77143-76-1

Usage

Uses

It is employed as intermediate for pharmaceutical.

InChI:InChI=1/C10H10Br2O2/c1-2-14-10(13)9(12)7-3-5-8(11)6-4-7/h3-6,9H,2H2,1H3

Upstream product

• 758692-47-6 ethyl α-diazo-α-(4-bromophenyl)acetate 
• 14062-25-0 Ethyl 4-bromophenylacetate 

Downstream Products

• 77143-74-9 2-{4-[(4-Bromo-phenyl)-ethoxycarbonyl-methoxy]-phenyl}-propionic acid methyl ester 
• 938453-24-8 5-(4-bromophenyl)-2-[(S)-1-(4-fluorophenyl)ethylamino]thiazol-4(5H)-one 
• 1221966-46-6 ethyl 2-azido-2-(4-bromophenyl)acetate 
• 1334550-67-2 3-[5-(4-bromophenyl)-4-hydroxythiazol-2-yl]thiobenzamide 
• 1334550-68-3 5-(4-bromophenyl)-2-[3-(4-hydroxy-5-phenylthiazol-2-yl)phenyl]thiazol-4-ol 
• 1334550-66-1 3-[5-(4-bromophenyl)-4-hydroxythiazol-2-yl]benzonitrile 
• 1334550-57-0 5,5'-bis(4-bromophenyl)-2,2'-bithiazole-4,4'-diol 
• 1454928-62-1 ethyl 2-acetoxy-2-(4-bromophenyl)acetate 
• 28718-78-7 5-Brom-2-(4-bromphenyl)-1-benzofuran 
• 1233941-59-7 5-(4-bromophenyl)-2-(pyridin-2-yl)-1,3-thiazol-4-ol 
• 14062-25-0 Ethyl 4-bromophenylacetate 
• 90841-19-3 3-(4-bromo-phenyl)-piperazin-2-one 

Relevant academic research and scientific papers

Bromination of α-Diazo Phenylacetate Derivatives Using Cobalt(II) Bromide

A method for the bromination of α-diazo phenylacetate derivatives using cobalt(II) bromide is described. This bromination reaction features a short reaction time, broad substrate scope, operational simplicity, acid-free conditions, and gram-scalability. (Figure presented.).

Discovery of 2-oxy-2-phenylacetic acid substituted naphthalene sulfonamide derivatives as potent KEAP1-NRF2 protein-protein interaction inhibitors for inflammatory conditions

Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor which regulates the constitutive and inducible transcription of a wide array of genes and confers protection against a variety of pathologies. Directly disrupting Kelch-like ECH-associated protein 1 (KEAP1)-NRF2 protein-protein interaction (PPI) has been explored as a promising strategy to activate NRF2. We reported here the first identification of a series of 2-oxy-2-phenylacetic acid substituted naphthalene sulfonamide derivatives as potent KEAP1-NRF2 inhibitors. Our efforts led to the potent small molecule KEAP1-NRF2 inhibitor, 20c, which exhibited a Kd of 24 nM to KEAP1 and an IC50 of 75 nM in disrupting KEAP1-NRF2 interaction. Subsequent biological studies provided consistent evidence across mouse macrophage cell-based and in vivo models that 20c induced NRF2 target gene expression and enhanced downstream antioxidant and anti-inflammatory activities. Our study not only demonstrated that small molecule KEAP1-NRF2 PPI inhibitors can be potential preventive and therapeutic agents for diseases and conditions involving oxidative stress and inflammation but also enriched the chemical diversity of the KEAP1-NRF2 inhibitors.

INHIBITORS OF HEPATITIS C VIRUS REPLICATION

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Construction of Pyrrolo[1,2-a]indoles via Cobalt(III)-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Base-Promoted Cyclization

A cobalt(III)-catalyzed cross-coupling reaction of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. The prepared 2-enaminylated indoles could be conveniently converted into pyrrolo[1,2-a]indoles, which are an important class of compounds in medicinal chemistry.

TYK2 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

Discovery of MK-8742: An HCV NS5A inhibitor with broad genotype activity

The NS5A protein plays a critical role in the replication of HCV and has been the focus of numerous research efforts over the past few years. NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays, making them attractive components for inclusion in all oral combination regimens. Early work in the NS5A arena led to the discovery of our first clinical candidate, MK-4882 [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin- 2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical proof-of-concept studies in HCV-infected chimpanzees harboring chronic genotype 1 infections resulted in significant decreases in viral load after both single- and multiple-dose treatments, viral breakthrough proved to be a concern, thus necessitating the development of compounds with increased potency against a number of genotypes and NS5A resistance mutations. Modification of the MK-4882 core scaffold by introduction of a cyclic constraint afforded a series of tetracyclic inhibitors, which showed improved virologic profiles. Herein we describe the research efforts that led to the discovery of MK-8742, a tetracyclic indole-based NS5A inhibitor, which is currently in phase 2b clinical trials as part of an all-oral, interferon-free regimen for the treatment of HCV infection. Effective treatment of chronic hepatitis C with direct-acting antivirals will require combination therapy with multiple agents that target different steps in the viral replication cycle and impose a high barrier to resistance. MK-8742 is a potent inhibitor of hepatitis C virus non-structural protein 5A (HCV NS5A) that is being developed as a component of an once-daily, all-oral, interferon-free regimen for the treatment of chronic HCV infection. Copyright

A one-pot preparation of 5-oxo 2,4-disubstituted 2,5-dihydro-1 H -imidazol-2-carboxylates from α-bromo esters

Nucleophilic substitution of a bromine atom by the azide group in aryl- and heteroaryl -α- bromoacetates triggers cascade reactions leading to imidazolin-5-ones formation. The α-azidoacetate intermediates undergo a transformation into non-isolable 2-imino

A practical synthesis of biaryls via a thermal decarboxylative Pd-catalyzed cross-coupling reaction operating at moderate temperature

The palladium-catalyzed decarboxylative cross-coupling of aminothiophene carboxylate and 1-bromo-4-chlorobenzene to produce 3-amino-2-(4-chlorophenyl) thiophene (2) is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and TBAB. Through use of a mixed-solvent system of DMF and NMP, it was possible to operate the cross-coupling system at 80 °C. An assessment of carbon dioxide liberation, which provides insight into the reaction operating parameters, is also discussed.

Generation of iminyl copper species from α-azido carbonyl compounds and their catalytic C-C bond cleavage under an oxygen atmosphere

Figure presented A copper-catalyzed reaction of α-azidocarbonyl compounds under an oxygen atmosphere is reported where nitriles are formed via C-C bond cleavage of a transient iminyl copper intermediate. The transformation is carried out by a sequence of denitrogenative formation of iminyl copper species from α-azidocarbonyl compounds and their C-C bond cleavage, where molecular oxygen (1 atm) is a prerequisite to achieve the catalytic process and one of the oxygen atoms of O2 was found to be incorporated into the β-carbon fragment as a carboxylic acid.

Further studies with the 2-amino-1,3-thiazol-4(5H)-one class of 11β-hydroxysteroid dehydrogenase type 1 inhibitors: Reducing pregnane X receptor activity and exploring activity in a monkey pharmacodynamic model

A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic