31238-50-3

Upstream product

• 615-43-0 2-iodophenylamine 
• 29800-93-9 diethyl phosphite 
• 762-04-9 phosphonic acid diethyl ester 
• 13294-40-1 ortho-nitro-phenylphosphonate diethylique 
• 42822-64-0 [2-(N-acetyl)aminophenyl]phosphonic acid diethyl ester 
• 615-36-1 2-bromoaniline 
• 122-52-1 triethyl phosphite 
• 577-19-5 2-nitrophenyl bromide 
• 10113-38-9 N-(2-bromophenyl)formamide 
• 762-04-9 Diethyl phosphonate 
• 1263913-86-5 (2-bromophenyl)carbamic acid 9H-fluoren-9-ylmethyl ester 
• 1263914-10-8 N-(9H-fluoren-9-ylmethoxycarbonyl)-2-aminophenylphosphonic acid diethyl ester 
• 608-30-0 2,6-dibromoaniline 
• 615-57-6 2,4-dibromo-aniline 

Downstream Products

• 71838-14-7 (2-iodophenyl)phosphonate de diethyle 
• 34595-07-8 2-Cyanphenylphosphonsaeurediethylester 
• 42822-64-0 [2-(N-acetyl)aminophenyl]phosphonic acid diethyl ester 
• 1158383-76-6 diethyl 2-(n-octylsulfonamido)phenylphosphonate 

Relevant academic research and scientific papers

Direct phosphonylation of mono- and dihalogenoanilines

The Pd(0)-catalyzed coupling reaction of diethyl phosphite to bromoaniline precursors or derivatives could not be realized at the ortho- position. On the other hand, the photoactivated substitution with diethyl phosphite anion was readily applied to unprotected mono- and dihalogenoanilines; the ortho-substitution was more rapid than the para, but side-products resulting from dehalogenation reactions were also formed. New fluorophosphonoanilines 8 and diphosphonoanilines 9 have been prepared.

Synthesis of Diethoxy Arylphosphoryl Functionalized, Fully Substituted 5-Triazenyl-1,2,3-triazoles via Chelation-Assisted Interrupted Domino Reaction of ortho -Azidophosphonates with Copper(I) Alkynes

We describe the synthesis of 1,4-disubstituted 5-triazenyl- 1,2,3-triazoles bearing diethoxy arylphosphoryl moieties via a domino reaction between ortho-azidophosphonates and premade copper(I) alkynides involving chelation-assisted [3+2] cycloaddition fol

Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C allosteric NS5B RdRp inhibitor

Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells, and as a consequence is an attractive target for selective inhibition. This paper describes the discovery of a novel family of HCV NS5B non-nucleoside inhibitors inspired by the bioisosterism between sulfonamide and phosphonamide. Systematic structural optimization in this new series led to the identification of IDX375, a potent non-nucleoside inhibitor that is selective for genotypes 1a and 1b. The structure and binding domain of IDX375 were confirmed by X-ray co-crystalisation study.

Solvent-controlled lithiation of PC-N-heterocycles: Synthesis of mono- and bis(trimethylsilyl)-tert-butyl-dihydrobenzazaphospholes - A new type of highly bulky and basic phosphine ligands

The influence of solvents on the lithiation of N-methyl-1,3- benzazaphospholes is reported; these are accessible via catalytic phosphonylation of 2-bromoanilines, subsequent reduction to 2-phosphinoanilines and acid-catalysed disproportionative ring closure with excess paraformaldehyde. Reactions with tBuLi in polar solvents (THF, Et2O), particularly in the presence of tBuOK, lead to 2-lithiobenzazaphospholes (CH-lithiation) whereas hydrocarbons favour normal (hexane) or inverse (toluene) addition at the PC bond. Reactive Li-species were trapped by ClSiMe3, present during the lithiation in hydrocarbons, and give rise to 2- and 3-trimethylsilyl-dihydro-1,3-benzazaphospholes, respectively. In hexane, via preferred lithiation of the primary adduct, the 2,2′- bis(trimethylsilyl)-dihydro-1,3-benzazaphosphole is the main product. 5-Methyl-1,3-benzazaphosphole, with NH function, reacts in toluene in the normal mode to 3-tert-butyl-1,2-bis(trimethylsilyl)-5-methyl- dihydrobenzazaphosphole. The sterically demanding tert-butyl and trimethylsilyl groups are arranged in anti-position as shown by crystal structure analyses, the second 2-SiMe3 group in gauche position. The P-tert-butyl-2, 2′-bis(trimethylsilyl)-dihydrobenzazaphospholes represent a new type of sterically congested dialkylaryl phosphine ligands with increased basicity by the +I-effect of the silyl groups and +M-effect of the basic nitrogen in o-position.

