1252018-10-2

Basic information

• Product Name: 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one
• Synonyms: 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one;(R)-4-[4-[(3-Chloro-2-hydroxypropyl)amino]phenyl]morpholin-3-one;4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-p ropyl)amino)phenyl]morpholin-3-one 2-[(2R)-2-hydroxy-3-{[4-(3-oxomorph olin-4-yl)phenyl]amino}propyl]-1H-is oindole-1,3(2H)-dione 2-[[(5S)-2-Oxo-3-[4-(3-oxo-4-morpho linyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1
• CAS NO: 1252018-10-2
• Molecular Formula: C₁₃H₁₇ClN₂O₃
• Molecular Weight: 284.73868
• Mol File: 1252018-10-2.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 604.5±55.0 °C(Predicted)
• Appearance: /
• Density: 1.349±0.06 g/cm3 (20 oC 760 Torr), Calc.*
• PKA: 13.53±0.20(Predicted)
• CAS DataBase Reference: 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one(1252018-10-2)
• EPA Substance Registry System: 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one(1252018-10-2)

Safety Data

• Hazardous Substances Data: 1252018-10-2(Hazardous Substances Data)

Usage

Description

4-[4-(N-(3-Chloro-(2R)-2-hydroxy-1-propyl)amino)phenyl]morpholin-3-one, also known as Rivaroxaban Impurity E, is a chemical compound derived from Rivaroxaban (R538000). It is characterized by its unique molecular structure, which includes a morpholinone ring and a chloro-hydroxypropyl side chain. 4-[4-(N-(3-Chloro-(2R)-2-hydroxy-1-propyl)amino)phenyl]morpholin-3-one is of interest due to its association with Rivaroxaban, a widely used antithrombotic agent and FXa inhibitor.

Uses

Used in Pharmaceutical Industry:
4-[4-(N-(3-Chloro-(2R)-2-hydroxy-1-propyl)amino)phenyl]morpholin-3-one is used as an impurity in the production of Rivaroxaban, an antithrombotic agent. Its presence in the manufacturing process is crucial for ensuring the quality and safety of the final drug product. As an impurity, it is essential to monitor and control its levels to maintain the efficacy and safety profile of Rivaroxaban.
Additionally, understanding the properties and effects of Rivaroxaban Impurity E can contribute to the development of new therapeutic strategies and drug candidates in the pharmaceutical industry. Its unique chemical structure may offer insights into the design of novel antithrombotic agents or other related compounds with potential applications in various medical fields.

Upstream product

• 51594-55-9 (R)-(-)-epichlorohydrin 
• 438056-69-0 4-(4-aminophenyl)morpholin-3-one 
• 106-50-3 1,4-phenylenediamine 
• 350-46-9 4-Fluoronitrobenzene 
• 446292-04-2 4-(4-nitrophenyl)-3-morpholinone 
• 100-00-5 4-chlorobenzonitrile 
• 586-78-7 para-nitrophenyl bromide 
• 146824-93-3 (R)-4-chloromethyl-[1,3,2]dioxathiolane 2,2-dioxide 

Downstream Products

• 1252018-25-9 methyl N-(3-chloro-(2R)-2-hydroxy-1-propyl)-N-[4-(3-oxo-4-morpholinyl)phenyl]carbamate 
• 898543-06-1 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholin-3-one hydrochloride 
• 721401-53-2 5-chloro-N-{(R)‐2‐hydroxy‐3‐[4‐(3-oxo-4-morpholinyl)phenylamino]-propyl}thiophene-2-carboxamide 
• 1252018-26-0 4-[4-((R)-5-(iodomethyl)-2-oxo-oxazolidin-3-yl)phenyl]-morpholin-3-one 
• 1403383-55-0 (S)-4-(4-((3-amino-2-hydroxypropyl)amino)phenyl)morpholin-3-one hydrochloride 
• 1403383-56-1 (S)-4-[4-[(3-amino-2-hydroxypropyl)amino]phenyl]-3-morpholinone 
• 482306-32-1 5-chloro-N-({(5)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophenecarboxamide 
• 1770812-37-7 (S)-4,5-dichloro-N-[[2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl]methyl]-2-thiophenecarboxamide 
• 1415566-28-7 N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide 
• 1411775-01-3 4-{4-[(5S)-aminomethyI-2-oxo-1,3-oxazolidine-3-yl]-phenyl}-morphoIine-3-one acetate 
• 1372665-04-7 4-{4-[(5S)-5-((dibenzylamino)methyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one 
• 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 
• 1252018-09-9 4-[4-(N-((R)-2,3-epoxy-1-propyl)amino)phenyl]morpholin-3-one 

Relevant articles and documents

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.

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.

4 - (nitro-phenyl) - 3-preparation of morpholinones the advantage cuts down Sha Ban method and using the same method of preparation

The invention relates to the technical field of preparation of rivaroxaban and an intermediate thereof and particularly relates to a preparation method of 4-(nitrobenzophenone)-3-morpholone which is prepared from halogenated nitrobenzene, ethanolamine and chloroacetyl chloride through a one-pot method. The method for preparing rivaroxaban comprises the steps of reducing 4-(nitrobenzophenone)-3-morpholone into 4-(aminophenyl)-3-morpholone; enabling 4-(aminophenyl)-3-morpholone to react with R-epichlorohydrin to obtain a product; enabling the product to react with N, N-carbonyldiimidazole to obtain a product; enabling the product to react with tert-butyl iminodicarboxylate; preparing hydrochloride; enabling hydrochloride to react with 5-penphene-2-carbonyl chloride. The preparation method of 4-(nitrobenzophenone)-3-morpholone is capable of realizing one-pot production and free of purifying intermediate products in the process, so that the operation process is simplified, the time is saved, and the labor cost is reduced; the preparation method of 4-(nitrobenzophenone)-3-morpholone is low in raw material price, high in obtained product yield and easy to realize large-scale industrial production; in addition, the method for preparing rivaroxaban is cheap, nontoxic and harmless in raw material, simple in process and high in product yield.