the replacement of 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl] oxy]-1(2H)-pyridineboronic acid 1,1-dimethylethylene ether on 2,3,4,7-tetrahydro-5-[[(trifluoromethyl)sulfonyl] oxy] -1(1H)- aspengrove acid 1,1-dimethylethylene ester (example 75, step 1 (A)) has been specified in the title compound, NMR (CDCl3, 400 MHz) 7,31, 7,12-6,95, 5,84, 4,76, 4,00, 3,98, 3,76, 3,61, 3,58, 2,51, 1,97, 1,85 and of 1.42.

Stage 3: (S)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl] -2,3,4,7-tetrahydro-1H-azepin-5-yl]phenyl]-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 70 (stage 3) with negligible the ro-1(2H)- pyridineboronic acid 1,1-dimethylethylene ester to (S)-5-[4-[5- [(acetylamino) methyl]-2-oxo-3 - oxazolidinyl] - 2-forfinal] -2,3,4,7 - tetrahydro-1H - azepin-1 - carboxylic acid 1,1-dimethylethylene ester (example 75, step 2) has been specified in the title compound, VRMS: calculated for C22H26F1N3O6: 448,1884; found: 448,1888.

Example 76. (S)-(-)-N-[[3-[4-[1-(Hydroxyacetic)-2,3,4,7 - tetrahydro-1H-azepin-5-yl]-3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 71, with minor changes, but replacing (S)-(-)-N- [[2-oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl]-5,6-dihydro-2H - pyridine-3-yl] phenyl] -5-oxazolidinyl] methyl] ndimethylacetamide (S)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -2,3,4,7-tetrahydro-1H-azepin-5-yl] -phenyl] -5 - oxazolidinyl] methyl] ndimethylacetamide (example 75, step 3) has been specified in the title compound, NMR (CDCl3, 400 MHz, mixture of rotamers) 7,41, 7,09-7,18, 6,07, 6,00, 5,87, 4,78, 4,25, 4,21, 4,05, 3,92, 3,87, 3,78, 3,67, 3,51, 2,63, 2,03 and of 1.97 and VRMS: calculated for C20H24F1N3O5: 405,1700; found: 405,1694.

Example 77. (S)-(-)-N-[[2-Oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl] -2,3,6,7-tetrahydro - 1H-azepin-4-yl] phenyl]-5-oxazolidinyl] methyl] ndimethylacetamide

Stage 1: (S)-4-[4-[5-[(Acetylamino)methyl]-2-oxo-3 - oxazolidinyl]-2-forfinal] -2,3,6,7-tetrahydro-1H-azepin-1 - carboxylic acid 1,1-dimethylethylene ether

Following the General l] oxy]-1(2H)- pyridineboronic acid 1,1-dimethylethylene ether on 2,3,6,7-tetrahydro-4-[[(trifluoromethyl) sulfonyl] oxy]-1(1H)-aspengrove acid 1,1 - dimethylethylene ester (example 75, stage 1 (B)) has been specified in the header of the connection, so pl. 164-165oC.

Stage 2: (S)-(-)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy) acetyl] -2,3,6,7-tetrahydro-1H-azepin-4-yl]phenyl]-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 70 (stage 3), with minor changes, but with replacement (S)-(-)-3-[4-[5-[(acetylamino)methyl]- 2-oxo-3-oxazolidinyl] -2-forfinal] -5, 6 - dihydro-1(2H)- pyridineboronic acid 1,1-dimethylethylene ester to (S)-4-[4- [5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl] -2-forfinal) - 2,3,6,7-tetrahydro-1H-azepin-1-carboxylic acid 1,1 - dimethylethylene ester (example 77, step 1) has been specified in the title compound, NMR (CDCl3, 400 MHz, mixture of rotamers) 7,39, 7,15, 8,22, 5,90, 4,79, 4,04, 3,80-3,50, 2,70, 2,50, 2,19 and 2.02. Anal. calculated for C22H26F1N3O6: C, 59 05; H, 5,86; N, 9,39. Found: C, 58,70; H, 5,80; N, 9,43.

