100986-89-8

Basic information

• Product Name: Levofloxacin carboxylic acid
• Synonyms: Levefluorocarboxylic Acid;Levofloxacin Related Compound B (35 mg) ((S)-9,10,difluro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid);Levo Q Acid(oxa-2,3 dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic Acid;7H-Pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid,9,10-difluoro-2,3-dihydro-3-Methyl-7-oxo-,(3S)-;(S)-(-)-9,10-Difluoro-2,3-dihydro-3-Methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, 97+%;(3S)-9,10-Difluoro-2,3-dihydro-3-Methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic Acid;(S)-(-)-9,10-Difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxadine-6-carboxylic Acid;Levofloxacin USP Related CoMpound B (EP IMpC)
• CAS NO: 100986-89-8
• Molecular Formula: C₁₃H₉F₂NO₄
• Molecular Weight: 281.21
• EINECS: 1533716-785-6
• Product Categories: LEVOFLOXACIN INTERMIDATE;Benzoxazines;Chiral Building Blocks;Heterocyclic Building Blocks;Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 100986-89-8.mol

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 459.2 °C at 760 mmHg
• Flash Point: 231.5 °C
• Appearance: /
• Density: 1.61 g/cm³
• Vapor Pressure: 3.14E-09mmHg at 25°C
• Refractive Index: 1.635
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly)
• PKA: 4.87±0.40(Predicted)
• CAS DataBase Reference: Levofloxacin carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Levofloxacin carboxylic acid(100986-89-8)
• EPA Substance Registry System: Levofloxacin carboxylic acid(100986-89-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-36/37/3
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 100986-89-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Levofloxacin intermediate.

InChI:InChI=1/C13H9F2NO4/c1-5-4-20-12-9(15)8(14)2-6-10(12)16(5)3-7(11(6)17)13(18)19/h2-3,5H,4H2,1H3,(H,18,19)/t5-/m0/s1

Upstream product

• 188058-81-3 (+)-ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-[(1-acetoxyprop-2(S)-yl)amino]acrylate 
• 188058-77-7 (-)-ethyl 1,4-dihydro-1-[1(S)-(acetoxymethyl)ethyl]-4-oxo-6,7,8-trifluoroquinoline-3-carboxylate 
• 188058-75-5 (+)-ethyl 2-(2-nitro-3,4,5-trifluorobenzoyl)-3-[(1-acetoxyprop-2(S)-yl)amino]acrylate 
• 103995-33-1 3-(2,3,4,5-tetrafluorophenyl)-3-oxo-2-(ethoxymethylene)-propanoic acid ethyl ester 
• 91040-39-0 (+/-)-9,10-difluoro-3-hydroxymethyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid ethyl ester 
• 100986-87-6 (-)-ethyl 9,10-difluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylate 
• 113472-54-1 (-)-ethyl 9,10-difluoro-2,3-dihydro-3-iodomethyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylate 
• 180529-26-4 (+) ethyl 2-(2,3,4,5-tetrafluoro)benzoyl-3-[(1-acetoxy-prop-2(S)-yl)amino]acrylate 
• 60-29-7 diethyl ether 
• 138998-47-7 ethyl α<(N,N-dimethylamino)methylene>-2,3,4,5-tetrafluoro-β-oxobenzenepropanoate 
• 110548-04-4 (-)-ethyl 2-<<<(R)-1-hydroxyprop-2-yl>amino>methylene>-3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate 
• 106939-31-5 (S)-3-(3,5-Dinitro-benzoyloxymethyl)-8,9-difluoro-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid ethyl ester 
• 100986-91-2 (+/-)-ethyl 9,10-difluoro-2,3-dihydro-3-(3,5-dinitrobenzoyloxy)methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylate 
• 110548-02-2 (+)-ethyl 2-<<<(S)-1-hydroxyprop-2-yl>amino>methylene>-3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate 

Downstream Products

• 100986-85-4 levofloxacin 
• 138199-71-0 levofloxacin hemihydrate 
• 117707-40-1 S-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(1-piperazinyl)-7-oxo-7H-pyrido-<1,2,3-de><1,4>benzoxazine-6-carboxylic acid 
• 1422376-41-7 (S)-10-(4-(3-(benzylamino)-2-hydroxypropyl)piperazin-1-yl)-9-fluoro-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 
• 1422376-42-8 (S)-9-fluoro-3,7-dihydro-10-(4-(2-hydroxy-3-(phenylamino)propyl)piperazin-1-yl)-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 
• 1422376-36-0 (S)-9-fluoro-3,7-dihydro-3-methyl-10-(4-((oxiran-2-yl)methyl)piperazin-1-yl)-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 

Relevant articles and documents

Novel ofloxacin derivatives: Synthesis, antimycobacterial and toxicological evaluation

Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 μM and 0.09 μM against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91 - log 10 protections, respectively, at the dose of 50 mg/kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC50 of 10.0 μg/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections.

Preparation method of levofloxacin intermediate

The invention relates to a preparation method of a levofloxacin intermediate, which comprises the following steps: adding a compound shown as a formula I into water, adding alkali under the conditionof introducing gas to carry out alkaline hydrolysis, and further reacting with acid to obtain a compound shown as a formula II. The method has the advantages of simple post-treatment, low impurity content in the product, and no need of adding an organic solvent.

Synthesis method of levofloxacin carboxylic acid (by machine translation)

The method comprises the following steps, mixing: dimethylaminopropyl methacrylate with an acid-binding agent in an organic solvent A, and then carrying out an amine exchange reaction A, to obtain N,N -tetrafluorobenzoyl - 3 3 3 3 3-dimethylaminopropyl A acrylate as shown in formula III B, in the reaction mixture A to obtain a mixture liquid, and a mixed solution 2 - (2, 3, 4, 5) - condensation reaction A; to obtain the compound. A. The reaction liquid L - is dissolved in an organic solvent, The reaction solution 2 - (2, 3, 4, 5) - is obtained by a condensation reaction with a mixture solution.) - The method comprises the following steps, (II). The method comprises the following steps of: adding B aminopropanol, to the reaction solution; and HCl, HOAc, H carrying out an amine exchange reaction with a mixed solution of N- propyl methyl acrylate. 2 The reaction of the acid system of O to give the levofloxacin carboxylic acid. of formula V prevents the preparation N,N - dimethylaminoethyl acrylate from being unstable and difficult, unsafe and expensive sodium ethoxide, to corrosion of the device. (by machine translation)

ANTIBIOTIC RESISTANCE BREAKERS

The invention relates to antibiotic compounds of formula (A1) and pharmaceutically acceptable salts, solvates, tautomers and combinations thereof, wherein X and L are optional linkers and one of RA or R1 comprises Ar1, wherein Ar1 is an antibiotic resistance breaker moiety which comprises an optionally substituted C6-10 aryl, C7-13 aralkyl, C5-10 heteroaryl, C6-13 heteroaralkyl, C5-10 heterocyclyl, C6-13 heterocyclalkyl, C3-10 carbocyclyl, C4-13 carbocyclalkyl, -C(=NR')-NR'R'' or –CH2- CH=CH2 group; wherein after administration of the compound to a bacterial infection this moiety reduces or prevents efflux. The invention also discloses pharmaceutical compositions comprising compounds of formula (A1) and the use of such compounds as medicaments, in particular, to treat bacterial infections, such as drug-resistant bacterial infections.

Environment-friendly method for preparing levofloxacin hydrochloride

The invention provides an environment-friendly method for preparing levofloxacin hydrochloride. The method comprises the following steps: preparing 3-(2-hydroxy-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate, preparing levo-oxy main naphthenic acid, and preparing the levofloxacin hydrochloride. The method provided by the invention is concise, low in production cost, high in product yield, good in quality, economic and environment-friendly, fewer three wastes are discharged, and most byproducts are effectively separated and recycled, so that the method is convenient for industrial production and has great popularization significance.

