362610-10-4

Upstream product

• 403-32-7 (4-fluorophenyl)glyoxal 
• 762292-74-0 2,2-difluoro-2-(4-fluorophenyl)ethanol 
• 405-99-2 para-fluorostyrene 
• 118887-66-4 1-(2-bromo-1-fluoroethyl)-4-fluorobenzene 
• 762292-69-3 1-(2-bromo-1,1-difluoroethyl)-4-fluorobenzene 
• 762292-71-7 2,2-difluoro-2-(4-fluorophenyl)ethyl acetate 

Downstream Products

• 762292-79-5 ethyl 3,3-difluoro-3-(4-fluorophenyl)-2-hydroxypropionate 
• 762292-82-0 ethyl 3,3-difluoro-3-(4-fluorophenyl)-2-oxopropionate 
• 762292-85-3 3,3-difluoro-3-(4-fluorophenyl)-2-oxopropionic acid 
• 762292-76-2 3,3-difluoro-3-(4-fluorophenyl)-2-hydroxypropionitrile 

Relevant academic research and scientific papers

HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS

The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α- difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α- oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro- β-phenylalanine derivatives (4). Enantiomerically pure β,β- difluorophenylalanine (L-4a) was obtained when α,α-difluoro-α- phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pKa values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (Ki 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.

Polyfluoroether derivatives via nucleophilic fluorination of glyoxal hydrates with Deoxofluor

Various glyoxal hydrates have been reacted with Deoxofluor [(CH3OCH2CH2)2NSF3]. In concentrated solutions of dichloromethane, Deoxofluor (1) efficiently fluorinates a variety of glyoxal hydrates, RCOC

Concentration-dependent reactions of deoxofluor with arylglyoxal hydrates: A new route to polyfluoro ethers

(Equation presented) In concentrated solutions (CH2Cl2) at 25°C, arylglyoxal hydrates, ArCOCHO·H2O (Ar = 3,4-OCH2O-C6H3-, 4-MeO-C6H4-, 4-Me-C6H4-, 4-F-C6H4-, Ph-, S-CH=CH-CH=C-) (2a-f) with Deoxofluor gave fluorinated ethers, ArCF2CHFOCHFCF2Ar, (3a-f) in >90% yields as meso/racemic mixtures (～1:1). Under very dilute conditions, mixtures of ArCF2CHO (major) (4a-f) and ArCF2CF2H (6a-f) (minor) were obtained. The structures of 3b (racemic) and 4a (meso) have been confirmed by single-crystal X-ray analysis.