Example 78. (S)-(-)-N-[[3-[4-[1-(Hydroxyacetic)-2,3,6,7 - tetrahydro-1H-azepin-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 71, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [3-fluoro-4-[1- [(acetoxy) acetyl]-5,6-dihydro - 2H-pyridine-3-yl] phenyl] -5 - oxazolidinyl] methyl] ndimethylacetamide (S)-(-)-N-[[2-oxo-3- [3 - fluoro-4-[1-[(acetoxy) acetyl]-2,3,6,7-tetrahydro - 1H-azepin-4 - DCl3, 400 MHz, mixture of rotamers) 7,41, 7,13, 6,08, 5,90, 4,78, 4,22, 4,04, 3,85-3,59, 3,51-3,41, 2,70, 2,52 and 2.02. Anal. calculated for C20H24F1N3O5: C, 59,25; H, 5,97; N, 10,36. Found: C, 58,91; H, 6 04; N, 10,19.

Example 79. (5S)-(-)-N-[[3-[4-[1-(Hydroxyacetic) hexahydro - 1H-azepin-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]- ndimethylacetamide (mixture of diastereoisomers)

Following the General method of example 48 with minor changes, but replacing (S)-(-)-N- [[3-[4-(3,6-dihydro-2H-Piran-4-yl) -3-forfinal] -2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide (S)-(-) -N-[[3-[4- [1-(hydroxyacetic)-2,3,4,7 - tetrahydro-1-azepin-5 - yl] - 3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 76) and purification of the product by chromatography on silica gel (70-230 mesh, a mixture of methanol/methylene chloride (7,5/92,5 as eluent) has been specified in the title compound, VRMS: calculated for C20H26F1N3O5+H1: 408,1935; found: 408,1928.

Example 80. (S)-N-[[3-[3-Fluoro-4-(3,4-dihydro-2H-Piran-6-yl) phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 6-(Tributylstannyl)-3,4-dihydro-2H-dihydropyran

A solution of 3,4-dihydro-2H-dihydropyran (2,000 g of 23.8 mmol) and N,N,N', N'-tetramethylethylenediamine (0,50 ml, to 3.09 mmol) under nitrogen atmosphere was cooled to 0oC and was treated with n-Breda throughout the night. The resulting mixture was cooled to -78oC, was added to her dry tetrahydrofuran (20 ml) and then tributyltinchloride (6,40 ml of 23.8 mmol). The mixture was stirred at -78oC for 1 hour and then warmed to ambient temperature for 2 hours. The reaction mixture was diluted with diethyl ether (50 ml), transferred into a separating funnel and washed with 5% aqueous ammonium hydroxide solution and saturated salt solution. The organic layer was dried, filtered and concentrated to obtain the crude product. Distillation of the residue under reduced pressure gave 1.80 g (47%) indicated in the title compound with a purity of 55%.

Stage 2: (S)-N-[[3-[3-Fluoro-4-(3,4-dihydro-2H-Piran-6-yl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

A solution of (S)-N-[[3-[3-Fluoro-4-itfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (0,200 g of 0.53 mmol) in 1-methyl-2-pyrrolidinone (5 ml) under nitrogen atmosphere was treated with Pd2dba3(0,018 g, 0.02 mmol) and three(2-furyl)phosphine (0,009 g, 0.04 mmol). After stirring for 10 minutes at ambient temperature the mixture was treated with 6- (tributylstannyl)-3,4-dihydro-2H-dihydropyran (0,538 g, purity 55%, 0.80 mmol). The medium was aspirated and filled the sparse volume with nitrogen three times, after which the mixture nagrevaya environment and poured into ethyl acetate. The precipitate was removed by filtration through Celite. The filtrate was transferred into a separating funnel and washed with water and saturated salt solution, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was chromatographically on silica gel by elution with hexane, a mixture of 20% acetone/hexane and then with a mixture of 5% methanol/dichloromethane. Appropriate fractions were combined and concentrated in vacuum to obtain 0,196 g of the product contained a small amount of 1 - methyl-2-pyrrolidinone. Recrystallization gave 0,128 g (68%) specified in the connection header. So pl. 161-163oC; MS(EI): m/z 334.

