6346-07-2

Usage

InChI:InChI=1/C16H17NO2/c1-19-15-9-7-14(8-10-15)16(18)17-12-11-13-5-3-2-4-6-13/h2-10H,11-12H2,1H3,(H,17,18)

Upstream product

• 64-04-0 phenethylamine 
• 100-09-4 4-methoxybenzoic acid 
• 156-28-5 2-phenylethylamine hydrochloride 
• 123-11-5 4-methoxy-benzaldehyde 
• 30364-57-9 4-methoxybenzoic acid 2,5-dioxo-1-pyrrolidinyl ester 
• 105-13-5 4-Methoxybenzyl alcohol 
• 1421426-87-0 4-methoxy-N-phenethylbenzimidoyl cyanide 
• 3424-93-9 4-methoxyphenylacetamide 
• 104-93-8 p-methylanizole 
• 1622923-47-0 potassium trifluoro(4-methoxybenzoyl)borate 
• 696-63-9 4-Methoxybenzenethiol 
• 201230-82-2 carbon monoxide 
• 69626-39-7 1-phenylbuta-2,3-dien-1-one 
• 1590361-11-7 O-diethylcarbamoyl-N-phenethylhydroxylamine 

Downstream Products

• 59224-73-6 1-(4'-methoxylphenyl)-3,4-dihydroisoquinoline 
• 17064-22-1 2-(4-methoxyphenyl)-5-phenyl oxazole 
• 81316-49-6 2-(4-methoxyphenyl)-5-phenyl-4,5-dihydrooxazole 
• 63272-45-7 4-bromo-2-(4-methoxy-phenyl)-5-phenyl-oxazole 
• 59224-74-7 1-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Development of a triazinedione-based dehydrative condensing reagent containing 4-(dimethylamino)pyridine as an acyl transfer catalyst

A new triazinedione-based reagent, (N,N′-dialkyl)triazinedione-4-(dimethylamino)pyridine (ATD-DMAP) was developed for the operationally simple dehydrative condensation of carboxylic acids. This reagent comprises an ATD core and DMAP as the leaving group, which is liberated into the reaction system to accelerate acyl transfer reactions. Upon adding ATD-DMAP to a mixture of carboxylic acids and alcohols in the presence of an amine base, the corresponding esters were formed rapidly at room temperature. Moreover, dehydrative condensation between carboxylic acids and amines using ATD-DMAP proceeded in high yield.

Discovery of quinuclidine modulators of cellular progranulin

Phenotypic screening of an annotated small molecule library identified the quinuclidine tetrahydroisoquinoline solifenacin (1) as a robust enhancer of progranulin secretion with single digit micromolar potency in a murine microglial (BV-2) cell line. Subsequent SAR development led to the identification of 29 with a 38-fold decrease in muscarinic receptor antagonist activity and a 10-fold improvement in BV-2 potency.

Allenone-Mediated Racemization/Epimerization-Free Peptide Bond Formation and Its Application in Peptide Synthesis

Allenone has been identified as a highly effective peptide coupling reagent for the first time. The peptide bond was formed with an α-carbonyl vinyl ester as the key intermediate, the formation and subsequent aminolysis of which proceed spontaneously in a racemization-/epimerization-free manner. The allenone coupling reagent not only is effective for the synthesis of simple amides and dipeptides but is also amenable to peptide fragment condensation and solid-phase peptide synthesis (SPPS). The robustness of the allenone-mediated peptide bond formation was showcased incisively by the synthesis of carfilzomib, which involved a rare racemization-/epimerization-free N to C peptide elongation strategy. Furthermore, the successful synthesis of the model difficult peptide ACP (65-74) on a solid support suggested that this method was compatible with SPPS. This method combines the advantages of conventional active esters and coupling reagents, while overcoming the disadvantages of both strategies. Thus, this allenone-mediated peptide bond formation strategy represents a disruptive innovation in peptide synthesis.

Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile

Proline racemases (PRAC), catalyzing the l-proline and d-proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T.?cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C.?difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4-oxopent-2-enoic acid TcPRAC irreversible inhibitors, we synthesized 4-aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C.?difficile. This study resulted in promising candidates and allowed for identification of (E)-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.

Cobalt catalysed aminocarbonylation of thiols in batch and flow for the preparation of amides

The synthesis of amides from thiols through a cobalt-catalyzed aminocarbonylation is shown. After optimizing all the reaction parameters, the methodology makes possible the obtention of amides with variable yields, while competing reactions such as the formation of disulfides and ureas can be limited. The process works well with aromatic thiols with electron donating groups (EDG) whereas other thiols give reaction with lower yields. The previous process has been transferred and optimized into flow equipment, thus allowing using less CO in a safer way, and permitting the scaling up of the synthesis. Two drugs, moclobemide and itopride were prepared with this methodology, albeit only in the second case with good results. A mechanistic pathway is proposed.

Chemoselective Amide-Forming Ligation Between Acylsilanes and Hydroxylamines Under Aqueous Conditions

We report the facile amide-forming ligation of acylsilanes with hydroxylamines (ASHA ligation) under aqueous conditions. The ligation is fast, chemoselective, mild, high-yielding and displays excellent functional-group tolerance. Late-stage modifications of an array of marketed drugs, peptides, natural products, and biologically active compounds showcase the robustness and functional-group tolerance of the reaction. The key to the success of the reaction could be the possible formation of the strong Si?O bond via a Brook-type rearrangement. Given its simplicity and efficiency, this ligation has the potential to unfold new applications in the areas of medicinal chemistry and chemical biology.

Visible Light-Driven Efficient Synthesis of Amides from Alcohols using Cu?N?TiO2 Heterogeneous Photocatalyst

Amides were synthesized from alcohols and amines in high yields using an in situ generated active ester of N-hydroxyimide with our developed Cu?N?TiO2 catalyst at room temperature using oxygen as a sole oxidant under visible light. The catalyst can be easily prepared, robust, and recycled four times without a considerable change in catalytic activity. This developed protocol applies to a wide substrate scope and has good functional group tolerance. The application of this amidation reaction has been successfully demonstrated for the synthesis of moclobemide, an antidepressant drug, and an analog of the itopride drug on a gram scale.

Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity

The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.

Development of Triazinone-Based Condensing Reagents for Amide Formation

Novel triazinone-based condensing reagents have been developed. The palladium-catalyzed O-N allylic rearrangement of 2-(allyloxy)-4,6-dichloro-1,3,5-triazine and subsequent regioselective substitution using alcohols and an amine afforded chlorotriazinones, which can be readily converted using N-methylmorpholine into the corresponding condensing reagents. The condensation of carboxylic acids and amines using these reagents proceeded to afford the desired amides in good yields. In comparison with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, the newly synthesized triazinone-based condensing reagents exhibited higher reactivity.

PROGRANULIN MODULATORS AND METHODS OF USING THE SAME

Provided herein are compounds that modulate progranulin and methods of using the compounds in progranulin-associated disorders, such as Frontotemperal dementia (FTD).