Method for preparing high-quality levofloxacin hydrochloride

The invention provides a method for preparing high-quality levofloxacin hydrochloride. The method comprises the following steps: preparation of 3-(2-hydroxy-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate, preparation of levo naphthenic acid and preparation of levofloxacin hydrochloride; the method is concise, the production cost is low, the product yield is high, quality is good, the method has the advantages of economic performance and environmental protection, three waste discharge capacity is little, effective separating and recycling on most by-product can be simultaneously realized, the method is convenient for industrial production, and has large popularization meaning.

Method for preparing levofloxacin hydrochloride

The invention provides a method for preparing levofloxacin hydrochloride. The method comprises preparation of 3-(2-hydroxyl-1-methyl-ethylamino)-2-(2,3,4,5-tetrafluorobenzoyl)-ethyl acrylate, preparation of levo-oxygen main naphthenic acid, and preparation of the levofloxacin hydrochloride. The method is simple, low in production cost, high in product yield, good in product quality, economical, environmentally friendly, and low in three-waste emission load, and realizes effective separation and recycling of most byproducts, is convenient for industrial production and has great significance of promotion.

Ofloxacin preparation method (by machine translation)

The invention provides a preparation method of ofloxacin. The preparation method comprises the following steps of: reacting (N,N)-dimethylamino ethyl acrylate with aminopropanols in methylbenzene; directly adding lewis base serving as a catalyst and trimethylchlorosilane to protect hydroxyl and amido; after reaction is completely finished, dropwise adding (2,3,4,5)-tetrafluorobenzoyl chloride; preserving heat; performing acid washing; removing protecting groups; concentrating an organic layer to obtain an oil layer; adding a proper amount of dimethyl formamide (DMF); diluting and dropwise adding backflow DMF having anhydrous potassium fluoride; recovering DMF and adding water to centrifuge; adding acid water into a solid to hydrolyze to obtain difluorocarboxylic acid; and completely reacting difluorocarboxylic acid and N-methyl piperazine in dimethylsulfoxide (DMSO) by using triethylamine as an acid-binding agent at 90-100 DEG C to obtain ofloxacin. According to the process, hydroxyl and amido are protected by using trimethylchlorosilane, so that the utilization degree of (2,3,4,5)-tetrafluorobenzoyl chloride is effectively increased, and the generation of impurities is reduced to ensure that the reaction yield of intermediate difluorocarboxylic acid is increased by 10 percent.

AN IMPROVED PROCESS FOR THE PREPARATION OF LEVOFLOXACIN HEMIHYDRATE

The present invention relates to an improved process for preparation of Levofloxacin hemihydrate having single individual impurity not more than 0.1% and free from particulate matter and from the other enantiomer (R-form) which comprises dissolving levofloxacin technical grade in aqueous alkaline solution, treating the resulting solution with activated carbon at room temperature, removing the undissolved particulate matter filtration, bringing the pH of the aqueous alkaline levofloxacin solution to neutral using dilute mineral acid, removing the precipitated particulate matter by filtration, acidifying the resulting solution, treating the acidified solution with activated carbon at room temperature, filtering the undissolved particulate matter by filtration, neutralizing the acidic solution, filtering again to remove any particulate matter present and, extracting the resulting product with chlorinated solvent and concentrating under vacuum using aqueous tetrahydrofuran or in admixture with other organic solvents to get highly pure levofloxacin hemihydrate having single individual impurity is less than 0.1% and fee from particulate matter and from the other enantiomer (R-form).

Novel oxazolidinone-quinolone hybrid antimicrobials

Antimicrobial compounds incorporating oxazolidinone and quinolone pharmacophore substructures have been synthesized and evaluated. Representative analogues 2, 5, and 6 display an improved potency versus linezolid against gram-positive and fastidious gram-negative pathogens. The compounds are also active against linezolid- and ciprofloxacin-resistant Staphylococcus aureus and Enterococcus faecium strains. The MOA for these new antimicrobials is consistent with a combination of protein synthesis and gyrase A/topoisomerase IV inhibition, with a structure-dependent degree of the contribution from each inhibitory mechanism.