58457-64-0

Usage

Uses

Used in Pharmaceutical Industry:
2-Hydroxy-3-(trifluoromethyl)quinoxalin is used as a building block for the synthesis of pharmaceuticals. Its unique structure and functional groups make it a versatile intermediate for the production of diverse chemical compounds, which can be further utilized to develop new drugs with improved bioactivity and metabolic stability.
Used in Agrochemical Industry:
2-Hydroxy-3-(trifluoromethyl)quinoxalin is also used as a building block for the synthesis of agrochemicals. Its trifluoromethyl group contributes to the enhancement of bioactivity and metabolic stability, making it a valuable component in the development of effective and stable agrochemical products.

InChI:InChI=1/C9H5F3N2O/c10-9(11,12)7-8(15)14-6-4-2-1-3-5(6)13-7/h1-4H,(H,14,15)

Upstream product

• 13089-11-7 methyl 3,3,3-trifluoropyruvate 
• 95-54-5 1,2-diamino-benzene 
• 10321-14-9 α,α-dihydroxytrifluoropropionic acid 
• 13081-18-0 ethyl-3,3,3-trifluoropyruvate 
• 1196-57-2 quinoxalin-2⁽¹⁾-one 
• 2926-29-6 Langlois reagent 
• 431-72-1 3,3,3-trifluoro-2-oxopropanoic acid 
• 428-59-1 Hexafluoropropene oxide 
• 134641-36-4 methyl 3,3-dicyano-2-(trifluoromethyl)acrylate 
• 39971-65-8 bis(((trifluoromethyl)sulfinyl)oxy)zinc 
• 1196-57-2 2-hydroxyquinoxaline 

Downstream Products

• 1142190-60-0 3-(trifluoromethyl)quinoxaline-2-carboxylic acid 
• 254732-51-9 2-chloro-3-(trifluoromethyl)quinoxaline 
• 299434-96-1 4-benzoyl-3-cyclopropylethynyl-3-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-1H-quinoxalin-2-one 
• 299434-73-4 4-benzyl-3-cyclopropylethynyl-3-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-1H-quinoxalin-2-one 
• 253691-05-3 2-cyclopropylethynyl-3-(4-methoxy-benzyloxy)-2-trifluoromethyl-2H-quinoxaline-1-carboxylic acid ethyl ester 
• 253690-99-2 2-(4-methoxy-benzyloxy)-3-trifluoromethyl-quinoxaline 

Relevant academic research and scientific papers

Antiplasmodial 2-thiophenoxy-3-trichloromethyl quinoxalines target the apicoplast of Plasmodium falciparum

The identification of a plant-like Achille's Heel relict, i.e. the apicoplast, that is essential for Plasmodium spp., the causative agent of malaria lead to an attractive drug target for new antimalarials with original mechanism of action. Although it is not photosynthetic, the apicoplast retains several anabolic pathways that are indispensable for the parasite. Based on previously identified antiplasmodial hit-molecules belonging to the 2-trichloromethylquinazoline and 3-trichloromethylquinoxaline series, we report herein an antiplasmodial Structure-Activity Relationships (SAR) study at position two of the quinoxaline ring of 16 newly synthesized compounds. Evaluation of their activity toward the multi-resistant K1 Plasmodium falciparum strain and cytotoxicity on the human hepatocyte HepG2 cell line revealed a hit compound (3k) with a PfK1 EC50 value of 0.3 μM and a HepG2 CC50 value of 56.0 μM (selectivity index = 175). Moreover, hit-compound 3k was not cytotoxic on VERO or CHO cell lines and was not genotoxic in the in vitro comet assay. Activity cliffs were observed when the trichloromethyl group was replaced by CH3, CF3 or H, showing that this group played a key role in the antiplasmodial activity. Biological investigations performed to determine the target and mechanism of action of the compound 3k strongly suggest that the apicoplast is the putative target as showed by severe alteration of apicoplaste biogenesis and delayed death response. Considering that there are very few molecules that affect the Plasmodium apicoplast, our work provides, for the first time, evidence of the biological target of trichloromethylated derivatives.

