203452-46-4

Basic information

• Product Name: (2R)-2-benzylpiperidine
• Synonyms: (2R)-2-benzylpiperidine
• CAS NO: 203452-46-4
• Molecular Weight: 175.274
• Mol File: 203452-46-4.mol

Chemical Properties

• Melting Point: 45-50°C
• CAS DataBase Reference: (2R)-2-benzylpiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: (2R)-2-benzylpiperidine(203452-46-4)
• EPA Substance Registry System: (2R)-2-benzylpiperidine(203452-46-4)

Safety Data

• Hazardous Substances Data: 203452-46-4(Hazardous Substances Data)

Usage

Uses

Chiral building block developed using Liverpool ChiroChem-patented technology.

Upstream product

• 126410-30-8 (S)-1-phenylbut-3-en-2-amine 
• 103127-52-2 ((S)-1-benzylallyl)carbamic acid tert-butyl ester 
• 72155-45-4 Boc-L-phenylalaninal 
• 87694-53-9 Boc-Phe-OH N,O-dimethyl hydroxamate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 95018-41-0 2-benzyl-3,4,5,6-tetrahydropyridine 
• 32838-55-4 2-benzylpiperidine 
• 1643770-97-1 (S)-2,2-dimethyl-5-oxo-3-(2-phenylacetyl)imidazolidin-1-yl 2-methoxy-2-phenylacetate 
• 135469-76-0 6-phenylhex-5-yn-1-amine 
• 1346681-71-7 (1E)-4-hydroxy-1-mesityl-4-methylpent-1-en-3-one 
• 99112-89-7 (S)-6-benzyl-1,2,3,6-tetrahydropyridine 

Downstream Products

• 2055172-61-5 (R)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone 

Relevant articles and documents

Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors

Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights to Realize the Enantioselective Synthesis of Piperazines

An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η6-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated.

An (R)-imine reductase biocatalyst for the asymmetric reduction of cyclic imines

Although the range of biocatalysts available for the synthesis of enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over-expressed the gene for an (R)-imine reductase [(R)-IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole-cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)-IRED was screened against a panel of cyclic imines and two iminium ions and was shown to possess high catalytic activity and enantioselectivity. Preparative-scale synthesis of the alkaloid (R)-coniine (90 % yield; 99 % ee) from the imine precursor was performed on a gram-scale. A homology model of the enzyme active site, based on the structure of a closely related (R)-IRED from Streptomyces kanamyceticus, was constructed and used to identify potential amino acids as targets for

Stereoelectronic basis for the kinetic resolution of n-heterocycles with chiral acylating reagents

The kinetic resolution of N-heterocycles with chiral acylating agents reveals a previously unrecognized stereoelectronic effect in amine acylation. Combined with a new achiral hydroxamate, this effect makes possible the resolution of various N-heterocycles by using easily prepared reagents. A transition-state model to rationalize the stereochemical outcome of this kinetic resolution is also proposed.

Catalytic asymmetric synthesis of substituted morpholines and piperazines

Under two conditions: Hydroamination catalyzed by group 4 metals is featured in the modular and enantioselective synthesis of 3-substituted morpholines and the diastereoselective synthesis of 2,5-substituted piperazines. Copyright

Expanded substrate scope and catalyst optimization for the catalytic kinetic resolution of N-heterocycles

The scope, reactivity, and selectivity of the chiral hydroxamic acid-catalyzed kinetic resolution of chiral amines are improved by a new catalyst structure and a more environmentally friendly reaction protocol. In addition to increasing selectivity across all substrates, these conditions make possible the resolution of N-heterocycles containing lactams or other basic functional groups that can inhibit the catalyst.

Catalytic kinetic resolution of cyclic secondary amines

The catalytic resolution of racemic cyclic amines has been achieved by an enantioselective amidation reaction featuring an achiral N-heterocyclic carbene catalyst and a new chiral hydroxamic acid cocatalyst working in concert. The reactions proceed at room temperature, do not generate nonvolatile byproducts, and provide enantioenriched amines by aqueous extraction.

1,2,4 TRIAZOLO [4, 3 -A] [1,5] BENZODIAZEPIN-5 (6H) -ONES AS AGONISTS OF THE CHOLECYSTOKININ-1 RECEPTOR (CCK-IR)

This invention relates to CCK-1 R agonists of Formula (I) wherein R1-R5 and X are as defined in the specificiation, as well as pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating obesity, type 2 diabetes and associated diseases.

1,4-Bis(arylsulfonyl)-1,2,3,4-tetrahydropyridines in synthesis. Intramolecular alkylation reactions and stereoselective synthesis of anti-2,6-disubstituted piperidines

1,4-Bis(arylsulfonyl)-1,2,3,4-tetrahydropyridines 1 having R1 containing aromatic groups undergo intramolecular electrophilic aromatic substitution reactions to give benzo-fused bicyclo[3.3.1] systems with chemoselectivities which depend on the nature of the acidic reagent used. Cationic hydrogenation of the C-5-C-6 double bond in substrates 1 substituted at C-6 provides an entry to anti-2,6-disubstituted piperidines upon desulfonylation.