Synthesis of Triazolyl‐Substituted 3‐Aminopiperidines by Huisgen‐1,3‐Dipolar Cycloaddition – New Scaffolds for Combinatorial Chemistry

Schramm, Heiko; Saak, Wolfgang; Hoenke, Christoph; Christoffers, Jens

doi:10.1002/ejoc.200901458

Cited by 21 publications

(6 citation statements)

References 22 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gratifyingly, no epimerization was observed in this study. As for regioselectivity, nucleophilic addition occurred predominantly at the C4 position, which is consistent with the results observed for other nucleophiles with 6-membered piperidines . As a control experiment, a reaction without a base was conducted to show the necessity for the reaction to proceed (entry 1).…”

Section: Resultssupporting

confidence: 83%

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Abe,

Coleman,

Presley

et al. 2024

J. Org. Chem.

View full text Add to dashboard Cite

Sp 3 -enriched small molecules play a critical role in developing drug candidates. While designing analogues with greater sp 3 character, a methodology utilizing a less explored cyclic-aziridine amide ring-opening reaction to generate sp 3enriched scaffolds has been developed and reported. This methodology enables rapid access to substructures with higher fsp 3 values, attracting greater attention within the past few decades. The reaction exhibits a wide reaction scope, featuring a highly sterically hindered phenolic ether, thiophenolic ethers, protected aniline formations, and aliphatic/heteroaromatic ring-containing aziridine amides as substrates. Additionally, this reaction provides access to congested tertiary ether formations through regioselective transformation, applicable to an extensive range of drug discovery targets, construction of complex small molecules, and natural product syntheses. The scaffolds developed show improved physicochemical properties.

show abstract

Section: Resultssupporting

confidence: 83%

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Abe,

Coleman,

Presley

et al. 2024

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…[6a] For this purpose, we first prepared perfluorinated azide 8 from the respective iodide R F CH 2 CH 2 I following the procedure of Read et al[31d] Conversion of azide 8 with TMSC≡CH in the presence of CuSO 4 and sodium ascorbate was directly followed by treatment of the reaction mixture with TBAF (Scheme ). Compound 9 was obtained in 71 % yield after chromatography . Initial attempts of alkylation 1,2,3‐triazole ( 10 ) with R F CH 2 CH 2 I failed, whereas the use of R F CH 2 CH 2 OTf [prepared from the respective alcohol R F CH 2 CH 2 OH (“6:2 FTOH") according to a literature procedure] as alkylating reagent gave compound 9 in 10 % yield.…”

Section: Resultsmentioning

confidence: 99%

Perfluorinated 1,2,3‐ and 1,2,4‐Triazolium Ionic Liquids

Alpers

Muesmann²,

Temme³

et al. 2018

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

Dialkyl triazolium triflimides with perfluorinated side chains were prepared as hydrophobic ionic liquids (ILs) for surface impregnation. The key feature of the new materials are relatively short perfluorohexyl residues (nC6F13 = RF) as the fluorinated part of the cations, making the target compounds beneficial alternatives to established products because of their enhanced degradability and therefore lower bioaccumulativity. As heterocyclic scaffold, either 1,2,3‐triazole or 1,2,4‐triazole were chosen. As the two alkyl moieties, either two RFCH2CH2 groups or one RFCH2CH2 and one Et residue were applied. The diethyl congeners were also prepared. Fluorinated starting materials were RFCH2CH2OTf as alkylating reagent or RFCH2CH2N3 as 1,3‐dipole for a copper catalyzed cycloaddition (CuAAC) with trimethylsilyl acetylene. After sequential CuAAC and alkylation reactions, the triflimide salts were finally obtained from the intermediate iodides or triflates with the aid of an ion exchange resin. Out of 14 triazolium salts prepared, four compounds have finally been identified as hydrophobic ILs (contact angles between 85° and 100° with mp. < 100 °C), being promising materials for surface impregnation: the 1,2,3‐triazolium triflate and triflimide with two fluorinated alkyl residues, and the 1,2,4‐triazolium triflimides (two regioisomers) with one fluorinated alkyl residues and one ethyl group.

show abstract

“…This indicates that halogen bonding is one of the main stabilizing interactions for these solvents in the crystal structure. One example of these structures is t -butyl(1-((4-bromophenyl)sulfonyl)-4-(4-methyl-1 H -1,2,3-triazol-1-yl)piperidin-3-yl)carbamate chloroform solvate, CSD refcode KUWWOP, CCDC 757872 (Figure ), from the misclassified chloroform data set. On the basis of the size, branching, and number of polar hydrogen atoms, this molecule was predicted not to form a chloroform solvate at a probability of 0.534.…”

Section: Resultsmentioning

confidence: 99%

Prediction of Hydrate and Solvate Formation Using Statistical Models

Takieddin

Khimyak

Fábián

2015

Crystal Growth & Design

View full text Add to dashboard Cite

Novel, knowledge-based models for the prediction of hydrate and solvate formation are introduced, which require only the molecular formula as input. A dataset of more than 19,000 organic, non-ionic and non-polymeric molecules was extracted from the Cambridge Structural Database. Molecules that formed solvates were compared with those that did not using molecular descriptors and statistical methods, which allowed the identification of chemical properties that contribute to solvate formation. The study was conducted for five types of solvates: ethanol, methanol, dichloromethane, chloroform and water solvates. The identified properties were all related to the size and branching of the molecules and to the hydrogen bonding ability of the molecules. The corresponding molecular descriptors were used to fit logistic regression models to predict the probability of any given molecule to form a solvate. The established models were 2 able to predict the behavior of ~80% of the data correctly using only two descriptors in the predictive model.

show abstract

Synthesis of Triazolyl‐Substituted 3‐Aminopiperidines by Huisgen‐1,3‐Dipolar Cycloaddition – New Scaffolds for Combinatorial Chemistry

Cited by 21 publications

References 22 publications

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Perfluorinated 1,2,3‐ and 1,2,4‐Triazolium Ionic Liquids

Prediction of Hydrate and Solvate Formation Using Statistical Models

Contact Info

Product

Resources

About

Synthesis of Triazolyl‐Substituted 3‐Aminopiperidines by Huisgen‐1,3‐Dipolar Cycloaddition – New Scaffolds for Combinatorial Chemistry

Cited by 21 publications

References 22 publications

Rapid sp3-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Rapid sp3-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Perfluorinated 1,2,3‐ and 1,2,4‐Triazolium Ionic Liquids

Prediction of Hydrate and Solvate Formation Using Statistical Models

Contact Info

Product

Resources

About

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction

Rapid sp³-Enriched Scaffold Generation via a Selective Aziridine Amide Ring-Opening Reaction