19352-59-1

Upstream product

• 4053-35-4 1,2-Dihydro-7-methylquinolin-2-one 
• 19342-88-2 3-chloro-N-(4-methylphenyl)propionamide 
• 7446-70-0 aluminium trichloride 
• 19352-22-8 3-chloro-N-(3-methylphenyl)propionamide 
• 24623-20-9 2,3-dihydro-6-methyl-1H-inden-1-one 
• 1536478-34-8 N-(5-methyl-2-vinylphenyl)formamide 
• 1536478-77-9 N-(2-bromo-5-methylphenyl)formamide 
• 108-44-1 1-amino-3-methylbenzene 
• 107-18-6 allyl alcohol 
• 99843-45-5 methyl (E)-3-(4′-methyl-2′-nitrophenyl)acrylate 
• 89-62-3 4-methyl-2-nitroaniline 
• 201230-82-2 carbon monoxide 
• 126759-35-1 4-methyl-2-nitro-1-vinylbenzene 
• 79-06-1 2-propenamide 

Downstream Products

• 58960-03-5 7-methyl-1,2,3,4-tetrahydroquinoline 

Relevant academic research and scientific papers

Visible-Light Induced C(sp2)?H Amidation with an Aryl–Alkyl σ-Bond Relocation via Redox-Neutral Radical–Polar Crossover

We report an approach for the intramolecular C(sp2)?H amidation of N-acyloxyamides under photoredox conditions to produce δ-benzolactams with an aryl-alkyl σ-bond relocation. Computational studies on the designed reductive single electron transfer strategy led us to identify N-[3,5-bis(trifluoromethyl)benzoyl] group as the most effective amidyl radical precursor. Upon the formation of an azaspirocyclic radical intermediate by the selective ipso-addition with outcompeting an ortho-attack, radical–polar crossover was then rationalized to lead to the rearomative ring-expansion with preferential C?C bond migration.

HETEROCYCLIC COMPOUNDS AND USES THEREOF

Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, lI-P, or III. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH).

Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.

RETRACTED ARTICLE: Site-selective enzymatic C-H amidation for synthesis of diverse lactams

A major challenge in carbon?hydrogen (C?H) bond functionalization is to have the catalyst control precisely where a reaction takes place. In this study, we report engineered cytochrome P450 enzymes that perform unprecedented enantioselective C?H amidation reactions and control the site selectivity to divergently construct b-, g-, and d-lactams, completely overruling the inherent reactivities of the C?H bonds. The enzymes, expressed in Escherichia coli cells, accomplish this abiological carbon?nitrogen bond formation via reactive iron-bound carbonyl nitrenes generated from nature-inspired acyl-protected hydroxamate precursors. This transformation is exceptionally efficient (up to 1,020,000 total turnovers) and selective (up to 25:1 regioselectivity and 97%, please refer to compound 2v enantiomeric excess), and can be performed easily on preparative scale.

Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones

A fast and effective one-pot tandem process that generates Heck coupled products from readily available anilines via stable aryl diazonium tosylate salts was developed. The mild and simple procedure involves rapid formation of aryl diazonium salts using a polymer-supported nitrite reagent and p-tosic acid, followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using 2-nitroanilines as substrates, the one-pot tandem process was extended for the direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4-dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion channel modulator.

Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives

The transition metal-catalyzed reductive cyclization of o-nitrostyrene in the presence of carbon monoxide (CO) has been developed to be a general synthetic route to an indole skeleton, wherein CO was used as a reductant to deoxidize nitroarene into nitrosoarene and/or nitrene with CO2 release, but the selective insertion of CO into the heterocyclic product with higher atom economy has not yet been realized. Herein, the Pd-catalyzed reduction of o-nitrostyrene by CO and its regioselective insertion were efficiently achieved to produce synthetically useful five- and six-membered benzo-fused lactams. Detailed investigations revealed that the chemoselectivity to indole or lactam was sensitive to the nature of the counteranions of Pd2+ precursors, whereas ligands significantly decided the carbonylative regioselectivity by different reaction pathways. Using PdCl2/PPh3/B(OH)3 (condition A), an olefin hydrocarboxylation was primarily initiated followed by partial reduction of the NO2 moiety and cyclization reaction to give N-hydroxyl indolin-2-one, which was further catalytically reduced by CO to afford the indolin-2-one as the final product with up to 95% yield. When the reaction was conducted under the Pd(TFA)2/BINAP/TsOH·H2O system (condition B), complete deoxygenation and carbonylation of the NO2 group occurred initially to yield the corresponding isocyanate followed by internal hydrocyclization to generate 3,4-dihydroquinolin-2-one with up to 98% yield. Importantly, the methodology could be efficiently applied in the synthesis of marketed drug Aripiprazole.

Traceless Directing-Group Strategy in the Ru-Catalyzed, Formal [3 + 3] Annulation of Anilines with Allyl Alcohols: A One-Pot, Domino Approach for the Synthesis of Quinolines

A unique, ruthenium-catalyzed, [3 + 3] annulation of anilines with allyl alcohols in the synthesis of substituted quinolines is reported. The method employs a traceless directing group strategy in the proximal C-H bond activation and represents a one-pot Domino synthesis of quinolines from anilines.

INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL

Compounds of Formula I and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Regiodivergent access to five- and six-membered benzo-fused lactams: Ru-catalyzed olefin hydrocarbamoylation

We report herein a new strategy of the Ru-catalyzed intramolecular olefin hydrocarbamoylation for the regiodivergent synthesis of five- and six-membered benzo-fused lactams starting from N-(2-alkenylphenyl)formamides. Using a combined catalyst of Ru3

Multicomponent multicatalyst reactions (MC)2R: One-pot synthesis of 3,4-dihydroquinolinones

A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical.