120690-68-8

Upstream product

• 872-85-5 pyridine-4-carbaldehyde 
• 4009-98-7 (methoxymethyl)triphenylphosphonium chloride 

Downstream Products

• 6302-13-2 4-<2-(4-pyrrolyl)ethyl>pyridine 

Relevant academic research and scientific papers

Catalytic Amination of β-(Hetero)arylethyl Ethers by Phosphazene Base t-Bu-P4

We describe the catalytic amination of β-(hetero)arylethyl ethers with amines using the organic superbase t-Bu-P4 to obtain β-(hetero)arylethylamines. The reaction has a broad substrate scope and allows the transformations of electron-deficient and electron-neutral β-(hetero)arylethyl ethers with various amines including pyrrole, N-alkylaniline, diphenylamine, aniline, indole, and indoline derivatives. Mechanistic studies indicate a two-reaction pathway of MeOH elimination from the substrate to form a (hetero)arylalkene followed by the hydroamination of the alkene.

Alkylidene Dihydropyridines As Synthetic Intermediates: Model Studies toward the Synthesis of the Bis(piperidine) Alkaloid Xestoproxamine C

Results of model studies demonstrating a stereoselective synthetic route to tricyclic analogues of the bis(piperidine) alkaloid xestoproxamine C are presented. Dearomatization of a tricyclic pyridine derivative to afford an alkylidene dihydropyridine (anhydrobase) intermediate followed by catalytic heterogeneous hydrogenation was used to install the correct relative stereochemistry about the bis(piperidine) ring system. Other key features of these model studies include development of an efficient ring-closing metathesis procedure to prepare macrocyclic derivatives of 3,4-disusbstituted pyridines, intramolecular cyclizations of alkylidene dihydropyridines to establish pyridine-substituted pyrrolidines and piperidines, successful homologation of pyridine-4-carboxaldehydes using formaldehyde dimethyl thioacetal monoxide (FAMSO), and application of B-alkyl Suzuki coupling to assemble substituted pyridines.

Novel Compounds

The invention relates to heteroaromatic carboxamides of formula (I), wherein A, R1, R2 and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts: Reaction with thiol groups giving rise to chromophoric (E)-1-alkyl-4-[2-(alkylsulfanyl)-1-ethenyl]pyridinium salts

(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (SNV) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO with an activation energy of 14 kcal mol-1. At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a second-order reaction (k = 4100 M-1s-1 at 30°C) and gave the corresponding substitution product with an intense long wavelength absorption band (λmax = 360 nm, ε = 27500 M-1cm-1). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.