CN103119040A - Process for making linezolid - Google Patents
Process for making linezolid Download PDFInfo
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- CN103119040A CN103119040A CN2011800459835A CN201180045983A CN103119040A CN 103119040 A CN103119040 A CN 103119040A CN 2011800459835 A CN2011800459835 A CN 2011800459835A CN 201180045983 A CN201180045983 A CN 201180045983A CN 103119040 A CN103119040 A CN 103119040A
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- BLJTYFFZQFSUJV-BBRMVZONSA-N Cc1cc(N(C[C@@](C2)([C@H]2N(C=O)C(I)=O)O2)C2=O)ccc1NCCO Chemical compound Cc1cc(N(C[C@@](C2)([C@H]2N(C=O)C(I)=O)O2)C2=O)ccc1NCCO BLJTYFFZQFSUJV-BBRMVZONSA-N 0.000 description 1
- XBMUYGZFPVBOFO-ZBFHGGJFSA-N O=CN[C@H](C1)[C@]1(CN1c(cc2F)ccc2N2CCOCC2)OC1=O Chemical compound O=CN[C@H](C1)[C@]1(CN1c(cc2F)ccc2N2CCOCC2)OC1=O XBMUYGZFPVBOFO-ZBFHGGJFSA-N 0.000 description 1
- 0 OCCN*(ccc(N(C1)C(O)O[C@]1(C1)[C@]1N(C=O)C=O)c1)c1F Chemical compound OCCN*(ccc(N(C1)C(O)O[C@]1(C1)[C@]1N(C=O)C=O)c1)c1F 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Abstract
The present invention relates to a process for making the compound 3-(3-fluoro-4-(morpholin-4-yl)phenyl)-2-oxooxazolidin-5(S)-ylmethyl)amine of formula (II) and/or an acid addition salt thereof comprising b) reacting the compound of formula (VII) wherein L is a leaving group, with a metal salt of diformylamide of formula (VIII) wherein Me+ is a sodium or potassium cation, b) subjecting the reaction product of the step (a) comprising, alone or in admixture, compounds of formula (IXa) and/or (IXb), to a reaction with an acid, and to the making of linezolid by acetylation of the compound of formula (II).
Description
Background of invention
The present invention relates to a kind of improved method for the preparation of the compound Linezolid.
Linezolid is a kind of can as the pharmaceutical active compounds of antiseptic-germicide, for example, being used for the treatment of the dieletic foodstuff that is caused by gram positive bacterium and infecting.Linezolid is represented by following formula (I).
Commercially available pharmaceutical composition be for venoclysis sterile isotonic solution, be used for oral tablet and be used for oral aqueous suspensions.They by Pfizer company with trade(brand)name ZYVOX list marketing.
The molecule of Linezolid has an asymmetric carbon in molecule, make to form two kinds of enantiomorphs; Commercially available compound is (S)-enantiomorph.In above-mentioned commercially available composition, Linezolid exists with free alkali form.
Hereinafter, the title Linezolid will be as N-(3-(3-fluoro-4-(morpholine-4-yl) phenyl)-2-oxo
Azoles alkane-5 (S)-ylmethyl) common name of ethanamide uses, unless opposite explanation is arranged.
Linezolid is originally presented in the WO95/07271 (EP0717738, US5,688,792) of Upjohn company.
Known multiple method for the preparation of Linezolid in this area.Particularly, important method is that wherein final step comprises with acetyl halide or diacetyl oxide the amine precursor of formula (II) is carried out acetylizad method (referring to for example, WO2005099353).
This amine precursor (II) can be made by plurality of raw materials, for example:
A) by the trinitride (WO2006/091731, WO95/07271, US5837870, WO2009/063505, US7291614) with suitable reductive agent reduction-type (III)
Initial compounds (III) can make (WO2005/099353) by corresponding tosylate or the muriate of following general formula (VII).
B) by for example using the phthalimide compound of methylamine (WO95/07271) or hydrazine (US5837870) breakdown (IV)
Initial compounds (IV) can make (WO2005/099353) from identical tosylate or muriate as described in aforementioned a) item, or by cyclisation
Oxazolidine ring makes (WO99/24393, WO2006/008754)
C) by processing (WO95/07271) with the ammonium hydroxide in Virahol or THF or depress with ammonia treatment (WO97/37980) adding, make from the sulphonate of formula (V)
D) by the following imines (VI) of reduction:
Wherein R2 is chloro-phenyl-, bromophenyl or 2,4 dichloro benzene base section (WO2007/116284).
