93246-53-8

Usage

Chemical Properties

Brown Solid

Uses

Intermediate in the synthesis of Linezolid (L466500).

InChI:InChI=1/C10H13FN2O/c11-9-7-8(12)1-2-10(9)13-3-5-14-6-4-13/h1-2,7H,3-6,12H2

Upstream product

• 110-91-8 morpholine 
• 369-34-6 3,4-difluoronitrobenzene 
• 1321455-47-3 1-tert-butyl-N-(3-fluoro-4-morpholinophenyl)-1,1-dimethylsilanamine 
• 367-11-3 ortho-difluorobenzene 
• 588708-64-9 3-fluoro-4-(morpholin-4-yl)benzonitrile 
• 64248-62-0 3,4-Difluorobenzonitrile 
• 455-86-7 3,4-Difluorobenzoic acid 
• 100-00-5 4-chlorobenzonitrile 
• 350-31-2 1-chloro-2-fluoro-4-nitrobenzene 
• 2689-39-6 3-fluoro-4-(4-morpholinyl)nitrobenzene 

Downstream Products

• 588708-64-9 3-fluoro-4-(morpholin-4-yl)benzonitrile 
• 691862-67-6 1-(3-fluoro-4-morpholin-4-yl-phenyl)-1H-pyrrole-3-carbaldehyde 
• 912552-55-7 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-oxo-propyl)-carbamic acid benzyl ester 
• 912552-54-6 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-hydroxy-propyl)-carbamic acid benzyl ester 
• 912552-56-8 ((S)-2,3-Dihydroxy-propyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-carbamic acid benzyl ester 
• 168828-82-8 (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol 
• 168828-90-8 (S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine 
• 165800-03-3 linezolid 
• 168828-84-0 (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one 
• 174649-09-3 (R)-methyl methanesulfonate 
• 216869-07-7 (R)-[{N-3-(3-fluoro-4-morpholinophenyl)-2-oxo-oxazolidin-5-yl}methyl]isothiocyanate 
• 216868-96-1 (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyldithiocarbamate 
• 198410-26-3 4-Nitro-benzenesulfonic acid (R)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester 
• 239438-43-8 C₂₈H₃₂F₂N₄O₈ 

Relevant academic research and scientific papers

Novel 3-fluoro-4-morpholinoaniline derivatives: Synthesis and assessment of anti-cancer activity in breast cancer cells

Heterocyclic morpholine compounds are well-known for their anti-cancer activity. In this study, novel morpholine and its sulfonamide derivatives were designed and synthesized as potential anti-tumor agents. The new compounds were obtained from amine derivatives via nucleophilic addition reactions, providing the desired products in 70 to 90% yield. The docking analysis was performed for all thirty-one compounds. Out of them, we represent the docking poses for compounds NAM-5 and NAM-7 as representatives. After docking analysis, compounds NAM-5 and NAM- 7 were tested for in vitro antitumor activity against breast cancer cell lines (MCF-7 and MDA-MB-231) and healthy mouse embryonic fibroblast cell line (3T3L-1). Amongst these, sulfonamide group-containing compound NAM-5 showed significant anti-proliferative activity with IC50 of 1.811 μM and 2.143 μM for MCF-7 and MDA-MB-231 cells, respectively. On the other hand, NAM-7 showed good anti-proliferative activity against MCF-7 (IC50 1.883 μM) but slightly lower activity against MDA-MB-231 cells (IC50 4.688 μM). The activity of both the compound was also tested on 3T3L-1 Cell line which showed activity similar to clinically approved anti-cancer drug doxorubicin (DOX). The cell death analysis by flow-cytometry confirmed apoptosis mediated cell death in 3T3L-1, MCF-7 and MDA-MB-231 cells when treated with the NAM-5 and NAM-7, respectively. The results demonstrated that the synthesized sulfonamide derivatives have significant potential as anti-cancer agents and have a substantial importance in cancer therapeutics with favourable safety profile. Structural analysis of docked poses of sulfonamide derivatives attempts to shed light on the structural basis of sulfonamide derivatives based anti-cancer effect.

Biorenewable carbon-supported Ru catalyst for: N -alkylation of amines with alcohols and selective hydrogenation of nitroarenes

Herein, we developed a renewable carbon-supported Ru catalyst (Ru/PNC-700), which was facilely prepared via simple impregnation followed by the pyrolysis process. The prepared Ru/PNC-700 catalyst demonstrated remarkable catalytic activity in terms of conversion and selectivity towards N-alkylation of anilines with benzyl alcohol and chemoselective hydrogenation of aromatic nitro compounds. In addition, local anesthetic pharmaceutical agents (e.g., butamben and benzocaine), including key drug intermediates, were synthesized in excellent yields under mild conditions and in the presence of water as a green solvent. Moreover, the prepared Ru/PNC-700 catalyst could be easily recovered and reused up to five times without any apparent loss in activity and selectivity.