Example 81. (S)-N-[[3-[3-Fluoro-4-[1-(carbobenzoxy)-3 - azetidinol]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Stage 1: 3-(4-Amino-2-forfinal)-3-hydroxy-1-(1,1 - diphenylmethyl)azetidin

To a stirred solution of 1-(3-forfinal)-of 2.2.5.5 - tetramethyl-1-Aza-2,5-disilacyclobutane (example 20, step 1) (6.0 g, with 23.7 mmol) at -78oC in nitrogen atmosphere in dry THF (75 ml) was added dropwise sec-utility (22.5 ml of 1.3 M solution in cyclohexane, 29.5 mmol). After 2 hours, was added dropwise a solution of 1-(1,1-diphenylmethyl)azetidin-3-one (5.6 g, 23.6 mmol) in dry THF (60 ml) and continued stirring at -78oC for 2 hours, the ammonium chloride (75 ml) and then water (200 ml). The mixture was extracted with ether (500 ml), washed with saturated salt solution (100 ml), dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in methanol (150 ml) was added anhydrous potassium carbonate (6.0 g, to 43.5 mmol), then stirred overnight. The suspension was filtered and the filtrate evaporated. The residue was distributed between ether (500 ml) and water (200 ml). The aqueous phase was extracted with additional ether (200 ml) and the combined ethereal extracts were washed with saturated salt solution (100 ml), dried on magnesium sulfate, filtered and evaporated to obtain an orange foamy substance. Chromatography on silica gel (150 g, 40-60 μm) with elution with a mixture of 25-50% ethyl acetate/hexane gave specified in the title compound as a pale yellow foamy substance.1H NMR (CDCl3) 2,62, 3,53, 3,78, 4,41, 6,36, 6,41, 7,03, 7,14-7,30, 7,39-7,47.

Stage 2: 3-(N-Carbobenzoxy-3-ftoranila-4-yl)-3-hydroxy - 1-(1,1-diphenylmethyl)azetidin

To a solution of 3-(4-amino-2-forfinal)-3-hydroxy-1-(1,1 - diphenylmethyl)azetidine (example 81, step 1, 5.10 g, 14.7 mmol) in acetone (7.5 ml) was added a solution of sodium bicarbonate (2,52 g, 30.0 mmol) in water (40 ml) to give a cream-colored suspension. Were added benzylchloride (to 2.57 g, 15.1 mmol) and Progetto (200 ml) and water (50 ml). The organic layer was washed with saturated salt solution (50 ml), dried over magnesium sulfate, filtered and evaporated, resulting remained foamy substance the color of amber. Chromatography on silica gel (150 g, 40-60 μm) with elution with a mixture of 1-2% methanol/methylene chloride gave specified in the title compound in the form of a foamy substance cream color. VRMS: theory. calculated: 483,2084 found: 483,2087.

Stage 3: N-Carbobenzoxy-3-(N-carbobenzoxy-3-ftoranila-4-yl)-3 - hydroxyazetidine

To a solution of 3-(N-carbobenzoxy-3-ftoranila-4 - yl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine (example 81, step 2, to 1.60 g of 3.32 mmol) in benzene (30 ml) were added benzylchloride (3.8 ml, to 26.6 mmol) followed by heating under reflux for 2 hours in nitrogen atmosphere. Evaporated benzene and the residue was chromatographically on silica gel (150 g, 40-60 μm) with elution with a mixture of 20-60% ethyl acetate/hexane. Got mentioned in the title compound as a white foamy substance.1H NMR (CDCl3) 2,32, 4,19, 4,42, 5,08, 5,17, 6,98, 7,11, 7,19, 7,24-7,43.

Stage 4: N-Carbobenzoxy-3-(N-carbobenzoxy-3-ftoranila - 4-yl)azetidin

To a solution of N-carbobenzoxy-3- (N - carbobenzoxy-3-ftoranila-4-yl) -3-hydroxyazetidine (12 ml) and the mixture was stirred for 2 days. Removal of solvent at 45oTo/0.75 mm gave the oil is amber in color. Chromatography on silica gel (150 g, 40-60 μm) with elution with a mixture of 1-3% methanol/chloroform gave specified in the title compound in the form of a solid substance, so pl. 95oC.

Stage 5: (R)-(-)-N-Carbobenzoxy-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3 - oxazolidinyl]phenyl]azetidin

To a stirred solution of N-carbobenzoxy-3- (N-carbobenzoxy-3-ftoranila-4-yl) azetidine (example 81, step 4, 3,63 g, at 8.36 mmol) at -78oC in nitrogen atmosphere in dry THF (30 ml) was added dropwise n-utility (the 5.25 ml of 1.6 M solution in hexane, to 8.40 mmol) followed by stirring for 2 hours. Was added a solution of R-glycidylether (1,21 g of 8.40 mmol) in dry THF (3.0 ml) and after 15 minutes, remove the cooling bath. After 18 hours the solvent was removed and the residue was distributed between ethyl acetate (150 ml) and a saturated solution of ammonium chloride (50 ml). The organic layer was washed with water (50 ml) and saturated salt solution (50 ml), dried over magnesium sulfate, filtered and evaporated, resulting in the remained oil

amber color. Chromatography on silica gel (150 g, 40-60 μm) with elution with a mixture of 2-5% methanol/chloroform gave specified in the title compound which is N-Carbobenzoxy-3-[2-fluoro-4-[5-[[(3- nitrophenyloctyl)oxy]methyl]-2-oxo-3-oxazolidinyl]-phenyl] azetidin

