US20070149522A1 - Method for producing 5-chloro-n-({(5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide - Google Patents

Method for producing 5-chloro-n-({(5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide Download PDF

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Publication number
US20070149522A1
US20070149522A1 US10/538,342 US53834203A US2007149522A1 US 20070149522 A1 US20070149522 A1 US 20070149522A1 US 53834203 A US53834203 A US 53834203A US 2007149522 A1 US2007149522 A1 US 2007149522A1
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Prior art keywords
chlorothiophene
carboxamide
oxo
reacting
preparing
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Abandoned
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US10/538,342
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English (en)
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Christian Thomas
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Bayer Pharma AG
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Bayer Healthcare AG
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Assigned to BAYER HEALTHCARE, AG reassignment BAYER HEALTHCARE, AG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: THOMAS, CHRISTIAN R.
Publication of US20070149522A1 publication Critical patent/US20070149522A1/en
Assigned to BAYER SCHERING PHARMA AG reassignment BAYER SCHERING PHARMA AG MERGER (SEE DOCUMENT FOR DETAILS). Assignors: BAYER HEALTHCARE AG
Assigned to BAYER SCHERING PHARMA AG reassignment BAYER SCHERING PHARMA AG CORRECTION IN COVER SHEET PREVIOUSLY RECORDED Assignors: BAYER HEALTHCARE AG
Priority to US12/556,158 priority Critical patent/US8106192B2/en
Abandoned legal-status Critical Current

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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
    • C07D413/12—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 chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to a process for preparing 5-chloro-N-( ⁇ (5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl ⁇ methyl)-2-thiophene-carboxamide starting from 5-chlorothiophene-2-carbonyl chloride, (2S)-3-aminopropane-1,2-diol and 4-(4-aminophenyl)-3-morpholinone.
  • the compound of the formula (I) acts as an inhibitor of clotting factor Xa and may be used as an agent for the prophylaxis and/or treatment of thromboembolic disorders, especially myocardial infarction, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transient ischemic attacks, peripheral arterial occlusive diseases, pulmonary embolisms or deep venous thromboses.
  • myocardial infarction especially myocardial infarction, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transient ischemic attacks, peripheral arterial occlusive diseases, pulmonary embolisms or deep venous thromboses.
  • WO-A 01/47919 also describes a method for preparing the compound of the formula (I) starting from 2-[(2S)-2-oxiranylmethyl]-1H-isoindole-1,3(2H)-dione (II), 4-(4-aminophenyl)-3-morpholinone (III) and 5-chlorothiophene-2-carbonyl chloride (IV):
  • the epoxyphthalimide (II) is prepared by reacting (2S)-1-chloropropane-2,3-diol (V) with potassium carbonate via the stage of (S)-glycidol (VI) and subsequent Mitsunobu reaction with phthalimide:
  • the glycidol (VI), especially in relatively large amounts, is polymerization-sensitive and thus not storage-stable, additionally toxic and potentially carcinogenic.
  • the Mitsunobu reaction in the preparation of compound (II) is technically costly and inconvenient, one reason being that racemization occurs readily in relatively large batches.
  • Another reason is that the atom economy is extremely unsatisfactory, since triphenylphosphine oxide and diisopropyl azodicarboxylate hydrazide are generated in stoichiometric amounts as waste materials.
  • the nitrogen atom in the oxazolidinone ring of the target molecule (I) is introduced in phthalimide-protected form.
  • the phthalic acid radical as a protecting group has to be removed in the further course of the synthesis, which means an increase in the number of stages and additional waste.
  • the compound of the formula (I) can be prepared in improved yield in a shortened reaction sequence using storage-stable and less toxic starting materials, starting from 5-chlorothiophene-2-carbonyl chloride (IV), (2S)-3-aminopropane-1,2-diol hydrochloride (VII) and 4-(4-aminophenyl)-3-morpholinone (III).
  • IV 5-chlorothiophene-2-carbonyl chloride
  • VII (2S)-3-aminopropane-1,2-diol hydrochloride
  • III 4-(4-aminophenyl)-3-morpholinone
  • 5-chlorothiophene-2-carbonyl chloride (IV) is prepared from 5-chlorothiophene-2-carboxylic acid.
  • Compound (IV) may be prepared under the customary reaction conditions for the preparation of carbonyl chlorides from the corresponding carboxylic acids. Preference is given to the reaction of 5-chlorothiophene-2-carboxylic acid with thionyl chloride as the chlorinating reagent in toluene as the solvent.
  • the reaction (IV)+(VII) ⁇ (VIII) may be effected under the reaction conditions customary for the formation of amide bonds from the appropriate carbonyl chlorides and amines. Preference is given to a biphasic system composed of aqueous sodium hydrogencarbonate solution and 2-methyltetrahydrofuran as the organic solvent. (2S)-3-Aminopropane-1,2-diol is used in the form of the free base or in the form of the acid addition salt. Preference is given to the hydrochloride (VII) which crystallizes better than the free base and can therefore be handled readily. To increase the reaction yield, optionally either an excess of amine is used or an auxiliary base is added.
  • reaction is effected generally within a temperature range of from 0° C. to 40° C., preferably of from 5° C. to 30° C.
  • N—((S)-2,3-dihydroxypropyl)-5-chlorothiophene-2-carboxamide (VIII) is converted to N—((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX)
  • the reaction (VIII) ⁇ (IX) is carried out with from 1 to 5, preferably from 3 to 5, in particular 4, equivalents of a solution of hydrobromic acid in acetic acid, optionally in the presence of acetic anhydride.
  • the reaction temperature is between 20° C. and 80° C., preferably between 60 and 65° C.
  • the amount of methanol added may be varied over a wide range; preference is given to using from 40 to 80 mol, in particular from 50 to 60 mol, of methanol per mole of (VIII).
  • the solvents are distilled off, preferably under reduced pressure. The remaining distillation residue is optionally also neutralized before the filtration of the product.
