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Nickel-catalyzed difunctionalization of unactivated alkenes initiated by unstabilized enolates

This report demonstrates the possibility of a nickel-catalyzed difunctionalization of unactivated alkenes initiated by an unstabilized enolate nucleophile. The process tolerates a diverse range of electrophiles, including aryl, heteroaryl, alkenyl, and amino electrophiles. An electron-deficient phosphine ligand and a tetrabutylammonium salt additive were crucial for promoting efficient vicinal difunctionalization.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists

The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2?,6?-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to beta-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4?-(2-ethoxyethoxy)-2?,6?-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Regiospecific alkyl addition of (hetero)arene-fused thiophenes enabled by a visible-light-mediated photocatalytic desulfuration approach

A photoredox-mediated, regiospecific alkyl addition reaction of (hetero)arene-fused thiophenes has been developed, employing bench-stable N-benzoyl alkyl-sulfinamides as the alkyl sources. This protocol offers a unique desulfuration approach to generate alkyl radicals that proceeds via nitrogen-centered radical intermediates.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Synthesis of Diiodinated All-Carbon 3,3?-Diphenyl-1,1?-spirobiindene Derivatives via Cascade Enyne Cyclization and Electrophilic Aromatic Substitution

A synthetic method for the construction of diiodinated all-carbon spirobiindene derivatives has been developed from the reaction of propargyl alcohol-tethered alkylidenecyclopropanes with iodine. The reaction proceeded through an iodination-initiated cascade intramolecular enyne cyclization and electrophilic aromatic substitution reaction process in 1,2-dichloroethane upon heating, giving desired spirocyclic products in moderate to excellent yields. Further transformation of the obtained products has also been presented.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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1, 1, 2, 2 – Tetraborate ethylene, and preparation method and application thereof (by machine translation)

The invention discloses 1, 1, 2, 2 – tetraborate ethylene and a preparation method and application, 1, 1, 2, 2 – tetraborate ethylene, and the structural formula thereof is: Where. 1, 1, 2, 2 – Tetraborate ethylene and halogenated aromatic hydrocarbon are coupled to obtain a tetraaryl substituted ethylene compound, and a novel and rapid way is provided for synthesis of the tetraaryl substituted ethylene compound. (by machine translation)

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 2. 6,6-dimethylbicyclo[3.1.1]heptane derivatives

In an earlier paper, we reported that novel prostaglandin D2 (PGD2) receptor antagonists having the bicyclo[2.2.1]heptane ring system as a prostaglandin skeleton were a potent new class of antiallergic agents and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, we synthesized PGD2 receptor antagonists having the 6,6-dimethylbicyclo [3.1.1]heptane ring system. These derivatives have the amide moiety, in contrast to those with the bicyclo[2.2.1]heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo[3.1.1]heptane ring also exhibited strong activity in PGD2 receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacological profiles. In particular, compound 45 also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (45, S-5751) is now being developed as a promising alternative antiallergic drug candidate.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Direct Carboxylation of Electron-Rich Heteroarenes Promoted by LiO-tBu with CsF and [18]Crown-6

We herein demonstrate that the combination of LiO-tBu, CsF, and [18]crown-6 efficiently promotes the direct C?H carboxylation of electron-rich heteroarenes (benzothiophene, thiophene, benzofuran, and furan derivatives). A variety of functional groups, including methyl, methoxy, halo, cyano, amide, and keto moieties, are compatible with this system. The reaction proceeds via the formation of a tert-butyl carbonate species.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Deprotonative Silylation of Aromatic C-H Bonds Mediated by a Combination of Trifluoromethyltrialkylsilane and Fluoride

A method for the deprotonative silylation of aromatic C-H bonds has been developed using trifluoromethyltrimethylsilane (CF3SiMe3, Ruppert-Prakash reagent) and a catalytic amount of fluoride. In this reaction, CF3SiMe3 is considered to act as a base and a silicon electrophile. This process is highly tolerant to various functional groups on heteroarenes and benzenes. Furthermore, this method can be applied to the synthesis of trimethylsilyl group-containing analogs of TAC-101, which is a bioactive synthetic retinoid with selective affinity for retinoic acid receptor alpha (RAR-alpha) binding. We also report further transformations of the silylated products into useful derivatives.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Rhodium-Catalyzed 1,1-Hydroacylation of Thioacyl Carbenes with Alkynyl Aldehydes and Subsequent Cyclization

A rhodium-catalyzed 1,1-hydroacylation of thioacyl carbenes with alkynyl and alkenyl aldehydes and subsequent 6-endo-trig/dig cyclization are realized, giving structurally diverse 4H-thiopyran-4-ones and 2,3-dihydro-4H-thiopyran-4-ones in moderate to good yields. The oxidative addition of Rh(I) to aldehydes is proposed to be the turnover-limiting step. Manipulations of estrones demonstrate the applications of our formal (3 + 3) transannulations in the structural modifications of natural products.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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PIPERIDINE DERIVATIVES FOR GPR119 AGONIST

The present invention relates to novel piperidine derivatives, stereoisomers thereof or pharmaceutically acceptable salts thereof; methods for preparing the compound; and pharmaceutical compositions comprising the compound. The novel piperidine derivatives, according to the present invention, having an effect as GPR119 agonist can be used for treatment of metabolic disorders, including diabetes mellitus (especially type II) and related disorders.

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Reference£º
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem