An oxazolidinone compound, a synthetic method and application thereof

Abstract

The application discloses an oxazolidinone compound and a synthesis method and application thereof, which couples a compound with a structural formula IV and a compound with a structural formula V under the action of a catalyst to obtain a compound with a structural formula II, and then phosphorylates the compound with the structural formula II to obtain a compound with a structural formula I. 1 is methyl, ethyl, propyl or cyclopropyl, ethenyl; R 2 is F; R 3 is F, CH3, C2H5, CF3, CHF2, CH2F or cyclopropyl; X is chlorine (Cl), bromine (Br), iodine (I), substituted boric acid or substituted boric acid ester. The compound has strong bacteriostatic activity on methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.

Description

Technical Field

[0001] This invention relates to the field of biochemistry, and more specifically to an oxazolidinone compound, its synthesis method, and its application. Background Technology

[0002] Oxazolidinone derivatives have been used in various forms as antibacterial drugs, with tedizolid being one of the more effective ones. The structure of tedizolid is shown in structural formula III below.

[0003]

[0004] Its phosphate ester is effective in treating acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive bacteria such as Staphylococcus aureus (including methicillin-resistant and methicillin-sensitive strains), various Streptococcus spp., and Enterococcus faecalis. To develop an oxazolidinone compound with stronger antibacterial activity, this invention synthesized a series of compounds based on the tepidilamide structure. Summary of the Invention

[0005] In view of this, the present invention provides an oxazolidinone compound, its synthesis method and application. Antibacterial experiments show that these new compounds have stronger antibacterial effects compared with tepidizolamide.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] An oxazolidinone compound, characterized in that it specifically comprises the following compounds:

[0008] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (referred to as compound 1)

[0009] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (referred to as compound 2)

[0010] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (referred to as compound 3)

[0011] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (compound 4 for short)

[0012] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (compound 5 for short)

[0013] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (compound 6 for short)

[0014] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (compound 7 for short)

[0015] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one (compound 8 for short)

[0016] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 9 for short)

[0017] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (referred to as compound 10)

[0018] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (referred to as compound 11)

[0019] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (referred to as compound 12)

[0020] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 13)

[0021] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 14 for short)

[0022] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 15 for short)

[0023] S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 16 for short)

[0024] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 17 for short)

[0025] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 18)

[0026] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 19 for short)

[0027] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (referred to as compound 20)

[0028] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (referred to as compound 21)

[0029] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 22 for short)

[0030] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidin-2-one (compound 23 for short)

[0031] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 24)

[0032] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 25 for short)

[0033] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 26 for short)

[0034] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 27 for short)

[0035] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 28)

[0036] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 29 for short)

[0037] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 30 for short)

[0038] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 31 for short)

[0039] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 32 for short)

[0040] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 33)

[0041] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 34 for short)

[0042] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 35 for short)

[0043] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 36 for short)

[0044] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 37)

[0045] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 38)

[0046] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 39 for short)

[0047] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one (compound 40)

[0048] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 41 for short)

[0049] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one (compound 42 for short)

[0050] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one (compound 43 for short)

[0051] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidin-2-one (compound 44 for short)

[0052] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 45 for short)

[0053] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one (compound 46)

[0054] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidin-2-one (compound 47)

[0055] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidin-2-one (compound 48)

[0056] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 49)

[0057] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 50)

[0058] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 51 for short)

[0059] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 52 for short)

[0060] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 53 for short)

[0061] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 54 for short)

[0062] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 55)

[0063] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 56 for short)

[0064] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 57 for short)

[0065] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 58)

[0066] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 59 for short)

[0067] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidin-2-one (compound 60)

[0068] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 61 for short)

[0069] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 62)

[0070] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 63)

[0071] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 64)

[0072] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 65)

[0073] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 66)

[0074] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 67)

[0075] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 68)

[0076] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 69 for short)

[0077] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 70)

[0078] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 71 for short)

[0079] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 72)

[0080] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 73 for short)

[0081] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one (compound 74)

[0082] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 75 for short)

[0083] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one (compound 76 for short)

[0084] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 77)

[0085] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one (compound 78)

[0086] The specific reaction equation for the synthesis method of this invention is expressed as follows:

[0087]

[0088] In the formula: R 1 Methyl, ethyl, propyl, or cyclopropyl, vinyl; R 2 For F; R 3 It is F, CH3, C2H5, CF3, CHF2, CH2F or cyclopropyl; X is chlorine (Cl), bromine (Br), iodine (I), substituted boric acid or substituted borate ester.

[0089] Further, the catalyst in step (1) is selected from copper iodide, bis(triphenylphosphine) palladium chloride, palladium chloride, palladium acetate, bis(tri-tert-butylphosphine) palladium chloride, 1,1'-bis(di-tert-butylphosphine)ferrocene palladium dichloride, bis(diphenylphosphine)ferrocene palladium dichloride, (1,1'-bis(diphenylphosphine)ferrocene) nickel dichloride, triphenylphosphine ruthenium chloride, bis(acetonitrile) palladium (II), 1,4-bis(diphenylphosphinebutane) palladium dichloride, bis(di-tert-butylphenylphosphine) palladium dichloride (II), bis(triphenylphosphine) palladium acetate, 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (II), and bis(4-dimethylaminophenyldi-tert-butylphosphine) palladium dichloride (II).