  • N—((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX) is reacted with 4-(4-aminophenyl)-3-morpholinone (III) to give N— ⁇ (R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl ⁇ -5-chlorothiophene-2-carboxamide (X)
  • the solvent for the reaction (IX)+(III) ⁇ (X) may be varied widely; preference is given to toluene.
  • the reaction temperature is between 80° C. and 200° C.; preference is given to a range between 90° C. and 110° C.
  • the reaction is effected optionally in the presence of an auxiliary base, for example triethylamine, diisopropylethylamine or collidine; preference is given to using collidine.
  • the stoichiometry of the reaction and the reaction time are variable over a wide range; preference is given to a ratio of compound (IX) to compound (III) to collidine of 1.2 to 1.0 to 1.0 and a reaction time of from 4 to 8 hours, especially of from 5 to 6 hours.
  • N— ⁇ (R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl ⁇ -5-chlorothiophene-2-carboxamide (X) is reacted with phosgene or a phosgene equivalent to give 5-chloro-N-( ⁇ (5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl ⁇ methyl)-2-thiophene-carboxamide (I).
  • one or more equivalents of phosgene or phosgene equivalents are used in the presence of inert solvents or solvent mixtures.
  • Phosgene equivalents are, for example, phosgene replacements such as di- or triphosgene, or carbon monoxide equivalents, for example N,N-carbonylbisimidazole.
  • Preference is given to using from 1 to 2 equivalents, in particular from 1.1 to 1.3 equivalents, of N,N-carbonylbisimidazole in a solvent mixture of 1-methyl-2-pyrrolidone and toluene.
  • a clarifying filtration and/or a recrystallization optionally follows.
  • the reaction is effected generally within a temperature range of from 20° C. to 150° C., preferably of from 30° C. to 110° C., in particular of from 75° C. to 85° C.
  • the individual stages of the process according to the invention may be carried out at standard, elevated or at reduced pressure (for example of from 0.5 to 5 bar). In general, standard pressure is used.
  • the solvents are distilled off under reduced pressure at approx. 95 mbar.
  • the remaining suspension is admixed with 50 ml of 1-butanol and 350 ml of water.
  • the precipitated product is filtered off with suction, washed with water and dried.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pulmonology (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
US10/538,342 2003-01-07 2003-12-24 Method for producing 5-chloro-n-({(5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide Abandoned US20070149522A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/556,158 US8106192B2 (en) 2003-01-07 2009-09-09 Method for producing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10300111A DE10300111A1 (de) 2003-01-07 2003-01-07 Verfahren zur Herstellung von 5-Chlor-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid
DE10300111.5 2003-01-07
PCT/EP2003/014871 WO2004060887A1 (de) 2003-01-07 2003-12-24 Verfahren zur herstellung von 5-chlor-n-({5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid

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PCT/EP2003/014871 A-371-Of-International WO2004060887A1 (de) 2003-01-07 2003-12-24 Verfahren zur herstellung von 5-chlor-n-({5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid

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US12/556,158 Active 2024-06-25 US8106192B2 (en) 2003-01-07 2009-09-09 Method for producing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide

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US (2) US20070149522A1 (ja)
EP (1) EP1583761B1 (ja)
JP (1) JP4667044B2 (ja)
AU (1) AU2003296728A1 (ja)
CA (1) CA2512504C (ja)
DE (2) DE10300111A1 (ja)
ES (1) ES2360097T3 (ja)
WO (1) WO2004060887A1 (ja)

Cited By (25)

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Publication number Priority date Publication date Assignee Title
US20040242660A1 (en) * 2001-06-20 2004-12-02 Alexander Straub Substituted oxazolidinones for combinational therapy
US20070026065A1 (en) * 2004-12-24 2007-02-01 Bayer Healthcare Ag Solid, modified-release pharmaceutical dosage forms which can be administered orally
US20080090815A1 (en) * 1999-12-24 2008-04-17 Alexander Straub Substituted oxazolidinones and their use in the field of blood coagulation
US20080306070A1 (en) * 2005-10-04 2008-12-11 Bayer Healthcare Ag Combination Therapy Comprising Substituted Oxazolidinones for the Prevention and Treatment of Cerebral Circulatory Disorders
US20090004265A1 (en) * 2005-01-31 2009-01-01 Bayer Healthcare Ag Prevention and Treatment of Thromboembolic Disorders
US20090036504A1 (en) * 2005-09-23 2009-02-05 Bayer Healthcare Ag 2-Aminoethoxyacetic Acid Derivatives and Their Use
US20090048173A1 (en) * 2004-05-13 2009-02-19 Wolfgang Eisert Use Of Dipyridamole For Treatment Of Resistance To Platelet Inhibitors
US20100081807A1 (en) * 2003-01-07 2010-04-01 Bayer Healthcare Ag Method for producing 5-cloro-n-(methyl)-2-thiophenecarboxamide
US20100120718A1 (en) * 2006-11-02 2010-05-13 Bayer Schering Pharma Aktiengesellschaft Combination therapy of substituted oxazolidinones
US20100152189A1 (en) * 2005-10-04 2010-06-17 Bayer Healthcare Ag Novel polymorphous form and the amorphous form of 5-chloro-n-({ (5s)-2-oxo-3[4-(3-oxo-4-morpholinyl(-phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide
US7816355B1 (en) 2009-04-28 2010-10-19 Apotex Pharmachem Inc Processes for the preparation of rivaroxaban and intermediates thereof
