228728-82-3

Basic information

• Product Name: 5,7-Difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester
• Synonyms: 5,7-Difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester
• CAS NO: 228728-82-3
• Molecular Formula: C12H9F2NO3
• Molecular Weight: 253.2015664
• Mol File: 228728-82-3.mol

Chemical Properties

• Boiling Point: 338.2°C at 760 mmHg
• Flash Point: 158.3°C
• Appearance: /
• Density: 1.386g/cm³
• Vapor Pressure: 9.99E-05mmHg at 25°C
• Refractive Index: 1.537
• CAS DataBase Reference: 5,7-Difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 5,7-Difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester(228728-82-3)
• EPA Substance Registry System: 5,7-Difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester(228728-82-3)

Safety Data

• Hazardous Substances Data: 228728-82-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C12H9F2NO3/c1-2-18-12(17)7-5-15-9-4-6(13)3-8(14)10(9)11(7)16/h3-5H,2H2,1H3,(H,15,16)

Upstream product

• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 372-39-4 3,5-difluoroaniline 
• 185010-69-9 2-[(3,5-Difluoro-phenylamino)-methylene]-malonic acid diethyl ester 

Downstream Products

• 1373767-19-1 ethyl 5,7-difluoro-2-(3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-20-4 ethyl 5,7-difluoro-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate 
• 1373767-21-5 ethyl 5,7-difluoro-4-oxo-2-(3-(trifluoromethoxy)phenyl)-1,4-dihydroquinoline-3-carboxylate 

Relevant articles and documents

Conjugate Addition Routes to 2-Alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-Alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates

Under CuBr·SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6-substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray crystallography).

QUINOLIN-4-ONE AND 4(1H)-CINNOLINONE COMPOUNDS AND METHODS OF USING SAME

The present disclosure relates to quinolin-4-one and 4(1H)-cinnolinone compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into tissue cells.

Fluorine walk: The impact of fluorine in quinolone amides on their activity against African sleeping sickness

Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity. This ‘fluorine walk’ led to new compounds with improved metabolic stability and consistent activity against T. b. brucei. The ability of the new quinolone amides to cross the BBB was confirmed using an 18F-labelled quinolone amide derivative by means of ex vivo autoradiography of a murine brain.

Lead optimization of 3-carboxyl-4(1 H)-quinolones to deliver orally bioavailable antimalarials

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

An NMR study of halogenated 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylates

Ethyl 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylate and 29 of its mono-, di-and tri-fluoro and/or -chloro derivatives were synthesized and their 1H, 13C and 19F NMR spectra were recorded. 1H, 13C and 19F chemical shifts, JHH, JFH, JCF and JFF coupling constants are reported. The 13C substituent chemical shift values of the chloro and fluoro substituents were calculated by linear multiple regression.