446292-08-6

Usage

Uses

Used in Pharmaceutical Industry:
1H-ISOINDOLE-1,3(2H)-DIONE, 2-[[(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]-5-OXAZOLIDINYL]METHYL]is used as a key intermediate in the synthesis of rivaroxaban, an anticoagulant medication. Rivaroxaban is the first orally active direct factor Xa inhibitor, which plays a significant role in the coagulation cascade and is essential for the prevention and treatment of blood clot-related disorders.
Used as Rivaroxaban Intermediate:
1H-ISOINDOLE-1,3(2H)-DIONE, 2-[[(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]-5-OXAZOLIDINYL]METHYL]is specifically utilized in the production of rivaroxaban, which is a vital drug in the prevention and treatment of various blood clot-related conditions, such as deep vein thrombosis, pulmonary embolism, and stroke. Its role as an intermediate in the synthesis of rivaroxaban highlights its importance in the pharmaceutical industry and its contribution to the development of life-saving medications.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C22H19N3O6/c26-19-13-30-10-9-23(19)14-5-7-15(8-6-14)24-11-16(31-22(24)29)12-25-20(27)17-3-1-2-4-18(17)21(25)28/h1-8,16H,9-13H2/t16-/m1/s1

Upstream product

• 446292-07-5 2-((2S)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione 
• 530-62-1 1,1'-carbonyldiimidazole 
• 161596-47-0 (S)-N-glycidylphthalimide 
• 438056-69-0 4-(4-aminophenyl)morpholin-3-one 
• 122-98-5 2-Anilinoethanol 
• 446292-04-2 4-(4-nitrophenyl)-3-morpholinone 
• 29518-11-4 4-phenylmorpholin-3-one 
• 1252018-28-2 4-{4-[(5R)-5-(chloromethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one 
• 1074-82-4 potassium phtalimide 
• 1252018-10-2 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)amino)phenyl]morpholin-3-one 
• 136918-14-4 phthalimide 
• 1446022-14-5 butyric acid-2(R)-2-hydroxy-3-[4-(3-oxo-morpholin-4-yl)phenylamino]-propyl ester 
• 1446022-15-6 butyric acid-2-oxo-5(R)-3-[4-(3-oxomorpholin-4-yl)-phenyl]oxazolidin-5-yl-methyl ester 
• 1117893-60-3 4-{4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one 

Downstream Products

• 366789-02-8 Rivaroxaban 
• 898543-06-1 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one hydrochloride 
• 1365267-37-3 (S)-2-(((2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)oxazolidin-5-yl)methyl)carbamoyl)benzoic acid 
• 1430407-74-1 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one malonate 
• 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 
• 446292-10-0 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one 
• 1445-69-8 2,3-dihydrophthalazine-1,4-dione 

Relevant academic research and scientific papers

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 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 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.

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.

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.

Identification and Synthesis of Impurities During a Novel Process Development of Rivaroxaban

During the development of rivaroxaban, seven process-related impurities have been identified and synthesized. These structures are confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The impurities (S)-2-(2-((4-(5-(aminomethyl)-2-oxooxazolidin-3-yl)phenyl)amino)ethoxy)acetohydrazide (A) and (S)-4-(4-(((2-oxooxazolidin-5-yl)methyl)amino)phenyl)morpholin-3-one (F) are confirmed and distinguished from their isomers by single-crystal diffraction. This work proves to be valuable in regard to complying with regulatory norms and assessing the quality of rivaroxaban.

Intermediate for synthesizing rivaroxaban, synthesizing method and application

The invention discloses an intermediate for synthesizing rivaroxaban, a synthesizing method and application. The synthesizing method comprises the following steps: firstly, carrying out addition reaction on a structure of formula II and a structure of formula III to obtain a corresponding amino alcohol compound, and then carrying out cyclization reaction on the amino alcohol compound and a carbonylation reagent to obtain a compound of the structure of formula I; carrying out oxidation reaction on the compound of the structure of formula I and an oxidizing agent to obtain a compound of a structure of known formula IV; secondly, desorbing phthaloyl from the compound of the structure of formula IV according to a known method to obtain a compound of a structure of known formula V; and finally,carrying out acylation reaction on the compound of the structure of formula V to obtain the rivaroxaban (a structure of formula VI). The solvent used in the addition reaction is isopropanol or ethanol, and the addition reaction is carried out at a room temperature or under a heating condition. The intermediate for synthesizing the rivaroxaban, the synthesizing method and the application are designed. The intermediate for synthesizing the rivaroxaban has the advantages of cheap and easily obtained raw materials, gentle and easily operated reaction conditions, environmental protection and lesspollution, high yield and purity, easiness in industrialization and the like.

ONE POT SYNTHESIS FOR THE PREPARATION OF SUBSTITUTED PHTHALIMIDO OXAZOLIDINONE ANTIBACTERIALS AND OXAZOLIDINONE ANTIHAROMBOTICS COMPOUNDS BY USING RECYCLABLE HETEROGENEOUS CATALYST

A novel one pot and high yield process for the preparation of substituted phthalimidooxazolidinone compounds by using recyclable heterogeneous catalyst and preparation of oxazolidinoneantibacterials and oxazolidinoneantithrombotics thereof.

Preparation process for rivaroxaban

The invention provides a preparation process for rivaroxaban, and particularly relates to the technical field of pharmaceutical chemistry. The preparation process comprises the following steps: (S)-4-chloro-3-hydroxylbutyronitrile reacts with phthalimide potassium salt, (S)-4-(1,3-dioxoisoindol-2-yl)-3-hydroxybutyramide is obtained by nitrile group hydrolysis, (S)-2-[[2-oxo-1,3-oxazolidine-5-yl]methyl]-1H-isoindol-1,3(2H)-diketone is obtained by rearrangement under the action of iodobenzene, and carries out Ullmann coupling with 4-(4-bromophenyl)morpholine-3-ketone, so that 2-[[(S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidine-5-yl]methyl]-1H-isoindol-1,3(2H)-diketone is obtained, and by hydrazinolysis and amidation, rivaroxaban is obtained. The preparation process has the advantages of easiness in operation, moderate reaction conditions and higher yield.

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.