174649-09-3

Basic information

• Product Name: (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate
• Synonyms: (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate;(R)-[3-(3-Fluoro-4-Morpholinophenyl)-2-oxo-5-oxazolidinyl]Methyl Methanesulfonat;(R)-(3-(3-flouro-4-Morpholinophenyl)-2-oxo-5-oxazolidinyl)Methyl Methanesulfonate;(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate;(5R)-3-[3-Fluoro-4-(4-Morpholinyl)phenyl]-5-[[(Methylsulfonyl)oxy]Methyl]-2-oxazolidinone;2-Oxazolidinone, 3-[3-fluoro-4-(4-Morpholinyl)phenyl]-5-[[(Methylsulfonyl)oxy]Methyl]-, (5R)-;Linezolid related Compound;Linezolid USP RC D
• CAS NO: 174649-09-3
• Molecular Formula: C₁₅H₁₉FN₂O₆S
• Molecular Weight: 374.3845632
• EINECS: 1592732-453-0
• Mol File: 174649-09-3.mol
• Article Data: 19

Chemical Properties

• Melting Point: 183-185℃
• Boiling Point: 592.7±50.0 °C(Predicted)
• Appearance: /
• Density: 1.418
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly, Heated), DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 5.71±0.40(Predicted)
• CAS DataBase Reference: (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate(174649-09-3)
• EPA Substance Registry System: (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate(174649-09-3)

Safety Data

• Hazardous Substances Data: 174649-09-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate is used as a synthetic intermediate for the production of Linezolid Dimer (L466520), which is an impurity in the manufacturing process of the antibacterial agent Linezolid (L466500). Its role in the synthesis process is crucial for the development and optimization of the final antibacterial product, ensuring its efficacy and safety for medical use.
Used in Research and Development:
In addition to its application in the pharmaceutical industry, (R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate may also be utilized in research and development for the exploration of new compounds and their potential applications. Its unique structure and properties make it a valuable candidate for further study, potentially leading to the discovery of novel drugs or therapeutic agents with improved properties and reduced side effects.
Used in Quality Control and Regulatory Compliance:
The compound may also be employed in quality control processes and regulatory compliance within the pharmaceutical industry. As an intermediate in the synthesis of Linezolid Dimer, it is essential to monitor and control the presence of this compound during the production of Linezolid (L466500). This ensures that the final product meets the required safety and efficacy standards, protecting patients and maintaining the integrity of the pharmaceutical market.

Upstream product

• 496031-56-2 (R)-(3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl acetate 
• 868405-66-7 N-[3-chloro-2-(R)-hydroxypropyl]-3-fluoro-4-(morpholin-4-yl)aniline 
• 565176-83-2 N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline 
• 168828-81-7 benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate 
• 239438-39-2 C₃₁H₃₆F₂N₄O₈ 
• 239438-43-8 C₂₈H₃₂F₂N₄O₈ 
• 905945-96-2 (R)-2-(3-Fluoro-4-morpholin-4-yl-phenylamino)-1-{(4R,5R)-5-[(R)-2-(3-fluoro-4-morpholin-4-yl-phenylamino)-1-hydroxy-ethyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-ethanol 
• 2689-39-6 3-fluoro-4-(4-morpholinyl)nitrobenzene 
• 369-34-6 3,4-difluoronitrobenzene 
• 93246-53-8 3-fluoro-4-(morpholinyl)aniline 
• 912552-56-8 ((S)-2,3-Dihydroxy-propyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-carbamic acid benzyl ester 
• 912552-54-6 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-hydroxy-propyl)-carbamic acid benzyl ester 
• 912552-55-7 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-oxo-propyl)-carbamic acid benzyl ester 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 168828-89-5 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione 
• 165800-03-3 linezolid 
• 1236077-59-0 (5S)-(N)-[[(3-fluoro-4-(4-morpholinyl)phenyl)-2-oxo-5-oxazolidinyl]methyl]bromide 

Relevant articles and documents

Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains

Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain (Sn), and two linezolid precursors (4and7), and they were evaluated in antibacterial assays. Interestingly, due to the intrinsic antibacterial activity of the amino-oligoethylene linezolid analogues, these conjugated nanomaterials showed significant antibacterial activity against various tested bacterial strains in a radial diffusion assay and microdilution method, including Gram negative strains asEscherichia coli(11 mm, 6.25 μg mL?1) andSalmonella typhi(14 mm, ≤0.78 μg mL?1), which are not inhibited by linezolid. The results show a significant effect of the oligoethylene chain length over the antibacterial activity. Molecular docking of amino-oligoethylene linezolid analogs shows a more favorable interaction of theS2-7analog in the PTC ofE. coli.

