34402-92-1

Upstream product

• 1878-66-6 4-chlorophenylacetic Acid 
• 52449-43-1 (4-chloro-phenyl)-acetic acid methyl ester 
• 616-38-6 carbonic acid dimethyl ester 
• 108-90-7 chlorobenzene 
• 108-59-8 malonic acid dimethyl ester 
• 553-90-2 Dimethyl oxalate 

Downstream Products

• 118459-48-6 2-(4-chlorophenyl)propanedioic acid 
• 441798-36-3 C₁₉H₂₀BrClN₆O₄S 
• 441795-23-9 C₂₃H₂₀BrClN₆O₄S 
• 441795-22-8 C₁₉H₁₉ClN₄O₄S 
• 441797-27-9 C₁₇H₁₄Cl₂N₄O₂S 

Relevant academic research and scientific papers

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2-Amino Acids

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β2,2-amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity.

Organocatalytic Enantioselective Decarboxylative Protonation Reaction of Meldrum's Acid Derivatives under PTC Conditions

An original organocatalyzed enantioselective protonation sequence of a transient quaternary ammonium enolate species has been developed by starting from readily available disubstituted Meldrum's acid derivatives and phenols. Under phase-transfer-catalytic (PTC) conditions, chiral nonracemic 2-aryl propionic ester derivatives were obtained in good isolated yields with enantioselectivities up to 70 % ee. The usefulness of the approach was demonstrated by the synthesis of enantioenriched (S)-ibuprofen.

Gold(I)-Catalyzed Enantioselective Desymmetrization of 1,3-Diols through Intramolecular Hydroalkoxylation of Allenes

A gold(I)-catalyzed enantioselective desymmetrization of 1,3-diols was achieved by intramolecular hydroalkoxylation of allenes. The catalyst system 3-F-dppe(AuCl)2 /(R)-C8-TRIPAg proved to be specifically efficient to promote the desymmetrizing cyclization of 2-aryl-1,3-diols, which have proven challenging substrates in previous reports. Multisubstituted tetrahydrofurans were prepared in good yield with good enantioselectivity and diastereoselectivity by this method.

The discovery of N -[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]- N ′-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ET B receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clinical trial for pulmonary arterial hypertension.

4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors

A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.

Arylalkane-sulfonamides having endothelin-antagonist activity

The invention relates to novel aryl-alkane-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

Novel arylethene-sulfonamides

The invention relates to novel aryl-ethene-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

Anti-mycobacterial 4-hydroxy-3-phenylpyridin-2(1H)-ones

4-Hydroxy-3-phenylpyridin-2 (1H)-ones with different substituents either at N-1 or in the phenyl group were synthesized by reaction of ethyl β-aminocrotonates with dialkyl malonates or 'magic malonates' (2,4,6-trichlorophenyl malonates).The evaluation of these compounds on Mycobacterium tuberculosis H37Ra, Escherichia coli B and Staphylococcus aureus ATCC 25923 showed significant inhibitory effects on M tuberculosis (5g and 5s, MIC=8μg/ml).A structure-activity relationship is discussed.

DIMETHYL ARYLMALONATES FROM CERIUM(IV) AMMONIUM NITRATE PROMOTED REACTIONS OF DIMETHYL MALONATE WITH AROMATIC COMPOUNDS IN METHANOL

Aromatic compounds undergo homolytic malonylation by reaction with cerium(IV) ammonium nitrate and dimethyl malonate in methanol at room temperature.