Development of a Large-Scale Route to Glecaprevir: Synthesis of the Macrocycle via Intramolecular Etherification

Glecaprevir was identified as a potent hepatitis C virus (HCV) protease inhibitor, and a large-scale synthesis was required to support the late-stage clinical trials and subsequent commercial launch. The large-scale synthetic route to glecaprevir required the development of completely new synthetic approaches to the two key structural features: the 18-membered macrocycle 3 and the difluoromethyl-substituted cyclopropyl amino acid 4. In this first manuscript, we describe the route development for the macrocycle 3; the second manuscript will describe the development of a new synthetic route to the difluoromethyl-substituted cyclopropyl amino acid 4 and the final assembly of glecaprevir. The large-scale synthetic route to the macrocycle employed a unique intramolecular etherification reaction as the key step in the macrocycle synthesis, avoiding the scalability limitations of the ring-closing metathesis (RCM) reaction of the enabling route. The large-scale synthetic route to the macrocycle was successfully used to produce the amount of glecaprevir required to support the late-stage clinical development.

Visible Light-Induced Photocatalytic C?H Perfluoroalkylation of Quinoxalinones under Aerobic Oxidation Condition

An efficient approach using a photocatalytic strategy for C?H perfluoroalkylation of quinoxalinones under aerobic oxidation condition has been developed. Such transformation employs readily available sodium perfluoroalkanesulfinates as perfluoroalkylation reagents and demonstrates good functional group compatibility, affording corresponding products in moderate to good yields. Compared with previous procedures, this protocol uses oxygen as oxidant, and avoids the use of external additive. A radical mechanism is involved in this perfluoroalkylation reaction. (Figure presented.).

Direct C?H Trifluoromethylation of Quinoxalin-2(1H)-ones under Transition-Metal-Free Conditions

Disclosed herein is a direct C?H trifluoromethylation of quinoxalin-2(1H)-ones with sodium trifluoromethanesulfinate. This protocol affords a series of 3-trifluoromethylquinoxalin-2(1H)-one derivatives in moderate to excellent yields under transition-metal-free conditions. The present methodology features utilization of the inexpensive trifluoromethyl source without transition-metal-catalysts, mild reaction conditions and high functional group tolerance, which promises a convenient and efficient access to pharmaceutically interesting quinoxalinones. (Figure presented.).

3-trifluoromethyl quinoxalinone compound preparation method

The invention discloses a 3-trifluoromethyl quinoxalinone compound preparation method which comprises the following steps of in an inert gas atmosphere, adding a quinoxalinone compound, sodium trifluoromethanesulfinate and an oxidant in a solvent, performing reaction for 6-18 h at the temperature of 0-75 DEG C, and performing column chromatography separation and purification to obtain 3-trifluoromethyl substituted quinoxalinone compound. The 3-trifluoromethyl quinoxalinone compound preparation method provided by the invention is low in reagent cost, mild in reaction condition and simple in aftertreatment and is suitable for industrial production.

Synthetic route to anti-viral agents

The invention provides methods of synthesizing a viral protease inhibitor in high yield, without using expensive catalysts or challenging reaction conditions.

Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress

We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40–Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4.

Synthesis of new 2-substituted 3-(tri(di)fluoromethyl)-quinoxalines from 3-(trifluoromethyl)quinoxalin-2(1H)-oneand 3-(tri(di)fluoromethyl)quinoxaline-2-carboxylic acids

[Figure not available: see fulltext.] Starting from 3-(trifluoromethyl)quinoxalin-2(1H)-one, a wide range of new 2-substituted 3-(trifluoromethyl)quinoxalines were obtained, including amino, bromo, chloro, hydrazino, phenyl, α-furyl, formyl, methylsulfanyl, and methylsulfonyl derivatives. 3-(Tri(di)-fluoromethyl)quinoxaline-2-carboxylic acids were obtained for the first time and used for the synthesis of 2-amino-3-(tri(di)-fluoromethyl)quinoxalines and 2-(2-aminothiazol-4-yl)-3-(trifluoromethyl)quinoxaline.

Radical C-H functionalization of heteroarenes under electrochemical control

Electrochemical reactions are shown to be effective for the C-H functionalization of a number of heterocyclic substrates that are recalcitrant to conventional peroxide radical initiation conditions. Monitoring reaction progress under electrochemical conditions provides mechanistic insight into the C-H functionalization of a series of heterocycles of interest in medicinal chemistry.

MACROCYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS

The present invention relates to novel macrocyclic compounds and methods of treating a hepatitis C infection in a subject in need of such therapy with said macrocyclic compounds. The present invention further relates to pharmaceutical compositions compris