199186-69-1

Usage

Uses

Used in Medicinal Chemistry:
(R)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline is utilized as a key intermediate in the synthesis of various pharmaceutical agents due to its unique structural features and potential biological activity. Its chiral nature allows for the development of enantiomer-specific drugs, which can have different pharmacological effects and reduce potential side effects.
Used in Drug Development:
In the pharmaceutical industry, (R)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline serves as a promising candidate for drug development. Its tetrahydroquinoline core and the presence of a fluorine atom may enhance the compound's lipophilicity, metabolic stability, and receptor binding affinity, which are crucial factors in the design of effective drugs.
Used in Bioactive Compound Research:
(R)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline is employed as a starting point for research into new bioactive compounds. Its structural features can be modified to explore a range of biological activities, such as antimicrobial, antiviral, anticancer, or central nervous system effects, contributing to the discovery of novel therapeutic agents.
Used in Chemical Synthesis:
As a chemical compound with a tetrahydroquinoline core and a fluorine substituent, (R)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline is used in the synthesis of a variety of complex organic molecules. Its unique properties can be leveraged to create new chemical entities with potential applications in various fields, including materials science and specialty chemicals.

Upstream product

• 1128-61-6 6-fluoro-2-methyl-quinoline 
• 42835-89-2 6-fluoro-1,2,3,4-tetrahydro-2-methylquinoline 
• 147851-69-2 (R)-2-phenoxypropionyl chloride 
• 623-03-0 4-Cyanochlorobenzene 
• 98-56-6 4-chlorobenzotrifluoride 
• 54731-09-8 N-tosyl-L-prolyl chloride 
• 3183-10-6 N-phthalimide-L-leucinyl chloride 
• 32150-91-7 phthaloyl-L-phenylalanyl chloride 
• 51091-84-0 (S)-naproxenoyl chloride 

Downstream Products

• 1128-61-6 6-fluoro-2-methyl-quinoline 
• 233765-85-0 9-fluoro-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid ethyl ester 
• 215178-95-3 R-(+)-flumequine 
• 233765-83-8 2-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-ylmethylene)-malonic acid diethyl ester 

Relevant academic research and scientific papers

Resolution of the flumequine intermediate 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline

Racemic 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) was resolved by the N-phthaloyl derivative of the (R)-enantiomer. The enantiomeric mixture was very effectively enriched by recrystallisation from either the melt (working best for mixtures of relatively high starting enantiomeric purities) or from solution of its hydrochloride salt (giving good results when applied for mixtures of moderate to medium enantiomeric purities). Copyright (C) 2000 Elsevier Science Ltd.

Low-Temperature Nickel-Catalyzed C?N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand

The transition-metal-catalyzed C?N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as ?50 °C), enantioselective Ni-catalyzed C?N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2-symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.

Development of efficient solid chiral catalysts with designable linkage for asymmetric transfer hydrogenation of quinoline derivatives

This vertically self-pillared (VSP) structure extends the application range of traditional porous materials with facile mass/ion transport and enhanced reaction kinetics. Here, we prepare a single crystal metal-organic framework (MOF), employing the ZIF-67 structure as a proof of concept, which is constructed by vertically self-pillared nanosheets (VSP-MOF). We further converted VSP-MOF into VSP-cobalt sulfide (VSP-CoS2) through a sulfidation process. Catalysis plays an important role in almost all battery technologies; for metallic batteries, lithium anodes exhibit a high theoretical specific capacity, low density, and low redox potential. However, during the half-cell reaction (Li++e=Li), uncontrolled dendritic Li penetrates the separator and solid electrolyte interphase layer. When employed as a composite scaffold for lithium metal deposition, there are many advantage to using this framework: 1) the VSP-CoS2 substrate provides a high specific surface area to dissipate the ion flux and mass transfer and acts as a pre-catalyst, 2) the catalytic Co center favors the charge transfer process and preferentially binds the Li+ with the enhanced electrical fields, and 3) the VSP structure guides the metallic propagation along the nanosheet 2D orientation without the protrusive dendrites. All these features enable the VSP structure in metallic batteries with encouraging performances.

Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification of analogues that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.

Deracemization of Phenyl-Substituted 2-Methyl-1,2,3,4-Tetrahydroquinolines by a Recombinant Monoamine Oxidase from Pseudomonas monteilii ZMU-T01

A monoamine oxidase (MAO5) from Pseudomonas monteilii ZMU-T01 was first heterologously expressed in Escherichia coli BL21(DE3) and then used as a biocatalyst for the deracemization of racemic 2-methyl-1,2,3,4-tetrahdroquinoline derivatives to yield the unreacted R enantiomer with up to >99 % ee. Sequence alignment revealed that MAO5 shared 14.7 % identity toward the well-studied monoamine oxidase (MAO-N).

Enantioselective hydrogenation of N-heteroaromatics catalyzed by chiral diphosphine modified binaphthyl palladium nanoparticles

The first application of binaphthyl-stabilized palladium nanoparticles (Bin-PdNPs) with chiral modifiers in asymmetric hydrogenation of N-heteroaromatics is revealed. With an appropriate ratio of R-BINAP/Bin-PdNPs used, the pre-prepared chiral nanocatalyst achieves asymmetric hydrogenations of 2-substituted quinolines with good to excellent yields and moderate enantioselectivities, which showed superior catalytic properties to the R-BINAP/Pd complex. Moreover, this protocol is also applicable to 2-substituted indoles.

Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functional groups. The most potent EPAC inhibitor 12a exists as a mixture of inseparable E (major) and Z (minor) rotamers. The rotation about the N-formyl group indeed impacts the activity against EPAC.

Acylative kinetic resolution of racemic heterocyclic amines with (R)-2-phenoxypropionyl chloride

The acylative kinetic resolution of racemic heterocyclic amines such as 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines, 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine, 2-methyl-1,2,3,4-tetrahydro-quinolines and 2-methylindoline with enantiopure (R)-2-phenoxypropionyl chloride has been studied. It has been found that acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine proceeds with the best stereoselectively when compared with other racemic amines. An efficient method for the preparation of (S)-3,4-dihydro-3-methyl-2H-[1,4]benzothiazine (99.4% ee) via a kinetic resolution protocol was developed. The possibility of recycling (R)-2-phenoxypropionic acid has been demonstrated.

A supramolecularly tunable chiral diphosphine ligand: Application to Rh and Ir-catalyzed enantioselective hydrogenation

A supramolecularly tunable chiral bisphosphine ligand bearing two pyridyl-containing crown ethers, (-) or (+)-Xyl-P16C6-Phos, was fabricated and utilized in the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid esters and Ir-catalyzed asymmetric hydrogenation of quinolines in high yields with excellent enantioselectivities (90-99% ee). Up to a 22% enhancement in enantioselectivity was achieved by the addition of certain amounts of alkali ions (Li+, Na+ or K+), which could be selectively recognized and effectively complexed by the crown ethers on the chiral Xyl-P16C6-Phos.

Solvent-Regulated Asymmetric Hydrogenation of Quinoline Derivatives in Oligo(Ethylene Glycol)s through Host–Guest Interactions

The asymmetric hydrogenation of quinolines in oligo(ethylene glycol)s (OEGs) and poly(ethylene glycol)s (PEGs) with chiral cationic ruthenium diamine complexes has been investigated. Interestingly, in liquid PEGs or long-chain OEGs, the Ru catalysts lost their reactivity. Upon the addition of a little MeOH, the hydrogenation of quinoline was switched “ON”. Evidence from mass spectrometry and control experiments revealed that encapsulation of the quinolinium salt by PEG or long-chain OEG molecules through supramolecular interactions is possibly the main reason for such a switchable hydrogenation reaction. Moreover, the asymmetric hydrogenation of 2-substituted quinoline derivatives was achieved in triethylene glycol (3-OEG), thereby affording 1,2,3,4-tetrahydroquinolines with excellent reactivities and enantioselectivities (up to 99 % ee). Furthermore, the Ru catalyst could be readily recycled for both pure 3-OEG and biphasic 3-OEG/n-hexane systems without a clear loss of reactivity and enantioselectivity.