cas 446292-07-5, 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-

Articles about 446292-07-5Total 32 be found

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Preparation method of rivaroxaban intermediate
The invention provides a preparation method of a rivaroxaban intermediate. The preparation method comprises: (1) carrying out a reaction on a compound A and a compound B in an alcohol or an alcohol aqueous solution to obtain a compound C; and (2) reacting the compound C with N,N'-carbonyldiimidazole in a reaction solvent selected from acetonitrile or butyronitrile to obtain a reaction solution containing a compound D, and performing cooling crystallization to obtain a compound D.
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(2020/05/02)

Oxazolidinone derivative and preparation method thereof
The invention relates to a preparation method of an oxazolidinone compound impurity 5-chloro-nitrogen-[[(5S)-2-oxo-3-[4-acetamidophenyl]-1, 3- oxazolidine-5-yl]methyl] thiophene-2-methanamide (formulaI) in rivaroxaban. According to a preparation method, 4-aminoacetanilide (formula II) and (S)-N-epoxypropyl phthalimide (formula III) are used as raw materials, and the impurity is obtained through ring opening coupling, ring closing, protecting group removal and condensation reaction. The compound represented by formula I can be applied to rivaroxaban bulk drug quality control and qualitative and quantitative research and detection of impurities.
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Paragraph 0018

(2020/03/05)

Preparation method of 4-(4-aminophenyl)morpholin-3-one derivative
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a 4-(4-aminophenyl)morpholin-3-one derivative. The preparation method comprises the following steps: reacting 4-(4-aminophenyl)morpholin-3-one serving as a raw material with a first reactant to obtain a first intermediate product; and in a first solvent and with the first intermediate product as a raw material, adding (S)-N-(2,3-epoxypropyl)phthalimide in batches in multiple times, and carrying out a reaction at a first temperature to obtain a target product, namely the 4-(4-aminophenyl)morpholin-3-one derivative. According to the method, the solvent is optimized, so a conversion rate is improved; the mode of feeding in batches in multiple times and a post-treatment mode (concentration, crystallization, filtration, drying and the like) are used, so the target product with high yield is obtained; and the target product is the 4-(4-aminophenyl)morpholin-3-one derivative, and the method has important significance in effectively controlling the quality of rivaroxaban.
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Paragraph 0042; 0045

(2020/09/30)

Preparation method of rivaroxaban intermediate
The invention belongs to the field of drug synthesis, and relates to a preparation method of a rivaroxaban intermediate. The rivaroxaban intermediate is further used for preparing rivaroxaban, and thesynthesis method has the advantages of simple operation, high product yield and high purity, and can meet the requirements of industrial production.
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Paragraph 0023; 0024

(2020/04/17)

Preparation method and use of rivaroxaban intermediate
The present invention relates to a preparation method of a rivaroxaban intermediate I. The method provided by the invention has the advantages of greatly shortening the reaction time, easy preparationby scale, simple operation, good stability, high purity, low environmental pollution and suitable for industrial production.
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Paragraph 0020; 0021; 0022; 0023; 0024-0027

(2019/04/26)

A method for preparing [...]
The invention discloses a preparation method of rivaroxaban, which includes the steps of 1) performing a one-step cyclization reaction to an intermediate, N-(4-aminophenyl)-2-(2-haloethyoxyl)acetamide, to prepare a key intermediate, 4-(4-aminophenyl)-3-morpholinone, of the rivaroxaban; 2) performing a series reactions comprising ring opening with an epoxide, a substitution reaction, a ring formation reaction and the like to the 4-(4-aminophenyl)-3-morpholinone to obtain an intermediate, 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-one; and 3) performing a substitution reaction to the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-one with 2-chloroformyl-5-chlorothiophene to obtain the rivaroxaban. The whole preparation process is short in route, is high in yield, is less in pollution, can avoid usage of expensive metal palladium for nitroreduction and is suitable for industrial production.
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(2018/05/16)

AN IMPROVED PROCESS FOR THE PREPARATION OF RIVAROXABAN INVOLVING NOVEL INTERMEDIATE
The present invention relates to the novel key intermediate, 4-{4-[(5S)-(Aminomethyl)-2- oxo-l,3-oxazolidin-3-yl]-phenyl}-morpholin-3-one perchlorate, in the synthesis of rivaroxaban. The invention further relates to the crystalline form of novel intermediate, the process to prepare the novel intermediate and method of preparing rivaroxaban using this novel intermediate. The invention provides an improved and efficient process for preparation of Rivaroxaban.
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Page/Page column 12

