Transnistria phenyloxazolidine or its pharmaceutically acceptable salts or hydrates

 

(57) Abstract:

Usage: in the chemistry of heterocyclic compounds with antibacterial activity. Disclosed Transnistria phenyloxazolidine General formula I, where R1- C1- C8-alkyl, R2and R3are the same or different and are selected from hydrogen, fluorine or chlorine, where R4selected from the group consisting of (a), (b) or (C), where R5is selected from the group consisting of hydrogen, -OR6, -SR6-THE OTHER7, -NR7R12, (d), (e), (f), (g), (h) or (i), where R6- H, C1- C8-alkyl, possibly substituted C1- C8-alkoxylate, C2- C8alkenyl-C1- C8-alkyl or phenyl-C1- C8-alkyl, where R7- C1- C8-alkyl, optionally substituted by hydroxy, phenyl or C1- C8-alkoxycarbonyl, C3- C8-cycloalkyl, C2- C8-quinil - C1- C10-alkyl, C2- C8alkenyl-C1- C10-alkyl, where R8is hydrogen, C1- C8-alkyl, C1- C8-acyl, where R9and R10may be the same or different and represent H or C1- C8-alkyl, where R11Is h, hydroxy or and what I can use as antibacterial agents. 18 C.p. f-crystals, 3 tables.

This invention relates to new transelement phenyloxazolidine compounds, which are used as antibacterial agents.

Oxazolidinones are a class of orally-active synthetic antibacterial agents, and there are numerous references in science, considering a number of oxazolidinone derivatives. For example, there are a number of links and 3-phenyl-2-oxazolidinone compounds having one, two or three substituent in the phenyl ring. Links, considering the only substitution in the phenyl ring include U.S. patents NN4948801, 4461773, 4340606, 4476136, 4250318, 4128654 and Re 29607. Additional references 3-[(monosubstituted)phenyl] -2-oxazolidinone can be found in the publication EP 0312000 Jregory et al. , J. Med. Chem., 32 : 1673 (1989), Jregory et al., J. Med. Chem., 33 : 2569 (1990), Part et al., J. Med. Chem., 35 : 1156 (1992) and Wang et al., Fetrahedron, 45 : 1323 (1989). Compounds of this type also include antibacterial DuP 721.

3-[(di-, tri - or (condensed core)-substituted)phenyl]-2-oxazolidinone are described in U.S. patents NN 4977173, 4921869 and 4801600; publications EP 0316594, 0184170 and 0127902; PCT application PCT/US 89/03548, PCT/US 90/06220, PCT/US 92/08267 and the application for U.S. patent N 07/880492 may 8, 1992

Nobacteria agents. Compounds of the invention differ 3-phenyl-2-oxazolidinone with treponeme or substituted treponeme ring in the para-position of the phenyl ring and optionally with an additional substituent in the form of various radicals in the meta-position of the phenyl ring.

The following links describe 3-phenyl-2-oxazolidinone, with the only substitution in the phenyl ring.

U.S. patent N 4948801 describes 3-[(aryl and heteroaryl)phenyl]-2-oxazolidinone having antibacterial activity.

U.S. patent N 4476136 considers 3-[(p-arylalkyl, arylalkyl and arylacetylenes substituted)phenyl]-5-(aminomethyl)-2-oxazolidinone, which have antibacterial activity.

U.S. patent N 4461773 considers substituted 3-phenyl-5-(hydroxymethyl)-2-oxazolidinone, which have antibacterial activity.

U.S. patent N 4340606 considers substituted 3-[(p-alkylsulfonyl)phenyl] -5-(hydroxymethyl)- or (acyloxymethyl)-2-oxazolidinone having antibacterial activity in mammals.

U.S. patent N 4250318 considers substituted 3-phenyl-5-(hydroxymethyl)-2-oxazolidinone with antidepressant use.

U.S. patent N 4128654 considers as plant diseases.

Replacing U.S. patent 29607 considers substituted 3-phenyl-5-(hydroxymethyl)-2-oxazolidinone that has antidepressant, anxiolytic and sedative (calming) use.

Belgian patent N 892270 considers 3-[(arylalkyl, arylalkyl and arylacetylenes substituted)phenyl]-5-(aminomethyl)-2-oxazolidinone, corresponding to U.S. patent N 4476136 above.

Publication of the European patent N 0352781 considers aryl - and heteroarylboronic 3-phenyl-2-oxazolidinone, corresponding to U.S. patent N 4948801 above.

Publication of the European patent N 0312000, as described in Derwent 89-116142/16, considers phenylmethyl and pyridylmethylamine 3-phenyl-2-oxazolidinone.

Work Part et al., J. Med. Chem., 35 : 1156 (1992), W. A. Jregory et al., J. Med. Chem., 33 : 2569 (1990) and J. Med. Chem., 32 : 1673 (1989), C. J. Word et al. , Fetrahedron, 45 : 1323 (1989) and A. M. Slee et al., Anfemicrofial. Agenfsand Chemofherapy, 31 : 1791 (1987) and D. C. Eusfice et al., Anfimicrobial Agents and Chemofherapy, 32 : 1218 (1988) are more recent references dealing 3-[(monosubstituted)phenyl]-2-oxazolidinone.

The following links are considering 3-[(disubstituted)phenyl]-3-[tizamidine)phenyl] - 3-[(condensed ring-substituted)phenyl]-2-oxazolidinone.

Patent school is th ring (formula XIII).

U.S. patents NN 4921869 and 4801600 consider 6'-indolinyl or alkanolamides, where the nitrogen indolinyl is in the meta position relative to the nitrogen oxazolidinone.

U.S. patent N 4705799 considers substituted aminomethylenemalonate derivatives, including sulfides, sulfoxidov, sulfones and sulfonamides, which possess antibacterial activity.

The work of C. H. Park et al., J. Med. Chem., 35 : 1156 is more recent reference, considering 3-[(disubstituted)phenyl]-3-[tizamidine)phenyl] - 3-[(condensed ring-substituted)phenyl]-2-oxazolidinone.

Publication of the European patent N0316594 considers substituted 3-(styryl)-2-oxazolidinone, corresponding to U.S. patent N 4977173 above.

The publication of the European patent NN 0184170 and 012792 correspond to U.S. patent N 4705799 discussed above.

PCT/US 89/03548 and PCT/US 90/06220 consider 3-[(condensed ring-substituted)phenyl] -2-oxazolidinone, which are used as antibacterial agents.

PCT/US 92/08267 considers substituted aryl - and heterogenisation, which are used as antibacterial agents.

Application for ptx2">

None of the above links does not consider Transnistria phenyloxazolidine of the present invention.

Brief description of the invention.

Compounds having a General formula I

< / BR>
in which R1(a) hydrogen, (b) C1- C8- alkyl, optionally substituted by one or more fluorine, chlorine, hydroxy, alkoxy, acyloxy; (C) C3- C6-cycloalkyl; (d) amino; (e) C1- C8- alkylamino; (f) C1- C8-dialkylamino; (g) C1- C8-alkoxy;

R2and R3are the same or different and are selected from the group consisting of (a) hydrogen, (b) fluorine (C) chlorine (d) C1- C8- alkyl, (e) trifloromethyl, (f) hydroxy, (g) C1- C8-alkoxy, (h) nitro, (i) amino, provided that when R2and R3are the same;

R4is selected from the group consisting of

< / BR>
< / BR>
where R and Raare the same or different and are selected from the group consisting of C1- C8- alkyl, optionally substituted with chlorine, fluorine, hydroxy, C1- C8-alkoxy, amino, C1- C8- alkylamino, C1- C8-dialkylamino;

R5is selected from the group consisting of hydrogen, OR6<6- alkyl, optionally substituted by one or more Halogens, (C) C1- C6-alkyl, optionally substituted amino, C1- C8-alkylamino, C1- C8- dialkylamino, (d) C1- C8-alkyl, optionally substituted by one or more hydroxyl, amino, alkylamino, dialkylamino; (e) C1- C8-alkyl, optionally substituted by one or more C1- C8-alkoxylate, (f) C2- C8alkenyl - C1- C8-alkyl, optionally substituted amino, C1- C8-alkylamino, C1- C8-dialkylamino, (g) C2- C8-quinil - C1- C8-alkyl, optionally substituted amino, C1- C4-alkylamino, C1- C8-dialkylamino, (h) C2- C8-acyl, optionally substituted by hydroxyl, amino, C1- C8-alkylamino, C1- C4-dialkylamino; (i) phenyl - C1- C8-alkyl, optionally substituted by phenyl, amino, C1- C8-alkylamino, C1- C8-dialkylamino, (j) pyridyl - C1- C8-alkyl, optionally substituted by pyridyl amino, C1- C8-alkylamino, C1- C8-dialkylamino, (k) amino, optionally substituted by one or two C1- C6-scarlet chlorine, hydroxy, amino, C1- C8-alkylamino, C1- C8-dialkylamino, phenyl, pyridyl, C1- C8-alkoxy, C1- C8-alkoxycarbonyl-residues, (c) C3- C8-cycloalkyl, optionally substituted amino, C1- C8-alkylamino or C1- C8-dialkylamino; (d) amino, (e) C1- C8-alkylamino, (f) C1- C8-dialkylamino, (g) hydroxyl, (h) C1- C8-alkoxyl, (i) C2- C8alkenyl - C1- C10-alkyl, optionally substituted amino, C1- C4-dialkylamino, C1- C4-alkylamino, (j) C2- C8-quinil - C1- C10-alkyl, optionally substituted amino, C1- C4-alkylamino, C1- C4-dialkylamino;

R8(a) hydrogen, (b) C1- C8-alkyl, (c) C3- C8-cycloalkyl, (d) C1- C3-acyl, (e) C1- C8-alkoxycarbonyl, (f) C1- C8-alkylsulfonyl;

R9and R10may be the same or different and represent (I) hydrogen, (b) C1- C8- alkyl,

R11(a) hydrogen, (b) hydroxy, (c) C1- C8-alkoxy, (d) amino, (e) alkylamino, (f) C1- C8-dialkylamino, (g) C1- C8- alkyl, SUB> - C1- C8-alkyl;

and its pharmaceutically acceptable salts and hydrates.

Transnistria phenyloxazolidine General formulas (Ia), (Ib), (Ic) and (Id) contain at least one chiral center. For professionals it is obvious that, when there is one chiral center, the compound may exist as one or two optical isomers of [(R)- and (S)-enantiomers] or their racemic mixture. As a separate [(R)- and (S)-enantiomers and mixtures thereof, are included in the scope troposheric phenyloxazolidine invention. In the case when there are additional chiral centers, the resulting diastereomers in racemic and enriched enantiomer forms are also included in the scope of antibacterial agents (Ia), (Ib), (Ic) and (Id), as claimed in the invention.

The preferred absolute configuration oxazolidinones of this invention is such as represented by the General structural formulas (Ia) to (Id). The absolute configuration is (S) Cohn - Jhgold - Prelog nomenclature system. It is (S)-enantiomer, which is an antibacterial active optical isomer. The racemic mixture is used in the same way and for the same purpose, that of pure (S)-enantiomer; the difference contactolatino effect, as in the case of (S)-enantiomer.

Preferred variants of the invention are oxazolidinone represented by the General structural formulae (Ia) and (Ib).

More preferred compounds are the compounds (Ia) and (Ib) in which R2is hydrogen, and R3is hydrogen or fluorine. The most preferred compounds are the compounds (Ia) and (Ib), where R2and R3- fluorine, and R1is methyl.

Detailed description of the invention.

The content of carbon atoms of different hydrocarbon residues is indicated by the indices denoting the minimum and maximum number of carbon atoms in the residue; console Ci- Cjspecifies the remainder from an integer number of carbon atoms from i to j, inclusive. Thus, C1- C8-alkyl refers to alkyl, with a number of carbon atoms from 1 to 8, inclusive, or stands, ethyl, propylene, hexyl, heptyl, octile and their isomeric forms.

The term C1- C8-alkylamino means aminoacetate containing one alkyl portion having from 1 to 8 carbon atoms. The term C1- C8-dialkylamino means aminooctanoic containing two alkyl portion having from 1 to 8 carbon anajet, the residue may be substituted by 1 to 4 of the above mentioned substituents. For example, C1- C8-alkyl, optionally substituted with chlorine, fluorine, hydroxy, C1- C8-alkoxy, amino, C1- C8-alkylamino, C1- C8-dialkylamino, includes 1-chloropropyl, 1-forprofile-3-chloropropyl, 3-forproper, 1-hydroxybutyl, 2-hydroxybutyl, 1-methoxypropyl, 1-octyloxyphenyl, 1-aminopropyl, 1-aminoethyl, 1-butylamine, 1-dibutylamino etc.

Obtaining compounds of General formula (Ia)

Methods for obtaining compounds of the invention are shown in schemes 1 to 7. Scheme 1 - 4 show the receipt enriched enantiomer troposheric of oxazolidinones. Scheme 5 - 7 show the receipt of racemic intermediates and analogues. Professionals in this field should be clear that minor modifications of the presented schemes of synthesis allows to obtain more examples troposheric phenyloxazolidine.