It chilled with ice to a solution of (R)-(-)-N-carbobenzoxy - 3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3-oxazolidinyl]-phenyl] azetidine (example 81, step 5, and 2.79 g, 6,97 mmol) and triethylamine (1,41 g, 14.0 mmol) in methylene chloride (40 ml) was added 3 - nitrobenzenesulfonamide (1.70 g, to 7.67 mmol). After 16 hours was added water (50 ml) and methylene chloride (100 ml). The organic layer was washed with saturated salt solution (50 ml), dried over magnesium sulfate, filtered and evaporated. The residue was chromatographically on silica gel (150 g, 40-60 μm) with elution with a mixture of 25-100% ethyl acetate/hexane and the result was indicated in the title compound as a sticky foam substance. FAB-BPMC: theory. calculated: 586,1290 (M+1); found: 586,1295.

Stage 7: (S)-(-)-N-Carbobenzoxy-3-[2-fluoro-4-[5 - azidomethyl-2-oxo-3-oxazolidinyl]phenyl]azetidin

A mixture of sodium azide (1.44 g, 22,1 mmol) and (R)-(-)-N - carbobenzoxy-3- [2-fluoro-4-[5- [[(3-nitrophenyloctyl] - oxy]methyl] -2-oxo-3-oxazolidinyl] phenyl] azetidine (example 81, step 6, 2,60 g of 4.44 mmol) in DMF (30 ml) was stirred for 16 hours, then filtered. Solvent was removed under 38oTo/0.75 mm and the residue was extracted with ethyl acetate (100 pieces) and washed with water (3 x 50 ml) and saturated salt solution (50 ml). After drying over sulfate is the use of a mixture of 1-3% methanol/methylene chloride gave specified in the title compound as a pale yellow foamy substance. FAB-BPMC: theory. calculated: 426,1577 (M+1); found: 426,1580.

Step 8: (S)-(-)-N-Carbobenzoxy-3-[2-fluoro-4-[5 - aminomethyl-2-oxo-3-oxazolidinyl]phenyl]azetidin

To a stirred solution of (S)-(-)-N-carbobenzoxy-3- [2-fluoro-4- [5-azidomethyl-2-oxo-3-oxazolidinyl] phenyl] -azetidine (example 81, step 7, 1.63 g, of 3.84 mmol) in dry THF (20 ml) was added triphenylphosphine (1,11 g, to 4.23 mmol). After 3 hours, water was added (0,69 ml, 38.4 mmol) and the reaction mixture was stirred for 2 days, then evaporated solvents. The residue was chromatographically on silica gel (150 g, 40-60 μm) with elution with a mixture of 5-10% methanol/chloroform. Allocated is specified in the title compound as a viscous colorless oil. FAB-BPMC: theory. calculated 400,1672 (M+1); found: 400,1676.

Stage 9: (S)-N-[[3-[3-Fluoro-4-[1-(carbobenzoxy)-3 - azetidinol]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

To a stirred solution of (S)-(-)-N-carbobenzoxy-3- [2 - fluoro-4- [5-aminomethyl-2-oxo-3-oxazolidinyl] phenyl]-azetidine (example 81, step 8, 1.42 g, of 3.56 mmol) in methylene chloride (30 ml) was added pyridine (1.0 ml), acetic anhydride (1.0 ml) and a few crystals of 4-dimethylaminopyridine, after which the mixture was stirred for 1 hour. Remove the solvents under 38oTo/0.75 mm and the remainder of khromatograficheskie in the form of a white foamy substance. FAB - BPMC: theory. calculated 442,1778 (M+1); found: 442,1777.

