An efficient route to 6-(het)aryl-2-methyl-2,3-dihydro-1H-pyridin-4-ones as potential nAChRs ligands

Leflemme, Nicolas; Dallemagne, Patrick; Rault, Syl­vain

doi:10.1016/j.tet.2004.03.085

Cited by 12 publications

(5 citation statements)

References 48 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis of 2-pyridinones may be carried out by the oxidation of N -substituted pyridinium salts, the reaction of β-dicarbonyl compounds or α,β-unsaturated ketones with malononitrile or similar active methylene compounds, , the reaction of α-oxoketenedithioacetals with cyanoacetamide in the presence of a base, the cycloaddition of 2-azadienes with acetylenic dienophiles, the reaction of lithium dienediolates and nitriles, and the reaction of acyl isocyanates and trimethylsilylketene . Previous syntheses of 2,3-dihydro-1 H -pyridin-4-ones include multistep protocols commencing from β-amino-β-arylpropionic acids, 4-methoxypyridine, and t -butyl enaminoesters . The syntheses of 2,3-dihydro-1 H -pyridin-4-ones using the aza-Diels−Alder reaction and 5,6-dihydro-1 H -pyridin-4-ones from the reaction of a ketene dithioester with methylamine have also been reported .…”

Section: Six-membered Heterocycles With One Heteroatommentioning

confidence: 99%

Solvent-Free Heterocyclic Synthesis

et al. 2009

View full text Add to dashboard Cite

Clarissa P. Frizzo was born in Ivora ´, Rio Grande do Sul state, Brazil, in 1983. She received her undergraduate degree in Pharmacy from the Federal University of Santa Maria in 2005, and in 2007 she obtained her M.Sc. degree from the Federal University of Santa Maria, under the supervision of Professor Marcos A. P. Martins, working with the use of ionic liquids in the synthesis of heterocycles. She started her Ph.D. studies under the supervision of Professor Marcos A. P. Martins, and currently she is focusing on her Sandwich Ph.D. in the Universidade Nacional de Educacio ´n a Distancia in Spain, under the guidance of Professor Rosa M. Claramunt Vallespı ´, where she is studying the supramolecular structure of heterocycles. Dayse das Neves Moreira was born in Canguc ¸u, Rio Grande do Sul state, Brazil, in 1984. She received her undergraduate degree in Chemistry from the Federal University of Pelotas, RS, in 2006, and in 2008 she received her M.S. degree, from the Federal University of Santa Maria, RS, Brazil, working under the direction of Professor Marcos A. P. Martins, working with the use of ionic liquids in the synthesis of heterocycles. Currently, she is a Ph.D. student with Professor Marcos A. P. Martins in the Department of Chemistry of the Federal University of Santa Maria. Her major research interest is to develop new methodologies to synthesize heterocyclic compounds. Lilian Buriol was born in Santa Izabel do Oeste, Parana ´(PR) state, Brazil, in 1984. She received her undergraduate degree in Chemistry from the State University of Centro-Oeste (PR). In 2008, she completed her M.S. degree at the same university under the supervision of Professor Yohandra R. Torres, working with oil and ethanol extracts of propolis. After that, she started her Ph.D. studies in the Department of Chemistry of the Federal University of Santa Maria under the supervision of Professor Marcos A. P. Martins. Her research interest is to develop new methodologies to synthesize heterocyclic compounds along the lines of green chemistry.

show abstract

Section: Six-membered Heterocycles With One Heteroatommentioning

confidence: 99%

Solvent-Free Heterocyclic Synthesis

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Boc groups on the N1 position of dihydro-4-pyridones are much more challenging to remove than standard alkyl-amino Boc groups, requiring up to 24 hours using TFA in CH 2 Cl 2 . 38 Several conditions were attempted (TFA in CH 2 Cl 2 , HCl in dioxane/EtOAc, phenol and TMSCl in CH 2 Cl 2 ) 39 that provided only trace amounts of product. The Boc-amino group on C3 was cleanly deprotected within an hour applying any of these conditions, but longer reaction times to remove the second Boc group resulted in extensive decomposition.…”

Section: Resultsmentioning

confidence: 99%

“…Deprotection of the TBS group using HF·pyridine proceeded smoothly; however, the final bis-Boc deprotection of 32 proved unconquerable. Boc groups on the N1 position of dihydro-4-pyridones are much more challenging to remove than standard alkyl-amino Boc groups, requiring up to 24 h using TFA in CH 2 Cl 2 . Several conditions were attempted (TFA in CH 2 Cl 2 , HCl in dioxane/EtOAc, phenol and TMSCl in CH 2 Cl 2 ) that provided only trace amounts of product.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a 3-Amino-2,3-dihydropyrid-4-one and Related Heterocyclic Analogues as Mechanism-Based Inhibitors of BioA, a Pyridoxal Phosphate-Dependent Enzyme

