1-Ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate

Base Information

• Chemical Name: 1-Ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate
• CAS No.: 70458-96-7
• Molecular Formula: C16H18FN3O3
• Molecular Weight: 319.336
• Hs Code.: 29335990
• Mol file: 70458-96-7.mol

Synonyms:1-ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate

Chemical Property of 1-Ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate

Chemical Property:

• Appearance/Colour: Off-white to light yellow cryst powder
• Vapor Pressure: 2.6E-20mmHg at 25°C
• Melting Point: 220 °C
• Boiling Point: 555.8 °C at 760 mmHg
• PKA: pKa1 6.34; pKa2 8.75(at 25℃)
• Flash Point: 289.9 °C
• PSA: 74.57000
• Density: 1.344 g/cm³
• LogP: 1.66210
• Storage Temp.: 2-8°C
• Solubility.: Very slightly soluble in water, slightly soluble in acetone and in ethanol (96 per cent).
• Water Solubility.: Soluble in acetic acid. Also soluble in acetone or cloroform. Slightly soluble in water
• XLogP3: -0.9
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 319.13321961
• Heavy Atom Count: 23
• Complexity: 513

Purity/Quality:

99% ^*data from raw suppliers

Norfloxacin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-37/39-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CCN1C=C(C(=O)C2=CC(=C(C=C21)N3CC[NH2+]CC3)F)C(=O)[O-]
• Uses: Norfloxacin belongs to third-generation quinolone antibacterial agent developed by Japanese Kyorin Company in 1978. It has features of broad antibacterial spectrum and strong antibacterial activity. It has a strong antibacterial effect against Escherichia coli, pneumobacillus, Aerobacter aerogenes, and Aerobacter cloacae, Proteus, Salmonella, Shigella, Citrobacter and Serratia. It is clinically used for treating the susceptible strain’s causing infections of urinary system, intestinal, respiratory system, surgery, gynecology, ENT and dermatology. It can also be used for the treatment of gonorrhea. It finds it application as a fluorinated quinolone antibacterial. It is clinically used to treat urinary tract infections and prostatitis. In neutrophils from cirrhotic subjects, norfloxacin increases expression of IL-10 and heme oxygenase 1 (HO-1) and decreases expression of pro-inflammatory cytokines. Additionally, when complexed with gold(III), norfloxacin binds DNA and inhibits cellular proliferation in several cancer cell lines. An antibacterial. Fluorinated quinolone antibacterial Pefloxacin derivative as antibacterial. Fluorinated quinolone antibacterial.
• Production method: Nitration of o-dichlorobenzene or the chlorination of nitro chlorobenzene can both generate 3, 4-dichloro-nitrobenzene. It then undergoes reflux with potassium fluoride in dimethyl sulfoxide for being fluorinated to give 3-chloro-4-fluoro-nitrobenzene. In the presence of hydrochloric acid or aqueous acetic acid, it is further reduced by iron to 3-chloro-4-fluoro-aniline. 3-chloro-4-fluoro-aniline was then subject to reflux together with triethyl orthoformate and diethyl malonate (generate diethyl ethoxymethylenemalonate) in the presence of ammonium nitrate to give the condensation product with heating and cyclization in diphenyl ether or liquid paraffin to form the 7-chloro-6-fluoro-4-hydroxyquinoline-3-carboxylate with ethylation and further hydrolyzation to obtain the ethylated product. Finally, the ethylated product is condensed with piperazine to obtain norfloxacin. Its technology is relatively mature with a relative high yield being generally 40% to 65%. However, when introducing the piperazinyl group to the 7 position, the byproduct with the fluorine atom in 6 position can account for about 25%. It is hard for separation that can affect the yield. The overall yield calculated based on nitro chlorobenzene is above 8%. Before the introduction of the pyrazine ring, 1-ethyl-6-fluoro-7-chloro-1,4-dihydro-4-oxo-quinoline-8-carboxylic acid ethyl ester should first react with fluoroboric acid or a boron trifluoride-diethyl ether or boron acetate to have the carbonyl group in 4 position form boron chelate. Further re-introduction of pyrazinyl can reduce the side reactions of the displacement of the position 7’s fluorine and can increase the yield by 15%, as well as improve the quality of the product. There are many studies regarding the synthesis of norfloxacin at home and abroad. But there have not been too many way for being used in industrial production. The improvement of its synthesis route can be mainly reflected in two aspects. First, improve the process of forming a ring; the second is doing sth on the introduction of piperazine group.
• Description: Norfloxacin is the first of the third generation nalidixic acid analogs to reach the marketplace. It exhibits potent in vitro and in vivo activity against Pseudomonas, enteric gram-negative rods and gram-positive cocci. Norfloxacin is orally effective in the treatment of urinary tract infections, including those due to organisms refractory to many other agents. Norfloxacin is a fluoroquinolone antibiotic that inhibits the growth of Gram-positive and Gram-negative bacteria (MICs = 4 and 1 μg/ml for S. aureus and P. aeruginosa, respectively). It also inhibits the growth S. pseudintermedius, S. aureus, E. coli, Pasturella, and S. canis isolates from dogs (mean MIC50s = 0.25, 1, 0.03, 1, and 1 μg/ml, respectively). Topical administration of norfloxacin (0.1% v/v) reduces corneal ulcer size in a rabbit model of P. aeruginosa corneal infection. It also prevents encrusted cystitis in bladder and increases survival in a rat model of Corynebacterium group D2 infection when administered at a dose of 80 mg/kg per day. Formulations containing norfloxacin have been used to treat urinary tract and gynecological infections.
• Therapeutic Function: Antibacterial
• Clinical Use: Complicated and uncomplicated urinary tract infections (including prophylaxis in recurrent infections), prostatitis Uncomplicated gonorrhea Gastroenteritis caused by Salmonella, Shigella and Campylobacter spp., Vibrio cholerae Conjunctivitis (ophthalmic preparation)
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline: possibly increased risk of convulsions, increased levels of aminophylline. Analgesics: increased risk of convulsions with NSAIDs. Anticoagulants: anticoagulant effect of coumarins enhanced. Antimalarials: manufacturer of artemether with lumefantrine advises avoid. Ciclosporin: increased risk of nephrotoxicity. Muscle relaxants: possibly increases tizanidine concentration. Theophylline: possibly increased risk of convulsions; increased levels of theophylline.

