A facile synthesis of 7-halo-5H-indeno[1,2-b]pyridines and -pyridin-5-ones

DuPriest, Mark T.; Schmidt, Charles L.; Kuzmich, Daniel; Williams, Stanly B.

doi:10.1021/jo00361a015

Cited by 45 publications

(22 citation statements)

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“…5,5-Bis(4-pyridinylmethyl)-5H-indeno[1,2-b]pyridine, Hemihydrate (2). To a suspension of sodium hydride (60% in oil, 3.34 g, 83.5 mmol) in 100 mL of THF at room temperature were added a solution of 4-azafluorene (14) 41,42 (4.16 g, 25 mmol) and 1 drop of ethanol. A solution of 4-picolyl chloride in benzene (prepared from 9.79 g, 59.7 mmol, of the hydrochloride salt, free-based with sodium carbonate, extracted into benzene, and dried over sodium sulfate) was subsequently added to the reaction mixture via addition funnel.…”

Section: -Fluoro-4-(iodomethyl)pyridine (13)mentioning

confidence: 99%

2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

et al. 1998

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In an effort to improve the pharmacokinetic and pharmacodynamic properties of the cognition-enhancer linopirdine (DuP 996), a number of core structure analogues were prepared in which the 4-pyridyl pendant group was systematically replaced with 2-fluoro-4-pyridyl. This strategy resulted in the discovery of several compounds with improved activity in acetylcholine (ACh) release-enhancing assays, in vitro and in vivo. The most effective compound resulting from these studies, 10, 10-bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (9), is between 10 and 20 times more potent than linopirdine in increasing extracellular hippocampal ACh levels in the rat with a minimum effective dose of 1 mg/kg. In addition to superior potency, 9 possesses an improved pharmacokinetic profile compared to that of linopirdine. The half-life of 9 (2 h) in rats is 4-fold greater than that of linopirdine (0.5 h), and it showed a 6-fold improvement in brain-plasma distribution over linopirdine. On the basis of its pharmacologic, pharmacokinetic, absorption, and distribution properties, 9 (DMP543) has been advanced for clinical evaluation as a potential palliative therapeutic for treatment of Alzheimer's disease.

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Section: -Fluoro-4-(iodomethyl)pyridine (13)mentioning

confidence: 99%

2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

et al. 1998

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“…22,23 Substrates 1–6 and 9 were synthesized via Suzuki coupling of 2-bromo-3-methylpyridine with the corresponding arylboronic acids. 24 Pyridine substrates 11–13 were also prepared Suzuki couplings of 2-bromopyridine derivatives with o-tolylphenylboronic acid.…”

Section: Methodsmentioning

confidence: 99%

Palladium-catalyzed C–H arylation using aryltrifluoroborates in conjunction with a MnIII oxidant under mild conditions

et al. 2013

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This paper describes the development of a mild Pd-catalyzed C–H arylation reaction using potassium aryltrifluoroborates in conjunction with Mn(OAc)3 as the oxidant. The scope of this transformation is explored with a variety of different aryltrifluoroborates and arylpyridine substrates. Preliminary mechanistic studies suggest that the reaction proceeds via a high-valent Pd mechanism with C–H activation occurring at or before the rate determining step.

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“…[82] Halo-substituted 4-azafluorenes 8 and 9 were obtained in low yields from the corresponding 5-haloindanones. [83] Azafluorenones 10-13 were obtained via the Pdcatalyzed cyclization of (2-chloropyridin-3-yl)aryl ketones and (2-chlorophenyl)pyridyl ketones, [84,85] or (bromopyridyl)(bromophenyl)methanol. [86] These compounds were brominated at the benzene ring to form mono-and dibromo derivatives 14 and 15 (Scheme 4).…”

Section: Azafluorenesmentioning

confidence: 99%

Synthesis of Heteroarene‐Fused Cyclopentadienes and Related Compounds Suitable for Metallocene Preparation

Nifant’ev

Ivchenko

2020

Adv Synth Catal

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Metallocene catalysis is widely used in transformations of unsaturated organic compounds, including the bulk industrial synthesis of polyolefins. Over the last few decades, the electronic and structural properties of their η5‐coordinated ligands have been modified by introducing electron‐donating, electron‐withdrawing, and sterically hindered substituents to obtain desirable catalytic properties for the metallocenes. An efficient way to design η5‐coordinated ligands is to exploit the annelation of heterocyclic fragments with a cyclopentadiene ring. In the present review, we summarize, systematize, and analyze synthetic approaches to heterocycle‐fused cyclopentadienes suitable for metallocene catalyst preparation.

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A facile synthesis of 7-halo-5H-indeno[1,2-b]pyridines and -pyridin-5-ones

Cited by 45 publications

References 0 publications

2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

Palladium-catalyzed C–H arylation using aryltrifluoroborates in conjunction with a MnIII oxidant under mild conditions

Synthesis of Heteroarene‐Fused Cyclopentadienes and Related Compounds Suitable for Metallocene Preparation

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