As shown in scheme 1, the intermediate compound 6 (obtained, as shown in schemes 3 and 4) reacts with a new troponin 7 (obtained from known protropin 8, Banwell et al., Org. Prep. Proc. (1988) 393; Banwell et al. , Felrahedron Zett. , (1985), 25, 4543, as shown at the bottom of the diagram (1) in the presence of Aspin)-allodiploid in an appropriate solvent, such as N, N-dimethylformamide (DMF) or 1,4-dioxane, at an appropriate temperature (usually 70 - 100o(C) obtaining the product of the combination 9. The connection 9 is an example troposheric phenyloxazolidine patterns Ia and can be modified further if necessary, by the reaction of 9 with an appropriate nucleophile such as an amine, in an appropriate solvent system such as toluene or tetrahydrofuran/water at the corresponding temperature (from room temperature up to the boiling point of the solvent) with additional examples (Ia). Methoxy group of compound (9) can also be replaced by an alternative alkoxylation in the interaction of 9 with the desired alcohol, usually in excess, in the presence of catalytic amounts of a base, for example sodium hydride, to obtain the specified adduct (see experimental part). Professionals it is clear that R1the group may already be present in tropane 7 to phase conjugation in the presence of palladium catalyst. Experts also clear that the variation with the applied patrapada (see above Fakaya et al., J. Am. Chem. Soc., (1978), 100, 1778, and so on) and Vice-various intermediate compounds allow to obtain other enriched amantadine.

Figure 2 shows an alternative synthesis, in which the bromine - or iodine-containing intermediate compound 6 (obtained as shown in schemes 3 and 4) shall halogen Metallostroy reaction with getting metallizovannogo derivative 10 (M = Me3Sn or ZnX), which then reacts combination with bromocriptinum 8 in the presence of an appropriate palladium catalyst such as tetrakis (triphenylphosphine)palladium or bis(triphenylphosphine)palladium chloride, in an appropriate solvent such as N, N-dimethylformamide (DMF) or 1,4-dioxane, at an appropriate temperature (usually 70 - 100o(C) obtaining the product of the combination 9. If necessary, the connection 9 can then further react as described above.

Scheme 3 shows the receiving enriched enantiomers of compounds of structure 6, which are required for obtaining optically active troposheric phenyloxazolidine (Ia) (see schemes 1 and 2), which are the subject of this invention. A key first stage in this process involves the reaction of optionally substituted phenylisocyanate (II) with commercially available (-)-(R)-glycidylether, use conditions, applied for the first time in unlocking glycidylether in this reaction to produce oxazolidinone intermediates is discussed in U.S. patent N 4705799. There are also publications in the open literature, for example Jregory et al., J. Med. Chem., (1989), 32, 1673. Butyryl-group is then removed by reaction with an alcoholate, preferably sodium methylate in methanol to obtain alcohol 13 (R = H). Compound 13 is then translated into the corresponding methylsulfonate (R = So2Ch3or arylsulfonate (R = So2Ar)-derivative, preferably mesilate or toilet, the effects of methanesulfonanilide/pyridine or methansulfonate/triethylamine/dichloromethane or para-toluensulfonate/pyridine. The resulting sulfonate is then reacted with an azide such as sodium azide or potassium hydroxide in an aprotic solvent such as DMF or 1-methyl-2-pyrrolidone, optionally in the presence of a catalyst such as 18-crown-6 at a temperature of from 50 to 90oWith giving azide 14. Azide 14 is then reduced under hydrogenation with palladium on carbon or platinum catalyst in an appropriate solvent, such as ethyl acetate or methanol. Alternatively, the azide can be restored by treatment with trivalent phosphorus compound such as triphenylphosphine, in the presence of water and in an appropriate solvent, such as tetrahydrofuran (THF). Aminomethyl connection, the received vossoedinenii structure 15. For example, the amine can react with chloride or acid anhydride in a basic solvent such as pyridine, in a temperature range from -30 to 50oWith obtaining acylated intermediate compound 15, where R1- optionally substituted alkyl. Professionals understand that other acyl groups of this invention can be easily attached to aminomethyl intermediate connection using standard acylation methods known to experts. Intermediate compound 15 iadarola chloride and iodine in acetic/triperoxonane acid at a temperature from 0 to 70oWith or iodine and trifurcation silver with obtaining enriched enantiomer iodinecontaining intermediate compound 6 (X = Y). The alternate connection 15 may broniruutsja N-bromosuccinimide to obtain the brominated related compounds 6 (X = Br).

Figure 4 is a variation of the method presented in scheme 3, where iodine - or promoteto (X) structure 6 is already present in arylisocyanate 16 used in the first stage of the process. When ispolzovanie reactions shown in scheme 3, arylisocyanate 16 first turns into oxazolidinone 17, and then in promezutocnie, such as triphenylphosphine, in the presence of water and in an appropriate solvent, such as THF. The acylation get aminomethyl intermediate connection then gives enriched enantiomer connection 6.

In scheme 4A shows an alternative way to obtain the enriched enantiomer of intermediate compounds of structure 13 (see scheme 3) and 18 (see figure 4). In this sequence the corresponding cyclopentadienyl aniline, easily get the standard response of the Schotten's-Bauman or by other known methods, deprotonized H-butyllithium in an appropriate solvent, such as THF, and at a corresponding temperature, such as from to -78 -68oC. Adding industrial (-)-(R)-glycidylether followed by warming to room temperature and then directly gives hydroxymethylbilane phenyloxazolidine intermediate compound 13 (A = H) and 18 (A = Br, I). Compounds 13 and 18 can be easily converted into enriched enantiomer Transnistria phenyloxazolidine General formulas (Ia) - (Id) using the processes shown in schemes 1 to 4.

Figure 5 shows the receiving racemic troposheric oxazolidinone antibacterial Agay is her Schotten's-Bauman, handled two equivalents of H-utility in THF in a temperature range from -78 to -40oAnd then extinguished by tributyltinchloride obtaining tin-derived 21 (R = n-Bu). Connection 21 then reacts with patrapada 8 in the presence of an appropriate palladium catalyst such as tetrakis (triphenylphosphine)palladium or bis(triphenylphosphine)allodiploid in an appropriate solvent, such as N, N-dimethylformamide (DMF) or 1,4-dioxane, at an appropriate temperature (usually 70 - 100o(C) obtaining the product of a combination of 22. Allilirovanie product 22 is accompanied by deprotonation of an appropriate base, such as sodium hydride, in an appropriate solvent, such as THF, and then treating the reaction mixture with allylbromide, optionally in the presence of catalytic source of iodide, such as tetrabutylammonium iodide, in the temperature range from room temperature up to the boiling point of the solvent, obtaining 23. Intermediate compound 23 is subjected to reaction cyclocarbonate Cardillo-Ohno, including the processing of connection 23 iodine in an appropriate solvent, such as chloroform, and at a corresponding temperature, usually room temperature, obtaining prevedeno in connection 25, which is an example of analogs of structure Ia, three consecutive reactions. They include azzameen, restoring to the corresponding aminoethylethanolamine and acylation, which are held as indicated below. Professionals should be understood that variants of the substituents of different residues allow you to get other racemic Transnistria phenyloxazolidine General formulas Ia - Id, which are the subject of this invention.

Scheme 6 shows another variant of the synthesis of racemic oxazolidine structure Ia, which can be considered as hybrid schemes 1, 2 and 5. Cyclobenza-derived 26, obtained from the corresponding aniline standard reaction Schotten's-Baumen first allylurea by deprotonation of an appropriate base, such as sodium hydride, in an appropriate solvent, such as THF, and then the reaction mixture is processed by allylbromide, optionally in the presence of catalytic source of iodine, such as tetrabutylammonium, in the interval tempratur from room temperature up to the boiling point of the solvent to obtain compound 27. Intermediate compound 27 is subjected to reaction cyclocarbonate Cardillo-Ohno, at the existing temperature, usually room temperature, obtaining iododeoxyuridine 28. Iodide 28 then reacts with an azide source such as sodium azide or potassium, in an aprotic solvent such as DMF or 1-methyl-2-pyrrolidine, optionally in the presence of a catalyst such as 18-crown-6 at a temperature of from 50 to 90oC obtaining azide 29. Azide 29 is then reduced by hydrogenation with palladium on carbon or platinum catalyst in an appropriate solvent, such as ethyl acetate or methanol. Alternatively, the azide can be restored by treatment with trivalent phosphorus compound such as triphenylphosphine, in the presence of water and in an appropriate solvent, such as THF. Aminomethyl compound obtained from azide 29, then alleroed known to specialists reactions with intermediate compounds of structure 30. Bromination or iodination of the phenyl ring compounds 30 using the conditions noted above for obtaining optically active intermediate compound 6, then gives racemic compound 31. The intermediate structure 31 can be converted into racemic Transnistria phenyloxazolidine General formula Ia in the same ways, and 2). For professionals it is clear that variants of the substituents of different residues allow you to get other racemic Transnistria phenyloxazolidine General formulas Ia - Id, which are the subject of this invention.

7 represents a variant of the method shown in scheme 6, where the bromine - or iodine-atom structure 31 is already present in Cyclopentasiloxane the source material 32. Allilirovanie connection 32, as described above, gives the adduct 33. Godzillatron adduct 33 under the reaction conditions, Cardillo-Ohno gives iododeoxyuridine intermediate connection 34. Azide-substitution gives azidopyridine 35, which is restored to its reaction with trivalent phosphorus compound such as triphenylphosphine, in the presence of water and in an appropriate solvent, such as THF. The acylation get aminomethyl intermediate connection then gives racemic compound 31, which can be easily transformed into the racemic compound Ia. Minimal modification of this scheme will allow staff to gain additional examples of oxazolidinones General formulas Ia - Id.

The source materials used in the methods of schemes 1 to 7 are either Seri is citiesi acceptable acid additive salts of compounds of General formula I, when there is a core group, such as aminoacetic. Especially preferred are salts derived from salts of mineral acids ( HCl, HBr, H3PO4H2SO4and so on), organic sulfonic acids (methanesulfonate, a pair of toluensulfonate and so on) and organic carboxylic acids (acetic acid, succinea acid, tartaric acid, citric acid, lactic acid, maleic acid, oxalic acid and so on; amino acids; acid carbohydrates, such as gluconic and galacturonan acid and so on). Also included are basically additive salts of compounds of General formula I, when present acidic group such as carboxylic acid, or when R1- hydroxyl group. Such salts include the following cations (but are not limited to: alkali metal ions, such as potassium, sodium, lithium; alkaline earth metal ions, such as magnesium or calcium; ammonium salts such as ammonium, tetrabutylammonium, and pyridine.

The compounds of this invention can be used orally, locally or parenterally. Usually, this antibacterial effective dose of the active component is in the range from about 0.1 to 100, more preferred is a dose is achieved, preferably, the individual doses and applied 2 to 4 times a day. The preferred method of application, as well as the specific dose for either parenteral or oral technique depends on factors including the nature of the infection (specifically microorganism, its virulence), the degree of infection and the age, weight, sex and General physical condition of the patient. Conventional pharmaceutical dosage forms suitable for parenteral (solution, suspension in oil) and oral (tablets, capsules, syrup, suspension, and so on) applications are known in the art and it is not unusual to use such forms dosage for troposheric of phenyloxazolidine General formula I.

In vitro antibacterial activity of various compounds of this invention against Staphylococcus auraus defined by well-known methods and is shown in table II. They are antibakterialnye agents used for treating infections in mammals (humans and animals, such as cattle, horses, sheep, dogs, cats, and so on) caused by gram-positive and anaerobic organisms. Transnistria phenyloxazolidine General formula I are also used for the treatment of patients INFI the treatment of patients infected with M. Tuberculosis and M. Avium.

Transnistria phenyloxazolidine General formula I may be used either individually or in combination with other antibacterial or aantibacterial agents, as known in the art.

The experimental part.

Example of getting 1. Tri-n-butyl[4-(carbobenzoxy)-phenyl]tin.

N-cyclobenza-4-bromaniline (is 3.08 g, 11.2 mmole) is dissolved in 50 ml of anhydrous THF and the solution cooled to -78oC in a bath of dry ice/acetone. Then within 5 min is added a solution of n-utility (1.1 M in hexane, Aldrich, 23,52 mmole). The solution becomes bright yellow. The solution is stirred for 10 min and suppressed tri-n-butylalcohol (3,83 g, 11,76 mmole). The yellow suspension becomes colorless solution. After stirring for 30 min and heating to -20oC the reaction is extinguished saturated water rotworm NH4Cl (50 ml). The reaction mixture is poured into a separating funnel with 250 ml of ether and 100 ml of water. The mixture is shaken and the organic phase is separated and dried over anhydrous Na2SO4, filtered and concentrated to obtain oil, which is purified by chromatography on silica gel by elution with a mixture of 20:1 g is)

Rel.intens. 460(25), 404(5), 227,91(100)

1H NMR (Dl3): of 7.48-7,31 (m, N), 5,19 (s, 2H), 1.55V to 1.47 (m, 6N), 1,38-of 1.26 (m, 6N), of 1.03 (t, 6N, J = 8,33 Hz), 0,877 (t, N, J = 7,26 Hz).

Example of getting a 2. N-(carbobenzoxy)-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)aniline.