WO2012051692A1 (en) 2010-10-18 2012-04-26 Apotex Pharmachem Inc. Processes for the preparation of rivaroxaban and intermediates thereof
CN102753537A (zh) * 2010-02-10 2012-10-24 桑多斯股份公司 制备利伐沙班的方法
CN102822167A (zh) * 2010-01-04 2012-12-12 埃南蒂亚有限公司 用于制备利伐沙班的方法及其中间体
WO2013152168A1 (en) 2012-04-06 2013-10-10 Indiana University Research And Technology Corporation Processes for preparing rivaroxaban
CN103351385A (zh) * 2013-06-28 2013-10-16 浙江燎原药业有限公司 一种利伐沙班中间体的制备方法
WO2013164833A1 (en) * 2012-05-02 2013-11-07 Symed Labs Limited Improved process for preparing rivaroxaban using novel intermediates
US8586082B2 (en) 2005-10-04 2013-11-19 Bayer Intellectual Property Gmbh Solid orally administerable pharmaceutical dosage forms with rapid active principle release
CN103524447A (zh) * 2013-10-24 2014-01-22 山东铂源药业有限公司 一种利伐沙班中间体4-（4-氨基苯基）-3-吗啉酮的合成方法
CN103724336A (zh) * 2013-12-24 2014-04-16 悦康药业集团有限公司 一种新型抗凝血药物的合成方法
CN103864771A (zh) * 2012-12-13 2014-06-18 北京京卫信康医药科技发展有限公司 一种利伐沙班的制备方法
WO2016045586A1 (zh) * 2014-09-26 2016-03-31 华北制药集团新药研究开发有限责任公司 苯并恶唑并恶嗪酮类化合物的制备方法及其中间体和晶型
US9402851B2 (en) 2003-11-27 2016-08-02 Bayer Intellectual Property Gmbh Process for the preparation of a solid, orally administrable pharmaceutical composition
US9556163B2 (en) 2011-05-06 2017-01-31 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Process for the preparation of a rivaroxaban and intermediates formed in said process
CN109280053A (zh) * 2018-10-11 2019-01-29 东南大学 利伐沙班噁唑烷杂质对照品及其制备方法

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004002044A1 (de) 2004-01-15 2005-08-04 Bayer Healthcare Ag Herstellverfahren
EP1571154A1 (en) * 2004-03-03 2005-09-07 Aventis Pharma Deutschland GmbH Beta-aminoacid-derivatives as factor Xa inhibitors
DE102005047564A1 (de) * 2005-10-04 2007-05-31 Bayer Healthcare Ag Amorphe Form von 5-Chlor-N-({(5S)2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl)-methyl)-2-thiophencarboxamid
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WO2009018807A1 (de) * 2007-08-06 2009-02-12 Schebo Biotech Ag Oxazolidinone als faktor xa- inhibitoren, verfahren zu ihrer herstellung und ihre verwendung in der therapie
US20100168111A1 (en) * 2008-12-31 2010-07-01 Apotex Pharmachem Inc. Polymorphic form of 5 chloro n {[(5s) 2 oxo 3 [4 (3 oxomorpholin 4 yl)phenyl]oxa-zolidin 5 yl]-methyl}thiophene 2 carboxamide
SI2459555T1 (sl) 2009-07-31 2022-03-31 Krka, D.D., Novo Mesto Postopek kristalizacije rivaroksabana
EP2404920A1 (en) 2010-07-06 2012-01-11 Sandoz AG Crystalline form of Rivaroxaban dihydrate
CN104693139B (zh) * 2011-01-07 2017-04-19 浙江九洲药业股份有限公司 一种合成利伐沙班中间体的新工艺
US9221771B2 (en) 2011-04-11 2015-12-29 Sandoz Ag Method for the preparation of substituted oxazolidinones
ES2395304B1 (es) 2011-05-20 2014-01-16 Interquim, S.A. Procedimiento de obtención de una tiofen-2-carboxamida.
US20140378682A1 (en) 2011-09-08 2014-12-25 Cadila Healthcare Limited Processes and intermediates for preparing rivaroxaban
HU230734B1 (hu) 2011-10-10 2017-12-28 EGIS Gyógyszergyár Nyrt Gyógyászati készítmény előállítására alkalmazható rivaroxaban kokristályok
CZ2012111A3 (cs) 2012-02-16 2013-08-28 Zentiva, K.S. Zpusob prípravy rivaroxabanu zalozený na vyuzití (S)-epichlorhydrinu
CZ2012114A3 (cs) 2012-02-17 2013-02-20 Zentiva, K.S. Zpusob prípravy rivaroxabanu zalozený na úspore 1,1´ -karbonyldiimidazolu
CN103288814B (zh) 2012-02-24 2016-07-06 国药集团国瑞药业有限公司 一种利伐沙班中间体的制备方法
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US10040786B2 (en) 2014-10-22 2018-08-07 Zaklady Farmaceutyczne Polphamra Sa Process for preparing a polymorph of rivaroxaban
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CN109481445A (zh) * 2018-12-19 2019-03-19 黄泳华 含有吗啉酮类化合物的组合物
GB202102575D0 (en) 2021-02-23 2021-04-07 Teva Pharmaceutical Industries Ltd Fixed-dose pharmaceutical compositions
EP4201933A1 (en) 2021-12-23 2023-06-28 Zaklady Farmaceutyczne Polpharma S.A. Crystallisation process for rivaroxaban

Citations (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2811555A (en) * 1955-05-02 1957-10-29 Eastman Kodak Co Reduction of 2-nitroso-5-diethylaminotoluene
US3279880A (en) * 1965-07-12 1966-10-18 Eastman Kodak Co Polyester textile material dyed with 1-hydroxy-4-n-p-(2'-pyrrolidonyl-1-) phenyl-amino anthraquinones
US4128654A (en) * 1978-02-10 1978-12-05 E. I. Du Pont De Nemours And Company 5-Halomethyl-3-phenyl-2-oxazolidinones
US4250318A (en) * 1977-08-26 1981-02-10 Delalande S.A. Novel 5-hydroxymethyl oxazolidinones, the method of preparing them and their application in therapeutics
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4500519A (en) * 1978-11-06 1985-02-19 Choay S.A. Mucopolysaccharides having biological properties, preparation and method of use
US4705779A (en) * 1983-03-11 1987-11-10 Biogal Gyogyszergyar Of Debrecen And Alkaloida Vegyeszeti Gyar Of Tiszavasvari Pharmaceutical compositions of anti-pancreatic inflammatory effect
US4765989A (en) * 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4948801A (en) * 1988-07-29 1990-08-14 E. I. Du Pont De Nemours And Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
US4977173A (en) * 1987-10-21 1990-12-11 E. I. Du Pont De Nemours And Company Aminomethyl oxooxazolidinyl ethenylbenzene derivatives useful as antibacterial agents
US5002937A (en) * 1988-07-05 1991-03-26 Boehringer Mannheim Gmbh Diphosphonic acid compounds and use for calcium metabolism disorders
US5254577A (en) * 1988-07-29 1993-10-19 The Du Pont Merck Pharmaceutical Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
US5349045A (en) * 1993-01-26 1994-09-20 United States Surgical Corporation Polymer derived from cyclic amide and medical devices manufactured therefrom
