446292-07-5

Basic information

• Product Name: 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-
• Synonyms: 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-;4-[((2R)-Hydroxy-3-phthaliMido)propylaMine]phenyl-3-Morpholinone;2-[(2R)-2-Hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-1H-isoindole-1,3(2H)-dione;2-[(2R)-2-hydroxy-3-{[4-(3-oxoMorpholin-4-yl)phenyl]aMino}p ropyl]-1H-isoindole-1,3(2H)-dione;(R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)-amino)propyl)isoindoline-1,3-dione;Rivaroxaban interMediate B;2-[(2R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)anilino]propyl]isoindole-1,3-dione;Rivaroxaban Phthalimido Descarbonyl Impurity
• CAS NO: 446292-07-5
• Molecular Formula: C₂₁H₂₁N₃O₅
• Molecular Weight: 395.413
• EINECS: 1806241-263-5
• Product Categories: Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Intermediate of Rivaroxaban
• Mol File: 446292-07-5.mol

Chemical Properties

• Boiling Point: 734.905 °C at 760 mmHg
• Flash Point: 398.256 °C
• Appearance: /
• Density: 1.421
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.672
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 13.91±0.20(Predicted)
• Water Solubility: 37mg/L at 20℃
• CAS DataBase Reference: 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-(446292-07-5)
• EPA Substance Registry System: 1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-(446292-07-5)

Safety Data

• Hazardous Substances Data: 446292-07-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1H-ISOINDOLE-1,3(2H)-DIONE, 2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]is used as a Rivaroxaban (R538000(P)) intermediate for the development of novel antithrombotic agents. Rivaroxaban is a highly potent and selective, direct FXa inhibitor, which plays a crucial role in the prevention and treatment of various thrombotic disorders.
As a Rivaroxaban intermediate, this compound contributes to the synthesis of a drug that has the potential to revolutionize the management of thrombotic conditions, such as deep vein thrombosis and pulmonary embolism, by providing an effective and targeted treatment option.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C21H21N3O5/c25-16(12-24-20(27)17-3-1-2-4-18(17)21(24)28)11-22-14-5-7-15(8-6-14)23-9-10-29-13-19(23)26/h1-8,16,22,25H,9-13H2/t16-/m1/s1

Upstream product

• 161596-47-0 (S)-N-glycidylphthalimide 
• 438056-69-0 4-(4-aminophenyl)morpholin-3-one 
• 5455-98-1 2-oxiranylmethylisoindole-1,3-dione 
• 122-98-5 2-Anilinoethanol 
• 446292-04-2 4-(4-nitrophenyl)-3-morpholinone 
• 29518-11-4 4-phenylmorpholin-3-one 
• 136918-14-4 phthalimide 
• 1252018-10-2 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)amino)phenyl]morpholin-3-one 
• 1074-82-4 potassium phtalimide 
• 106-50-3 1,4-phenylenediamine 

Downstream Products

• 446292-08-6 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione 
• 1263103-46-3 methyl (S)-2-hydroxy-3-(1,3-dioxoisoindolin-2-yl)propyl-4-(3oxomorpholino)phenylcarbamate 
• 1263103-47-4 5-chloro-thiophene-2-carboxylic acid-1-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-{methoxycarbonyl-[4-(3-oxo-morpholin-4-yl)-phenyl]-amino}-ethyl ester 
• 1430407-74-1 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one malonate 
• 898543-06-1 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one hydrochloride 
• 1430407-73-0 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one oxalate 
• 1446022-16-7 (S)-4-(4-(5-(aminomethyl)-2-oxo-oxazolidin-3-yl)phenyl)morpholin-3-one formate salt 
• 1446022-18-9 (S)-4-(4-(5-(aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one L-(+)-mandelate 
• 1450876-94-4 2-((2R)-2-hydroxy-3-(N-(4-(3-oxomorpholin-4-yl)phenyl)-1H-imidazol-1-yl-carboxamido)propyl)-1H-isoindol-1,3(2H)-dione 
• 1616563-62-2 N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)formamide 
• 1616563-61-1 5-chloro-N-formyl-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide 
• 446292-10-0 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one 
• 1403383-55-0 (S)-4-(4-((3-amino-2-hydroxypropyl)amino)phenyl)morpholin-3-one hydrochloride 
• 1643354-27-1 2,2'-((2R,2'R)-((4-(3-oxomorpholino)phenyl)azadiyl)bis(2-hydroxypropane-3,1-diyl))bis(isoindoline-1,3-dione) 

Relevant articles and documents

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.

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.

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.

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.

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.

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.

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.

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)

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)

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.