Tri-n-butyl[4-(carbobenzoxy)phenyl]tin (726 mg, 1.4 mmole) dissolved in 10 ml of 1,4-dioxane and added 5-bromo-2-methoxycyclohexyl-2,4,6-triene-1-he (215 mg, 1.0 mmol). The resulting suspension escaped by passing a mixture of N2(3 times). Added the catalyst bis(triphenylphosphine)palladium-(II)chloride and the mixture is heated to the boiling temperature under nitrogen atmosphere. The course of the reaction is monitored by TLC. The reaction ends after 2 hours the Reaction mixture is cooled to room temperature and concentrated under reduced pressure. The remainder suspendered in 75 ml of CH2Cl2and mixed with saturated aqueous KF (75 ml) for 15 minutes the Organic phase is separated and washed with water (50 ml) and brine (50 ml). The organic phase is dried over anhydrous Na2SO4, filtered and concentrated to obtain a yellow solid, which is purified by radial chromatography (elution with a mixture of CHCl3:EtOAc to 1:1 c 1% 195oC

MSVR (EI):[M]+est. for C22H19N2O4361/1314, exp. 361,1311

1H NMR (DCl3): 7,54-of 7.23 (m, 6N), at 6.84 (d, 2H), 5,23 (s, 1H), 3,98 (s, 3H);

Example of getting a 3. N-(2-propenyl)-N-(carbobenzoxy)-4-(4-methoxy-5-oxo-1,3,6-cyclopentadien-1-yl)aniline

N-(carbobenzoxy)-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)aniline (195 mg, 0.54 mmole) is suspended in 5 ml of dry THF and added to a 50% oil suspension of NaOH. Observed emission. The mixture was stirred at room temperature under nitrogen atmosphere for 20 min and added allylbromide simultaneously with Tetra-n-butylammonium. The mixture was stirred at room temperature under nitrogen atmosphere. After 3.5 h and analyzed by TLC, showing that 6 is consumed. The excess NaOH is consumed by adding 25 ml of phosphate buffer with a pH of 7. The mixture is poured into a separating funnel at the same time with 25 ml of water and the aqueous phase is extracted CH2Cl2(G ml). The combined organic phases are dried over anhydrous Na2SO4. Obtained after concentration of the organic phase oil is purified by radial chromatography with elution with 1% MeOH/CHCl3(300 ml) and 2% MeOH/CHCl3(100 ml). It turns out 198 mg specified in zagolovok
NO4est. 401,1627; exp. 401,1630

1H NMR (DCl3): 7,52 (DD, 1H, J =12,6 Hz), 7,46-7,42 (m, 2H), 7,34-7,33 (m, 8H), 7,26 (DD, 1H J =a 10.6 Hz), 6,845 (d, IH, J =a 10.6 Hz), to 5.93 (m, 1H), 5,20-5,18 (CL, 3H), 5,15-5,14 (m, 1H), 4,32 (d, 2H, J = 5.6 Hz), 3,99 (s, 3H).

Example 4. ()-5-(iodomethyl)-3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxazolidinone.

N-(2-propenyl)-N-(carbobenzoxy)-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)aniline (180 mg, 0,449 mmole) was dissolved in 8 ml of chloroform and added iodine (285 mg, 1.12 mmole). The mixture is grape purple and stirred at room temperature under nitrogen atmosphere. After 20 h reaction time TLC analysis establishes that 7 is consumed with the formation of a new product with low Rf. The reaction mixture is poured into a separating funnel at the same time with 50 ml of CHCl3and the solution washed with 20% aqueous sodium thiosulfate solution (25 ml). The organic phase is separated, dried over anhydrous Na2SO4, filtered and concentrated to obtain specified in the title compound as an orange solid, which is purified by radial chromatography (leaching 200 ml of 1% MeOH/CHCl3and 200 ml of 2% MeOH/CHCl3). Allocated 139 mg specified in the connection header is ASC. C 49,45; N. Of 3.69; N 3,20, exp. WITH 49,03; N 3,62; 3,00 N

Msvr for C18H16INO4est. 437,0126; exp. 437,0110

1H NMR (DCl3): 7.65 (d, 2H, J =8.8 Hz), 7,55 (DD, 1H, J =11,5, of 12.6 Hz), 7.52 (d, 2H, J =8,8 Hz), 7,34 (d, 1H, J =10.4 Hz), 7,28 (d, 1H, J =11.5 Hz), to 6.88 (d, 1H, J =a 10.6 Hz), 4,79 (m, 1H), 4,24 (t, 1H, J =8,9 Hz), 4.00 points (s, 3H), 3,855 (DD, 1H, J =9,2 Hz), 3,505 (DD, 1H, J =14,5 Hz).

Example of getting a 5. ()-5-(azidomethyl)-3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl-2-oxazolidinone

()-5-(iodomethyl)-3- [4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxazolidinone (125 mg, 0,286 mmole) was dissolved in 6 ml of dry MDF and added sodium azide (93 mg, 1,43 mmole) simultaneously with 18-crown-6 (10 mg). The mixture is heated to 60oC in nitrogen atmosphere and the reaction course is monitored by TLC. With TLC States that after 2 h 8 spent. The reaction mixture is cooled to room temperature and the DMF is removed under reduced pressure. The remainder suspendered in CHCl3(75 ml) and salts are removed by washing with water (230 ml). The organic phase is separated and washed with brine (30 ml). The organic phase is dried over anhydrous sodium sulfate, filtered and concentrated to obtain 105 mg specified in the connection header in the form of a yellow solid substance. The material is DOS is C18H16N4O4est. With 61,36; N 4,58; N 15,90, exp. WITH 61,08; N TO 4.52; N OF 15.75

Msvr for C18H16N4O4est. 352,1171, exp. 352,1169

1H NMR (DCl3): 7,645 (d, 2H, J =8,8 Hz) 7,545 (DD, 1H, J =16, 12,5 Hz) 7,515 (d, 2H, J =8,8 Hz), 7,34 (d, 1H, J =12,5 Hz) 7,285 (DD, 1H, J = a 10.6 Hz), 4,84-is 4.85 (m, 1H), 4,16 (t, 1H, J =8,9 Hz), 4.00 points (s, 3H), 3,91 (DD, 1H, J =8,9 Hz) 3,755 (DD, 1H, J =13,2 Hz) 3,625 (DD, 1H, J =13,2 Hz).

Example of getting a 6. Trimethyl(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)tin.

Hexamethyldisilane (305 mg, 0,930 mmole) was dissolved in 5 ml of 1,4-dioxane and the solution escaped purging with nitrogen (3 times). Added protropin 8 (200 mg, 0,930 mmole) simultaneously with addition of the catalyst bis(triphenylphosphine)palladium(II)chloride (16,3 mg, 2.5 mole.%). The mixture escaped and is heated to the boiling point of the solvent in a nitrogen atmosphere. The course of the reaction is monitored by TLC. The reaction mixture becomes dark when heated. With TLC States that after 1.5 h 3 spent. The reaction mixture is cooled to room temperature and concentrated under reduced pressure. It turns out the black oil, which is purified by chromatography on silica gel (elution with a mixture of 1:1 EtOAc:CHCl3c 1% MeOH). It turns specified in the header seediness for C11H16O2Sn : calc. 300, 0170, exp. 300,0159

1H NMR (DCl3): of 7.36 (d, 1H, J =11.8 Hz), of 7.23 (d, 1H, J = 9.6 Hz), to 7.15 (d, 1H, J =11.8 Hz), 6,725 (d, 1H, J =9.6 Hz), of 3.94 (s, 3H), 0,32 (s, N,119Sn J =is 129.3 Hz117Sn J =55,2 Hz115Sn J =52,9 Hz).

Example of getting a 7. (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl]metabotrol.

A mixture of lithium bromide (0,181 g of 2.08 mmole), oxide-n-butylphosphine (0,454 g of 2.08 mmole) and dry o-xylene (10 ml), dried azeotropic within 1 h After cooling below the boiling point of a solution of (R)- glycidylether (5,000 g, 34,68 mmole) and 3-perteneciente (4,755 g or of 3.96 ml, 34,68 mmole) in dry o-xylene (10 ml) is added over 10 min to a hot solution (partial boiling is observed in the process of adding). After the addition the solution was heated under reflux for 2 h and then to room temperature. The solvent is removed under vacuum and the residue chromatographically on silica gel with elution by the mixture hexane:ethyl acetate (6:1, 4:1 and then 2:1) to obtain the 8,758 g (90%) indicated in the title compounds as colorless syrup with the following characteristics:

[]2D5-46,7oC (with 1.0, CHCl3)

X (miner. m,) 1758, 1615, 1591, 1498, 1229, 1197, 1169 cm-1< / BR>
1N AGC), 4,88 (m, 1H), 4,39 (DD, 1H, J =12,3, 3.8 Hz), 4,32 (DD, 1H, J =12,3, a 4.7 Hz, 1H), 4,13 (t, 1H, J =9.0 Hz), 3,82 (DD, 1H, J =9,0 6,1 Hz), 2,33 (t, 2H, J =7,3 Hz), and 1.63 (m, 2H), to 0.92 (t, 3H, J =7.4 Hz).

MS m/z (Rel. intens.) 281 (33,1,M+), 193 (9,9), 180 (3,3), 150 (28,7), 148 (68,6), 137 (59,3), 123 (41,7), 95 (38,3), 43 (100).

SVR m/C for C14H16FNO4281,1068, est. 281,1063

Analysis for C14H16FNO4est. With 59,78; N 5,73; N 4,98, exp. WITH 59,98; N 5,72; N 4,88

Example of getting 8. (R)-3-(3-forfinal)-5-(hydroxymethyl)-2-oxoacetate

A solution of (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl]methylbutyrate (2,789 g to 9.91 mmole) in methanol (10 ml) is heated with 25% solution of sodium methylate in methanol (57 ml, 0.99 mmole) at room temperature. Using the method TLC (5% MeOH/CHCl3) is that after 45 min, the starting material had been consumed. The reaction mixture is thoroughly extinguished by adding 1 N HCl (0,99 ml, 0.99 mmole) and then concentrated in vacuo. After purification of the crude product by chromatography on silica gel with elution first with a mixture of 1:1 hexane:ethyl acetate and then ethyl acetate is obtained 1,903 g (91%) indicated in the title compound as a white solid with the following characteristics:

So pl. 106,5 - 107,5oC

[]2D5- 66,8o(1,1, CH3CN)

AND WHAT 1H), 7,32 ("dt", J =8,3, 6.5 Hz), 7.23 percent (DDD, 1H, J =8,3, 2,1 1,0 Hz), 6,84 (dddd, 1H, J =8,2, 8,2, of 2.5, 1.0 Hz), of 4.77 (m, 1H), 4,07-of 3.96 (m, 3H), 3,76 (DD, 1H, J =12,7, 3,9 Hz), 2,44 (SHS, 1H).

MS m/z (Rel. int.) 211 (100, M+), 180 (6,8), 136 (34,3), 124 (84,7) 95 (71,6).

SVR m/C 211,0641 (C10H10FNO3est. 211,0645)

Analysis for C10H10FNO3est. With 56,87; N. Of 4.77; N 6,63 ex. WITH 56,85; N 4,94; N 6,56

The enantiomeric excess oxazolidinone alcohol is determined by its interaction with (R)-(+)--methoxy--(trifluoromethyl)-phenylacetic acid (BCA, DMAR, CH2Cl2, room temperature) and the study of the spectrum of H'-NMR of the obtained ester Moser. A certain percentage of 95%.

Example of getting a 9. (R)-3-(3-forfinal)-5-(hydroxymethyl)-2-oxoacetate

A solution of N-(carbobenzoxy)-3-foronline (1,000 g, 4,08 mmole) in dry tetrahydrofuran (10 ml) is cooled in a bath of dry ice/acetone at a temperature of about -78oC and then added n-butelli (1,87 ml of 1.6 M solution in hexane, only 2.91 mmole). Then the syringe is added (R)-glycidylether (0,420 g or 0,413 ml, only 2.91 mmole) and the reaction mixture remains in the cooling bath for the night, reaching room temperature. The reaction mixture was extinguished by careful addition of a saturated aqueous solution hlotse dichloromethane. The combined organic extracts are dried over sodium sulfate, filtered and concentrated under vacuum to obtain an oil which is purified by chromatography on silica gel with elution with a mixture of 10% acetonitrile/chloroform containing 1% methanol, obtaining 0,555 g (90% compared to glycidylether) specified in the title compounds as white solids, identical in all respects to the sample obtained as described in the previous experimental technique.

Example 10. (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl-4-methylbenzenesulfonate

A solution of(R)-[3-(3-forfinal)-5-(hydroxymethyl)-2-oxoacridine (1,800 g, charged 8.52 mmole) in dry pyridine (10 ml) is cooled to about 5oC and then processed by paratoluenesulfonyl (1,706 g of 8.95 mmole). The solution remains at this temperature until the morning. By TLC (5% methanol/chloroform or 1: 1 hexane: ethyl acetate) determined that the starting material had been consumed. The reaction mixture is poured into a mixture of ice water (30 ml) and the resulting precipitate is collected by filtration under vacuum through a funnel with a porous synthetic glass. The collected solid is washed with cold water, dried under vacuum, paracrystalline Gogo substances with the following characteristics:

So pl. 114 - 115oC

[]2D5-62,6o(C. of 1.0, CH3CN)

X (miner. m) 1751, 1617, 1591, 1499, 1415, 1362, 1227, 1202, 1191, 1172, 1093, 967 cm-1< / BR>
1H NMR (DCl3, 300 MHz) : for 7.78 (d, 2H, J = 8,4 Hz), 7,38 ("dt", 1H, J = 11,2, 2.3 Hz), was 7.36 (d, 2H, J =7.8 Hz), 7,33 ("dt", 1H, J =8,3, and 6.6 Hz), 7,16 (DDD, 1H, J =8,3, 2,2, 1.0 Hz), 6,86 (dddd, 1H, J =8,2, 8,2, of 2.5, 1.0 Hz), 4,84 (m, 1H), 4,29 (DD, 1H, J =11,1, 4,1 Hz), 4,24 (DD, 1H, J = 11,1, 4.6 Hz), 4,10 (t, 1H, J =9.1 Hz), 3,88 (DD, 1H, J =9,2, 6,0 Hz), the 2.46 (s, 3H).