Technology Process of 1-Ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate

There total 49 articles about 1-Ethyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-ylquinoline-3-carboxylate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 91.7%

piperazine (110-85-0) + 7-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (68077-26-9) → 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (70458-96-7)

Guidance literature:

With aluminum tri-bromide; In ethanol; at 65 ℃; for 5h; Temperature; Solvent; Reagent/catalyst;

Reference yield: 90.9%

1-ethyl-6-fluoro-7-chloro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid sodium salt + piperazine (110-85-0) → 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (70458-96-7)

Guidance literature:

With aluminum (III) chloride; In i-Amyl alcohol; at 140 ℃; for 8h; Solvent; Temperature;

Reference yield: 84.0%

ethyl 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (74011-47-5) → 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (70458-96-7)

Guidance literature:

With hydrogenchloride; In water; acetic acid;

upstream raw materials:

piperazine

7-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

ethyl 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate

N-<(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl>norfloxacin

Downstream raw materials:

Pefloxacin

N-ethoxycarbonyl NFLX

N-<(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl>norfloxacin

7-(4-allylpiperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Refernces

• 1、 Mokrushina,Kotovskaya,Baskakova,Petrova,Kolmakova,Charushin,Rusinov,Chupakhin. "Improved method for the synthesis of norfloxacin". . p. 540 - 542. Retrieved 1996.
• 2、 Wallace, Michael D.,Waraich, Nidda F.,Debowski, Aleksandra W.,Corral, Maxime G.,Maxwell, Anthony,Mylne, Joshua S.,Stubbs, Keith A.. "Developing ciprofloxacin analogues against plant DNA gyrase: A novel herbicide mode of action". supporting information. p. 1869 - 1872. Retrieved 2018/02/23.
• 3、 -. "A high-efficient environment friendly preparation method of quinolone ciprofloxacin drug (by machine translation)". Paragraph 0026; 0029; 0030. . Retrieved 2019/01/04.