US5532255A (en) * 1993-05-01 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Adhesion receptor antagonists
US5561148A (en) * 1993-09-23 1996-10-01 Merck Patent Gesellschaft Mit Beshrankter Haftung Adhesion receptor antagonists III
US5654435A (en) * 1991-11-01 1997-08-05 Pharmacia & Upjohn Company Substituted arylphenyloxazolindinones
US5656571A (en) * 1995-04-05 1997-08-12 Deerpoint Industries, Inc. Polyolefinic adjuvants
US5688792A (en) * 1994-08-16 1997-11-18 Pharmacia & Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
US5792765A (en) * 1996-02-06 1998-08-11 Bayer Aktiengesellschaft Substituted oxazolidinones
US5827857A (en) * 1996-01-16 1998-10-27 Bayer Aktiengesellschaft Pyrido-fused thienyl- and furanyl-oxazolidinones
US5910504A (en) * 1995-02-03 1999-06-08 Pharmacia & Upjohn Hetero-aromatic ring substituted phenyloxazolidinone antimicrobials
US5922708A (en) * 1996-02-06 1999-07-13 Bayer Aktiengesellschaft Heteroaryl-oxazolidinones
US5935724A (en) * 1997-04-04 1999-08-10 Wilson Greatbatch Ltd. Electrochemical cell having multiplate electrodes with differing discharge rate regions
US5972947A (en) * 1995-07-07 1999-10-26 Roche Diagnostics Gmbh Oxazolidinone derivatives, processes for the production thereof and pharmaceutical agents containing these compounds
US5977373A (en) * 1997-07-11 1999-11-02 Pharmacia & Upjohn Company Thiadiazolyl and oxadiazolyl phenyl oxazolidinone antibacterial agents
US5998406A (en) * 1997-11-12 1999-12-07 Pharmacia & Upjohn Company Oxazolidinone derivatives and pharmaceutical compositions
US6069160A (en) * 1995-04-21 2000-05-30 Bayer Aktiengesellschaft Heteroatom-containing benzocyclopentane-oxazolidinones
US6218413B1 (en) * 1997-05-30 2001-04-17 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US6251869B1 (en) * 1998-05-18 2001-06-26 Pharmacia & Upjohn Company Enhancement of oxazolidinone antibacterial agents activity by using arginine derivatives
US6265178B1 (en) * 1997-12-05 2001-07-24 Pharmacia & Upjohn Company Assay for determining oxazolidinone antibiotics having minimum monoamine oxidase inhibitory activity
US6281210B1 (en) * 1999-12-14 2001-08-28 Pharmacia & Upjohn Company Benzoic acid esters of oxazolidinones having a hydroxyacetylpiperazine substituent
US6294201B1 (en) * 1997-10-12 2001-09-25 Bayer Aktiengesellschaft Osmotic medicament releasing system
US20010029351A1 (en) * 1998-04-16 2001-10-11 Robert Falotico Drug combinations and delivery devices for the prevention and treatment of vascular disease
US20010046987A1 (en) * 1999-12-21 2001-11-29 Hester Jackson B. Oxazolidinones having a sulfoximine functionality
US6458793B1 (en) * 1997-07-29 2002-10-01 Zeneca Limited Heterocyclic derivatives which inhibit factor Xa
US20030153610A1 (en) * 1999-12-24 2003-08-14 Alexander Straub Substituted oxazolidinones and their in the field of blood coagulation
US20030161882A1 (en) * 2002-02-01 2003-08-28 Waterman Kenneth C. Osmotic delivery system
US20040102450A1 (en) * 1998-01-27 2004-05-27 Aventis Pharmaceuticals Inc. Substituted oxoazaheterocyclyl compounds
US20040162427A1 (en) * 2001-03-07 2004-08-19 Ulrich Rosentreter Substituted 2,6-diamino-3,5-dicyano-4-aryl-pyridines and their use as adenosine receptor-selective ligands
US6805881B1 (en) * 1998-09-18 2004-10-19 Bayer Aktiengesellschaft Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same
US6818243B2 (en) * 1999-12-28 2004-11-16 Ajinomoto Co., Inc. Crystals of aspartame derivative
US20040242660A1 (en) * 2001-06-20 2004-12-02 Alexander Straub Substituted oxazolidinones for combinational therapy
US20050064006A1 (en) * 2001-10-24 2005-03-24 Bayer Aktiengesellschaft Stents
US20050182055A1 (en) * 2004-01-15 2005-08-18 Bayer Healthcare Ag Preparation process
US20050261502A1 (en) * 2001-03-05 2005-11-24 Ulrich Rosentreter Substituted 2-oxy-3,5-dicyano-4-aryl-6-aminopyridines and use thereof
US7034017B2 (en) * 2001-02-09 2006-04-25 Bayer Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US7045631B2 (en) * 2001-07-16 2006-05-16 Bayer Aktiengesellschaft Substituted 2-thio-3, 5-dicyano-4-phenyl-6-aminopyridines and their use as adenosine receptor-selective ligands
US20060154969A1 (en) * 2001-03-07 2006-07-13 Ulrich Rosentreter Adenosine receptor selective modulators
US7078417B2 (en) * 2001-03-30 2006-07-18 Bayer Aktiengesellschaft Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines with adenosine receptor-binding activity and their use as cardiovascular preparations
US7109218B2 (en) * 2001-12-11 2006-09-19 Bayer Healthcare Ag Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines and the use of the same
US7129255B2 (en) * 2001-03-30 2006-10-31 Bayer Aktiengesellschaft Substituted 2-carba-3,5-dicyano-4-aryl-6-aminopyridines and the use of the same as selective ligands of the adenosine receptor
US20070026065A1 (en) * 2004-12-24 2007-02-01 Bayer Healthcare Ag Solid, modified-release pharmaceutical dosage forms which can be administered orally
US20080026057A1 (en) * 2003-11-27 2008-01-31 Bayer Healthcare Ag Process for the Preparation of a Solid, Orally Administrable Pharmaceutical Composition

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4259201A (en) * 1979-11-09 1981-03-31 The Procter & Gamble Company Detergent composition containing organic peracids buffered for optimum performance
NZ206600A (en) 1983-05-11 1987-01-23 Alza Corp Osmotic drug delivery device
ES8506659A1 (es) 1983-06-07 1985-08-01 Du Pont Un procedimiento para la preparacion de nuevos derivados del amino-metil-oxooxazolidinil-benzeno.