Except imines (VI), every kind of method in aforementioned synthetic method all is based on the step of the raw material that transforms general formula (VII)
Wherein L is the leavings group that is fit to, for example halogen or alkylsulfonyloxy or aryl-sulfonyl oxygen group,
Described conversion is by carrying out with nitrogen nucleophile (trinitride salt, phthalic imidine salt, ammonia or ammonium hydroxide) reaction, if necessary, carry out subsequently formed reaction intermediate (for example, compound (III) or compound (IV)) is converted into the step of amino/compound (II).Be apparent that, prepare the critical aspects of arbitrary route acquisition business success in the said synthesis route that initial amine compound (II) is the acquisition Linezolid with good yield and purity.Yet, known method has multiple shortcoming, the for example serious toxicity of trinitride salt and explosion hazard, use long reaction times and hazardous agents (hydrazine, methylamine) in the phthalic imidine intermediate, low yield in the ammonium hydroxide method and many by products, or with ammonia react in harsh reaction conditions.
Therefore, although still there is improved demand in the synthetic method of known many preparation compounds (II) and Linezolid in the prior art.Alternative method with a kind of amine intermediate for the preparation of Linezolid is desirable, and the method is simple, carry out under the reaction conditions of gentleness and do not show above-mentioned shortcoming.
Summary of the invention
The present invention relates to prepare the discovery of improving one's methods of Linezolid, described method is simple aspect processing condition, and the amount of the byproduct of reaction that provides is few.
One main aspect, the invention provides the compound 3-(3-fluoro-4-(morpholine-4-yl) phenyl) of a kind of preparation formula (II)-2-oxo
Azoles alkane-5 (S)-ylmethyl) method of amine and/or its acid salt,
The method comprises
A) make the compound of formula (VII)
Wherein L is leavings group, with the reacting metal salt of the diformyl acid amides of formula (VIII)
Me wherein
+Sodium or potassium cationic,
B) make the reaction product of step (a), it comprises the mixture of formula (IXa) and compound (IXb),
The reaction of experience and acid is preferably with the reaction of hydrochloric acid.Described leavings group is halo group or alkylsulfonyloxy or aryl-sulfonyl oxygen group preferably.By acetylize, compound (II) is converted into Linezolid, preferably with the form of acid salt, more preferably in water.
According to another aspect of the present invention, provide the method for the preparation of Linezolid, the method is included in the water soluble acid additive salt that makes formula (II) compound in water-bearing media under the existence of alkali
With acetyl halide or acetic anhydride.
Detailed Description Of The Invention
Prepare according to of the present invention the compound that the raw material that uses in the method for Linezolid is general formula (VII)
Wherein L is leavings group, typically is the halo group, or alkylsulfonyloxy or aryl-sulfonyl oxygen group." halo " group comprises chloro or bromo group, preferred chloro group." alkyl " comprises C
1-C
4Alkyl, and be preferably methyl." aryl " comprises phenyl, and it can be randomly by at least one C
1-C
4Alkyl, nitro, hydroxyl, C
1-C
4Alkoxyl group replaces, and preferably p-methylphenyl or p-nitrophenyl.
Described compound is as known in the art, perhaps can prepare according to procedures known in the art, and for example the hydroxy-methyl compound from corresponding formula (X) prepares.
It is the metal-salt of the diformyl acid amides of formula (VIII) that agent is accompanied in second reaction.
" Me
+" sodium or potassium, preferably sodium typically.Compound (VIII) is as known in the art, and usually can obtain by corresponding metal methoxide salt and formamide, referring to US5488188 and US5599986.It can be used as the solid separation and obtains, and stores under envrionment conditions.
Reaction between compound (VII) and compound (VIII) typically can be carried out in inert solvent, described inert solvent is the aprotic solvent of polarity preferably, N for example, dinethylformamide, dimethyl sulfoxide (DMSO), acetonitrile, N-Methyl pyrrolidone, N,N-dimethylacetamide or acetone and their mixture.Typically, the mol ratio between compound (VII) and compound (VIII) is 1:1 to 1:3, and preferred approximately 1:1.1 is 1:1.7 extremely approximately.Temperature of reaction typically is 50～100 ℃, is preferably 60～90 ℃.Under these conditions, the reaction times is approximately 0.5～2 hour.Reaction process can be passed through the general analysis technology, for example monitors by TLC or HPLC.