(2018/07/31)

Synthesis method of [...] process impurities (by machine translation)
The invention discloses a method for synthesizing [...] process impurities, which belongs to the technical field of chemical pharmacy, to 4 - (4 - aminophenyl) morpholine - 3 - one (2), (S)- N - glycidol phthalimide (3) generating 2 - [(2 R) - 2 - hydroxy - 3 - [[4 - (3 - oxo - 4 - morpholinyl) phenyl] amino] propyl] - 1 H - isoindole - 1, 3 (2 H) - dione (4); compound (4) s hydrolysis, into salt generating (S)- 4 - (4 - ((3 - amino - 2 - hydroxy-propyl) aminophenyl) morpholine - 3 - one hydrochloride (5); compound (5) with 5 - chloro - 2 - acyl chloride thiophene (6) generating (S)- 5 - chloro - N - (3 - (5 - [...] - 2 - formyl amino) - 2 - hydroxy-propyl) - N - (4 - (3 - oxo-morpholino) phenyl) thiophene - 2 - carboxamide (1), to synthesize high-purity of [...][...] impurity can be used as a benefit finished product detection and analysis of the impurities in the standard, thereby improving the [...] finished product detection and analysis of the impurity and the accurate localization of the qualitative, conducive to strengthening the impurity of the control, and then [...] quality of the finished product, the present invention provides a method of cheap raw material, the operation is simple, the yield of product is 70% ± 5%, HPLC purity ≥ 98%. (by machine translation)
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Paragraph 0014; 0015; 0016; 0017

(2018/07/07)

A process for preparing 4 - (4 - aminophenyl) - 3 - morpholinon method (by machine translation)
The invention discloses a process for preparing 4 - (4 - aminophenyl) - 3 - morpholone (type IV) method, which belongs to the field of chemical synthesis. The specific method comprises: intermediate N - (4 - aminophenyl) - 2 - (2 - halo ethoxy) acetamide (type III) by the one-step cyclization reaction systems benefit cuts down Sha Ban key intermediate 4 - (4 - aminophenyl) - 3 - morpholone (type IV), wherein X represents halogen. The prepared 4 - (4 - aminophenyl) - 3 - morpholinon purity is good, the reaction yield is high, can be as high as 87% of the left and right, and the preparation process avoids the use of expensive metal palladium on nitro reduction, the operation is simple, and is suitable for industrial production. (by machine translation)
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(2017/08/24)

Synthesis of 4 - {4 - [(5 S) - 5 - (aminomethyl) - 2 - oxo - 1, 3 - oxazolidine - 3 - yl] phenyl} morpholine - 3 - one method
The invention provides a method of synthesizing 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-one, wherein the method includes the steps of (1) performing a one-step cyclization reaction to an intermediate N-(4-aminophenyl)-2-(2-haloethyoxyl)acetamide to prepare 4-(4-aminophenyl)-3-morpholinone; and (2) carrying out a ring-opening reaction with an epoxy compound, a substitution reaction, a cyclization reaction and like to the 4-(4-aminophenyl)-3-morpholinone to obtain the key intermediate, 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-one, of rivaroxaban. The method is high in yield, is less in pollution, is free of an expensive metal palladium for performing nitro-reduction during the process and is suitable for industrial production.
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(2018/03/13)

The preparation method of the the advantage cuts down Sha Ban
The invention provides a preparation method of rivaroxaban, which uses 4-(4-iodophenyl)-3-morpholone and (S)-(+)-N-(3-amino-2-hydroxyisopropyl)phthalimide as initial raw materials. The synthesis route is simple, the reaction conditions in each reaction are mild, and the product is easy to separate; and thus, the reaction yield is high, the product purity is high, and the method can be used for industrial production.
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Paragraph 0093-0094

(2017/04/21)