Eiden

Aldrich

2017

J. Org. Chem.

View full text Add to dashboard Cite

Amiclenomycin (ACM) is a chemically unstable antibiotic with selective activity against Mycobacterium tuberculosis (Mtb) due to mechanism-based inhibition of BioA, a pyridoxal 5′-phosphate (PLP) dependent aminotransferase. The first-generation ACM analogue dihydro-2-pyridone 1 is semi-stable and maintains a similar bioactivation mechanism concluding with covalent labeling of the PLP cofactor. To improve on 1, we report the synthesis of dihydro-4-pyranone 2, dihydro-4-pyridone 3 and dihydro-4-thiopyranone 13, which were rationally designed to boost the rate of enzyme inactivation by lowering the pKa of their α-protons. We employed a unified synthetic strategy for construction of the desired heterocycles featuring α-amino ynone generation followed by 6-endo-dig cyclization. However, competitive 5-exo-dig cyclization, β-elimination of the ynone, and dimerization of the resultant α-amino carbonyls all complicated the syntheses of the dihydro-4-pyranone and dihydro-4-pyridone scaffolds. These obstacles were overcome by Teoc protection of the β-amino group in the assembly of 3 and Boc-MOM protection of the α-amino group in the synthesis of 2, enabling the efficient construction of 2 and 3 in seven steps from commercially available starting materials. Dihydro-4-pyridone 3 possessed improved enzyme inhibition as measured by its kinact value against BioA, validating our pKa–based design strategy.

show abstract

“…14 The selectivity depends upon the halogens and their positions in the pyridine ring. Systematic studies by Rault et al 5,[23][24][25][26][27][28] and Bryce et al [29][30][31][32] resulted in the preparation of shelf-stable halopyridinylboronic acids and esters. 3-and 4-Halopyridines bearing other functional groups such as 6´-methoxy, 22,31 6´-ethoxy 29 and 6´-trifluoromethyl 32 also undergo such transformations with yields typically between 60 and 90%.…”

Section: The Synthesis Of Pyridinylboronic Acids and Esters By Halogementioning

confidence: 99%

Recent progress in the synthesis of pyridinylboronic acids and esters

Liu¹,

Milo²,

Lai

2013

Arkivoc

View full text Add to dashboard Cite

Recent progress in the synthesis of (un)substituted pyridinylboronic acids and esters is reviewed. Five approaches to the synthesis of (un)substituted pyridinylboronic acids and esters are summarized: (1) halogen-metal exchange (HMe) and borylation, (2) metal-hydrogen exchange via directed ortho-metallation (DoM) followed by borylation, (3) palladium-catalyzed crosscoupling of halopyridines with tetraalkoxydiborane or dialkoxyhydroborane (4) iridium or rhodium catalyzed C-H or C-F borylation, and (5) exchange / borylation 2.1.1. The general procedure of halogen-metal (Li or Mg) exchange / borylation 2.1.2. The selectivity of halogen-metal (Li or Mg) exchange / borylation 2.1.3. The synthesis of 2-pyridinylboronic acids and esters by halogen-organometal (Li or Mg) exchange / borylation 2.1.4. The synthesis of pyridinediboronic acids via halogen-organotin (Sn) exchange / borylation 2.2. The synthesis of pyridinylboronic acids and esters by directed ortho-metalation (DoM) / borylation 2.2.1. The general procedure of directed ortho-metalation (DoM) / borylation 2.2.2. The selectivity of directed ortho-metalation (DoM) / borylation 2.3. The synthesis of pyridinylboronic acids and esters by palladium-catalyzed cross-coupling of halopyridines with tetraalkoxydiboron or dialkoxyhydroborane 2.4. The synthesis of pyridinylboronic acids and esters by iridium-or rhodium-catalyzed

show abstract

An efficient route to 6-(het)aryl-2-methyl-2,3-dihydro-1H-pyridin-4-ones as potential nAChRs ligands

Cited by 12 publications

References 48 publications

Solvent-Free Heterocyclic Synthesis

Solvent-Free Heterocyclic Synthesis

Synthesis of a 3-Amino-2,3-dihydropyrid-4-one and Related Heterocyclic Analogues as Mechanism-Based Inhibitors of BioA, a Pyridoxal Phosphate-Dependent Enzyme

Recent progress in the synthesis of pyridinylboronic acids and esters

Contact Info

Product

Resources

About