335640-50-1

Basic information

• Product Name: 5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLIC ACID
• Synonyms: 5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLIC ACID;5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid
• CAS NO: 335640-50-1
• Molecular Formula: C₁₁H₈ClNO₄
• Molecular Weight: 253.64
• Mol File: 335640-50-1.mol
• Article Data: 1

Chemical Properties

• Melting Point: 294.9-295.1 °C
• Boiling Point: 396.6°Cat760mmHg
• Flash Point: 193.7°C
• Appearance: /
• Density: 1.644g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.691
• PKA: 1.16±0.20(Predicted)
• CAS DataBase Reference: 5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLIC ACID(335640-50-1)
• EPA Substance Registry System: 5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLIC ACID(335640-50-1)

Safety Data

• Hazardous Substances Data: 335640-50-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C11H8ClNO4/c1-13-6-4-2-3-5(12)7(6)9(14)8(10(13)15)11(16)17/h2-4,14H,1H3,(H,16,17)

Upstream product

• 67-56-1 methanol 
• 248281-84-7 laquinimod 
• 64-17-5 ethanol 

Downstream Products

• 248281-84-7 laquinimod 
• 1214267-09-0 N-ethyl-N-D₅-phenyl-1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide 

Relevant articles and documents

Synthesis and reactivity of laquinimod, a quinoline-3-carboxamide: Intramolecular transfer of the enol proton to a nitrogen atom as a plausible mechanism for ketene formation

5-Chloro-N-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3- quinolinecarboxamide (laquinimod, 2) is an oral drug in clinical trials for the treatment of multiple sclerosis. The final step in the synthesis of 2 is a high-yielding aminolysis reaction of ester 1 with N-ethylaniline. An equilibrium exists between 1 and 2, and removal of formed methanol during the reaction is a prerequisite for obtaining high yields of 2 from 1. The reactivity of 1 and 2 is explained by a mechanistic model that involves a transfer of the enol proton to the exocyclic carbonyl substituent with concomitant formation of ketene 3. This proton transfer is especially facilitated for 2 because the intramolecular hydrogen bond to the carbonyl oxygen is weakened due to steric interactions. Both 1 and 2 undergo solvolosis reactions that obey first-order reaction kinetics, further supporting the theory that these two molecules are able to decompose unimolecularly into ketene 3. The solvent-dependent spectroscopic features of 2 indicate that the molecule mainly resides in two conformations. One conformation is favored in nonpolar solvents and is likely the result of intramolecular hydrogen bonding. The other conformation is favored in polar solvents and probably exhibits less intramolecular hydrogen bonding.