A method for preparing the advantage cuts down Sha Ban
The invention discloses a preparation method for rivaroxaban. A target product, namely rivaroxaban is obtained by a five-step reaction of amino-substitution, chloro-substitution, cyclization, elimination and substitution. The preparation method for rivaroxaban, which is disclosed by the invention, is cheap and easily-available in raw materials, stable in reaction condition, simple to operate, high in productivity, and simple in aftertreatment, and the reaction cost is reduced; a crude product obtained after reaction is high in purity, so that the high-purity rivaroxaban can be easily obtained by purification, and is more suitable for industrialized production.
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(2017/08/26)

Preparation method of Rivaroxaban intermediate
The invention provides a preparation method of a Rivaroxaban intermediate. The method includes: a compound with a structure as shown in formula (I) is allowed to have mixed reaction with phosgene in the presence of a catalyst and a solvent so as to prepare the Rivaroxaban intermediate. The preparation method has the advantages that the method is high in reaction yield, the prepared Rivaroxaban intermediate contains few impurities, and the Rivaroxaban intermediate high in purity can be obtained through beating only.
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Paragraph 0044; 0046-0047

(2017/08/28)

PROCESS FOR THE PREPARATION OF RIVAROXABAN
The present invention relates to an environmentally friendly process for preparing rivaroxaban. The present invention provides a process for preparing rivaroxaban of formula I, the process comprising: reacting a compound of formula VI with a base in the presence of a solvent to form a compound of formula VII; and condensing the compound of formula VII with a compound of formula VIII or a compound of formula IX in the presence of a solvent to prepare rivaroxaban of formula I, wherein the solvent used in both steps comprises water.
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(2016/03/22)

AN IMPROVED PROCESS FOR PREPARATION OF RIVAROXABAN
The present invention relates to an improved process for the preparation of Rivaroxaban of formula (I) in high yield and purity. More particularly, the present invention is directed to an improved and greener process for preparation of Rivaroxaban employing isolated compound of formula (II) in high yield which substantially eliminates potential impurities.
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Page/Page column 18

(2016/12/26)

PROCESS FOR PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
An improved process for the preparation of Rivaroxaban wherein the process substantially eliminates the potential impurities. process for preparation of Rivaroxaban which uses a novel intermediate. A process for preparing the novel intermediate which is used for the preparation of Rivaroxaban.
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Paragraph 0117

(2015/02/18)

PROCESS FOR THE SYNTHESIS OF RIVAROXABAN AND INTERMEDIATE FOR THE PRODUCTION THEREOF
A process is described for the production of Rivaroxaban, a compound having the following structural formula: (I) by means of obtaining a novel intermediate of said process.
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Page/Page column 6

(2016/01/12)

PROCESSES AND INTERMEDIATES FOR PREPARING RIVAROXABAN
The invention discloses processes for the preparation of rivaroxaban and its pharmaceutically acceptable salts, solvates, and hydrates thereof. The invention also relates to novel intermediates for the preparation of rivaroxaban.
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(2015/01/07)

RIVAROXABAN INTERMEDIATE AND PREPARATION THEREOF
This invention relates to novel intermediate, formula (A) for rivaroxaban and process for the preparation thereof. Further it extends to the process for preparation of rivaroxaban by using the said novel intermediate, by treating with 5-chlorothiophene carbonyl chloride to form the rivaroxaban derivatives of formula (B). The obtained formula (B) further treated with acid to form rivaroxaban.
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Paragraph 047

(2014/07/21)

PROCESSES AND INTERMEDIATES FOR PREPARING RIVAROXABAN
The invention discloses processes for the preparation of rivaroxaban and its pharmaceutically acceptable salts, solvates, and hydrates thereof. The invention also relates to novel intermediates for the preparation of rivaroxaban.
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(2013/07/19)

A PROCESS FOR PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
An improved process for the preparation of Rivaroxaban; wherein the said process substantially eliminates the potential impurities. The present invention also relates to process for preparation of Rivaroxaban using a novel intermediate. The present invention also relates to a process for preparing the novel intermediate, used for preparation of Rivaroxaban.
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Page/Page column 26

(2013/08/28)

PROCESS FOR PREPARING FACTOR XA INHIBITORS
The present invention relates to a process for the manufacturing of a rivaroxaban or a pharmaceutically acceptable salt thereof, wherein the process comprises obtaining an acid addition salt of a 4-{4-[(5S))-5-(aminomethyl)-2-oxo-1,3-oxozoladine-3- yl]phenyl}morpholin-3-one, and reacting the acid addition salt with the suitable reagents to obtain rivaroxaban or a salt thereof.
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Page/Page column 31

