59089-68-8

Usage

Uses

Used in Pharmaceutical Industry:
2',4'-Difluoro-4-hydroxy biphenyl is used as an intermediate in the synthesis of Diflunisal (D445752), which is an analgesic and anti-inflammatory drug. Its role in the synthesis process is crucial for the development of effective pain relief and inflammation management medications.
As an intermediate, 2',4'-Difluoro-4-hydroxy biphenyl contributes to the production of Diflunisal by undergoing a series of chemical reactions that ultimately result in the formation of the desired analgesic and anti-inflammatory compound. This makes it an essential component in the pharmaceutical industry for the development and manufacturing of pain relief and inflammation management drugs.

Upstream product

• 59089-67-7 4-(2,4-difluorophenyl)phenyl acetate 
• 106-41-2 4-bromo-phenol 
• 497-19-8 sodium carbonate 
• 144025-03-6 2,4-difluorophenylboronic acid 
• 90101-30-7 2,4-difluoro-4'-methoxybiphenyl 
• 540-38-5 p-Iodophenol 
• 37847-52-2 2,4-difluorobiphenyl 
• 33527-94-5 4-acetoxyiodobenzene 

Downstream Products

• 98496-95-8 (+/-)-2-<4-(2,4-difluorophenyl)phenoxy>propionic acid 
• 849633-94-9 methyl 2-[(3-{3-[(2',4'-difluorobiphenyl-4-yl)oxy]propoxy}phenyl)sulfanyl]benzoate 
• 849633-90-5 methyl 4-[(4-{3-[(2',4'-difluorobiphenyl-4-yl)oxy]propoxy}phenyl)sulfanyl]benzoate 
• 849633-92-7 methyl 2-[(4-{3-[(2',4'-difluorobiphenyl-4-yl)oxy]propoxy}phenyl)sulfanyl]benzoate 
• 849633-91-6 methyl 4-[(4-{4-[(2',4'-difluorobiphenyl-4-yl)oxy]butoxy}phenyl)sulfanyl]benzoate 
• 849633-95-0 methyl 2-[(3-{4-[(2',4'-difluorobiphenyl-4-yl)oxy]butoxy}phenyl)sulfanyl]benzoate 
• 849633-96-1 methyl 4-[(3-{4-[(2',4'-difluorobiphenyl-4-yl)oxy]butoxy}phenyl)sulfanyl]benzoate 
• 849633-93-8 methyl 2-[(4-{4-[(2',4'-difluorobiphenyl-4-yl)oxy]butoxy}phenyl)sulfanyl]benzoate 
• 131587-93-4 3-[2-(2',4'-Difluoro-biphenyl-4-yloxy)-ethyl]-3H-quinazolin-4-one 
• 1300668-29-4 2,4-difluoro-4'-(3-nitro-benzyloxy)-biphenyl 
• 1300668-16-9 N-[3-(2',4'-difluoro-biphenyl-4-yloxymethyl)-phenyl]-succinamic acid 
• 1300668-32-9 [3-(2',4'-difluoro-biphenyl-4-yloxymethyl)-phenyl]-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Aniline analogs as glycogen synthase activators

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.

Diflunisal Analogues Stabilize the Native State of Transthyretin. Potent Inhibition of Amyloidogenesis

Analogues of diflunisal, an FDA-approved nonsteroidal antiinflammatory drug (NSAID), were synthesized and evaluated as inhibitors of transthyretin (TTR) aggregation, including amyloid fibril formation. High inhibitory activity was observed for 26 of the compounds. Of those, eight exhibited excellent binding selectivity for TTR in human plasma (binding stoichiometry > 0.50, with a theoretical maximum of 2.0 inhibitors bound per TTR tetramer). Biophysical studies reveal that these eight inhibitors dramatically slow tetramer dissociation (the rate-determining step of amyloidogenesis) over a duration of 168 h. This appears to be achieved through ground-state stabilization, which raises the kinetic barrier for tetramer dissociation. Kinetic stabilization of WT TTR by these eight inhibitors is further substantiated by the decreasing rate of amyloid fibril formation as a function of increasing inhibitor concentration (pH 4.4). X-ray cocrystal structures of the TTR·182 and TTR·202 complexes reveal that 18 and 20 bind in opposite orientations in the TTR binding site. Moving the fluorines from the meta positions in 18 to the ortho positions in 20 reverses the binding orientation, allowing the hydrophilic aromatic ring of 20 to orient in the outer binding pocket where the carboxylate engages in favorable electrostatic interactions with the ε-ammonium groups of Lys 15 and 15′. The hydrophilic aryl ring of 18 occupies the inner binding pocket, with the carboxylate positioned to hydrogen bond to the serine 117 and 117′ residues. Diflunisal itself appears to occupy both orientations based on the electron density in the TTR·12 structure. Structure-activity relationships reveal that para-carboxylate substitution on the hydrophilic ring and dihalogen substitution on the hydrophobic ring afford the most active TTR amyloid inhibitors.

Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid

A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising the reaction of an organometallic derivative with a suitable substituted benzene in the presence of a transition-metal based catalyst is described.

Process for the preparation of 4-(2,4-difluorophenyl)-phenyl 4-nitro-benzoate

A process for the preparation of 4-(2,4-difluorophenyl)-phenyl 4-nitro-benzoate, an intermediate for the preparation of 5-(2,4-difluorophenyl)-salicylic acid, which is a drug known with the international non-proprietary name Diflunisal, is described.

Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid

A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising the reaction of an organometallic derivative with a suitable substituted benzene in the presence of a transition-metal based catalyst is described.

Process for preparing 4-(2,4-difluorophenyl)-salicyclic acid

5-(2,4-difluorophenyl)salicylic acid, an anti-inflammatory, anti-pyretic, analgesic agent is prepared by: (1) diazotizing 2,4-difluoroaniline in the presence of benzene to yield 2,4-difluorobiphenyl; (2) Friedel-Crafts acylation to produce 2',4'-difluoro-4-alkanoylbiphenyl; (3) oxidation of the alkanoyl group to produce 2',4'-difluoro-4-alkanoyloxybiphenyl; (4) hydrolysis of the alkanoyl group to produce 4-(2,4-difluorophenyl)phenol; and (5) Kolbe-Schmitt carboxylation to produce the final product.