MS m/z (Rel. int.) 365 (70,6, M+), 149 (100), 122 (32,8), 91 (52,8)

SVR m/C 365,0738; (est. for C17H16FNO5S: 365,0733)

Analysis for C17H16FNO5S calc. With 55,88; N To 4.41; N 3,83 exp. WITH 55,96; N. OF 4.38; N 3,80

Example of getting 11. (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl]-methylated

A solution of (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl] -methyl-4-methylbenzenesulfonate (2,340 g, 6,40 mmole) in dry DMF (60 ml) is treated with solid sodium azide (3,331 g, 51,23 mmole) at room temperature. The suspension obtained is heated at 65oC for 4.5 h and then cooled to room temperature and left to stand until morning. The reaction mixture was then diluted with ethyl acetate and water, transferred into a separating funnel and extracted with ethyl acetate. United an ethyl acetate extract promyvayut in the title compounds as white solids, which is actually clean. Defined by the following characteristics:

So pl. 81 - 82oC

[]2D5to 136.5o(C. 0,9, CHCl3).

X (miner. m) 2115, 1736, 1614, 1591, 1586, 1497, 1422, 1233, 1199, 1081, 1049 cm-1< / BR>
1H NMR (DCl3, 300 MHz) : 7,45 ("dt", 1H, J = 11,2, 2.3 Hz), 7,34 ("dt", 1H, J =8,3, 6.4 Hz), 7.23 percent (DDD, 1H, J =8,1, 2,1, 1.0 Hz), 6,86 (dddd, 1H, J =8,2, 8,2 to 2.5, 1.0 Hz), to 4.81 (m, 1H), 4,9 (t, 1H, J =8,9 Hz), 3,86 (DD, 1H, J =9,0, 6.2 Hz), and 3.72 (DD, 1H, J =13,2, and 4.5 Hz), 3,60 (DD, 1H, J = 13,2, 4,4 Hz).

MS m/z (Rel. intens. ) 236 (59,0, M+), 179 (94,9), 136 (59,5), 122 (62,4), 109 (71,8), 95 (100), 75 (40,7).

SVR m/C 236,0708 (est. For C10H9FN4O2: 236,0709)

Analysis for C10H9FN4O2: calc. With 50,85; N 23,84; N 23,72, exp. WITH 50,74; N 3,76; N 23,71

Example 12. (S)-N-[[3-(3-forfinal)-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

A solution of (R)-[3-(3-forfinal)-2-oxo-5-oxazolidinyl]methylated (8,200 g, 34,71 mmole) in ethyl acetate (100 ml) is treated 10% palladium on carbon (0,820 g) in a nitrogen atmosphere. The nitrogen atmosphere is replaced with hydrogen for balloons by repeated evacuation and filling. After stirring in an atmosphere of hydrogen for 17 h with TLC (5% methanol/chloroform) is that azide spent polnostyu,40 mmole). The reaction mixture was stirred 1 h at room temperature and then filtered through celite washing gaskets with ethyl acetate. The filtrate is concentrated under vacuum and the residue dissolved in dichloromethane. Added diethyl ether and the precipitate discarded. After standing in the refrigerator until the morning of the solid is collected by vacuum filtration, washed with cold hexane and dried under vacuum to obtain 4,270 g specified in the title compounds as white solids. Another 3,700 g is obtained from the mother liquor with a total yield of 91%. In another experience the crude product is purified by chromatography on silica gel with elution with a mixture of 5% methanol/chloroform. Received the following features:

So pl. 140 - to 140.5oC

[]2D5- 6,6o(C. of 1.0, CHCl3).

Example of receipt 13. (S)-N-[[3-(3-fluoro-4-itfeel)-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

(S)-N-[[3-(3-forfinal)-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (0,0280 g, 1,11 mmole) was dissolved in a mixture of acetic acid (20 ml) and triperoxonane acid (5 ml) and then processed by odnonogaya (2,343 g, 14,43 mmole) at room temperature. Dark red-brown mixture was stirred at room temperature in the atmosphere AZM ether, the solid is collected by vacuum filtration through a porous filter made of synthetic glass and washed with Et2O. the Crude solid product is dissolved in hot chloroform, to improve the dissolution add a little methanol, transferred to a separating funnel and washed with saturated aqueous sodium bicarbonate, 20% aqueous sodium thiosulfate solution and brine. The organic phase is dried over sodium sulfate, filtered and concentrated to obtain 0,295 g (70%) indicated in the title compounds as white solids. Received the following characteristics:

So pl. 185,5 - 186,5oC

[]2D5- 37,6o(C. of 1.0, DMF).

Example of getting a 14. ()-5-atsetamidometil-3-(4'-trimethylolpropane)-oxazolidin-2-he

The solution hexamethyldisilane (1,772 g, 5.41 mmole) and ()-5-atsetamidometil-3-(4'-iodophenyl)-oxazolidin-2-it (1,840 g, 5,11 mmole) in 23 ml of dioxane alternately pumped in is filled with nitrogen three times. Then added bis(triphenylphosphine)palladium (II) chloride (0,155 g, 0.22 mmole), the system is again pumped in is filled with nitrogen three times and heated at 96oC during the night. The solvents are evaporated and the crude material is purified on a column Packed kr is the use of a gradient of methanol/chloroform), obtaining 1,148 g (56,5%) of the desired material as a white solid with So pl. = 130 - 132oC together with 0,537 g (26.5 per cent) is slightly less pure material.

1H NMR (CDCl3, 300 MHz) : of 7.48 (s, 4H), of 6.71 (PCs, 1H, J = 6.0 Hz), of 4.77 (DDD, 1H, J = 13,2 Hz, J' = 8,7 Hz, J = 4.5 Hz), of 4.05 (t, 1H, J = 9.0 Hz), 3,80 (DD, 1H, J = 9.0 Hz, J' = 6.6 Hz), 3,63 (DD, 2H, J = 6.0 Hz, J' = 4.5 Hz), a 2.01 (s, 3H), 0,28 (t, 9H, J = 27,0 Hz).

X (miner.m, cm-1) 3356 (m), 1746 (s), 1665 (C).

MS: m/e (Rel. the spread. ) 398 (8,8,M+), 383 (100), 382 (36,9), 381 (75,3), 380 (29,0), 379 (42,7), 43 (23,1), 29 (27,5).

fine. mass calc. for C15H22N2O3Sn : 398,0650; exp. 398,662.

Analysis for C15H22N2O3Sn: calc. C 45,37; H 5,58; N 7,06, exp. C 45,28; H 5,51; N 6,87

TLC: 5% methanol/chloroform, Rf= 0.34 in.

Example of receipt 15. (R)-[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methanol

A solution of N-carbobenzoxy-3,5-diferencia (10,9 g, 30,01 mmole) in dry THF (250 ml) cooled to -78oC, then processed by adding dropwise n-utility (19.7 ml, 31,51 mmole) for 15 minutes, the Reaction mixture was stirred at -78oC for 1 h, and then processed by adding dropwise (R)-(-)-glycidylether (4,67 ml, 33,01 mmole) for 10 minutes. The reaction mixture was stirred at -78o4Cl (300 ml) and brine (300 ml). The organic layer is dried over anhydrous Na2SO4, filtered and then concentrated under reduced pressure oil is Golden in color. Oil chromatographies on silica gel (250 g of silica gel, elution gradient 0 to 3% MeOH in 10% CH3CN/CHCl3with getting 6,82 g (99%) indicated in the title compound as a white waxy solid with

So pl. 84 - 85oC and SWR(M+) est. for C10H9NO3F2229,0550; exp. 229,0552.

Example of 16. (R)-[[3-(3-differenl)-2-oxo-5-oxazolidinyl] methyl]-p-toluensulfonate

(R)-[3-(3-differenl)-2-oxo-5-oxazolidinyl] methanol (4.68 g, 20,42 mmole) was dissolved in pyridine (35 ml) and then cooled to 0oC (ice bath). The cold solution is then treated pair-toluensulfonate (4,67 g, 24,50 mmole). The reaction mixture was stirred under cooling overnight (17 h). The next morning the product precipitates in the quench the reaction with ice water (100 ml). The material has vacuum filtration and then dried overnight under high vacuum (20 h). It turns out 7,46 g (95%) indicated in the title compound as a white powdery solid with

So pl. 110,5 - 111,5
(R)-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methyl] para-toluensulfonate (7,34 g, 19,15 mmole) was dissolved in dry DMF and then treated solid NaN3(of 3.73 g, 57,44 mmole). The reaction mixture is heated at 60oC for 2.5 h and then cooled to room temperature overnight (17 hours). The completion of the reaction is monitored by TLC (6% CH3CN/CHCl3, UV short wave). The reaction mixture was concentrated in vacuum to obtain almost white solid. The crude product is dissolved in EtOAc (1 l) and then washed with water (400 ml). The water part is then extracted a large number of EtOAc (g ml). The combined organic extracts are washed with water (400 ml) and once with brine (400 ml). The organic portion is then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to obtain (4,45 g, 91%) indicated in the title compound in the form of almost white crystalline solid with

So pl. of 96.5 - 98oC and

MSVR (M+): calc. for C10H8N4O2F2254,0615; exp. 254,0609.

Example polucheniya. (S)-N-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methyl]the acetone is then processed by adding portions of triphenylphosphine (10,52 g, 40,13 mmole) in 30 min After 2 h, TLC (10% MeOH/CHCl3, UV short wave) is the completeness of the reaction. Then water is added (11,57 ml, 642 mmole) and the reaction mixture heated at 50oC for 4 hours. When cooled by TLC (10% MeOH/CHCl3, UV short wave) is that the reaction is incomplete, so added more water (2.9 ml). After a 4 hour additional heating (50oC) is the completeness of the reaction. The reaction mixture was then diluted with CH2Cl2(300 ml) and the product extracted 2N HCl (3 x 150 ml). The acid layer is carefully neutralized by adding 50% NaOH solution to pH 14. Modelchina aqueous phase is then extracted CH2Cl2(3 x 150 ml). The combined organic phases are dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get a 4.53 g (74%) of white crystalline solid. The crude amine (a 4.53 g) was dissolved in CH2Cl2(100 ml) and pyridine (10 ml). The solution is cooled to 0oC (ice bath) and then acetic anhydride (of 5.05 ml, 53,5 mmole) is added dropwise via the dropping funnel. The reaction mixture was stirred at room temperature overnight (20 h) the reaction. The reaction mixture was diluted with EtOAc (200 ml) and washed with 2N HCl (200 ml), saturated NaHCO3(200 ml) and brine (200 ml). The organic layer is dried over anhydrous Na2SO4, filtered and then concentrated under reduced pressure to get to 4.41 g (64% of total) specified in the title compounds as white solids with

So pl. 145 - 148oC and

MSVR (M+): calc. for C10H12N2O5F2270,0816; exp. 270,0815.

Example obtain 19. (S)-N-[[3-(4-iodine-3,5-differenl)-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

(S)-N-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide (1,25 g, with 4.64 mmole) was dissolved in glacial acetic acid (12 ml) and triperoxonane acid (3 ml) and then treated with solid iodine (4.52 g, of 27.84 mmole). The resulting dark purple solution was stirred at room temperature overnight (20 h). Orange solid settles out of solution almost immediately. The next morning the reaction mixture was diluted with ether (100 ml) and then filtered through a Frit. The orange solid is washed with a large quantity (3 x 50 ml of ether and then dissolved in a warm mixture of 10% MeOH/CHCl3. A solution of MeOH/CHCl3washed with 20% Na2S2O3, filtered and concentrated under reduced pressure to yield 1.31 g (71%) indicated in the title compound as a nearly white solid with

So pl. 192 - 193oC and

MSVR (M+): calc. for C12H11N2O3F2395,9784; exp. 395,9779.

An example of obtaining 20. N-carbobenzoxy-3,5-diptiranjan

3,5-diversitronics (10 g, 77,45 mmole) slowly added to the suspension NaHCO3(13,001 g, 154,9 mmole) in dry TGH (200 ml). This solution is cooled to 0oC (ice bath) and then treated dropwise with benzylchloride (22,11 ml, 154,9 mmole). After the addition the ice bath is removed and the reaction mixture stirred for 4 h under nitrogen atmosphere. At this point, with TLC (15% EtOAc/hexane, UV short wave) is the completeness of the reaction. The reaction is extinguished saturated NaHCO3(300 ml) and extracted CH2Cl2(G ml). The combined organic extracts are then washed by water (400 ml) and brine (400 ml). The organic layer is then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield a crystalline material, oiled amber color. This material chromatographies the blue in the form of a white solid with

So pl. 86 - 87oC and

MS (M+): calc. for C14H11F2NO2263; exp. 263.

Example of getting a 21. N-allyl-N-carbobenzoxy-3,5-diptiranjan

N-carbobenzoxy-3,5-diptiranjan (10 g, dissolved in minimum amount of THF, 37,99 mmole) is added dropwise to a pre-cooled (0oC, ice bath) suspension of NaH (60% in oil, 2.28 g, 56,99 mmole) in dry THF (150 ml). After the addition the reaction mixture was stirred at 0oC in nitrogen atmosphere for 30 minutes At this point is added to the catalyst (H-Bu)4NI 91,0 g, 10% by weight) and allylbromide (4,93 ml, 56,99 mmole). The reaction mixture is slowly heated to room temperature with stirring overnight (17 hours) in a nitrogen atmosphere. In the morning by TLC (15% EtOAc/hexane, UV short wave) is the completeness of the reaction. The reaction mixture is extinguished by water (150 ml) and then extracted EtOAc (g ml). The combined organic extracts are then washed with brine (400 ml) and dried over anhydrous Na2SO4. After drying, the solution is filtered and concentrated under reduced pressure to obtain a yellow oil. Oil chromatographies on silica gel (250 g) with elution 5% and 10% EtOAc/hexane to obtain 10/SUB>H15F2NO2303; exp. 303.

