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Rhodium-Catalyzed Synthesis of 4-Bromo-1,2-dihydroisoquinolines: Access to Bromonium Ylides by the Intramolecular Reaction of a Benzyl Bromide and an alpha-Imino Carbene

Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the alpha-imino rhodium carbene formed in the presence of the rhodium catalyst.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H3146N – PubChem

 

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Efficient asymmetric synthesis of Reissert compounds

Asymmetric synthesis of Reissert compounds 5, 12 was achieved using chiral acyl halides such as amino acid fluorides or (-)-(R)-menthylchloroformate and TMSCN. These are the first cases of asymmetric synthesis of unsubstituted isoquinoline-derived Reissert compounds with high stereoselectivities. The chiral Reissert compound 12 could be alkylated in position 1 affording 1-substituted Reissert compound 13 highly stereoselectively. The products are potential starting materials for unnatural amino acids and alkaloid analogues.

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6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists

A series of N-[{2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-pyridin-3-yl}methyl] N?-(6,6-fused heterocyclic) ureas have been investigated as hTRPV1 antagonists. Among them, compound 15 showed highly potent TRPV1 antagonism to capsaicin, with Ki(ant) = 0.2 nM, as well as antagonism to other activators, and it was efficacious in a pain model. A docking study of 15 with our hTRPV1 homology model indicates that there is crucial hydrogen bonding between the ring nitrogen and the receptor, contributing to its potency.

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Isoquinoline – Wikipedia,
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Phosphine-free palladium-catalyzed decarboxylative coupling of alkynylcarboxylic acids with aryl and heteroaryl halides

We herein report the design and development of a carboxyamido/carbene ligand and its Pd-complex for the decarboxylative coupling of alkynylcarboxylic acids with aryl and heteroaryl halides to afford arylalkynes. Copyright

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Isoquinoline – Wikipedia,
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PYRIDAZIN-3(2H)-ONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS

The invention relates to new therapeutically useful pyridazin-3(2H)-one derivatives of Formula (I) and to pharmaceutical compositions containing them. These compounds are potent and selective inhibitors of phosphodiesterase 4 (PDE4) and are thus useful in the treatment, prevention or suppression of pathological conditions, diseases and disorders known to be susceptible of being improved by inhibition of PDE4 such as asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable bowel disease.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H2912N – PubChem

 

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Reductive carbonylation of aryl halides employing a two-chamber reactor: A protocol for the synthesis of aryl aldehydes including 13C- and D-isotope labeling

A protocol has been developed for conducting the palladium-catalyzed reductive carbonylation of aryl iodides and bromides using 9-methylfluorene-9- carbonyl chloride (COgen) as a source of externally delivered carbon monoxide in a sealed two-chamber system (COware), and potassium formate as the in situ hydride source. The method is tolerant to a wide number of functional groups positioned on the aromatic ring, and it can be exploited for the isotope labeling of the aldehyde group. Hence, reductive carbonylations run with 13COgen provide a facile access to 13C-labeled aromatic aldehydes, whereas with DCO2K, the aldehyde is specifically labeled with deuterium. Two examples of double isotopic labeling are also demonstrated. Finally, the method was applied to the specific carbon-13 labeling of the beta-amyloid binding compound, florbetaben.

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Isoquinoline – Wikipedia,
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Palladium-catalyzed direct arylation of thiophenes bearing SO2R substituents

The palladium-catalyzed direct arylation of SO2R-substituted thiophene derivatives was found to proceed regioselectively at C5 and in high yields using a variety of aryl bromides and as low as 0.5-0.1 mol % of phosphine-free Pd(OAc)2 as the catalyst. For these reactions, sulfonyls, sulfonamides, or even a sulfonic ester as the thiophene substituents were successfully employed.

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Isoquinoline – Wikipedia,
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A photoredox-mediated direct cross-dehydrogenative coupling reaction to accomplish alpha-aminoalkylation of N-heteroarenes is reported. This mild reaction has a broad substrate scope, offers the first general method for synthesis of aminoalkylated N-heteroarenes without the need for substrate prefunctionalization, and is scalable to the gram level. Furthermore, the reaction was found to be applicable to other hydrogen donors besides amines (i.e., ethers, an aldehyde, a formamide, p-xylene, and alkanes), thus enabling the preparation of N-heteroarenes bearing various types of substituents.

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Isoquinoline – Wikipedia,
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A novel compound represented by the following formula (1) or a salt thereof [wherein R1, R5, R6, R7, and R8 represent hydrogen atom, a halogen atom, hydroxyl group, an alkyl group, an alkenyl group and the like; X1 . . . X2 represents ?CH(R2)?CH(R3)?, ?CH(R2)?CH(R3)?CH(R4)?, ?C(R2)?C(R3)?, or ?C(R2)?C(R3)?CH(R4)?(R2, R3, and R4 represent hydrogen atom, or an alkyl group); A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents ?CH(A3)-, ?CH(A3)-C(A4)(A41)-, ?CH(A3)-C(A4)(A41)-C(A5)(A51)-, or a single bond (A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group), and Z represents hydroxyl group, or ?N(A6)(A61)(A6 represents hydrogen atom, or an alkyl group, and A61 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like)], having an action of potently inhibiting phosphorylation of myosin regulatory light chain. [image]

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Reference:
Isoquinoline – Wikipedia,
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A cascade (cyclo)isomerization/elimination process produces novel isoquinoline derivatives of potential interest for pharmaceutical, biomedical, and energy-related research. Mechanistic experiments support a putative allenylpyridine (reminiscent of the Garratt-Braverman cyclization) as a key intermediate in the cascade process.

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Isoquinoline – Wikipedia,
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