DE3884563T2 (de) 1987-10-21 1994-02-17 Du Pont Merck Pharma Aminomethyl-oxo-oxazolidinyl-ethenylbenzen-Derivate, nützlich als antibakterielles Mittel.
US5139788A (en) * 1989-10-17 1992-08-18 Ecolab Inc. Noncontaminating antimicrobial composition
US5264229A (en) * 1992-04-20 1993-11-23 Degussa Corporation Shelf life extension for commercially processed poultry/fowl and seafood products using a specialized hydrogen peroxide
SK283420B6 (sk) 1992-05-08 2003-07-01 Pharmacia & Upjohn Company Antimikrobiálne oxazolidinóny obsahujúce substituované diazínové skupiny
JP3255499B2 (ja) * 1993-06-16 2002-02-12 花王株式会社 新規スルホナート、その製造法及びこれを含有する漂白剤組成物
US5362899A (en) * 1993-09-09 1994-11-08 Affymax Technologies, N.V. Chiral synthesis of alpha-aminophosponic acids
US5374369A (en) * 1993-10-14 1994-12-20 Lever Brothers Company, Division Of Conopco, Inc. Silver anti-tarnishing detergent composition
US5683977A (en) * 1995-03-06 1997-11-04 Lever Brothers Company, Division Of Conopco, Inc. Dry cleaning system using densified carbon dioxide and a surfactant adjunct
US5698506A (en) * 1995-05-19 1997-12-16 Lever Brothers Company, Division Of Conopco, Inc. Automatic dishwashing compositions containing aluminum salts
BR9610474A (pt) 1995-09-01 1999-03-02 Upjohn Co Feniloxazolidinonas tendo uma ligação c-c a anéis heterocíclicos com 4-8 membros
ES2214546T3 (es) 1995-09-15 2004-09-16 PHARMACIA & UPJOHN COMPANY N-oxidos de aminoariloxazolidinona.
US6310025B1 (en) * 1996-03-04 2001-10-30 The Procter & Gamble Company Laundry pretreatment process and bleaching compositions
US5968885A (en) * 1996-04-22 1999-10-19 Procter & Gamble Co. Bleaching compositions
MA25183A1 (fr) * 1996-05-17 2001-07-02 Arthur Jacques Kami Christiaan Compositions detergentes
GB9614238D0 (en) 1996-07-06 1996-09-04 Zeneca Ltd Chemical compounds
PT930076E (pt) 1996-07-15 2005-01-31 Sankyo Co Composicoes medicinais
US6273913B1 (en) 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
DE19730847A1 (de) 1997-07-18 1999-01-28 Bayer Ag Tricyclisch substituierte Oxazolidinone
US6444634B1 (en) * 1997-09-11 2002-09-03 The Procter & Gamble Company Bleaching compositions
DE19755268A1 (de) 1997-12-12 1999-06-17 Merck Patent Gmbh Benzamidinderivate
DE19802239A1 (de) 1998-01-22 1999-07-29 Bayer Ag Neue mit Bicyclen substituierte Oxazolidinone
JP2002501059A (ja) 1998-01-23 2002-01-15 ファルマシア・アンド・アップジョン・カンパニー オキサゾリジノンの組合せライブラリー、組成物および調製方法
DE19805117A1 (de) 1998-02-09 1999-08-12 Bayer Ag Neue Oxazolidinone mit azolhaltigen Tricyclen
US6346279B1 (en) * 1998-12-14 2002-02-12 Virox Technologies, Inc. Hydrogen peroxide disinfectant with increased activity
BR0108327A (pt) * 2000-02-15 2003-03-18 Procter & Gamble Método para a preparação de produtos têxteis em uma etapa
US6830591B1 (en) * 2000-02-15 2004-12-14 The Procter & Gamble Company Method for the use of hydrophobic bleaching systems in textile preparation
JP4562341B2 (ja) * 2000-02-15 2010-10-13 ストライク、インベストメンツ、リミテッド、ライアビリティ、カンパニー 疎水性漂白剤の使用による織物へのパーマネントプレス加工適用方法
DE10300111A1 (de) 2003-01-07 2004-07-15 Bayer Healthcare Ag Verfahren zur Herstellung von 5-Chlor-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid
EP1685841A1 (en) 2005-01-31 2006-08-02 Bayer Health Care Aktiengesellschaft Prevention and treatment of thromboembolic disorders
US7754670B2 (en) * 2005-07-06 2010-07-13 Ecolab Inc. Surfactant peroxycarboxylic acid compositions
DE102005045518A1 (de) 2005-09-23 2007-03-29 Bayer Healthcare Ag 2-Aminoethoxyessigsäure-Derivate und ihre Verwendung
DE102005047561A1 (de) 2005-10-04 2007-04-05 Bayer Healthcare Ag Feste, oral applizierbare pharmazeutische Darreichungsformen mit schneller Wirkstofffreisetzung
EP1934208B1 (de) 2005-10-04 2011-03-23 Bayer Schering Pharma Aktiengesellschaft Neue polymorphe form von 5-chlor-n-({ ( 5s )-2-0x0-3-[4-( 3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl} -methyl)-2-thiophencarboxamid
DE102005047558A1 (de) 2005-10-04 2008-02-07 Bayer Healthcare Ag Kombinationstherapie substituierter Oxazolidinone zur Prophylaxe und Behandlung von cerebralen Durchblutungsstörungen
DE102005048824A1 (de) 2005-10-10 2007-04-12 Bayer Healthcare Ag Behandlung und Prophylaxe von Mikroangiopathien

Patent Citations (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2811555A (en) * 1955-05-02 1957-10-29 Eastman Kodak Co Reduction of 2-nitroso-5-diethylaminotoluene
US3279880A (en) * 1965-07-12 1966-10-18 Eastman Kodak Co Polyester textile material dyed with 1-hydroxy-4-n-p-(2'-pyrrolidonyl-1-) phenyl-amino anthraquinones
US4250318A (en) * 1977-08-26 1981-02-10 Delalande S.A. Novel 5-hydroxymethyl oxazolidinones, the method of preparing them and their application in therapeutics
