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Initial process development and scale-up of the synthesis of a triple reuptake inhibitor ALB 109780

Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eatons reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald-Hartwig coupling to install a morpholine moiety, and palladium-catalyzed alpha-arylation of a dihydroisoquinolinone to construct the core structure.

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

 

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Sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as potent carbonic anhydrase II/IX/XII inhibitors

In the current work, we report the discovery of new sulfonate and sulfamate derivatives of benzofuran- and benzothiophene as potent inhibitors of human carbonic anhydrases (hCAs) II, IX and XII. A set of derivatives, 1a?t, having different substituents on the fused benzofuran and benzothiophene rings (R = alkyl, cyclohexyl, aryl, NH2, NHMe, or NMe2) was designed and synthesized. Most of the derivatives exhibited higher potency than acetazolamide as inhibitors of the purified hCAII, IX and XII isoforms. The most potent inhibitors for hCAII, hCAIX and hCAXII were 1g, 1b and 1d with an IC50 ¡À SEM values of 0.14 ¡À 0.03, 0.13 ¡À 0.03 and 0.17 ¡À 0.06 muM, respectively. In addition, compounds 1d and 1n exerted preferential inhibitory effect against hCAXII isozyme with good potencies. Some selected compounds were docked within the active pocket of these isozymes and binding of the molecules revealed that sulfonate and sulfamate rings were located towards the active cavity and compounds coordinated to zinc ions.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Heterogeneously catalyzed direct C-H thiolation of heteroarenes

The first general methodology for the direct thiolation of electron-rich heteroarenes was developed by employing Pd/Al2O3, a recoverable and commercially available heterogeneous catalyst, and CuCl2. This method represents an operationally simple approach for the synthesis of these valuable compounds. Preliminary mechanistic studies indicate a heterogeneous catalytic system, in which both metals play a complementary role in the formation of the thiolated products. (Hetero)genius: A general method for the direct thiolation of electron-rich heteroarenes was developed by employing Pd/Al2O3, a recoverable and commercially available heterogeneous catalyst, and CuCl2. Preliminary mechanistic studies indicate a heterogeneous active catalytic species, with the two metals playing complementary roles in the formation of the thiolated products.

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

 

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Photoinduced Hydroxylation of Organic Halides under Mild Conditions

Presented in this paper is photoinduced hydroxylation of organic halides, providing a mild access to a range of functionalized phenols and aliphatic alcohols. These reactions generally proceed under mild reaction conditions with no need for a photocatalyst or a strong base and show a wide substrate scope as well as excellent functional group tolerance. This work highlights the unique role of NaI that allows a challenging transformation to proceed under mild reaction conditions.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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NOVEL COMPOUND AND ORGANIC ELECTROLUMINESCENCE DEVICE COMPRISING SAME

The present invention relates to a novel compound and an organic electroluminescence device including the same, and the compound according to the present invention may be used in an organic material layer, preferably a light-emitting layer of an organic electroluminescence device, thereby enhancing the light-emitting efficiency, driving voltage, lifespan, and the like of the organic electroluminescence device.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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One-Pot Domino Synthesis of Diarylalkynes/1,4-Diaryl-1,3-diynes by [9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene] (Xantphos)?Copper(I) Iodide?Palladium(II) Acetate-Catalyzed Double Sonogashira-Type Reaction

The low loading combination of the complex [9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene] (Xantphos)copper(I) iodide and simple ligand-free palladium(II) acetate was found to be efficient for the domino synthesis of diarylalkynes by the reaction of aryl halides with trimethylsilylethynylene or bis(trimethylsilyl)acetylene in a single-step procedure. The unsymmetrical diarylalkynes can be obtained through a one-pot two-step approach. The reactions of aryl bromides with 1,4-bis(trimethylsilyl)butadiyne also furnished the corresponding 1,4-diaryl-1,3-diynes in a similar fashion. This route to diarylalkynes and 1,4-diaryl-1,3-diynes is complementary to previously reported synthetic procedures. (Figure presented.).

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

 

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SELECTIVE ESTROGEN RECEPTOR MODULATORS CONTAINING A PHENYLSULFONYL GROUP

The present invention relates to a selective estrogen receptor modulator of formula I or a pharmaceutical acid addition salt thereof; useful, e.g., for treating endometriosis and/or uterine leiomyoma/leiomyomata.

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

 

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[Cu(NHC)]-Catalyzed C-H Allylation and Alkenylation of both Electron-Deficient and Electron-Rich (Hetero)arenes with Allyl Halides

New reactivity of a [Cu(NHC)] (NHC=N-heterocyclic carbene) catalyst is disclosed for the efficient C-H allylation of polyfluoroarenes using allyl halides in benzene at room temperature. The same catalyst system also promotes an isomerization-induced alkenylation of initially the generated allyl arenes when the reaction is run in tetrahydrofuran. Significantly, not only electron-deficient but also electron-rich (hetero)arenes undergo this double-bond migration process, thus leading to alkenylated products. The present system features mild reaction conditions, broad scope with respect to the arene substrates and allyl halide reactants, good functional-group tolerance, and high stereoselectivity.

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

 

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Catalytic Deprotonative alpha-Formylation of Heteroarenes by an Amide Base Generated in Situ from Tetramethylammonium Fluoride and Tris(trimethylsilyl)amine

Heteroarene formylations in DMF solution proceed in the presence of an amide base catalyst generated in situ from tetramethylammonium fluoride (TMAF) and tris(trimethylsilyl)amine (N(TMS)3). The reaction proceeds at room temperature and has an operationally simple procedure. Various heteroarenes, including benzothiophene, thiophene, benzothiazole, oxazole, and indole derivatives, can be formylated with high functional group tolerance.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross-Coupling

Catalytic enantioselective conjunctive cross-coupling has been developed to construct tertiary alkylboronic esters. These reactions occur with good yield and enantioselectivity for a range of substrates. Mechanistic experiments reveal aspects of the catalytic cycle that allow hindered substrates to react without significant complicating side reactions.

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