An example of obtaining 22. 2()-[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] itmean

N-allyl-N-carbobenzoxy-3,5-diptiranjan (11.5g, 38.9 mmole) was dissolved in CHCl3(100 ml) and then treated with solid iodine (19,37 g, 76,19 mmole). The resulting solution was stirred at room temperature overnight (20 h) in nitrogen atmosphere. In the morning by TLC (15% EtOAc/hexane, UV short wave) is the completeness of the reaction. The reaction mixture is diluted with CHCl3(200 ml) and washed as 20% Na2S2O3(250 ml) and brine (250 ml). The organic layer is then dried over anhydrous Na2SO4, filtered and concentrated to obtain oil gold color. Oil chromatographies on silica gel (300 g) with elution as 15% and 50% EtOAc/hexane to obtain 12,67 g (98%) indicated in the title compound in the form of a cream solid color with msvr (M+) est. for C10H8F2INO2338,9570 exp. 338,9572.

Sample preparation 23. ()-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl]methyl]azide

()-[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] itmean (12,64 g of 37.3 mmole) was dissolved in DMF (100 ml) and then treated solid NaN3(7,28 g, to room temperature with stirring overnight (16 h). In the morning by TLC (6% CH3CN/CHCl3, UV short wave) is the completeness of the reaction. The reaction mixture was then extinguished with water (1000 ml) and extracted EtOAc (g ml). The combined organic extracts are washed again with water (400 ml) and once with brine (400 ml). The organic layer is then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 9,41 g (99%) indicated in the title compounds as pale yellow solids with so pl. 72 - 73oC;

MSVR (M+): calc. for C10H8F2N4O2254,0615; exp. 254,0617.

Example of getting 24. ()-N-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methyl]ndimethylacetamide

()-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methyl] azide (2,36 g of 9.30 mmole) was dissolved in 5% MeOH/EtOAc (200 ml) to obtain a transparent yellow solution. The solution escaped 3 times with nitrogen and then treated with 10% Pd-C (460 mg, 20% by weight). The solution escaped again (3 times) and the atmosphere replaced with hydrogen from a balloon. The reaction mixture was stirred at room temperature for 20 hours At this point by TLC (30% EtOAc/hexane, UV short wave) is determined by the completeness of the reaction. The reaction mixture is filtered through celite and the precipitate ajnogo colorless oil. This oil is re-dissolved in CH2Cl2(20 ml) and pyridine (10 ml) and then treated with acetic anhydride (1,76 ml, 18,60 mmole).

The reaction mixture was stirred overnight (17 h) at room temperature under nitrogen atmosphere. In the morning the reaction mixture was diluted with EtOAc (100 ml) and washed with 2N HCl (g ml), saturated NaHCO3(100 ml) and brine (100 ml). The organic layer is dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield a white solid. This solid chromatographies on silica gel (175 g) with elution by a gradient of 0.5 - 2% MeOH in CH3CN/CHCl3to obtain 1.07 g (42%) indicated in the title compounds as white solids with so pl. 131, 5mm - 132,5oAnd

MSVR (M+): calc. for C12H12F2N2O3270,0816; exp. 270,0810.

An example of obtaining 25. ()-N-[[3-(4-iodine-3,5-differenl)-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

()-N-[[3-(3,5-differenl)-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (500 mg, of 1.85 mmole) is dissolved in acetic acid (5 ml) and then treated ICl (1.8 g, 11.1 mmole). The obtained red-brown solution is stirred overnight (17 hours) at room temperature. In the morning A the solid is washed with a large quantity of ether (3 x 30 ml) and then dissolved in warm 10% MeOH/CHCl3(100 ml). This solution is washed with 20% Na2S2O3(100 ml), saturated NaHCO3(100 ml) and brine (100 ml). After drying over anhydrous Na2SO4the organic layer is filtered and then concentrated under reduced pressure to yield 387 mg specified in the title compounds as white solids. After 2 h an additional amount of the product falls from the filtrate. The solution is decanted and the remaining solid is washed with ether. Then this solid substance is dissolved in a warm mixture of 10% MeOH/CHCl3(50 ml) and then washed with 20% Na2S2O3(50 ml), saturated NaHCO3(50 ml) and brine (50 ml). The organic layer is dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield an additional 142 mg specified in the title compound as a nearly white solid. Allocated total number of 529 mg (72% yield) of the desired product with so pl. = 191 - 192oAnd SVR (M+): calc. for C12H11F2IN2O3395,9784; exp. 395,9774.

Example of receipt 26. ()-N-[[3-[4-(tributylstannyl-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

()-N-[[3-(4-iodine-3,5-differenl)-2-oxo-5-oxazolidinyl] mg, of 0.50 mmole). After 3-fold degassing of the reaction mixture with nitrogen is added bis(triphenylphosphine)palladium(II)chloride (9 mg, of 0.0125 mmole). The solution again escaped (3 times) and heated under reflux (110o(C) within 5 hours After that by TLC (10% MeOH/CHCl3, UV short wave) is determined by the completeness of the reaction. The solvent is removed under vacuum and the remaining oil chromatographies on silica gel (75 g) with elution by a gradient of 0.5 - 5% MeOH/CHCl3to obtain 105 mg, 97% indicated in the title compound in the form of a spongy pale yellow solid with msvr (M+): calc. for C15H20N2O3F2Sn 434,0461; exp. 434,0457.

Example 1. ()-ndimethylacetamide, N-[[3-[4-[(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]

()-5-(Azidomethyl)-3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-phenyl] -2-oxazolidinone (100 mg, 0,286 mmole) was dissolved in a mixture of 10 ml of EtOAc and 4 ml MeOH when exposed to ultrasound and soft heat. In a stream of nitrogen is added the catalyst (10% Pd/C, 50 mg). The bulb is pumped out and filled with nitrogen (three times), followed by replacing with hydrogen from a balloon. The mixture was stirred in hydrogen atmosphere at atmospheric pressure and the course of the reaction controlrooms celite and the filtrate concentrated under reduced pressure. The oil is dissolved in 10 ml of CH2Cl2and added 1 ml of pyridine simultaneously with acetic anhydride (500 μl). After 10 min, the reaction mixture is concentrated to a light yellow solid, which is purified by radial chromatography (elution 1 - 5% mixtures CHCl3/MeOH, 100 ml each). It turns out 78 mg specified in the title compound as a pale yellow solid.

So pl. 231 - 232oC.

Msvr est. for C20H20N2O5368,1372; exp. 368,1364.

1H NMR (CDCl3): to 7.61 (d, 2H, J = 8,8 Hz), 7,53-7,51 (m, 1H), 7,515 (d, 2H, J = 8,8 Hz), 7,34 (d, 1H, J = 11.7 Hz), 7,31-7,28 (m, 1H), 6,97 (PCs, 1H), 6.89 in (d, 1H, J = 11.7 Hz), 4,82 (m, 1H), 4,12 (t, 1H, J = 9.1 Hz), 4.00 points (s, 3H), of 3.85 (DD, 1H, J = 9,2 Hz), 3,67-the 3.65 (m, 2H), 2,03 (s, 3H).

Example 2. ()-Ndimethylacetamide, N-[[3-[4-[(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]

Trimatic(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)tin (50 mg, 0,167 mmole) was dissolved in 5 ml of 1,4-dioxane and added allied (50 mg, 0,139 mmole). The mixture escaped by passing nitrogen (3 times). Then add the catalyst bis(triphenylphosphine)palladium dichloride (10 mg) and the mixture is escaped for the last time. The mixture is heated to the boiling temperature under nitrogen atmosphere and the progress of the reactions is W the source material used. The reaction mixture is cooled to room temperature, followed by filtering the mixture through celite, which removes Pd-mobile from the mixture. The mother liquor is concentrated to obtain a solid residue, which is purified by radial chromatography. The silica is washed with mixtures from 1 to 5% CHCl3/MeOH portions in 100 ml. Fractions corresponding according to TLC valid sample 10, is collected and concentrated to obtain a yellow foam. The foam is dissolved in a minimum volume of CH2Cl2and adding ether lands solid. The solid is filtered, washed with ether and dried under vacuum to yield 37 g specified in the procurement of the connection. This material is identical in all respects valid sample when comparing the data of TLC,1H NMR, and so pl.

Example 3. () -Ndimethylacetamide, N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]

Areloaded 19 (50 mg, 0,132 mmole) was dissolved in 4 ml of 1,4-dioxane and added tropisternus II (to 43.5 mg, 0,146 mmole). The mixture escaped purging with nitrogen (3 times) and added the catalyst, Pd (Ph3P)2Cl2(9.3 mg). The mixture escaped to sing TLC is set, 19 consumed, the reaction mixture was concentrated to a brown solid, which is dissolved in 10% MeOH/CHCl3and filtered through a small layer of silica gel. The reaction mixture was concentrated to a solid, which is purified by radial chromatography with elution mixtures CHCl3/MeOH (with an increase from 1% to 6% in 75 ml volume). 40 mg specified in the connection header 20 in the form of an almost white solid.

So pl. 200 - 201oC.

Analysis for C20H19FN2O5: calc. With 62,17; H 4,96; N 7,25 exp. FROM 60.62; H 4,99; N 6,98

Msvr: calc. for C20H19FN2O5388,1278; exp. 386,1271

1H NMR (CDCl3): of 7.55 (d, 1H), 7,42 - 7,31 (m, 4H), 7,205 (d, 1H, J = 10.5 Hz), PC 6.82 (d, 1H, J = 10.5 Hz), 6,10 (PCs, 1H), 4,82 (m, 1H), 4.09 to (t, 1H, J = 9,00 Hz), 4.00 points (s, 3H), 3,85 (m, 1H), 3,70 (m, 2H), 2,04 (s, 3H).

The following is the methodology for substitution reactions methoxsalen examples of the General formula IaoC Ic.

Example 4. () -Ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[(phenylmethyl)-amino] -1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl].

()-Ndimethylacetamide, N-[[3-[(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl] methyl] (25 mg, 0.07 mmole) suspendered in a mixture of 1.5 ml b with TLC is set, 10 spent. The mixture is cooled to room temperature and diluted with 15 ml of ether. The precipitate is filtered and washed with ether. The bright yellow solid is dried under vacuum. Obtained 32 mg specified in the connection header.

So pl. 239 - 240oC.

Analysis for C26H25N3O4: calc. With 70,41; H of 5.68; N for 9.47 exp. WITH 70,06; H 5,67; N 9,41

Msvr: calc. for C26H25N3O4443,1845; exp. 443,1859.

1H NMR (CDCl3) : 7,66-rate of 7.54 (m, 3H), 7,465 (d, 1H), of 7.48-to 7.32 (m, 7H), 7,27 (d, 1H, J = 11.5 Hz), 6,70 (d, 1H, J = 11.5 Hz), 4,80 (m, 1H), 4,63 (s, 2H), 4,12 (t, 1H, J = 9.1 Hz), 3,85-of 3.80 (m, 1H), 3,65-3,59 (m, 2H), 2,02 (s, 3H).

When using a technique similar to the one used in example 4, but using the corresponding amine instead of benzylamine, make the following connections:

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[(diethyl)amino] -1,3,6-cycloheptatrien-2-yl)phenyl]-5-oxazolidinyl]methyl].

So pl. 164 - 165oC.

Msvr: calc. for C23H27N3O4409,2001; exp. 409,1994

1H NMR (CDCl3) : EUR 7.57-7,46 (m, 3H), 7,37-7,24 (m, 3H), 6,97 (d, 1H, J = 12,2 Hz) 6,655 (d, 1H, J = 11.2 Hz), 4,82 (m, 1H), 4,12 (t, 1H, J = 9.0 Hz), 3,88-a 3.83 (m, 1H).

()-ndimethylacetamide, N-[[2-oxo-3-[[4-[5-oxo-4-[(2-hydroxyethyl)amino] >1H23N3O5: +H1398,1716; exp. 398,1735

1H NMR (CDCl3) : 7,56-the 7.43 (m, 6N), 7,20 (d, 1H, J = 11.5 Hz), 4,78 - to 4.87 (m, 1H), 4,10 (t, 1H, J = 9.0 Hz), 3,94 (PCs, 2H), 3,86-a-3.84 (m, 1H), 3,66 (PCs, 2H), 3,53 (PCs, 2H), 2,03 (s, 3H).

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-(4-morpholinyl)-1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl];

So pl. 231 - 232oC.

Msvr: calc. for C23H25N3O5: 423,1794; exp. 423,1785

1H NMR (CDCl3) : 7,585 (d, 2H, J = 8,8 Hz) 7,485 (d, 2H, J = 8,8 Hz), 7,38 (DD, 1H, J = 12,5 Hz) 7,225 (DD, 1H, J = 10,7 Hz), 7,12 (d, 1H, J = 12,5 Hz) 6,775 (d, 1H, J = 10,7 Hz), 6,11 (PCs, 1H), to 4.81 (m, 1H), 4,10 (t, 1H, J = 9.1 Hz), 3,90 (PCs, 4H, J = 4.6 Hz), 3,835 (DD, 1H, J = 9.1 Hz), 3,70-to 3.67 (m, 2H), 3,39 (PCs, 4H, J = 4.6 Hz), 2,04 (s, 3H).

()-ndimethylacetamide, N-[[2-oxo-3[4-[5-oxo-4-[(cyclopropylamino)]-1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 233 - 234oC.