[0090] Furthermore, the catalyst in step (1) is selected from bis(diphenylphosphine)ferrocene]palladium dichloride.

[0091] Furthermore, in step (2), the halophosphate is selected from dimethyl chlorophosphate, diethyl chlorophosphate, dibenzyl chlorophosphate, dimethyl bromophosphate, diethyl bromophosphate, and dibenzyl bromophosphate.

[0092] Furthermore, in step (2), the halophosphate is selected from dimethyl chlorophosphate and dimethyl bromophosphate.

[0093] Furthermore, the compound of structural formula II is obtained by replacing the methyl substituent on the tetrazolium ring with ethyl, propyl, cyclopropyl, or vinyl; and / or modifying the hydroxymethyl group at the 5-position of the oxazolidinone with fluorine, methyl, ethyl, trifluoromethyl, difluoromethyl, fluoromethyl, or cyclopropyl to introduce a second chiral center, as shown in structural formula II:

[0094]

[0095] In the formula: R 1 Methyl, ethyl, propyl, or cyclopropyl, vinyl; R 2 For F; R 3 It can be F, CH3, C2H5, CF3, CHF2, CH2F or cyclopropyl.

[0096] Furthermore, the compounds of structural formula I specifically include, but are not limited to, the following compounds:

[0097] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 79)

[0098] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 80)

[0099] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-ketophosphate (compound 81)

[0100] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 82)

[0101] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-ketophosphate (compound 83)

[0102] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 84)

[0103] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 85)

[0104] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate (compound 86)

[0105] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 87)

[0106] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 88)

[0107] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-ketophosphate (compound 89)

[0108] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-ketophosphate (referred to as compound 90)

[0109] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 91)

[0110] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 92)

[0111] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 93)

[0112] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 94)

[0113] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 95)

[0114] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 96)

[0115] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate (compound 97)

[0116] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 98)

[0117] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-ketophosphate (compound 99)

[0118] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate (compound 100)

[0119] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 101)

[0120] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 102)

[0121] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (referred to as compound 103)

[0122] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 104)

[0123] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 105)

[0124] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate (compound 106)

[0125] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate (compound 107)

[0126] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate (compound 108)

[0127] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 109)

[0128] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 110)

[0129] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 111)

[0130] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 112)

[0131] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 113)

[0132] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 114)

[0133] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-ketophosphate (compound 115)

[0134] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-ketophosphate (compound 116)

[0135] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 117)

[0136] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 118)

[0137] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 119)

[0138] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-ketophosphate (compound 120)

[0139] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-ketophosphate (compound 121)

[0140] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate (compound 122)

[0141] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate (compound 123)

[0142] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate (compound 124)

[0143] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 125)

[0144] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-ketophosphate (compound 126)

[0145] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 127)

[0146] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 128)

[0147] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 129)

[0148] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 130)

[0149] (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 131)

[0150] (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 132)

[0151] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 133)

[0152] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 134)

[0153] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 135)

[0154] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 136)

[0155] (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 137)

[0156] (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 138)

[0157] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 139)

[0158] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 140)

[0159] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 141)

[0160] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 142)

[0161] (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 143)

[0162] (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 144)

[0163] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 145)

[0164] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 146)

[0165] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 147)

[0166] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 148)

[0167] (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 149)

[0168] (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 150)

[0169] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 151)

[0170] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-ketophosphate (compound 152)

[0171] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 153)

[0172] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-ketophosphate (compound 154)

[0173] (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 155)

[0174] (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-ketophosphate (compound 156)

[0175] Furthermore, the application of the compound with structural formula I prepared according to the above synthesis method in the preparation of drugs for treating bacterial infections.

[0176] Furthermore, the application of the compound with structural formula II prepared according to the above synthetic method in the preparation of drugs for treating bacterial infections.

[0177] As can be seen from the above technical solutions, compared with the prior art, the present invention discloses an oxazolidinone compound, its synthesis method and application. The compound synthesized by the method of the present invention can be used to treat bacterial infections in humans or other warm-blooded animals. The administration method can be extra-gastrointestinal or oral. Furthermore, the in vitro antibacterial test results of the present invention show that, compared with terdizolam, the compound of the present invention has stronger antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Detailed Implementation

[0178] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0179] Example 1

[0180] Weigh 1 g of 6-(2-ethyl-2H-tetrazol-5-yl)-3-bromopyridine and dissolve it in 10 ml of toluene. Then add triphenylphosphine palladium chloride, stir and heat to 40 °C, and add dropwise 1.2 g of (R)-3-(3-fluoro-4-bromophenyl)-5-(hydroxymethyl)oxazolidin-2-one in 5 ml of toluene solution. After the addition is complete, maintain the reaction temperature at 40-50 °C for 4 hours. Filter, evaporate the solvent to dryness, and recrystallize the residue from ethanol to give 1.2 g of a white solid compound 1. HPLC analysis showed a purity of 98.02%.

[0181] Example 2

[0182] Weigh 0.3 g of magnesium shavings and dissolve them in 10 ml of anhydrous tetrahydrofuran. Add 0.01 g of iodine and observe the reaction solution begin to bubble. Stir and add 1 g of 6-(2-ethyl-2H-tetrazol-5-yl)-3-bromopyridine in 5 ml of anhydrous tetrahydrofuran solution. After the addition is complete, heat and reflux for 2 hours. Then add 1.2 g of (S)-3-(3-fluoro-4-bromophenyl)-5-(hydroxymethyl)oxazolidine-2-one in 5 ml of anhydrous tetrahydrofuran solution and reflux for 4 hours. Add 1 ml of water and stir for 10 minutes. Filter, evaporate the solvent to dryness, and recrystallize the residue from ethanol to give 1.1 g of a white solid compound 2. HPLC analysis showed a purity of 98.11%.

[0183] Example 3

[0184] Compound 3 was synthesized using a method similar to that in Example 1.

[0185] Example 4

[0186] DMSO (100 mL), (5R)-3-(4-bromo-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (10.00 g, 34.5 mmol), pinacol diboronate (17.52 g, 69.0 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (1.39 g, 1.7 mmol), and potassium acetate (13.54 g, 138.0 mmol) were added to a 250 mL reaction flask. Under nitrogen protection, the mixture was heated to 80 °C and reacted for 14 h. Heating was stopped, and the mixture was cooled to room temperature. 500 mL of water was added, and the mixture was extracted with ethyl acetate (500 mL × 3). The organic layers were combined, and the resulting organic phase was washed with saturated brine (400 mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated, and used directly in the next reaction step.

[0187] The concentrated product from the above steps was added to a 250 mL reaction flask, along with 1,4-dioxane (100 mL), 5-bromo-2-(2-methyl-2H-tetrazole-5-yl)pyridine (compound 3) (8.28 g, 34.5 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (0.57 g, 0.7 mmol), and cesium carbonate aqueous solution (50 mL, containing 33.72 g cesium carbonate, 103.5 mmol). Under nitrogen protection, the mixture was heated to 70 °C and reacted for 3 h. Dichloromethane (100 mL × 3) was then added for extraction. The separated organic phase was washed with saturated brine (100 mL), dehydrated with anhydrous sodium sulfate, filtered, concentrated under vacuum, and purified by column chromatography to obtain 10.60 g of compound 1, with a yield of 82.9% and a purity of 98.34% as determined by HPLC.

[0188] A series of similar compounds were synthesized using methods similar to those described in Examples 1, 2, and 4. The raw materials and products used are shown in Table 1.

[0189] Table 1

[0190]

[0191]

[0192] A series of similar compounds were synthesized using methods similar to those described in Examples 1, 2, and 4. The raw materials and products used are shown in Table 2.

[0193] Table 2

[0194]

[0195]

[0196] Example 5

[0197] 0.36 g of compound 1 was dissolved in 10 ml of acetonitrile, and 0.30 g of phosphorus oxychloride was added. The mixture was heated under reflux for 20 hours. After cooling to room temperature, 1 g of water was added, and the mixture was stirred for 1 hour. The solvent was evaporated under reduced pressure at 40 °C. The resulting residue was subjected to column chromatography and recrystallized from anhydrous ethanol to give 0.28 g of a white solid, compound 79, with a yield of 63% and an HPLC purity of 98.9%.

[0198] Example 6

[0199] 0.36 g of compound 1 was dissolved in 10 ml of acetonitrile, and 0.28 g of dimethyl chlorophosphate was added. The mixture was heated under reflux for 20 hours. After cooling to room temperature, 3 ml of methanol was added and stirred well. Then, 0.3 g of trimethylchlorosilane was added, and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated to dryness, and the resulting residue was subjected to column chromatography and recrystallized from anhydrous ethanol to give 0.33 g of a white solid, compound 79, with a yield of 74% and an HPLC purity of 99.2%.

[0200] Compounds 80-156 were synthesized using methods similar to those in Examples 5 and 6.

[0201] Example 7

[0202] To test the antibacterial activity of these novel oxazolidinone compounds, the agar dilution method was used to test their inhibitory effects on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Antibacterial efficacy was expressed as the minimum inhibitory concentration (MIC). 50 The values ​​are expressed in μg / ml. The test results are shown in Table 3.

[0203] Table 3

[0204]

[0205]

[0206]

[0207] As shown in Table 3, the compounds of this invention exhibit more effective inhibition of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) compared to terdiazolamide phosphate. Therefore, the compounds of this invention are highly useful antibiotics.

Claims

1. An oxazolidinone compound, characterized in that, Selected from the following compounds: (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxymethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxyethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-trifluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxypropyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(hydroxyfluoromethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-difluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-2-fluoroethyl)oxazolidine-2-one phosphate; (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate; (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazole-5-yl)pyridin-3-yl)phenyl)-5-(1-hydroxy-1-cyclopropylmethyl)oxazolidine-2-one phosphate.

2. The use of the oxazolidinone compound of claim 1 in the preparation of a medicament for treating bacterial infections.

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