Assembly of 4‐Aminoquinolines via Palladium Catalysis: A Mild and Convenient Alternative to S<sub>N</sub>Ar Methodology.

Margolis, Brandon J.; Long, Kimberly A.; Laird, Dana L. T.; Ruble, J. Craig; Pulley, Shon R.

doi:10.1002/chin.200731120

Cited by 4 publications

(4 citation statements)

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“…A similar reaction with palladium catalysis was used to prepare the analogous ligand with X = NH ( 14 ) (Scheme ). The required amide 13 was readily prepared from 2-bromo- N -methyl- N -phenylpropanamide by conversion into the azide followed by reduction…”

Section: Results and Discussionmentioning

confidence: 99%

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

et al. 2014

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Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat Ki = 0.10 nM; human TSPO genotypes Ki = 1.4 nM; clogD = 4.18).

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Section: Results and Discussionmentioning

confidence: 99%

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

et al. 2014

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“…Of 12 C(3) substituted benzothiophenes, five antiplasmodials were more active than CQ against the CQS strain D6 and six were more active than MFQ against the MDR strain C235. Compounds without a chlorine atom at the quinoline C(7) position (54,62,66) were much less active than the whole benzothiophene series against all three P. falciparum strains. The introduction of fluorine and cyano group at positions C( 5) and C(6) (benzothiophene numbering) did not appreciably influence the benzothiophene−aminoquinoline hybrids' in vitro activity.…”

Section: ■ Resultsmentioning

confidence: 99%

“…General Procedure for Palladium Catalyzed Amination of Quinolines (12, 24−26, 32, 37−39, 44−45, and 69−76). 62 Vial was charged with mixture of Pd(OAc) 2 (4 mol %) and DPEphos (8 mol %)/SPhos (8 mol %) in dioxane and stirred for a few minutes in Ar at rt. Subsequently, a haloquinoline (1.0 equiv), amine (1.2 equiv), and K 3 PO 4 (2.5 equiv) were added to the reaction mixture.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

et al. 2015

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The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 μM and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 μM). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 ± 0.37 μM). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.

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“…Further, a halide exchange reaction was performed with 9 using a common chloride salt, lithium chloride, as a nucleophile in dioxane. In the final step, C−N coupling of 4-chloro-2-methylquinoline (10) and the commercial 2-amino-5-diethylaminopentane using another previously published procedure 95 with Pd-(OAc) 2 , DPEphos, and K 3 PO 4 offered a mild and convenient pathway to afford the chloroquine derivative 11 from 4p.…”

Section: Functionalization Of Steroidsmentioning

confidence: 99%

Understanding the Visible-Light-Initiated Manganese-Catalyzed Synthesis of Quinolines and Naphthyridines under Ambient and Aerobic Conditions

Patra

Bhattacherya

et al. 2022

ACS Catal.

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Polyaromatic N-heterocycles are some of the most common building blocks in natural products and active pharmaceutical ingredients. Significant efforts have been devoted to developing catalytic protocols, including those which use an acceptorless dehydrogenation strategy at elevated temperatures, to produce polyaromatic N-heterocycles like quinolines and naphthyridines. However, photoinitiated catalysis driven by visible light offers a milder and often more selective protocol as an alternative to thermal reactions. Here, we present the catalytic syntheses of quinolines and naphthyridines from ortho-aminobenzyl alcohols and ketones using the photocatalyst [Mn(L 1 H)(CO) 3 Br] (L 1 H = 7-hydroxy-2-methyl-1,8-naphthyridine-N-oxide), bearing a phenolic unit on a 1,8-naphthyridine-N-oxide scaffold, under ambient and aerobic conditions with visible light illumination. We describe a broad, functional group-tolerant substrate scope of >30 examples under modest reaction conditions. A variety of 2-aminobenzyl alcohols containing electron-donating and electron-deficient groups and (2-aminopyridin-3-yl)methanol are converted to the corresponding quinolines and naphthyridines using ambient air as an oxidant in the presence of KOH. We synthesized a wide range of derivatives, including some of the bioactive antimalarial drug chloroquine and the steroids progesterone and pregnenolone to highlight the value-added applications of this catalytic protocol for pharmaceutical ingredient and natural product syntheses. We performed substrate viability, ultraviolet−visible, electron paramagnetic resonance, and X-ray photoelectron spectroscopy studies, as well as density functional theory calculations to gain mechanistic insights to the reaction pathway. The catalytic cycle involves condensation of the amino group in the ortho-aminobenzyl alcohol with the ketone initially, which is followed by aerobic oxidation of the benzyl alcohol to the corresponding benzaldehyde catalyzed by the photoinitiator [Mn(L 1 H)(CO) 3 Br] in the presence of visible light, and finally, a KOH-promoted condensation and cyclization to afford quinolines as the final products.

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Assembly of 4‐Aminoquinolines via Palladium Catalysis: A Mild and Convenient Alternative to S_NAr Methodology.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 4 publications

References 1 publication

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

Understanding the Visible-Light-Initiated Manganese-Catalyzed Synthesis of Quinolines and Naphthyridines under Ambient and Aerobic Conditions

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Assembly of 4‐Aminoquinolines via Palladium Catalysis: A Mild and Convenient Alternative to SNAr Methodology.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 4 publications

References 1 publication

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

Development ofN-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

Understanding the Visible-Light-Initiated Manganese-Catalyzed Synthesis of Quinolines and Naphthyridines under Ambient and Aerobic Conditions

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Assembly of 4‐Aminoquinolines via Palladium Catalysis: A Mild and Convenient Alternative to S_NAr Methodology.