MS (EI): m/z (Rel. int. ) 393 [M+] (68): 337(31), 222(30), 181(34), 42(100)

1H NMR (CDCl3): 7,88-of 7.48 (m, 6N), 7,195 (d, 1H, J = 12.1 Hz), 7,125 (d, 1H, J = 10,8 Hz), to 4.81 (m, 1H), 4,10 (t, 1H, J = 9.0 Hz), 3,875 (DD, 1H, J = 9.0 Hz), 3,64 (PCs, 2H, J = 5.5 Hz), 2,65-2,62 (m, 1H), 2,01 (s, 3H), 1,01-of 0.95 (m, 2H), as 0.73 and 0.68 (m, 2H).

()-ndimethylacetamide, N-[[2-oxo-3[4-[5-oxo-4-[(4-carboxaldehyde)piperazinil] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 255 - 257oWith (with (m, 3H), 7,28-of 7.23 (m, 1H), 7,18 (d, 1H, J = 12,5 Hz), PC 6.82 (d, 1H, J = 10,7 Hz), 6.73 x (PC, 1H), 4,80 (m, 1H), 4,11 (t, 1H, J = 9.0 Hz), 3,84-of 3.78 (m, 2H), 3,70-of 3.60 (m, 4H), 3,40 (PCs, 3H), 3,32 (PCs, 1H), 3,09 (PCs, 1H), 2,03 (s, 3H).

()-ndimethylacetamide, N-[[2-oxo-3[4-[5-oxo-4-[(2-propenyl)amino] -1,3,6-cycloheptatrien-1-yl]5-oxazolidinyl]methyl].

So pl. 213 - 215oC.

Msvr: calc. for C22H23N3O4: 393,1688; exp. 393,1673.

1H NMR (CDCl3): 7,62-the 7.43 (m, 6N), 7,25 (d, 1H, J = 12.1 Hz), 6,645 (d, 1H, J = 11,0 Hz), 6,00-6,63 (m, 1H), from 5.29 - of 5.26 (m, 1H), to 4.81 (m, 1H), 4,11 (t, 1H, J = 9.0 Hz), 4,06 (m, 2H), a 3.87-3,81 (m, 1H), 3,68-3,66 (m, 2H), 2,03 (s, 3H).

()-ndimethylacetamide, N-[[2-oxo-3[4-[5-oxo-4-[pyrrolidin-1-yl] -1,3,6-cycloheptatrien-1-yl]-5-oxazolidinyl]methyl].

So pl. 230 - 231oC.

Msvr: calc. for C23H25N3O4: 407,1845; exp. 407,1859.

1H NMR (CDCl3): 7,555 (d, 2H, J = 8,9 Hz) 7,455 (d, 2H, J = 8,9 Hz) 7,345 (DD, 1H, J = 10.1 Hz), 7,26 (DD, 1H, J = 11.3 Hz), 6,98 (d, 1H, J = 12.1 Hz), 6,78 (PCs, 1H), 6,445 (d, 1H, J = 11.2 Hz), 4,79 (m, 1H), 4,10 (t, 1H, J = 9.0 Hz), 3,825 (DD, 1H, J = 9.0 Hz), 3,69 (CL, 6N), 2,03 (s, 3H), 1,98 (s, 4H).

()-ndimethylacetamide, N-[[2-oxo-3[4-[5-oxo-4-(methylpiperazin-1-yl)-1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 204 - 206oC.

Msvr: calc. for C24H28N4O4: 436,2110; exp. 436,2117.

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[(cyclopentyl)] amino]-1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 208 - 210oC.

Msvr: calc. for C24H27N3O4: 421,2001; exp. 421,1987.

1H NMR (CDCl3): to 7.61 - 7,44 (m, 6N), 7,20 (d, 1H, J = 12.0 Hz), of 6.71 (d, 1H, J = 11.2 Hz), to 4.81 (m, 1H), 4,10 (t, 1H, J = 9.0 Hz), 4.00 points (m, 1H), 3,865 (DD, 1H, J = 10.0 Hz), 3,68 - 3,66 (m, 2H), 2,20 - 2,10 (m, 2H), 2,04 (s, 3H), 1,81 by 1.68 (m, 6N).

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[piperazine-1-yl] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. >300oC.

Msvr: calc. for C23H26N4O4: 422,1954; exp. 422,1964.

1H NMR (CDCl3): 7,585 (d, 2H, J = 8,8 Hz) 7,485 (d, 2H, J = 8,8 Hz) 7,395 (DD, 1H, J = 12,5 Hz) 7,255 (DD, 1H, J = 10,8 Hz), 7,12 (d, 1H, J = 12,5 Hz) 6,815 (d, 1H, J = 10,8 Hz), 6,70 (PCs, 1H), to 4.81 (m, 1H), 4,11 (t, 1H, J 9.0 Hz), 3,854 (DD, 1H, J was 8.8 Hz), 3,68 (m, 2H), 3,38 (PCs, 4H, J = 4,8 Hz), is 3.08 (PCs, 4H, J = 4,8 Hz), 2,03 (s, 3H).

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[n-butyl] amino] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 197 - 198oC.

1H NMR (CDCl3): 7,58 was 7.45 (m, 6H), - of 1.74 (m, 2H), 1,53 - of 1.45 (m, 2H), and 1.00 (t, 3H, J = 7.2 Hz).

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[CIS-3,5-dimethylpiperazine-1-yl)-1,3,6-cycloheptatrien-1-yl]-2-oxo-5-oxazolidinyl]methyl].

So pl. 142 - 144oC.

MS (EI): m/z (Rel. the intensive.) 450[M+](45), 380(54), 366(43), 367(53), 84(100).

1H NMR (CDCl3): 7,585 (d, 2H, J = 8,8 Hz) 7,475 (d, 2H, J = 8,8 Hz) 7,355 (DD, 1H, J = 12,5 Hz) 7,215 (DD, 1H, J = 10,8 Hz), 7,10 (d, 1H, J = 12,5 Hz), 6,79 (d, 1H, J = 10,8 Hz), 6,12 (PCs, 1H), 4,80 (m, 1H), 4,11 (t, 1H, J = 9.0 Hz), the 3.89 - 3,81 (m, 3H), 3,49 - 3,47 (m, 2H), and 3.16 (m, 2H), 2,45 (PCs, 2H, J = to 112.4 Hz), 2,04 (s, 3H), 1.18 to (W, 6H, J = 6,30 Hz).

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-[piperidine-1-yl] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 211 - 212oC.

Msvr: calc. for C24H27N3O4: 421,2001; exp. 421,2007.

1H NMR (CDCl3): 7,565 (d, 2H, J = 8,8 Hz), 7,465 (d, 2H, J = 8,8 Hz), 7,33 (DD, 1H, J = 12,4 Hz) 7,195 (DD, 1H, J and 10.8 Hz), 7,07 (d, 1H, J = 12,4 Hz), to 6.80 (d, 1H, J = 10,8 Hz), and 6.25 (PCs, 1H), to 4.81 (m, 1H), 4,10 (t, 1H, J = 9.0 Hz), 3,835 (DD, 1H, J = 9.0 Hz), 3.72 points - 3,61 (m, 2H), 3,41 - 3,39 (m, 4H), 2,04 (s, 3H), 1,74 - 1,72 (m, 6H).

()-ndimethylacetamide, N-[[2-oxo-3-[-[5-oxo-4-[3-trimethylpyrazine-1-yl] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 189 - 191oC.

Msvr: calc. for C24H28N4O4: 436,2110; exp. 436,2110.

1

()-ndimethylacetamide, N-[[2-oxo-3-[4-[5-oxo-4-(3-hydroxypyrrolidine-1-yl] -1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

So pl. 223 - 224oC.

Msvr: calc. for C23H25N3O5+ H1: 424,1872; exp. 424,1900.

1H NMR (CDCl3): 7,495 (d, 2H, J = 8,8 Hz) 7,395 (d, 2H, J = 8,8 Hz), 7,32 (d, 1H, J is 12.2 Hz), of 7.23 (d, 1H, J = 11.2 Hz), to 6.95 (d, 1H, J = 12,2 Hz) 6,465 (d, 1H, J = 11.2 Hz), to 4.81 (m, 1H), 4,56 (m, 1H), 4.09 to (t, 1H, J 9.0 Hz), 3,99 - 3,95 (sm, 1H), 3,85 - of 3.77 (m, 3H), 3,67 - 3,66 (m, 2H), 2,93 - is 2.88 (m, 1H), 2,07 (CL, 2H), 2,03 (s, 3H).

Example 5. ()-N-[[3-[4-(4-ethoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-ndimethylacetamide

A suspension of ()-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (0,100 g of 0.27 mmole) in absolute alcohol (10 ml) is treated with a catalytic amount of sodium hydride (5 mg, 60% dispersion in mineral oil). The mixture is heated to the boiling temperature under nitrogen atmosphere and at this time the mixture becomes homogeneous. 15 minutes after reaching the boiling point of the solution is cooled to room temperature and observed precipitation of solids. Reaccustom obtained 0,088 g (85%) indicated in the title compound as a pale yellow solid with the following characteristics:

So pl. 228 - 229oC.

1H NMR (CDCl3): of 7.60 (d, 2H, J = 8.7 Hz), 7,52-7,47 (m, 1H), of 7.48 (d, 2H, J = 8.5 Hz), 7,33-7,26 (m, 1H), 7,24 (d, 1H, J = 10.5 Hz), 6.87 in (d, 1H, J = a 10.6 Hz), 6,80 (PCs, 1H), 4,82 (m, 1H), 4,19 (q, 2H, J = 6.9 Hz), 4,11 ("t", 1H, J = 8,9 Hz), 3,86 (DD, 1H, J = 9,0, 6,8 Hz), 3.75 to of 3.60 (m, 2H), 2,03 (s, 3H), and 1.56 (t, 3H, J = 6.9 Hz).

MS m/z (relates. the intensive.) 382 (36,5, M+), 338(55,0), 310(26,3), 254 (26,8), 226(100).

SVR m/C 382,1536 (est. for C21H22N2O5: 382,1529).

Example 6. (S)-N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]ndimethylacetamide

The above suspension of (S)-N-[[3-[3-fluoro-4-itfeel)-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (4,200 g, 11.11 is mmole) and trimethyl(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)tin (4,150 g, 18,88 mmole) in 1,4-dioxane (50 mg) escaped pumping nitrogen. Added bis(triphenylphosphine)palladium (II) chloride (0,545 g, 0,78 mmole), the reaction mixture is again escaped and then the mixture is brought to boiling temperature in a nitrogen atmosphere. After 3 h with TLC is determined that iodide remains. Introduces an additional amount of the tin reagent (0.400 g, 1.34 mmole) and palladium catalyst (0,100 g of 0.14 mmole) and the mixture is boiled under reflux for 4 hours. Then the reaction mixture is cooled to comniittee through celite and concentrated under vacuum. The crude solid is ground to a powder in a mixture of dichloromethane/diethyl ether, the solid is filtered, washed with diethyl ether and dried under vacuum to obtain 4,200 g (98%) specified in the connection header. Defined by the following characteristics:

So pl. 227 - 228oC.

[]2D5= 39,5o(from 0.9, DMF).

Alternatively, the above-described oxazolidinedione is transformed into (S)-N-[[3-[3-fluoro-4-(tributylstannyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide using the conditions discussed for the corresponding racemic material in TR 7246-92-050. This tin-substituted intermediate compound (0,180 g, 0.43 mmole) and 5-bromo-2-methoxycyclohexyl-2,4,6-triene-1-he (0,103 g, 0.48 mmole) dissolved in dry DMF (3 ml) and the resulting solution escaped pumping nitrogen. Added bis(triphenylphosphine)palladium(II)chloride (0.015 g, 0.02 mmole), the reaction mixture is again escaped and heated at 80oC for 2 h With TLC States that some of the source material remains, therefore, introduces an additional amount of palladium catalyst (0.015 g) and the mixture is heated for another 5 hours, the Reaction mixture is concentrated under vacuum and the residue of chromatography, denticola in all respects with the compound obtained by the above method.

Example 7. ()-N-[[3-[4-(4-methoxy-3-oxo-1,4,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]ndimethylacetamide.

Dioxane (50 ml) solution of ()-5-atsetamidometil-3-(4'-trimethylolpropane)oxazolidin-2-it (1,172 g, 2,95 mmole) and 6-bromo-2-methoxycinnamate-2,4,6-triene-1-it (0,677 g, 3.13 mmole) in turn is pumped out and filled with nitrogen three times. Then added bis(triphenylphosphine)palladium(II)chloride (0,200 g to 0.28 mmole). The system is again pumped out and filled with nitrogen three times and heated overnight at 90oC. the Reaction is not finished, so added 0,103 g (0.15 mmole) of palladium catalyst and the system is pumped with nitrogen 4 times. After boiling under reflux for 2 h the mixture is filtered through a gasket diatomaceous earth, which is carefully washed with methylene chloride and methanol. The solvents are evaporated, yielding the crude material is purified on a column with SiO2-gasket (40 to 60 μm, 2.5 cm 26 cm, filled with a mixture of 1% methanol-chloroform containing chloroform, elution gradient of methanol/chloroform) to obtain 0.889 g (82% yield) of the desired material as a white solid. At - 214oFor the analysis.

1H NMR (CDCl3): 7,63 (d, 2H, J = 9.0 Hz), 7,60 (d, 2H, J = 9.0 Hz), 7,45 (s, 1H), 7,10 (m, 2H), 6.73 x (d, 1H, J = 8.7 Hz), 6,02 (PCs, 1H, J = 6.0 Hz), to 4.81 (m, 1H, 8 lines), of 4.12 (t, 1H, J = 9.0 Hz), 3,98 (s, 3H), of 3.78 (DD, 1H, J = 9.0 Hz, J = 6.9 Hz), 3,74 (DDD, 1H, J = 14,7, Hz, J' = 6,0 Hz, J = 3.3 Hz), to 3.64 (dt, 1H, J = 14,7, Hz, J' = 6,0 Hz), 2,04 (s, 3H).