Syntheses of 2-unsubstituted 1h-1,3-benzazaphospholes from n-formyl-2-bromoanilides

The phosphonylation of 2-bromo-formylanilides 1 with triethyl phosphite in the presence of preformed Pd(0)(triethyl phosphite)n catalyst furnished 2-phosphono-formanilides 2 in good yields. Reduction with excess LiAlH4 provided mainl

PC-N-Heterocycles: Synthesis of biaryl-type 1,3-benzazaphospholes with ortho-substituted phenyl or 2-heteroaryl groups

A facile synthesis of functionally substituted 2-(hetero)aryl 1,3-benzazaphospholes via nickel- or palladium-catalyzed phosphonylation of N-acyl-2-bromoanilides 1a-k with triethyl phosphite is presented. Anilidophosphonates 2a-g with naphthoyl-, o-substituted phenyl, furoyl- or thenoyl groups allow direct reductive cyclization with LiAlH4 to benzazaphospholes 3. The reaction of the o-bromoderivative 2d proceeds with concomitant replacement of bromine by hydrogen, whereas the electron-withdrawing pyridyl group of 2h prevents the synthesis of 3h by this short route. An alternative synthesis of 2-pyridylbenzazaphosphole 3hvia anilidophosphonates succeeded starting from Fmoc-anilinophosphonate 2kvia selective cleavage of the N-protecting group, reduction of the resulting phosphonoaniline to phosphinoaniline and cyclization with pyridine-2-carboxaldehyde via a dihydrobenzazaphosphole 8. N-Substituted pyridylmethylbenzazaphosphole 9 was detected as a side product. The structure elucidation of the new compounds is based on multinuclear NMR data and X-ray crystal structure analyses of a phosphonoanilide, underlining the dominance of N-H...OP hydrogen bonds over N-H...OC type hydrogen bonds, of 3h and a supramolecular associate of 3b and its unprecedented air oxidation product 10.

Design and synthesis of small molecule glycerol 3-phosphate acyltransferase inhibitors

The incidence of obesity and other diseases associated with an increased triacylglycerol mass is growing rapidly, particularly in the United States. Glycerol 3-phosphate acyltransferase (GPAT) catalyzes the ratelimiting step of glycerolipid biosynthesis, the acylation of glycerol 3-phosphate with saturated long-chain acyl-CoAs. In an effort to produce small molecule inhibitors of this enzyme, a series of benzoic and phosphonic acids was designed and synthesized. In vitro testing of this series has led to the identification of several compounds, in particular 2-(nonylsulfonamido)benzoic acid (15g), possessing moderate GPAT inhibitory activity in an intact mitochondrial assay.

Direct synthesis of amino-substituted aromatic phosphonates via palladium-catalyzed coupling of aromatic mono-and dibromides with diethyl phosphite

An efficient Pd-catalyzed carbon-phosphorus bond-forming route is described for the direct synthesis of diethyl arylphosphonates bearing amino and alkylamino groups on the aromatic ring. Copyright

AMIDES AS SPHINGOMYELINE INHIBITORS

The present invention, relates to compounds of formula (I), wherein A is hydrogen or (C1-4)alkyl, R1 is a group Y-R2, Y is not present or is (C1-4)alkylene, which alkylene optionally is substituted, e.g. one or

DIARYLUREA DERIVATIVES AND THEIR USE AS CHLORIDE CHANNEL BLOCKERS

The present invention relates to novel diarylurea derivatives useful as chloride channel blockers. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of bone metabolic diseases, diseases responsive to modulation of the mast cell or basophil activity, diseases responsive to inhibition of angiogenesis, or sickle cell anaemia, and to pharmaceutical compositions comprising the compounds of the invention.