Example 82. (S)-N-[[3-[3-Fluoro-4-[3-azetidinol] phenyl]-2-oxo-5 - oxazolidinyl]methyl]ndimethylacetamide

A solution of (S)-N-[[3-[3-fluoro-4-[1-(carbobenzoxy)-3 - azetidinol]phenyl]-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (example 81, step 9, 1.44 g, 3,26 mmol) in ethyl acetate (25 ml) and absolute ethanol (50 ml) was added 10% Pd/C (1.0 g) and was first made at a pressure of 30 psig (2.1 kg/cm2within 7 hours. Filtration and evaporation gave specified in the title compound as a white glassy solid. FAB-BPMC: theory. calculated 308,1410 (M+1); found: 308,1408.

Example 83. (S)-N-[[3-[3-Fluoro-4-[1-(carboxymethyl)-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

To a suspension of (S)-N-[[3-[3-Fluoro-4-[3-azetidinol]phenyl]- 2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide (example 82, 153 mg, 0.50 mmol) in chloroform (5 ml) were added triethylamine (150 μl, of 1.08 mmol) and methylchloroform (65 μl, 0.84 mmol) and the resulting mixture was stirred overnight. Added added chloroform (25 ml) and the solution was washed with water (15 ml) and saturated salt solution (15 ml). Drying over magnesium sulfate, filtration and evaporation gave a foam substance. Chromatography on silica gel (50 g, 40-60 μm) with elution with a mixture of 1-3% m is about 366,1465 (M+1); found: 366,1468.

Example 84. (S)-N-[[3-[3-Fluoro-4-[1-(formyl)-3-azetidinol]- phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

To a stirred suspension of (S)-N-[[3-[3-fluoro-4-[3-azetidinol] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (example 82, 153 mg, 0.50 mmol) in THF (5 ml) was added N-formylbenzoate (115 mg, 0.78 mmol) and the mixture was stirred overnight. Solvent was removed and the residue was chromatographically on silica gel (50 g, 40-60 μm) with elution with a mixture of 2-5% methanol/chloroform, the result of which has been specified in the title compound as a white foamy substance. FAB-BPMC: theory. calculated 336,1356 (M+1); found: 336,1357.

Example 85. (S)-(-)-N- [[3-[4-[1-(4-Oxo-2-thiazolyl) -4 - piperidinyl] -3-forfinal]-2-oxo-5 - oxazolidinyl] methyl]ndimethylacetamide

A mixture of (S)-(-)-N- [[2-oxo-3-[4-(4-piperidinyl)-3-forfinal] -5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 310 mg), methylthiocarbamate (121 mg, Bull. Chem. Soc. Jpn. 1972, 45(5), 1507) and glacial acetic acid (55 mg) in absolute ethanol (5 ml) was stirred while heating under reflux in an atmosphere of N2for 4 hours and then was cooled to ambient temperature, diluted with methylene chloride (45 ml), washed with water (2 x 15 ml) and saturated salt solution (20 ml), dried over anhydrous sulfa) with elution with a mixture of methanol/methylene chloride (4/96) and the fraction with Rf=0,47 according to TLC (methanol/chloroform, 10/90) were combined and concentrated to obtain specified in the connection header, so pl. 222-224oC (Razlog.).

Example 86. (S)-(-)-N-[[3-[4-[1-(4-Oxo-2-thiazolyl)-3,6 - dihydro-2H-pyridine-5-yl]-3-forfinal]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

Following the General method of example 85, with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl)-3-forfinal]-5-oxazolidinyl] methyl] ndimethylacetamide(S)-(-) -N-[[2-oxo-3-[4-(3, 6-dihydro-2H-pyridine-4-yl) -3-forfinal] - 5-oxazolidinyl] methyl] the ndimethylacetamide (example 38), have been specified in the header of the connection, so pl. 209-211oC(Razlog.).

Example 87. (S)-(-)-N-[[3-[4- [1-(5-Methyl-1,3,4-thiadiazole-2 - yl)-4-piperidinyl]-3-forfinal] -2-oxo-5-oxazolidinyl] -methyl] ndimethylacetamide

Stage 1: 2-Bromo-5-methyl-1,3,4-thiadiazole

To a solution of aqueous Hydrobromic acid (48%, 40 ml) containing a small amount of copper powder, -10oC was added a mixture of 2-amino-5-methyl-1,3,4-thiadiazole (2,88 g) and sodium nitrite (7,76 g) in portions over 45 minutes with vigorous stirring. The resulting mixture was stirred at -10oC for 1.5 hours and at ambient temperature for a further 1.5 hours and then cooled in an ice bath, neutralized the real jet paper no longer was under the influence of a mixture of blue, and filtered to remove insoluble product (washing with hot water). The filtrate was extracted with methylene chloride (4 x 100 ml) and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product, which was then chromatographically on silica gel (70-230 mesh, 75 g) with elution with a mixture of ethyl acetate/hexane (50/50). Pooling and concentration of fractions with Rf=0,78 according to TLC (methanol/chloroform, 10/90) were specified in the title compound, so pl. 107-108oC.