13With NMR (75,47 MHz, CDCl3): 23,11, 41,93, 47,46, 56,34, 72,00, 111,63, 118,25, 128,62, 129,52, 132,17, 135,72, 137,97, 138,75, 148,91, 154,38, 165,16, 170,63, 179,38.

X (miner. PM , cm-1): 3307(m), 1739(s), 1649(m), 1592(s), 1575(s), 1561(s).

MS: m/e (relates. the spread. ) 368(9,8 M+), 340(32,3), 296(24,1), 240(26,5), 237(20,5), 212(100), 199(34,3), 85(37,6), 56(28,2), 43(29,5), 29(34,1).

exact mass: calc. for C20H20N2O5368,1372; exp. 368,1385.

Analysis for C20H20N2O5: calc. With 65,21; N Vs. 5.47; N 7,60 exp. WITH 64,79; N 5,28; N 7,60

TLC: 5% methanol/chloroform: Rf = 0.21 in.

Example 8. ()-N-[[3-[4-(6-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]ndimethylacetamide (1C)

The combined acetonitrile solution (25 ml) ()-5-atsetamidometil-3-(4'-trimethylolpropane)oxazolidin-2-it (0,352 g of 0.89 mmole) and 4-bromo-2-metasilicate-2,4,6-triene-1-it (0,200 g of 0.93 mmole) pumped with nitrogen three times. Then added bis(triphenylphosphine)palladium(II)chloride (0,076 g of 0.11 mmole) and the system SN is m filtered through the gasket diatomaceous earth, which is thoroughly washed with methylene chloride. The solvents are evaporated to obtain a crude material which is purified on a column with SiO2-gasket (40 to 63 μm, 2.5 cm 27 cm, filled with 1% methanol/chloroform, containing chloroform and elution by a gradient of methanol-chloroform) to obtain the 0,277 g (85%) of the desired material as a yellow solid material. This material precrystallizer from acetone and water to obtain 0,123 g (38%) yellow solid with so pl. 107 - 110oC.

1With NMR (CDCl3, 300 MHz): 7,63 (d, 2H, J = 9.0 Hz), 7,56 (d, 2H, J = 9.0 Hz), 7,31 (m, 1H), 7,20 (DD, 1H, J = 12.0 Hz, J' = 0.9 Hz), 7,02 (DD, 1H, J = 7.5 Hz, J' = 0.9 Hz), 6,94 (s, 1H), 6,07 (t, 1H, J = 6.0 Hz), a 4.83 (m, 9 lines, 1H), 4,13 (t, 1H, J = 9.0 Hz), 3,99 (s, 3H), a 3.87 (DD, 1H, J = 9.0 Hz, J' = 6,9 Hz), 3,74 (DDD, 1H, J = 14,7 Hz, J' = 6.3 Hz, J = 3.6 Hz), 3,66 (dt, 1H, J = 14,7 Hz, J' = 6,0 Hz), 2,04 (s, 3H).

13With NMR (75,47 MHz, CDCl3): 23,12, 41,96, 47,55, 56,37, 72,09, 114,39, 118,55, 126,87, 128,39, 135,41, 136,52, 138,13, 139,06, 145,78, 154,22, 164,53, 171,09, 179,84

X (miner.oil, cm-1): 3469(W), 3288(W), 1745(s), 1662(m).

MS: m/e (relates.the soap.): 368(72,4, M+), 296(33,3), 237(35,9), 236(34,3), 212(100), 199(56,8), 85(53,8), 56(49,8), 44(30,3), 43(50,1);

exact mass: calc. for C20H20N2O5368,1372; exp. 368,1384.

Analysis for C20H20N2O5: calc. (C)amino-3-oxo-1,4,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]ndimethylacetamide (1b)

The solution metaxalon-substituted oxazolidinone (0,077 g of 0.21 mmole) and allylamine (3.5 ml, 46,6 mmole) is heated under reflux in a nitrogen atmosphere over night. The reaction mixture is then concentrated under vacuum to obtain crude material which is purified on a 1000 micron preparative TLC plate (250 microns, the leaching mixture of 75% acetone/methylene chloride 3 times) to obtain 0,033 g (40%) indicated in the title compound as yellow solids with so pl. 169 - 171oSimultaneously with 0,026 g (32%) of slightly less pure material.

1H NMR (CDCl3, 300 MHz): to 7.59 (CL, 4H), 7,47 (PCs, 1H, J = 6.0 Hz), 7,40 (d, 1H, J = 1.8 Hz), 7,25 (t, 1H, J = 10.5 Hz), to 6.88 (DD, 1H, J = 10.5 Hz, J' = 1.8 Hz), 6,51 (d, H, J = 10.5 Hz), 6,13 (PCs, 1H, J = 6.0 Hz), 5,94 (m, 1H, 10 lines), of 5.29 (m, 2H), to 4.81 (m, 1H, 9 lines), of 4.12 (t, 1H, J = 9.0 Hz), a 4.03 (t, 2H, J = 5.7 Hz), of 3.84 (DD, 1H, J = 9,3 Hz, J' = 6.9 Hz), to 3.73 (DDD, 1H, J = 14,7 Hz, = 6.0 Hz, J = 3.3 Hz), to 3.64 (dt, 1H, J = 14,7 Hz, J' = 6,0 Hz), 2,04 (s, 3H).

13With NMR (75.47 MHz, CDCl3) : 0,01, 23,13, 41,88, 45,15, 47,53, 71,95, 108,21, 117,57, 118,23, 123,78, 132,05, 135,46, 137,81, 139,38, 149,38, 154,06, 155,16, 170,63, 175,16

X (miner. oil, cm-1) 3348(m), 3293(m), 1745(s), 1662(s), 1589(s).

MS: m/e (relates. u.) 393(100,M+), 394(24,7), 265(18,7), 152(11,0), 56(33,0), 44(14,6), 43(22,9), 29(31,3)

exact mass: calc. for C22H23N3O
TLC: 2.5% methanol/chloroform, 2 : Rf = 0.36 and

Example 10. ()-N-[[3-[4-[4-(4-morpholinyl)-3-oxo-2,4,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (1b)

The solution metaxalon-substituted of oxazolidine (0.078 g of 0.21 mmole) and research (0.3 ml, of 3.43 mmole) in 3.5 ml of toluene is heated under reflux during the night. The solvents are evaporated and the crude material is purified on a preparative TLC plate (1000 μm, elution with a mixture of 3% methanol/methylene chloride 2 times) to give a quantitative yield of the desired material as a yellow solid, which was further purified by another preparative TLC plates (250 μm, elution with a mixture of 75% acetone/methylene chloride three times) to obtain 0,050 g (56%) indicated in the title compound as yellow solids with so pl. 143-144oC simultaneously with 0,016 g (18%) of slightly less pure material.

1H NMR (CDCl3, 300 MHz): 7,60 (d, 2H, J = 9.0 Hz), 7,58 (d, 2H, J = 9.0 Hz), 7,21 (d, 1H, J = 1.8 Hz), was 7.08 (t, 1H, J = 10,8 Hz), 6,93 (DD, 1H, J = 10,8 Hz, J' = 1.8 Hz), of 6.66 (d, 1H, J = 9.9 Hz), 6,30 (PCs, 1H, J = 6.3 Hz), 4,80 (m, 1H, lines 10), 4,11 (t, 1H, J = 9.0 Hz), 3,90 (t, 4H, J = 4,8 Hz), of 3.84 (DD, 1H, J = 9,3 Hz, J' = 6,9 Hz), 3,70 (DDD, 1H, J = 14,7 Hz, J' = 6.0 Hz, J = 3.3 Hz), to 3.64 (dt, 1H, J = 14,7 Hz, J' = 6,0 Hz), 3.37 (t, 4H, J = 4,8 Hz), 2.03 (s, 3H);

13With NMR (75,47 M the oil, cm-1) 3307(m), 1731(s), 1658(m), 1563(C).

MS: m/e (relates.the soap.): 423(100,M+), 424(27,0), 380(17,9), 379(23,9), 364(23,8), 280(28,5), 152(18,8), 86(34,7), 56(23,8), 29(23,3)

exact mass calc. for C23H25N3O5423, 1794; exp. 423,1814

Analysis for C23H25N3O5: calc: 65,23; N 5,95; N 9,92 exp.: WITH 63,83; N 5,90; N 9,66

TLC: 5% methanol/chloroform, Rf = 0,29.

Example 11. (S)-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

Adduct of Tris(dibenzylideneacetone)dipalladium(0)-chloroform (450 mg, 0,492 mmole) and triphenylphosphine (460 mg, 1,963 mmole) are mixed together for 5 min in 1.4-dioxane (25 ml) followed by addition of (S)-N-[[3-[4-iodine-3,5-differenl)-2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (1.3 g, or 3.28 mmole). After degassing the solution three times with nitrogen is added trimethyl(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)tin (1.47 g, to 4.92 mmole). The solution escaped again (3 times) and then heated under reflux (110oC) for 12 h under nitrogen atmosphere. After cooling by TLC (10% MeOH/CHCl3, UV short wave) is determined by the completeness of the completion of the reaction. The reaction mixture was concentrated under reduced pressure and then re-dissolved in CH2Cl22SO4. After drying, it is filtered and concentrated under reduced pressure to yield a brown solid. The crude product chromatographically on silica gel (175 g of silica gel, filled with 10% CH3CN/CHCl3with elution with a gradient of 1-5% MeOH in 10% CH3CN/CHCl3obtaining a pale yellow solid. This solid precrystallizer when dissolved in a mixture of CH2Cl2/MeOH and wiping a fine powder with ether to yield 907 mg (68%) indicated in the title compound as a nearly white solid with so pl. 129oC (decomposition) and SVR (M+) est. for C20H18N2O5F2404,1184; found 404,1184.

Example 12. ()-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide

()-N-[[3-[4-(tributylstannyl)-3,5-differenl] -2-oxo-5-oxazolidinyl] methyl] ndimethylacetamide (80 mg, 0,185 mmole) was dissolved in 1,4-dioxane (5 ml) and then treated with 5-bromo-2-metaxalonum (49.5 mg, 230 mmol). After 3-fold degassing the solution with nitrogen is added bis(triphenylphosphine)palladium (II) chloride (28 mg, 0.40 mmole). The solution again escaped (three times), after which the reaction mixture is heated (110oC) with inverse x is in the catalyst (28 mg, 0,040 mmole) and after degassing (x 3) the solution is again heated under reflux for 5 hours At this point, the reaction does not end there; the above process is repeated a third time with more fresh catalyst (28 mg). Finally the solvent is removed under vacuum and the residue dissolved in CH2Cl2(50 ml). A solution of CH2Cl2washed with aqueous KF (75 ml) and brine (50 ml). After drying over anhydrous Na2SO4the organic layer is filtered and concentrated under reduced pressure to obtain a solid substance in the form of foam. This solid is purified first preparative TLC (5% MeOH/CHCl3and then by radial chromatography (elution gradient 0 to 5% MeOH in 10% CH3CN/CHCl3) to obtain 7 mg (9%) specified in the connection header in the form of solid substances with the following features:

MSVR (M+) est. for C20H18F2N2O5404,1184; exp. 404, 1183

()-N-[[3-(4-iodine-3,5-differenl)-2-oxo-5-oxazolidinyl]-methyl]ndimethylacetamide (250 mg, 0,631 mmole) was dissolved in 1,4-dioxane (15 ml) and then processed by channeltron (226 mg, 0,757 mmole). After three degassing the solution with nitrogen is added bis(triphenylphosphine)palladium (II) chloride (70 mg, 0.10 mm At this point, the reaction is not terminated; added fresh catalyst (70 mg, 0.10 mmole), and after degassing (tried) the solution is again heated under reflux for 7 hours At this point, the solvent is removed under vacuum and the remaining oil dissolved in CH2Cl2(50 ml). CH2Cl2the solution is washed with aqueous KF (40 ml) and brine (40 ml). After drying over anhydrous Na2SO4the organic layer is filtered and concentrated under reduced pressure to yield a brown solid substance in the form of foam. This solid chromatographies on silica gel (100 g) with elution gradient 0 to 10% MeOH in 10% CH3CN/CHCl3to obtain the crude product. This product is again purified preparative TLC (5% MeOH/CHCl3with the release of 72 mg (28%) indicated in the title compound as a nearly white solid with so pl. 218oC (with decomposition), is identical in all respects with the compound obtained as described above.

In table. I represented the structural formulas of the compounds of examples 1-12, as well as additional physico-chemical characteristics of some compounds of formula I.

In table. II presents data on antibacterial activity in vitro of various compounds of formula I.

locatation-1-yl)phenyl]-2-oxo-5-oxazolidinyl methyl ndimethylacetamide.

2. ()-N-[[3-[4-(4-diethylamino-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

3. ()-ndimethylacetamide,N-[[2-oxo-3-[4-[5-oxo-4-[(phenylmethyl)-amino]-1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl].

4. ()-N-[[3-[4-[4-[(2-hydroxyethyl)amino]-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methylacetamide.