US4128654A (en) * 1978-02-10 1978-12-05 E. I. Du Pont De Nemours And Company 5-Halomethyl-3-phenyl-2-oxazolidinones
US4500519A (en) * 1978-11-06 1985-02-19 Choay S.A. Mucopolysaccharides having biological properties, preparation and method of use
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4705779A (en) * 1983-03-11 1987-11-10 Biogal Gyogyszergyar Of Debrecen And Alkaloida Vegyeszeti Gyar Of Tiszavasvari Pharmaceutical compositions of anti-pancreatic inflammatory effect
US4765989A (en) * 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4977173A (en) * 1987-10-21 1990-12-11 E. I. Du Pont De Nemours And Company Aminomethyl oxooxazolidinyl ethenylbenzene derivatives useful as antibacterial agents
US5002937A (en) * 1988-07-05 1991-03-26 Boehringer Mannheim Gmbh Diphosphonic acid compounds and use for calcium metabolism disorders
US4948801A (en) * 1988-07-29 1990-08-14 E. I. Du Pont De Nemours And Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
US5254577A (en) * 1988-07-29 1993-10-19 The Du Pont Merck Pharmaceutical Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
US5801246A (en) * 1991-11-01 1998-09-01 Pharmacia & Upjohn Company Substituted heteroarylphenyloxazolidinones
US5654435A (en) * 1991-11-01 1997-08-05 Pharmacia & Upjohn Company Substituted arylphenyloxazolindinones
US5654428A (en) * 1991-11-01 1997-08-05 Pharmacia & Upjohn Company Substituted heteroarylphenyloxazolidinones
US5756732A (en) * 1991-11-01 1998-05-26 Pharmacia & Upjohn Company Substituted heteroarylphenyloxazolidinones
US5929248A (en) * 1991-11-01 1999-07-27 Pharmacia & Upjohn Company Substituted heteroarylphenyloxazolidinones
US5349045A (en) * 1993-01-26 1994-09-20 United States Surgical Corporation Polymer derived from cyclic amide and medical devices manufactured therefrom
US5532255A (en) * 1993-05-01 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Adhesion receptor antagonists
US5561148A (en) * 1993-09-23 1996-10-01 Merck Patent Gesellschaft Mit Beshrankter Haftung Adhesion receptor antagonists III
US5688792A (en) * 1994-08-16 1997-11-18 Pharmacia & Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
US5910504A (en) * 1995-02-03 1999-06-08 Pharmacia & Upjohn Hetero-aromatic ring substituted phenyloxazolidinone antimicrobials
US5656571A (en) * 1995-04-05 1997-08-12 Deerpoint Industries, Inc. Polyolefinic adjuvants
US6069160A (en) * 1995-04-21 2000-05-30 Bayer Aktiengesellschaft Heteroatom-containing benzocyclopentane-oxazolidinones
US5972947A (en) * 1995-07-07 1999-10-26 Roche Diagnostics Gmbh Oxazolidinone derivatives, processes for the production thereof and pharmaceutical agents containing these compounds
US5827857A (en) * 1996-01-16 1998-10-27 Bayer Aktiengesellschaft Pyrido-fused thienyl- and furanyl-oxazolidinones
US5922708A (en) * 1996-02-06 1999-07-13 Bayer Aktiengesellschaft Heteroaryl-oxazolidinones
US5792765A (en) * 1996-02-06 1998-08-11 Bayer Aktiengesellschaft Substituted oxazolidinones
US5935724A (en) * 1997-04-04 1999-08-10 Wilson Greatbatch Ltd. Electrochemical cell having multiplate electrodes with differing discharge rate regions
US6218413B1 (en) * 1997-05-30 2001-04-17 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US5977373A (en) * 1997-07-11 1999-11-02 Pharmacia & Upjohn Company Thiadiazolyl and oxadiazolyl phenyl oxazolidinone antibacterial agents
US6458793B1 (en) * 1997-07-29 2002-10-01 Zeneca Limited Heterocyclic derivatives which inhibit factor Xa
US6294201B1 (en) * 1997-10-12 2001-09-25 Bayer Aktiengesellschaft Osmotic medicament releasing system
US5998406A (en) * 1997-11-12 1999-12-07 Pharmacia & Upjohn Company Oxazolidinone derivatives and pharmaceutical compositions
US6265178B1 (en) * 1997-12-05 2001-07-24 Pharmacia & Upjohn Company Assay for determining oxazolidinone antibiotics having minimum monoamine oxidase inhibitory activity
US20040102450A1 (en) * 1998-01-27 2004-05-27 Aventis Pharmaceuticals Inc. Substituted oxoazaheterocyclyl compounds
US20010029351A1 (en) * 1998-04-16 2001-10-11 Robert Falotico Drug combinations and delivery devices for the prevention and treatment of vascular disease
US6251869B1 (en) * 1998-05-18 2001-06-26 Pharmacia & Upjohn Company Enhancement of oxazolidinone antibacterial agents activity by using arginine derivatives
US6805881B1 (en) * 1998-09-18 2004-10-19 Bayer Aktiengesellschaft Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same
US6281210B1 (en) * 1999-12-14 2001-08-28 Pharmacia & Upjohn Company Benzoic acid esters of oxazolidinones having a hydroxyacetylpiperazine substituent