PROCESS FOR PREPARATION OF CRYSTALLINE FORM I OF LINEZOLID AND ITS COMPOSITIONS

The present invention relates to a process for the preparation of crystalline form I of linezolid, comprising providing a solution of linezolid in a solvent, crystallizing and recovering the solid of Linezolid in crystalline form I at elevated temperature. The present invention also relates to the use of crystalline form I of linezolid prepared by the method of the present invention for preparing pharmaceutical compositions.

Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives

Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5′-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity.

NOVEL PROCESS FOR PREPARATION OF LINEZOLID AND ITS NOVEL INTERMEDIATES

A novel process for preparing oxazolidinone antibacterial agent Linezolid including key intermediates of oxazolidinones comprising: reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; carbonylation to form oxazolidinone derivative; acetylation of (5R)-5-(chloromethyl)-3-(3-fluoro-4-morpholinophenyl-oxazolidin-2-one with sodium acetate to get novel intermediate; hydrolysis of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate; mesylation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol; reaction of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methane sulphonate with potassium phthalimide; hydrolysis of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl phthalimide with hydrazine hydrate; acetylation of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl amine with acetic anhydride yields Linezolid in high yield.

PROCESS FOR THE PREPARATION OF CRYSTALLINE LINEZOLID

The present invention discloses a stable crystalline Form-I of linesolid process for preparation thereof.

Novel promising linezolid analogues: Rational design, synthesis and biological evaluation

A new series of 5-substituted oxazolidinones derived from linezolid, having urea and thiourea moieties at the C-5 side chain of the oxazolidinone ring, were prepared and their in vitro antibacterial activity was evaluated. The compound 10f demonstrated high antimicrobial activity, comparable to that of linezolid against Staphylococcus aureus.

NOVEL PROCESS FOR PREPARATION OF LINEZOLID AND ITS NOVEL INTERMEDIATES

A novel process for preparing oxazolidinone antibacterial agent Linezolid including key intermediates of oxazolidinones comprising: reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; carbonylation to form oxazolidinone derivative; acetylation of (5R)-5-(chloromethyl)-3-(3-fluoro-4- morpholinophenyl-oxazolidin-2-one with sodium acetate to get novel intermediate; hydrolysis of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate; mesylation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol; reaction of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methane sulphonate with potassium phthalimide; hydrolysis of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl phthalimide with hydrazine hydrate; acetylation of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl amine with acetic anhydride yields Linezolid in high yield.

PROCESSES FOR THE PREPARATION OF LINEZOLID

Disclosed herein a process for preparing linezolid, wherein the resultant linezolide is devoid of impurities and involve easy and economical process. The present invention further relates to preparation of linezolid by employing an azide intermediate and process for said intermediate.

PROCESS FOR THE PREPARATION OF LINEZOLID

The present invention provides an improved process for the preparation of Linezolid of formula (D. The present invention relates to preparation of intermediate (R)-N-[[3-[3-fluoro-4-morpholinyl] phenyl |-2-oxo-5-oxazolidinyl] methanol of formula (II), Linezolid amine of formula (Ia) and their use in the preparation of Linezolid. The present invention further provides process for the preparation of Form I of Linezolid of formula (I).

Process for the preparation of an oxazolidinone antibacterial agent and intermediates thereof

Comprising a preparation process of linezolid from a compound of formula (IV) where R1 is selected from a (C4-C10)-alkyl radical which is attached to the N atom by a tertiary C atom, and a straight or branched (C3-C10)-alkenyl radical attached to the N atom such that the C=C double bond is separated from the N atom by a methylene group. Compound (IV) is submitted either first to an acetylation reaction and then to a dealkylation reaction or, alternatively, first to a dealkylation reaction and then to an acetylation reaction to yield linezolid. It also comprises new intermediate compounds useful in such a preparation process, which are obtained with high yields and high chemical and optical purity, and which are processed easily to linezolid.