After reaction is completed, advantageously be to remove the volatility resistates by for example evaporation, and remaining metal-salt is also removed, for example extract by water.
Reaction product comprises the mixture of formula (IXa) and compound (IXb).
The mutual ratio of these two kinds of compounds depends on that compound (VIII) is with respect to the relative quantity of compound (VII).In the situation of boundary line, reaction mixture includes only compound (IXa) and/or includes only compound (IXb).Because compound in next step (IXa) and compound (IXb) both can be converted into the amine of formula (II) comparably, objectively do not need they to be separated or improve their mutual ratios in mixture.Yet, do not get rid of by the two kind compound separation of suitable isolation technique with described reaction mixture, for example be used for the purpose of analyzing.Compound (IXa) and (IXb) can also obtain with the form of acid salt is such as hydrochloride, hydrobromate, vitriol, nitrate, phosphoric acid salt, formate, acetate, propionic salt, oxalate, malonate, maleate, fumaric acid hydrochlorate, Citrate trianion, malate etc.
Acid hydrolysis by gentleness is converted into formula (II) with the arbitrary compound in compound (IXa) and compound (IXb) and/or its mixture in next step compound.Typically, the acid that can be used for this purpose is strong mineral acid or organic acid, for example hydrochloric acid, sulfuric acid, phosphoric acid or Hydrogen bromide.Generally speaking, use the acid of mole scale.Hydrolysis can be carried out in solvent, and described solvent can be water, lower alcohol (C
1-C
4Fatty alcohol) or mixture both.Typical temperature of reaction is 0～80 ℃.Reaction process can by the analytical technology that is fit to, for example be monitored by HPLC or TLC.
Advantageously, can in a Pot devices, hydrolysing step and previous step be merged.
Because the by product that forms in remaining reagent and solvent and reaction process is volatile compound, the easiest method of removing them is evaporation, preferred vapourisation under reduced pressure.
The product of reaction comprises the amine compound of rough formula (II).It forms after hydrolysis, is corresponding acid salt (for example, hydrochloride or dihydrochloride), if necessary, can randomly by the alkaline purification with equivalent, its neutralization for unhindered amina, randomly be extracted subsequently.If necessary, crude compound (II) and/or its acid salt (for example hydrochloride or acetate) can be by known method purifying, and/or separate with any solid-state form, as disclosed in US2006/0258655.The hydrochloride of compound (II) or acetate are preferred salt.
Can by under condition well known in the art with acetyl halide or acetic anhydride, rough or purified amine (II) are converted into Linezolid.In a favourable method, described acetylize can be carried out under Schotten-Baumann reaction conditions or its change condition.Title " Schotten-Baumann reaction conditions " is illustrated under the existence of alkali and uses acetylation reagent.Typically, described acetylize is carried out in the two-phase solvent system that forms by water with the immiscible organic solvent of water.Alkali is present in aqueous phase, the acid neutralization that will generate during it will react, and raw material and product are retained in organic phase.With the limiting examples of the immiscible organic solvent of water be toluene, methylene dichloride and/or ether.
In the suitable change condition of Schotten-Baumann reaction conditions, with compound (II) in the situation that through or without separating the water soluble acid additive salt be converted into mineral acid or acetic acid, for example be converted into hydrochloride, hydrobromate, vitriol, nitrate, phosphoric acid salt and/or acetate.Described salt is dissolved in water-bearing media.This water-bearing media is single-phase, comprise water and may comprise solvent such as the alcohols that can dissolve each other with water, ester class etc., as long as polarity does not have to cause the change of following result: described water soluble acid additive salt is insoluble in described water-bearing media basically, and formed Linezolid also is insoluble in described water-bearing media basically.Preferably described water-bearing media (being preferably water) is cooled to as far as possible near 0 ℃; add acetylation reagent (being preferably diacetyl oxide); and start described acetylation by continuous adding alkali (preferred mineral alkali, for example sodium carbonate or sodium acetate).The Linezolid of expectation is precipitated out from moisture reaction mixture, because Linezolid is insoluble in described moisture reaction mixture.Under this change condition, avoided organic solvent fully.
The Linezolid that produces can be separated [I type (J.Med.Chem.39 (3) with any solid-state form as known in the art, 673 (1996)), II type (WO01/057035, US6,559,305), III type (WO2005/035530) and many other forms (WO2006/004922, US2006/0142283), amorphous form (WO2007/026369) and hydrated form (US2006/111350, EP20033960)], and/or can be converted into suitable acid salt.