Stage 2: (S)-(-)-N-[[3-[4-[1-(5-Methyl-1,3,4-thiadiazole-2-yl) (3,6-dihydro-2H-pyridine-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide

A mixture of (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl) -3-forfinal]- 5-oxazolidinyl] methyl] ndimethylacetamide (example 20, 550 mg), 2-bromo-5-methyl-1,3,4-thiadiazole (example 87, step 1, 323 mg) and potassium hydrogen phosphate (571 mg) in dimethyl sulfoxide (16 ml) was stirred in an atmosphere of N2when 100oC for 2 hours, cooled to ambient temperature, diluted with water (20 ml) and was extracted with methylene chloride (3 x 20 ml). The combined organic phase was washed with water (20 ml) and saturated salt solution (10 ml), dried over anhydrous sodium sulfate and kontsentrirovaniem gradient of methanol/methylene chloride (2/98 - 3/97). Pooling and concentration of fractions with Rf=0,44 according to TLC (methanol/chloroform, 10/90) were specified in the title compound, so pl. 193-195oC.

Example 88. (S)-(-)-N-[[3-[4-[1-(5-Methyl-1,3,4-thiadiazole-2 - yl]-3,6-dihydro-2H-pyridine-5-yl]-3-forfinal]-2-oxo-5 - oxazolidinyl]methyl]ndimethylacetamide

Following the General method of example 87 (stage 2), with minor changes, but replacing (S)-(-)-N-[[2-oxo-3- [4-(4-piperidinyl - 3-forfinal]-5-oxazolidinyl] methyl]ndimethylacetamide (S)-(-)-N-[[2-oxo-3- [4-(3,6-dihydro-2H-pyridine-4-yl)-3 - forfinal] -5-oxazolidinyl] methyl]ndimethylacetamide (example 38), have been specified in the header of the connection, so pl. 229-231oC (decomp.).

1. Derivatives of phenyloxazolidine General formula I

< / BR>
where X represents a) NR1b) S(O)gor c) O;

R1is a) H, b) C1-6alkyl, optionally substituted by one or more CN or halogen, C) -(CH2)h-phenyl, d) -COR1-1e) -COOR1-2f) -CO-(CH2)h-COR1-1, g) -SO2-C1-6alkyl or h) -(CO)i-Het, where Het is selected from thiazolyl, substituted NO2or oxo, indolyl, isoxazolyl, 1, 3, 4-thiadiazolyl, replaced by stands;

R1-1is a) H, b) C1-6alkyl, optionally substituted by one who alkyl, optional replaced IT, b) -(CH2)his phenyl;

R1-3represents (a) C1-6alkyl, b) -(CH2)h-phenyl, c)- (C1-6alkyl);

R2is a) H, b) C1-6alkyl, (C) F;

R3and R4are the same or different and are a) H, or b) halogen;

R5represents C1-6alkyl and C3-6cycloalkyl, optionally substituted by one or more Halogens;

g = 0, 1, or 2;

h = 1 or 2;

i = 0 or 1;

m= 0, 1, 2, 3;

n = 0, 1, 2, 3, provided that m and n taken together are equal to 1, 2, 3, 4 or 5;

or its pharmaceutically acceptable salt.

2. Connection on p. 1, where R1selected from the group comprising N, foradil, tianmei, methylsulphonyl, formyl, hydroxyacetic, acetyl, methoxyacetyl, benzyloxyethyl, acetoxyacetyl, dichloracetyl, methoxycarbonyl, tertbutoxycarbonyl, benzyloxycarbonyl, 3-hydroxypropionic, 3-methoxypropyl, 4-oxopentanoic, 2-indolocarbazole, 5-isoxazolone, 5-nitro-2-thiazolyl, 4-oxo-2-thiazolyl or 5-methyl-1, 3, 4-thiadiazole-2-yl.