5. ()-N-[[3-[4-[4-(4-morpholino)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

6. ()-N-[[3-[4-(4-cyclopropylamino-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

7. ()-N-[[3-[4-[4-(4-formyl-1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

8. ()-N-[[3-[4-[4-(2-propylamino)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

9. ()-N-[[3-[4-[4-(1-pyrrolidinyl)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

10. ()-N-[[3-[4-[4-(4-methyl-1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

11. ()-N-[[3-[4-(4-cyclopentylamine-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

12. ()-N-[[3-[4-[4-(1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1 and is)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

14. ()-N-[[3-[4-[4-(CIS-3,5-dimethyl-1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

15. ()-N-[[3-[4-[4-(1-piperidinyl)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

16. ()-N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

17. ()-N-[[3-[4-[4-(3-methyl-1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

18. ()-N-[[3-[4-[4-(3-hydroxy-1-pyrrolidinyl)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

19. (S)-N-[[3-fluoro-4(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

20. ()-N-[[3-[4-[4-methoxy-3-oxo-1,4,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

21. ()-N-[[3-[4-(6-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

22. ()-N-[[3-[4-(4-ethoxy-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

23. ()-N-[[3-[4-[4-(3-amino-1-pyrrolidinyl)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

24. ()-N-[[3-[4-[4-(1-methylethoxy)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxoa-5-oxazolidinyl]methyl]ndimethylacetamide.

26. ()-N-[[3-[4-[4-(2-propylamino)-3-oxo-1,4,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

27. ()-N-[[3-[4-[4-(4-morpholinyl-3-oxo-1,4,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

28. (S)-N-[[3-[4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

29. ()-N-[[3-[4-[4-(2-propylamino)-3-oxo-1,4,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

30. ()-N-[[3-[4-[-[[(methoxycarbonyl)methyl]amino)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

31. ()-N-[[3-[4-(4-methylamino-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

32. ()-N-[[3-[4-[4-(2,5-dihydro-1H-pyrrol-1-yl)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

33. ()-N-[[3-[4-[4-(2-propenyloxy)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

34. (S)-N-[[3-[3-fluoro-4-[(2-propylamino)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

35. ()-N-[[3-[4-[4-(2-methoxyethoxy)-5-oxo-1,3,6-cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

36. (S)-N-[[3-[3-fluoro-4-[(4-morpholino)-5-oxo-1,3,6-cycloheptatrien the activity of some compounds of formula I.

1. Transnistria phenyloxazolidine formula I

< / BR>
where R1- C1- C8-alkyl;

R2and R3are the same or different and are selected from hydrogen, fluorine or chlorine;

R4is selected from the group consisting of

< / BR>
< / BR>
< / BR>
where R5is selected from the group consisting of hydrogen, -OR6, SR6-THE OTHER7, -NR7R12,

< / BR>
< / BR>
< / BR>
< / BR>
where R6- H, C1- C8-alkyl, possibly substituted C1- C8-alkoxylate, C2- C8alkenyl-C1- C8-alkyl or phenyl-C1- C8-alkyl;

R7- C1- C8-alkyl, optionally substituted by hydroxy, phenyl or C1- C8-alkoxycarbonyl, C3- C8-cycloalkyl, C2- C8-quinil-C1- C10-alkyl, C2- C8alkenyl-C1- C10-alkyl;

R8is hydrogen, C1- C8-alkyl, C1- C8-acyl;

R9and R10may be the same or different and are hydrogen or C1- C8-alkyl;

R11is hydrogen, hydroxy or amino;

R12- C1- C8-alkyl,

or its pharmaceutically acceptable salts, or hydrates.

3. Connection on p. 2, selected from the group consisting of

()-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-diethylamino-5-oxo-1,3,6-cycloheptatrien-1-yl)-phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[2-oxo-3-[4-[5-oxo-4-[(phenylmethyl)amino] -1,3,6 - cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-[(2-hydroxyethyl)amino] -5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(4-morpholino)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-cyclopropylamino-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(4-formyl-1-piperazinil)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(2-propylamino)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(1-pyrrolidinyl)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(4-methyl-1-piperazinil)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-cyclopentylamine-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-what about the-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-butylamino-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(CIS-3,5-dimethyl-1-piperazinil)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(1-piperidinyl)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[3-fluorescent-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(3-methyl-1-piperazinil)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(3-hydroxy-1-pyrrolidinyl)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-ethoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(3-amino-1-pyrrolidinyl)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(1-metadataset)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[4-[4-(4-morpholino)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[4-(4-methods-1,3,6-cycloheptatrien-1-yl] phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-[[(methoxycarbonyl)methyl] amino] -5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-(4-methylamino-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(2,5-dihydro-1H-pyrrol-1-yl)-5-oxo-1,3,6-cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(2-propenyloxy-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-[3-the fluorescent-4-(2-propylamino)-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(3,5-dihydro-1(2H-pyridinyl)-5-oxo-1,3,6-cycloheptatrien-1-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(J)-N-[[3-[4-[4-(2-methoxyethoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluorescent-4-[(4-morpholino)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[3,5-Diptera-4-(methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[4-(4-methylamino-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-fluorescent-4-(4-methylamino-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[4-[4-(2-hydroxyethyl)amino] -5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide and

(S)-N-[[2-oxo-3-[3-fluoro-4-[5-oxo-4-(phenylmethoxy) 1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide.

4. Connection on p. 2, in which R2and R3selected from the group consisting of hydrogen and fluorine.

5. Connection on p. 4, selected from the group consisting of

()-N-[[3-[3-fluorescent-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluorescent-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluorescent-4-[(2-propylamino)-5-oxo-1,3,6 - cycloheptatrien-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluorescent-4-[(4-morpholino)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[3-fluorescent-4-(4-methylamino-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[2-oxo-3-[3-fluoro-4-[5-oxo-4-(phenylmethoxy)- 1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl]acetamide", she

(S)-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide and

()-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cyclohe-fluorescent-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

7. Connection on p. 5

(S)-N-[[3-[3-fluorescent-4-(4-methoxy-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

8. Connection on p. 5

(S)-N-[[3-[3-fluorescent-4-[(2-propylamino)-5-oxo-1,3,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

9. Connection on p. 5

(S)-N-[[3-[3-fluorescent-4-[(4-morpholino)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

10. Connection on p. 5

(S)-N-[[3-[3-fluorescent-4-[(4-methylamino)-5-oxo-1,3,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

11. Connection on p. 5

(S)-N-[[2-oxo-3-[3-fluoro-4-[5-oxo-4-(phenylmethoxy) 1,3,6-cycloheptatrien-1-yl]phenyl]-5-oxazolidinyl]methyl]ndimethylacetamide.

12. Connection on p. 5

(S)-N-[[3-[4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)-3,5-differenl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

13. Connection on p. 1, having the General formula Ib

< / BR>
where R1, R2, R3and R5defined in paragraph 1.

14. Connection on p. 5, selected from the group consisting of

()-N-[[3-[4-[4-methoxy-3-oxo-1,4,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]acetamide", she

()-N-[[3-[4-[4-(2-propenyl)amino-3-oxo-1,4,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazol the l]methyl]ndimethylacetamide and

()-N-[[3-[4-[4-(2-propylamino)-3-oxo-1,4,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

15. Connection on p. 14

()-N-[[3-[4-[4-methoxy-3-oxo-1,4,6 - cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

16. Connection on p. 14

()-N-[[3-[4-[4-(2-propylamino)-3-oxo-1,4,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

17. Connection on p. 14, selected from the group consisting of

()-N-[[3-[4-[4-(4-morpholinyl)-3-oxo-1,4,6 - cycloheptatrien-1-yl]phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide and

()-N-[[3-[4-[4-(2-propylamino)-3-oxo-1,4,6 - cycloheptatrien-1-yl] phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

18. Connection on p. 1, having the General formula Ic

< / BR>
where R1, R2, R3and R5defined in paragraph 1.

19. Connection on p. 18

()-N-[[3-[4-(6-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl] -2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide.

Priority signs:

08.12.92 - by all indications p. 1 claims, except for R12- C1- C8-alkyl;

13.01.93 - on the basis of R12- C1- C8-alkyl.

 

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2 ex, 5 tbl

FIELD: organic chemistry, medicine.

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32 cl, 4 dwg, 82 ex

FIELD: medicine, pharmaceutics.

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47 cl, 1 tbl, 54 ex

FIELD: organic chemistry, agriculture.

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16 cl, 6 tbl, 4 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

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10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, heterocyclic compounds, medicine.

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EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 3 ex

FIELD: organic chemistry, medicine, hormones.

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EFFECT: valuable properties of compounds.

20 cl, 13776 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to bicyclic heterocyclic substituted phenyloxazolidinones that represent compounds of the formula (I): wherein R is taken from the group consisting of -OH, O-heteroaryl, -N3, -OSO2R'', -NR'''R'''', or the formula: wherein: (ii) R'' represents direct or branched alkyl comprising up to 5 carbon atoms; (iii) R''' and R'''' are taken independently from the group consisting of hydrogen atom (H), -CO2-R1, -CO-R1, -CS-R1 and -SO2-R4 wherein R1 is taken among the group consisting of cycloalkyl comprising from 3 to 6 carbon atoms and direct or branched alkyl comprising up to 6 carbon atoms; R4 is taken from direct or branched alkyl comprising up to 4 carbon atoms; and R4a represents -CN or -NO2; R4b represents -SR4c, amino-group, -NHR4c or -NR4cR4d wherein R4c and R4d are taken independently from hydrogen atom (H) or alkyl; X represents from 0 to 4 members taken independently from the group consisting of halogen atom; and Y represents radical of the formula (II): or (III): wherein R5, R6, R7 and R8 represent independently hydrogen atom (H), or R and R6 and/or R7 and R8 form in common oxo-group; R9 and R10 represent independently hydrogen atom (H); A, B, C and D are taken from carbon atom (C) and nitrogen atom (N) to form phenyl ring or 5-6-membered heteroaromatic ring wherein the indicated heteroaromatic ring comprises from 1 to 4 members taken from the group consisting of nitrogen atom (N); Z is taken from alkyl, heteroaryl comprising nitrogen atom (N); and m represents 0 or 1. These compounds are useful as antibacterial agents and can be used for treatment of patient with the state caused the bacterial infection or with the bacterial infection caused by S. aureus and E. faecium.

EFFECT: valuable medicinal properties of compounds.

45 cl, 1 tbl, 50 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (1): wherein R1 means (C1-C6)-alkyl that can be substituted with phenyl; R2, R3, R4 and R5 represent independently each of other hydrogen halogen atom, nitro-group, (C1-C4)-alkyl, (C6-C10)-aryl-(C1-C4)-alkyloxy-, (C6-C10)-aryloxy-group, (C6-C10)-aryl that can be mono-, di- or tri-substituted with halogen atom; 2-oxopyrrolidine-1-yl, 2,5-dimethylpyrrole-1-yl or -NR6-A-R7 under condition that R2, R3, R4 and R5 can't mean simultaneously hydrogen atom and at least one residue among R2, R3, R4 and R5 represents 2-oxopyrrolidine-1-yl, 2,5-dimethylpyrrole-1-yl or -NR6-A-R7 at value R6 - hydrogen atom, (C1-C4)-alkyl or (C6-C10)-aryl-(C1-C4)-alkyl wherein aryl can be substituted with halogen atom; A means a simple bond, -COn, -SOn or -CONH; n = 1 or 2; R7 means hydrogen atom; (C1-C18)-alkyl or (C2-C18)-alkenyl that can be substituted from one to three times with (C1-C4)-alkyl, (C1-C4)-alkyloxy-group, -N-((C1-C4)-alkyl)2-group, -COOH, (C1-C4)-alkyloxycarbonyl, (C6-C12)-aryl, (C6-C12)-aryloxy-group, (C6-C12)-arylcarbonyl, (C6-C10)-aryl-(C1-C4)-alkoxy-group, halogen atom, -CF3 or oxo-group wherein aryl, in turn, can be substituted with halogen atom, (C1-C)-alkyl, aminosulfonyl- or methylmercapto-group; (C6-C10)-aryl-(C1-C4)-alkyl, (C5-C8)-cycloalkyl-(C1-C4)-alkyl, (C5-C8)-cycloalkyl, (C6-C10)-aryl-(C2-C6)-alkenyl, (C6-C10)-aryl, diphenyl, diphenyl-(C1-C4)-alkyl, indanyl that can be mono- or di-substituted with (C1-C18)-alkyl, (C1-C18)-alkyloxy-group, (C3-C8)-cycloalkyl, hydroxy-group, (C1-C4)-alkylcarbonyl, (C6-C10)-aryl-(C1-C4)-alkyl, (C6-C10)-aryl-(C1-C4)-alkyloxy-group, (C6-C10)-aryloxy-group, nitro-, cyano-group, (C6-C10)-aryl, fluorosulfonyl, (C1-C6)-alkyloxycarbonyl, (C6-C10)-arylsulfonyloxy-group, pyridyl, -NHSO2-(C6-C10)-aryl, halogen atom, -CF3 or -OCF3 wherein alkyl can be substituted once again with halogen atom, -CF3 or (C1-C4)-alkyloxy-group; or group Het-(CH2)r wherein r = 0, 1, 2 or 3 wherein Het means saturated or unsaturated 5-7-membered heterocycle comprising atoms nitrogen (N), oxygen (O) or sulfur (S) and can be condensed with benzene and substituted with (C1-C4)-alkyl, (C6-C10)-aryl, halogen atom, (C1-C4)-alkyloxy-group, (C6-C10)-aryl-(C1-C4)-alkyl, (C6-C10)-aryl-(C1-C)-alkylmercapto- or nitro-group and wherein aryl condensed with benzene can be, in turn, substituted with halogen atom, (C1-C4)-alkyloxy-group; and to their pharmacologically acceptable salts and additive salts of acids, and to a method for their preparing. Proposed compounds show inhibitory effect on activity of hormone-sensitive lipase.

EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.

14 cl, 199 ex

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