The Linezolid for preparing by the inventive method can be formulated as pharmaceutical composition or is used for pharmaceutical composition.The pharmaceutical composition that is fit to can comprise Linezolid and at least a pharmaceutically acceptable vehicle.Described composition can be used as antiseptic-germicide in the bacterial various diseases for the treatment of by some type, described treatment is to be undertaken by the described composition that the patient to this treatment of needs uses significant quantity.Especially, they can be used for treating the dieletic foodstuff infection that is caused by gram positive bacterium.Typically, described significant quantity is 1mg～500mg every day, shows with the scale of Linezolid alkali.
Further describe the present invention with reference to following non-limiting example.
Embodiment 13-(3-fluoro-4-(morpholine-4-yl) phenyl)-2-oxo
Azoles alkane-5 (S)-ylmethyl) amine (II) hydrochloride
Add the compound (VII) [L=tolysulfonyl oxygen base] of 225mg (0.5mmol) in the 5ml reaction flask that is equipped with magnetic stirring bar, add subsequently the diformyl sodium amide of 96mg (1mmol) and the dimethyl formamide of 2.5ml.Container is immersed oil bath, and this oil bath is preheating to 85 ℃, and stirs the mixture under the outside temperature of 85 ℃ 1 hour.At temperature (30mbar, 60 ℃) the evaporation volatile matter that reduces, resistates is mixed with the ethyl acetate of 10ml and use the 10ml water extraction.With the organic matter layer evaporate to dryness (45 ℃ 25mbar), obtain white solid.
With this solid and 10ml methanol mixed, and the concentrated hydrochloric acid (5.00mmol) of interpolation 0.438ml.Reaction mixture is warmed up to 65 ℃ and stirred 2 hours at this temperature in oil bath.With the mixture reduction vaporization, then with the toluene coevaporation (60 ℃ 25mbar), obtain the white glass shape solid of 220mg.
Embodiment 23-(3-fluoro-4-(morpholine-4-yl) phenyl)-2-oxo
Azoles alkane-5 (S)-ylmethyl) amine (II)
To be equipped with blade mechanical stirrer and combination has the 250ml three neck round-bottomed flasks of the Ar import of temperature sensor to be placed under argon gas atmosphere, and adds diformyl sodium amide (5.6g) and compound (VII) [L=tolysulfonyl oxygen base] (20.8g).Add DMF (52ml) and reaction mixture is joined 85 ℃ and kept 2 hours.Carefully hydrochloric acid (98ml) is joined in reaction mixture, make internal temperature be no more than 96 ℃.With heterogeneous reaction mixture be heated to 85 ℃ and make the reaction proceed 2.5 hours.Reaction mixture is transferred in the 500ml round-bottomed flask and cooling in ice-water bath.Add methylene dichloride (150ml) in flask.With the mixture vigorous stirring and add water (100ml) solution of NaOH (54.0g), make internal temperature be no more than 20 ℃.Mixture is filtered.Transfer in the 500ml separating funnel filtrate and the separation of organic substances layer.Filter cake is discarded.Water layer dichloromethane extraction (2x50ml).The organic matter layer Na that merges
2SO
4(25g) drying, filter and concentrate (60 ℃, 50mbar), obtain product, be filemot crystalline solid (18.87g).
Embodiment 3
Add " amine " (0.49g) in the 25ml round-bottomed flask that is equipped with magnetic stirring bar, add subsequently entry (8.30ml).Stir heterogeneous mixture and add hydrochloric acid (0.12mL, 35%).Obtain the solution of homogeneous.Solution is cooled to 0 ℃ in ice-water bath.Add diacetyl oxide (0.31mL), add subsequently sodium bicarbonate (0.45g).There is immediately carbonic acid gas to emit, and observes the formation of white depositions.Throw out is leached and filter cake water (10ml) is washed.Collect filter cake and spend the night in 70 ℃ of dryings (100mbar).Separate and obtain pale solid Linezolid (0.26g).
Claims (13)
1. the compound 3-of preparation formula (II) (3-fluoro-4-(morpholine-4-yl) phenyl)-2-oxo
Azoles alkane-5 (S)-ylmethyl) method of amine and/or its acid salt,
The method comprises
A) make the compound of formula (VII)
Wherein L is leavings group,
Reacting metal salt with the diformyl acid amides of formula (VIII)
Me wherein
+Sodium or potassium cationic,
B) make the reaction product of step (a), it comprises formula (IXa) and/or the compound (IXb) of independent or form of mixtures,
The reaction of experience and acid.