3. Connection on p. 1, where R2represents H, F or CH3.

4. Connection on p. 1, where R3and R4are the same or razluchnitsy one or more F or C1.

6. Connection on p. 1, where m = 1 and n = 0.

7. Connection on p. 1, where m and n taken together is equal to 2.

8. Connection on p. 1, where m and n taken together is equal to 3.

9. Connection on p. 1, where m and n taken together is equal to 4.

10. Connection on p. 1, which is an optically pure enantiomer having the S-configuration at C5 oxazolidinone rings.

11. Connection on p. 1, which is a

(S)-N-[[3-[3-fluoro-4-[1-(carbobenzoxy)-(3-methyl)-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[3-methyl-3-azetidinol]phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(carboxymethyl)-3-(3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl)methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(methoxyacetyl)-3-(3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-(3-methyl)azetidine] -phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(dichloroacetyl)-3-(3-methyl)-azetidine] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(3-methoxypropyl)-3-(3-methyl)-azetidine] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(3-hydroxypropyl)-3-(3-methyl)azetidine] phenyl]-2-oxo-5-oxazolidine the l]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-acetyl-3-(3-methyl) azetidine]-phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(2-foradil)-3-(3-methyl) -azetidine]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(lanmeter)-3-(3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(5-nitro-2-thiazolyl)-3-(3-methyl)azetidine]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(methanesulfonyl)-3-(3-methyl)-azetidine] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(benzyloxyethyl)-3-(3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(hydroxyacetic)-3- (3-methyl)-azetidine] phenyl)-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(carbobenzoxy)-3-azetidinol] -phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(carboxymethyl)-3-azetidinol] -phenyl] -2-oxo-5-oxazolidinyl]methyl)ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4- [1-(hydroxyacetic)-3-pyrrolidinyl] -phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(5S)-N-[[3-[ 3-fluoro-4-[1-(formyl)-3-pyrrolidinyl] -1-pyrrolidinecarboxylic acid methyl ester;

(S)-N-[[3-[3-fluoro-4-(3,4-dihydro-2H-Piran-6-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[3-fluoro-4-(dehydration-3-yl)phenyl]-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4-(2,5-dihydro-1-oxido-3-thienyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl)ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-(4,5-dihydro-1-oxido-3-thienyl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4-(2,5-dihydro-1,1-dioxido-3-thienyl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-(4,5-Ligero-1,1-dioxido-3-thienyl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-4-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] phenyl] -3,6-dihydro-1 (2H)-pyridineboronic acid fenilmetilovy ether;

(S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)phenyl] -5-oxazolidinyl] methyl] ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-[(benzyloxy)acetyl] -4-piperidinyl]-phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-4-piperidinyl] -phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-[(benzyloxy)acetyl] -4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-[(benzyloxy)acetyl]-4-piperidinyl]-3,5-differenl] -oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(indole-2-carbonyl] -4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(isoxazol-5-carbonyl)-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-(-)-N-[[3-[4-[1-(methylsulphonyl] -4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-4-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] -2-forfinal]-1-piperidinecarboxylic acid methyl ester;

(S)-(-)-N-[[3-[4-[1-(lanmeter)-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(2-foradil)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(formyl)-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl] ndimethylacetamide;

(S)-(-)-4-[4-[5-[[(2,2-dichloroacetyl)amino]methyl]-2-oxo-3-oxazolidinyl] -2-forfinal]-1-piperidinecarboxylic acid; 1,1-dimethylethylene ether;

(S)-(-)-2,2-dichloro-N-[[2-oxo-3-[3-fluoro-4-(4-piperidinyl)phenyl] -5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-2,2-dichloro-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -4-piperidinyl]phenyl]-3-oxazolidinyl)-methyl]ndimethylacetamide;

(S)-(-)-2,2-dichloro-N-[[2-oxo-3-[3-fluoro-4-[1-(hydroxyacetic)-4-piperidinyl]phenyl]-5-oxazolidinyl]-methyl)ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[3-fluoro-4- [1-[(acetoxy)acetyl] -4-piperidinyl] phenethyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[tetrahydro-2H-Piran-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide,