US20010046987A1 (en) * 1999-12-21 2001-11-29 Hester Jackson B. Oxazolidinones having a sulfoximine functionality
US20080200674A1 (en) * 1999-12-24 2008-08-21 Bayer Healthcare Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US20080090815A1 (en) * 1999-12-24 2008-04-17 Alexander Straub Substituted oxazolidinones and their use in the field of blood coagulation
US7157456B2 (en) * 1999-12-24 2007-01-02 Bayer Healthcare Ag Substituted oxazolidinones and their use in the field of blood coagulation
US20060258724A1 (en) * 1999-12-24 2006-11-16 Alexander Straub Substituted Oxazolidinones and Their Use in the Field of Blood Coagulation
US20030153610A1 (en) * 1999-12-24 2003-08-14 Alexander Straub Substituted oxazolidinones and their in the field of blood coagulation
US6818243B2 (en) * 1999-12-28 2004-11-16 Ajinomoto Co., Inc. Crystals of aspartame derivative
US7034017B2 (en) * 2001-02-09 2006-04-25 Bayer Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US20050261502A1 (en) * 2001-03-05 2005-11-24 Ulrich Rosentreter Substituted 2-oxy-3,5-dicyano-4-aryl-6-aminopyridines and use thereof
US20040162427A1 (en) * 2001-03-07 2004-08-19 Ulrich Rosentreter Substituted 2,6-diamino-3,5-dicyano-4-aryl-pyridines and their use as adenosine receptor-selective ligands
US20060154969A1 (en) * 2001-03-07 2006-07-13 Ulrich Rosentreter Adenosine receptor selective modulators
US7129255B2 (en) * 2001-03-30 2006-10-31 Bayer Aktiengesellschaft Substituted 2-carba-3,5-dicyano-4-aryl-6-aminopyridines and the use of the same as selective ligands of the adenosine receptor
US7078417B2 (en) * 2001-03-30 2006-07-18 Bayer Aktiengesellschaft Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines with adenosine receptor-binding activity and their use as cardiovascular preparations
US20040242660A1 (en) * 2001-06-20 2004-12-02 Alexander Straub Substituted oxazolidinones for combinational therapy
US7045631B2 (en) * 2001-07-16 2006-05-16 Bayer Aktiengesellschaft Substituted 2-thio-3, 5-dicyano-4-phenyl-6-aminopyridines and their use as adenosine receptor-selective ligands
US20050064006A1 (en) * 2001-10-24 2005-03-24 Bayer Aktiengesellschaft Stents
US7109218B2 (en) * 2001-12-11 2006-09-19 Bayer Healthcare Ag Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines and the use of the same
US20030161882A1 (en) * 2002-02-01 2003-08-28 Waterman Kenneth C. Osmotic delivery system
US20080026057A1 (en) * 2003-11-27 2008-01-31 Bayer Healthcare Ag Process for the Preparation of a Solid, Orally Administrable Pharmaceutical Composition
US20050182055A1 (en) * 2004-01-15 2005-08-18 Bayer Healthcare Ag Preparation process
US7351823B2 (en) * 2004-01-15 2008-04-01 Bayer Healthcare Ag Preparation process
US20070026065A1 (en) * 2004-12-24 2007-02-01 Bayer Healthcare Ag Solid, modified-release pharmaceutical dosage forms which can be administered orally

Cited By (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8530505B2 (en) 1999-12-24 2013-09-10 Bayer Intellectual Property Gmbh Substituted oxazolidinones and their use in the field of blood coagulation
US7585860B2 (en) 1999-12-24 2009-09-08 Bayer Schering Pharma Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US20080090815A1 (en) * 1999-12-24 2008-04-17 Alexander Straub Substituted oxazolidinones and their use in the field of blood coagulation
US20080200674A1 (en) * 1999-12-24 2008-08-21 Bayer Healthcare Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US20100137274A1 (en) * 1999-12-24 2010-06-03 Bayer Schering Pharma Ag Substituted oxazolidinones and their use in the field of blood coagulation
US8822458B2 (en) 1999-12-24 2014-09-02 Bayer Intellectual Property Gmbh Substituted oxazolidinones and their use in the field of blood coagulation
US8129378B2 (en) 1999-12-24 2012-03-06 Bayer Pharma Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US7576111B2 (en) 1999-12-24 2009-08-18 Bayer Schering Pharma Ag Substituted oxazolidinones and their use in the field of blood coagulation
US7592339B2 (en) 1999-12-24 2009-09-22 Bayer Schering Pharma Aktiengesellschaft Substituted oxazolidinones and their use in the field of blood coagulation
US7767702B2 (en) 2001-06-20 2010-08-03 Bayer Schering Pharma Aktiengesellschaft Substituted oxazolidinones for combinational therapy
US20100267685A1 (en) * 2001-06-20 2010-10-21 Bayer Schering Pharma Aktiengesellschaft Methods For The Prophylaxis And/or Treatment Of Thromboembolic Disorders By Combination Therapy With Substituted Oxazolidinones
US20040242660A1 (en) * 2001-06-20 2004-12-02 Alexander Straub Substituted oxazolidinones for combinational therapy