2. according to claim 1 method, wherein said leavings group L is halo group or (C
1-C
4)-alkylsulfonyloxy or aryl-sulfonyl oxygen, aryl wherein comprises phenyl, it can be randomly by at least one C
1-C
4Alkyl, nitro, hydroxyl or C
1-C
4Alkoxyl group replaces.
3. according to claim 2 method, wherein said leavings group L is chloro group, bromo group, sulfonyloxy methyl oxygen base, phenyl sulfonyloxy, p-methylphenyl sulfonyloxy or p-nitrophenyl sulfonyloxy.
4. according to claim 1～3 method, wherein said acid is strong mineral acid or organic acid, is preferably hydrochloric acid, sulfuric acid, phosphoric acid or Hydrogen bromide, and hydrochloric acid more preferably.
5. according to claim 1～4 method, wherein the reaction between compound (VII) and compound (VIII) is carried out in inert solvent, described inert solvent is the aprotic solvent of polarity preferably, more preferably be selected from N, dinethylformamide, dimethyl sulfoxide (DMSO), acetonitrile, N-Methyl pyrrolidone, N,N-dimethylacetamide or acetone and their mixture.
6. according to claim 1～5 method, wherein the mol ratio between compound (VII) and compound (VIII) is 1:1 to 1:3, preferred approximately 1:1.1 is to about 1:1.7.
7. according to claim 1～6 method, wherein the temperature of the reaction between compound (VII) and compound (VIII) is 50～100 ℃, preferred 60～90 ℃.
8. according to claim 1～7 method, wherein separating compound (II) from reaction mixture.
9. according to claim 1～8 method, it also comprises by the compound that makes formula (II) and/or its acid salt and acetyl halide or diacetyl oxide and preferably is translated into the step of Linezolid in reaction under the existence of alkali and/or in comprising the solvent systems of water and/or organic solvent.
10. according to claim 9 method, the compound of its Chinese style (II) are the form of the water soluble acid additive salt of itself and mineral acid or acetic acid, and described solvent systems is water.
11. prepare the method for Linezolid, it is included in water-bearing media, under the existence of alkali, makes the water soluble acid additive salt of formula (II) compound
With acetyl halide or acetic anhydride.
12. method according to claim 11, the water soluble acid additive salt of wherein said formula (II) compound are the form of the acid salt of itself and mineral acid or acetic acid.
13. the compound of formula (IXa) and/or compound (IXb)
And/or its acid salt is for the preparation of the purposes of Linezolid or its acid salt.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2010/005209 WO2012019632A1 (en) | 2010-08-11 | 2010-08-11 | Process for making linezolid |
| EPPCT/EP2010/005209 | 2010-08-11 | ||
| PCT/EP2011/062097 WO2012019862A1 (en) | 2010-08-11 | 2011-07-14 | Process for making linezolid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103119040A true CN103119040A (en) | 2013-05-22 |
Family
ID=42829562
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010800692515A Pending CN103140487A (en) | 2010-08-11 | 2010-08-11 | Process for making linezolid |
| CN2011800459835A Pending CN103119040A (en) | 2010-08-11 | 2011-07-14 | Process for making linezolid |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010800692515A Pending CN103140487A (en) | 2010-08-11 | 2010-08-11 | Process for making linezolid |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP2603505A1 (en) |
| CN (2) | CN103140487A (en) |
| WO (2) | WO2012019632A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2917189B1 (en) | 2012-11-09 | 2016-08-17 | Synthon BV | Process for making linezolid |
| WO2015068121A1 (en) | 2013-11-06 | 2015-05-14 | Unimark Remedies Ltd. | Process for preparation of crystalline form i of linezolid and its compositions |