(S)-(-)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)phenyl] -2-oxo-5-oxazolidinyl)methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[tetrahydro-2H-Piran-4-yl] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl] -2 - oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-forfinal]-2-oxo-5-oxazolidinyl)methyl]ndimethylacetamide S-oxide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl] -2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide S-oxide; (S)-(-)-N-[[3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3-[4-[1-(4-oxo-2-thiazolyl)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(5-methyl-1, 3, 4-thiadiazole-2-yl)-4-piperidinyl]-3-forfinal]-2-on the]-2-oxo-5-oxazolidinyl] methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(5-methyl-1, 3, 4-thiadiazole-2-yl)-3,6-dihydro-2H-pyridine-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl]-3-forfinal]-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -3,6-dihydro-2H-pyridine-4-yl]phenyl)-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-3,6-dihydro-2H-pyridine-4-yl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(formyl)-3,6-dihydro-2H-pyridine-4-yl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl)ndimethylacetamide;

(S)-(-)-4-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] -2-forfinal]-3,6-dihydro-1(2H)-pyridineboronic acid methyl ester;

(S)-(-)-N-[[2-oxo-3-[4-(3,6-dihydro-2H-pyridine-4-yl)-phenyl] -5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[4-[1-[(acetoxy)acetyl] -3,6-dihydro-2H-pyridine-4-yl]phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-3,6-dihydro-2H-pyridine-4-yl] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(formyl)-3,6-dihydro-2H-pyridine-4-yl] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-4-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] phenyl] -3,6-dihydro-1(2H)-pyridineboronic acid methyl ester;

(S)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetowhite-2H-pyridine-3-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[2-oxo-3-[3-fluoro-4-[1-(acetoxy)acetyl] -2,3,4,7-tetrahydro-1H-azepin-5-yl]phenyl]-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-2, 3, 4, 7-tetrahydro - 1H-azepin-5-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -2, 3, 6, 7-tetrahydro-1H-azepin-4-yl]phenyl]-5-oxazolidinyl]-methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-2, 3, 6, 7-tetrahydro-1H-azepin-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(5S)-(-)-N-[[3-[4-[1-(hydroxyacetic)hexahydro-1H-azepin-4-yl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -3,4-dihydro-2H-pyridine-5-yl]phenyl]-5-oxazolidinyl]methyl]-acetamide", she

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-3,4-dihydro-2H-pyridine-5-yl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide; or

(S)-(-)-N-[[3-[4-[1-formyl-4-fluoro-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

12. Connection on p. 11, which is:

(S)-N-[[3-[3-fluoro-4-[1-(carboxymethyl)-3-(3-methyl)-azetidine] phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-(3-methyl)azetidine] -phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(5S)-N-[[3-[3-fluoro-4-[1-(hydroxyacetic)-3-pyrrolidinyl ] FeNi the Nile]methyl]ndimethylacetamide;

(5S)-3-[4-[5-[(acetylamino)methyl] -2-oxo-3-oxazolidinyl] -2-forfinal] -1-pyrrolidinecarboxylic acid methyl ester;

(S)-(-)-N-[[3-[4-(1-(hydroxyacetic)-4-piperidinyl] -3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(formyl)-4-piperidinyl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-2,2-dichloro-N-[[2-oxo-3-[3-fluoro-4-[1-(hydroxyacetic)-4-piperidinyl]phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[2-oxo-3-[3-fluoro-4-[1-[(acetoxy)acetyl] -3,6-dihydro-2H-pyridine-4-yl]phenyl]-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-3,6-dihydro-2H-pyridine-4-yl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-Piran-4-yl)phenyl] -2-oxo-5-oxazolidinyl)methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-forfinal] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)-phenyl] -2-oxo-5-oxazolidinyl]methyl)ndimethylacetamide S,S-dioxide;

(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S,S-dioxide;
(S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide S-oxide;

(5S)-N-[[3-[3-fluoro-4-(2,5-dihydro-1-oxido-3-thienyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-N-[[3-[3-fluoro-4-(2,5-dihydro-1,1-dioxido-3-thienyl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(hydroxyacetic)-2, 3, 6, 7-tetrahydro-1H-azepin-4-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(4-oxo-2-thiazolyl)-3,6-dihydro-2H-pyridine-5-yl] -3-forfinal]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide;

(S)-(-)-N-[[3-[4-[1-(5-methyl-1, 3, 4-thiadiazole-2-yl)-3,6-dihydro-2H-pyridine-5-yl]-3-forfinal]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide; or

(S)-N-[[3-[3-fluoro-4-[1-(formyl)-3-azetidinol] phenyl] -2-oxo-5-oxazolidinyl]methyl)ndimethylacetamide.

 

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