US20100081807A1 (en) * 2003-01-07 2010-04-01 Bayer Healthcare Ag Method for producing 5-cloro-n-(methyl)-2-thiophenecarboxamide
US8106192B2 (en) 2003-01-07 2012-01-31 Bayer Pharma Aktiengesellschaft Method for producing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide
US9415053B2 (en) 2003-11-27 2016-08-16 Bayer Intellectual Property Gmbh Solid, orally administrable pharmaceutical composition
US9402851B2 (en) 2003-11-27 2016-08-02 Bayer Intellectual Property Gmbh Process for the preparation of a solid, orally administrable pharmaceutical composition
US20090048173A1 (en) * 2004-05-13 2009-02-19 Wolfgang Eisert Use Of Dipyridamole For Treatment Of Resistance To Platelet Inhibitors
US20070026065A1 (en) * 2004-12-24 2007-02-01 Bayer Healthcare Ag Solid, modified-release pharmaceutical dosage forms which can be administered orally
US9539218B2 (en) 2005-01-31 2017-01-10 Bayer Intellectual Property Gmbh Prevention and treatment of thromboembolic disorders
US20090004265A1 (en) * 2005-01-31 2009-01-01 Bayer Healthcare Ag Prevention and Treatment of Thromboembolic Disorders
US20090036504A1 (en) * 2005-09-23 2009-02-05 Bayer Healthcare Ag 2-Aminoethoxyacetic Acid Derivatives and Their Use
US7932278B2 (en) 2005-09-23 2011-04-26 Bayer Schering Pharma Aktiengesellschaft 2-aminoethoxyacetic acid derivatives and their use
US20100152189A1 (en) * 2005-10-04 2010-06-17 Bayer Healthcare Ag Novel polymorphous form and the amorphous form of 5-chloro-n-({ (5s)-2-oxo-3[4-(3-oxo-4-morpholinyl(-phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide
US20080306070A1 (en) * 2005-10-04 2008-12-11 Bayer Healthcare Ag Combination Therapy Comprising Substituted Oxazolidinones for the Prevention and Treatment of Cerebral Circulatory Disorders
US8586082B2 (en) 2005-10-04 2013-11-19 Bayer Intellectual Property Gmbh Solid orally administerable pharmaceutical dosage forms with rapid active principle release
US8188270B2 (en) 2005-10-04 2012-05-29 Bayer Schering Pharma Aktiengesellschaft Polymorphous form of 5-chloro-N-({(5S)-2-oxo-3[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide
US20100120718A1 (en) * 2006-11-02 2010-05-13 Bayer Schering Pharma Aktiengesellschaft Combination therapy of substituted oxazolidinones
US8101609B2 (en) 2009-04-28 2012-01-24 Apotex Pharmachem Inc. Processes for the preparation of rivaroxaban and intermediates thereof
US7816355B1 (en) 2009-04-28 2010-10-19 Apotex Pharmachem Inc Processes for the preparation of rivaroxaban and intermediates thereof
US20100273790A1 (en) * 2009-04-28 2010-10-28 Apotex Pharmachem Inc. Processes for the preparation of rivaroxaban and intermediates thereof
US20100273798A1 (en) * 2009-04-28 2010-10-28 Apotex Pharmachem Inc. Processes for the preparation of rivaroxaban and intermediates thereof
CN102822167A (zh) * 2010-01-04 2012-12-12 埃南蒂亚有限公司 用于制备利伐沙班的方法及其中间体
CN102753537A (zh) * 2010-02-10 2012-10-24 桑多斯股份公司 制备利伐沙班的方法
WO2012051692A1 (en) 2010-10-18 2012-04-26 Apotex Pharmachem Inc. Processes for the preparation of rivaroxaban and intermediates thereof
US9556163B2 (en) 2011-05-06 2017-01-31 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Process for the preparation of a rivaroxaban and intermediates formed in said process
WO2013152168A1 (en) 2012-04-06 2013-10-10 Indiana University Research And Technology Corporation Processes for preparing rivaroxaban
CN104487436A (zh) * 2012-05-02 2015-04-01 信谊实验室有限公司 使用新型中间产物制备利伐沙班的改良方法
US9376427B2 (en) 2012-05-02 2016-06-28 Symed Labs Limited Process for preparing rivaroxaban using intermediates
WO2013164833A1 (en) * 2012-05-02 2013-11-07 Symed Labs Limited Improved process for preparing rivaroxaban using novel intermediates
CN104487436B (zh) * 2012-05-02 2017-05-24 信谊实验室有限公司 使用中间产物制备利伐沙班的改良方法
CN103864771A (zh) * 2012-12-13 2014-06-18 北京京卫信康医药科技发展有限公司 一种利伐沙班的制备方法
CN103351385A (zh) * 2013-06-28 2013-10-16 浙江燎原药业有限公司 一种利伐沙班中间体的制备方法
CN103524447A (zh) * 2013-10-24 2014-01-22 山东铂源药业有限公司 一种利伐沙班中间体4-（4-氨基苯基）-3-吗啉酮的合成方法
CN103724336A (zh) * 2013-12-24 2014-04-16 悦康药业集团有限公司 一种新型抗凝血药物的合成方法
WO2016045586A1 (zh) * 2014-09-26 2016-03-31 华北制药集团新药研究开发有限责任公司 苯并恶唑并恶嗪酮类化合物的制备方法及其中间体和晶型
KR20170055551A (ko) * 2014-09-26 2017-05-19 놀스 차이나 파머수티컬 뉴 드럭 알앤디 씨오., 엘티디 벤조옥사졸옥사진 케톤계 화합물의 제조방법 및 이의 중간체와 결정형
US10106557B2 (en) 2014-09-26 2018-10-23 North China Pharmaceutical New Drug R&D Co., Ltd. Preparation method for benzoxazoleoxazine ketone compound and intermediate and crystal form thereof
KR102485412B1 (ko) 2014-09-26 2023-01-05 놀스 차이나 파머수티컬 뉴 드럭 알앤디 씨오., 엘티디 벤조옥사졸옥사진 케톤계 화합물의 제조방법 및 이의 중간체와 결정형
CN109280053A (zh) * 2018-10-11 2019-01-29 东南大学 利伐沙班噁唑烷杂质对照品及其制备方法

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