(2013/04/25)

A METHOD OF MANUFACTURING 2-({(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]- L,3-OXAZOLIDIN-5-YL}METHYL)-LH-ISOINDOL-L,3(2H)-DIONE WITH A HIGH OPTICAL PURITY
Highly optically pure 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin- 5-yl} methyl)- lH-isoindol- l,3(2H)-dione (I) is obtained by reaction of 2-((2R)-2-hydroxy-3-[4-(3- oxo-4-moφholinyl)phenyl]amino-propyl)- lH-isoindol- l,3(2H)-dione (III), containing the (2S)- isomer (Illb), with N,N-carbonyldiimidazole in tetrahydrofuran, preferably without the presence of the catalyst 4-dimethylaminopyridine, said reaction being carried out in such a manner that it is terminated at a moment when the reaction mixture still contains the unreacted compound of formula III in an amount which is in the range of a 3 to 5 fold the initial amount of the (2S)- isomer in the starting substance of formula III.
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Page/Page column 10

(2012/04/17)

PROCESSES FOR THE PREPARATION OF 4-{4-[5(S)-(AMINOMETHYL)-2-OXO-1,3-OXAZOLIDIN-3-YL]PHENYL} MORPHOLIN-3-ONE
The present invention provides processes for the preparation of 4-{4-[5(S)-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one which are simple, eco-friendly, cost-effective, reproducible, robust and are well amenable on industrial scale.
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(2012/03/27)

PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
Provided are process for the preparation of (R)- and/or (S)- Rivaroxaban, and compounds which are intermediate compounds used in the processes for the preparation of (R)- and/or (S)-Rivaroxaban.
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(2012/05/05)

PROCESSES FOR CRYSTALLIZATION OF RIVAROXABAN
The invention relates to rivaroxaban, more particularly to a process for preparation of rivaroxaban or a pharmaceutically acceptable salt or solvate thereof and its crystallization in order to obtain product having desired quality properties.
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(2011/02/24)

COMBINATION THERAPY OF SUBSTITUTED OXAZOLIDINONES
The present invention relates to combinations of A) oxazolidinones of the formula (I) with B) acetylsalicylic acid (aspirin) and C) an ADP receptor antagonist, in particular P2Y12 purinoreceptor blocker, to a process for producing these combinations and to the use thereof as medicaments, in particular for the prophylaxis and/or treatment of thromboembolic disorders.
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(2010/06/11)

MICROANGIOPATHY TREATMENT AND PREVENTION
The present invention relates to the use of selective factor Xa inhibitors, in particular of oxazolidinones of the formula (I) for the treatment and/or prophylaxis of microangiopathies and also their use for the production of medicaments for the treatment and/or prophylaxis of microangiopathies.
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(2010/07/04)

Combination Therapy Comprising Substituted Oxazolidinones for the Prevention and Treatment of Cerebral Circulatory Disorders
The present invention relates to combinations of A) oxazolidinones of the formula (I), with B) antiarrhythmics, processes for the production of these combinations, their use for the prophylaxis and/or treatment of diseases, and their use for the manufacture of medicaments for the prophylaxis and/or treatment of diseases, especially of thromboembolic disorders and/or complications.
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(2009/01/20)

Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4- (3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): An oral, direct factor Xa inhibitor
Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.
Roehrig, Susanne,Straub, Alexander,Pohlmann, Jens,Lampe, Thomas,Pernerstorfer, Josef,Schlemmer, Karl-Heinz,Reinemer, Peter,Perzborn, Elisabeth
p. 5900 - 5908
(2007/10/03)

Preparation process
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-thiophenecarboxamide starting from 2-[(2S)-2-oxiranylmethyl]-1H-isoindole-1,3(2H)-dione, 4-(4-aminophenyl)-3-morpholinone and 5-chlorothiophene-2-carbonyl chloride.
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Page/Page column 1; 3

(2008/06/13)

PRODUCTION METHOD
The invention relates to a method for producing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide from 2-[(2S)-2-oxiranylmethyl]-1H-isoindol-1,3(2H)-dione, 4-(4-aminophenyl)-3-morpholinone, and 5-chlorothiophene-2-carbonyl chloride.
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Page/Page column 7

(2008/06/13)