Discovery and optimization of withangulatin A derivatives as novel glutaminase 1 inhibitors for the treatment of triple-negative breast cancer

To develop novel GLS1 inhibitors as effective therapeutic agents for triple-negative breast cancer (TNBC), 25 derivatives were synthesized from the natural inhibitor withangulatin A (IC50 = 18.2 μM). Bioassay optimization identified a novel and

Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol

Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.

Benzofuroxan Derivatives as Potent Agents against Multidrug-Resistant Mycobacterium tuberculosis

Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5]oxadiazole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC90 values below 0.28 μM against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis.

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.

Pd/C-catalyzed transfer hydrogenation of aromatic nitro compounds using methanol as a hydrogen source

We describe the selective transfer hydrogenation of aromatic nitro compounds to anilines using Pd/C as a heterogeneous catalyst with methanol as a green reductant. Nitroarenes bearing both electron-releasing and electron-deficient groups are amenable to this method and enable the synthesis of corresponding arylamines in moderate to good selectivities including the synthesis of butamben, a local anesthictic drug molecule. This new concise protocol is simple, ligand-free and does not require the supply of external molecular hydrogen.

Catalytic production of anilines by nitro-compounds hydrogenation over highly recyclable platinum nanoparticles supported on halloysite nanotubes

Pt-nanoparticles supported on halloysite-nanotubes (HNTs) were selectively deposited onto the inner (Pt(IN)/HNT) or outer (Pt(OUT)/HNT) surface of the support to evaluate their operational stability on the cleaner and efficient hydrogenation of nitro compounds to produce their corresponding anilines. The formation of Pt0-aggregates on the inner or outer surfaces was observed, with mean particles sizes of 2.4–2.9 nm. The catalysts were evaluated using ethanol as solvent and nitrobenzene as a model substrate at a temperature of 298 K, under 1 bar of H2 pressure. The Pt(IN)/HNT catalyst showed better catalytic performance than Pt(OUT)/HNT, which was mainly attributed to the confinement effect of the Pt-nanoparticles inside the HNTs. However, the operational stability showed that Pt(OUT)/HNT retained its catalytic performance after 15 cycles, while the Pt(IN)/HNT catalyst suffered deactivation after the 5th cycle. The best catalytic system showed a moderate-to-high efficiency in the efficient hydrogenation of 7 nitro compounds used to produce their corresponding anilines, which are important pharmaceutical building blocks.

Noble metal nanoparticles supported on titanate nanotubes as catalysts for selective hydrogenation of nitroarenes

Platinum (Pt) and palladium (Pd) nanoparticles (NPs) supported on titanate nanotubes (TiNTs) Pt@TiNT and Pd@TiNT were prepared for the liquid-phase hydrogenation of nitroarenes at 25 °C Initially, TiNT was modified with 3-aminopropyl-trimethoxysilane to provide a strong anchoring site to trap the Pt and Pd NPs, which prevent the metal NPs from leaching. As-prepared 1 wt% of metal loading catalysts were characterized by transmission electron microscopy (TEM), nitrogen adsorption–desorption isotherms, X-ray diffraction, and X-ray photoelectron spectroscopy measurements. The TEM images confirmed that the Pt (1.70 ± 0.19 nm) and Pd (2.80 ± 0.43 nm) NPs were mainly confined into the channel of TiNTs. Both catalysts exhibited excellent catalytic performances for the reduction of nitrobenzene as a model compound under mild reaction conditions. The superior catalytic activity for the hydrogenation of nitroarenes is attributed to the small size of the Pt and Pd NPs. However, the operational stability showed that Pt@TiNT retained its catalytic performance after 10 cycles, while Pd@TiNT suffered deactivation by metal sintering after the sixth cycle. The Pt@TiNT system exhibited high efficiency in the hydrogenation of different substituted nitroarenes of pharmaceuticals interest, and it showed an excellent activity and selectivity toward the production of desired substituted anilines.

Synthesis method of linezolid intermediate

The invention provides a synthesis method of a linezolid intermediate 3-fluoro-4-(4-morpholinyl)aniline. The linezolid intermediate 3-fluoro-4-(4-morpholinyl)aniline is preferably obtained by taking acompound 3, 4-difluorobenzoic acid or 3, 4-difluorobenzonitrile as a raw material, performing morpholine substitution, converting into corresponding amide and performing Hofmann degradation. Comparedwith the prior art, the method has the advantages that the raw material and reagents used in the invention are cheap and easily available, most synthesis steps can be carried out under mild conditions, the environmental pollution is small, intermediate products and end products are easy to purify, the total yield is high, the nitration reaction is effectively avoided, the requirement on equipmentis not high, and the method is more suitable for industrial production.