| CN104262280B (en) * | 2014-09-22 | 2016-07-20 | 山东华生化学股份有限公司 | A kind of preparation method of linezolid |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1130379A (en) * | 1993-09-09 | 1996-09-04 | 厄普约翰公司 | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| US5688792A (en) * | 1994-08-16 | 1997-11-18 | Pharmacia & Upjohn Company | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| WO2007116284A1 (en) * | 2006-04-07 | 2007-10-18 | Pfizer Products Inc. | Process for preparing linezolid |
| CN101128442A (en) * | 2005-02-24 | 2008-02-20 | 特瓦制药工业有限公司 | Processes for the preparation of linezolid intermediate |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5488188A (en) | 1994-09-29 | 1996-01-30 | Merrell Dow Pharmaceuticals Inc. | Process for the preparation of (E)-1-amino-2-(fluoromethylene)-4-(p-fluorophenyl)butane, novel processes for preparing an intermediate thereof, and novel intermediates thereof |
| US5599986A (en) | 1994-09-29 | 1997-02-04 | Hoechst Marion Roussel Inc. | Process for the preparation of alkali metal salts of diformylamide |
| DE69709718T2 (en) | 1996-04-11 | 2002-06-20 | Upjohn Co | METHOD FOR PRODUCING OXAZOLIDINONES |
| CN101353313A (en) | 1997-11-07 | 2009-01-28 | 法玛西雅厄普约翰美国公司 | Process to produce oxazolidinones |
| US6444813B2 (en) | 2000-02-02 | 2002-09-03 | Pharmacia & Upjohn Company | Linezolid-crystal form II |
| AR027261A1 (en) | 2000-02-02 | 2003-03-19 | Upjohn Co | LINEZOLID CRYSTAL FORM II |
| ATE442364T1 (en) | 2003-10-16 | 2009-09-15 | Symed Labs Ltd | CRYSTALLINE FORM OF LINEZOLIDE |
| ES2294494T3 (en) | 2004-04-19 | 2008-04-01 | Symed Labs Limited | A NEW PROCEDURE FOR THE PREPARATION OF LINEZOLID AND RELATED COMPOUNDS. |
| EP1658275A1 (en) | 2004-06-29 | 2006-05-24 | Teva Pharmaceutical Industries Ltd | Crystalline form iv of linezolid |
| US20060111350A1 (en) | 2004-06-29 | 2006-05-25 | Judith Aronhime | Solid forms of linezolid and processes for preparation thereof |
| EP1768967B1 (en) | 2004-07-20 | 2009-04-22 | Symed Labs Limited | Novel intermediates for linezolid and related compounds |
| EP1866295A2 (en) | 2005-02-24 | 2007-12-19 | Teva Pharmaceutical Industries Ltd | Processes for the preparation of linezolid intermediate |
| WO2007026369A1 (en) | 2005-08-29 | 2007-03-08 | Symed Labs Limited | A novel amorphous form of linezolid |
| EP1760400B1 (en) | 2005-09-06 | 2009-01-07 | Ernst Schenkel | Water cooled grate element |
| EP2033960A3 (en) | 2007-09-04 | 2009-04-29 | Dipharma Francis S.r.l. | Linezolid crystalline hydrate form and linezolid salts |
| WO2009063505A2 (en) | 2007-10-08 | 2009-05-22 | Usv Limited | Process for preparation of (s) (n-[[3-[3-fluoro-4-(4-morpholinyl) hen l -2-oxo-5-oxazolidin l methyl]acetamide |
| EP2163547A1 (en) * | 2008-09-16 | 2010-03-17 | Unión Químico Farmacéutica, S.A. (UQUIFA) | Process for the preparation of an oxazolidinone antibacterial agent and intermediates thereof |
-
2010
- 2010-08-11 CN CN2010800692515A patent/CN103140487A/en active Pending
- 2010-08-11 EP EP10747831.5A patent/EP2603505A1/en not_active Withdrawn
- 2010-08-11 WO PCT/EP2010/005209 patent/WO2012019632A1/en active Application Filing
-
2011
- 2011-07-14 CN CN2011800459835A patent/CN103119040A/en active Pending
- 2011-07-14 WO PCT/EP2011/062097 patent/WO2012019862A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1130379A (en) * | 1993-09-09 | 1996-09-04 | 厄普约翰公司 | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| US5688792A (en) * | 1994-08-16 | 1997-11-18 | Pharmacia & Upjohn Company | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| CN101128442A (en) * | 2005-02-24 | 2008-02-20 | 特瓦制药工业有限公司 | Processes for the preparation of linezolid intermediate |
| WO2007116284A1 (en) * | 2006-04-07 | 2007-10-18 | Pfizer Products Inc. | Process for preparing linezolid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103140487A (en) | 2013-06-05 |
| WO2012019632A1 (en) | 2012-02-16 |
| WO2012019862A1 (en) | 2012-02-16 |
| EP2603505A1 (en) | 2013-06-19 |
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Application publication date: 20130522 |