154874-89-2

Upstream product

• 591-50-4 iodobenzene 
• 75844-69-8 t-butyl piperidinecarboxylate 
• 108-86-1 bromobenzene 
• 35469-40-0 6-phenyl-3,6-dihydro-2H-pyridin-1-ol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 57050-07-4 2-phenyl-3,4,5,6-tetrahydropyridine 
• 5414-21-1 5-bromopentan-1-nitrile 
• 3466-80-6 2-phenylpiperidine 
• 591-51-5 phenyllithium 
• 109398-68-7 toluene-4-sulphonic acid 5-phenyl-pentyl ester 
• 20620-59-1 5-phenyl-n-valeric acid methyl ester 
• 2270-20-4 5-Phenylpentanoic acid 
• 10521-91-2 5-phenylpentan-1-ol 
• 1078-58-6 diphenylzinc 

Downstream Products

• 1364780-88-0 C₁₆H₂₂LiNO₂ 
• 1364781-69-0 tert-butyl 2-butyl-2-phenylpiperidine-1-carboxylate 
• 1364781-74-7 tert-butyl 2-(methoxymethyl)-2-phenylpiperidine-1-carboxylate 
• 1364781-79-2 tert-butyl 2-(3-methylbut-2-enyl)-2-phenylpiperidine-1-carboxylate 
• 1364781-95-2 1-tert-butyl 2-methyl 2-phenylpiperidine-1,2-dicarboxylate 
• 1395055-68-1 (2R)-1-tert-butyl 2-ethyl 2-phenylpiperidine-1,2-dicarboxylate 
• 1364782-99-9 (2S)-tert-butyl 2-methyl-2-phenylpiperidine-1-carboxylate 
• 1395055-66-9 (2R)-tert-butyl 2-methyl-2-phenylpiperidine-1-carboxylate 

Relevant academic research and scientific papers

A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction

Background and Purpose: Beta cell apoptosis is a major feature of type 1 diabetes, and pro-inflammatory cytokines are key drivers of the deterioration of beta cell mass through induction of apoptosis. Mitochondrial stress plays a critical role in mediating apoptosis by releasing cytochrome C into the cytoplasm, directly activating caspase-9 and its downstream signalling cascade. We aimed to identify new compounds that protect beta cells from cytokine-induced activation of the intrinsic (mitochondrial) pathway of apoptosis. Experimental Approach: Diabetogenic media, composed of IL-1β, IFN-γ and high glucose, were used to induce mitochondrial stress in rat insulin-producing INS1E cells, and a high-content image-based screen of small molecule modulators of Casp9 pathway was performed. Key Results: A novel small molecule, ATV399, was identified from a high-content image-based screen for compounds that inhibit cleaved caspase-9 activation and subsequent beta cell apoptosis induced by a combination of IL-1β, IFN-γ and high glucose, which together mimic the pathogenic diabetic milieu. Through medicinal chemistry optimization, potency was markedly improved (6–30 fold), with reduced inhibitory effects on CYP3A4. Improved analogues, such as CAT639, improved beta cell viability and insulin secretion in cytokine-treated rat insulin-producing INS1E cells and primary dispersed islet cells. Mechanistically, CAT639 reduced the production of NO by allosterically inhibiting dimerization of inducible NOS (iNOS) without affecting its mRNA levels. Conclusion and Implications: Taken together, these studies demonstrate a successful phenotypic screening campaign resulting in identification of an inhibitor of iNOS dimerization that protects beta cell viability and function through modulation of mitochondrial stress induced by cytokines.

A Selenourea-Thiourea Br?nsted Acid Catalyst Facilitates Asymmetric Conjugate Additions of Amines to α,β-Unsaturated Esters

β-Amino esters are obtained with high levels of enantioselectivity via the conjugate addition of cyclic amines to unactivated α,β-unsaturated esters. A related strategy enables the kinetic resolution of racemic cyclic 2-arylamines, using benzyl acrylate as the resolving agent. Reactions are facilitated by an unprecedented selenourea-thiourea organocatalyst. As elucidated by DFT calculations and 13C kinetic isotope effect studies, the rate-limiting and enantiodetermining step of the reaction is the protonation of a zwitterionic intermediate by the catalyst. This represents a rare case in which a thiourea compound functions as an asymmetric Br?nsted acid catalyst.

[Co(TPP)]-Catalyzed Formation of Substituted Piperidines

Radical cyclization via cobalt(III)-carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five-membered N-heterocyclic pyrrolidines catalyzed by CoII porphyrins, the [Co(TPP)]-catalyzed formation of useful six-membered N-heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2-hydrogen-atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl-radical formation followed by radical-rebound ring closure to form the piperidines. Competitive 1,5-hydrogen-atom transfer from the β-position to the benzyl radical explained the formation of linear alkenes as side products.

Decarboxylative Negishi Coupling of Redox-Active Aliphatic Esters by Cobalt Catalysis

A cobalt-catalyzed decarboxylative Negishi coupling reaction of redox-active aliphatic esters with organozinc reagents was developed. The method enabled efficient alkyl–aryl, alkyl–alkenyl, and alkyl–alkynyl coupling reactions under mild reaction conditions with no external ligand or additive needed. The success of an in situ activation protocol and the facile synthesis of the drug molecule (±)-preclamol highlight the synthetic potential of this method. Mechanistic studies indicated that a radical mechanism is involved.

N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides

Metal-catalyzed intramolecular C?H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N-heterocyclic carbene ligands which catalyzes the intramolecular C(sp3)–H amination of a wide variety of alkyl azides under microwave-assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C?H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re-bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis-octahydroindole, and leelamine derivatives.

Metal-organic layers stabilize earth-abundant metal-terpyridine diradical complexes for catalytic C-H activation

We report the synthesis of a terpyridine-based metal-organic layer (TPY-MOL) and its metalation with CoCl2 and FeBr2 to afford CoCl2·TPY-MOL and FeBr2·TPY-MOL, respectively. Upon activation with NaEt3

Synthesis and kinetic resolution of N-Boc-2-arylpiperidines

The chiral base n-BuLi/(-)-sparteine or n-BuLi/(+)-sparteine surrogate promotes kinetic resolution of N-Boc-2-arylpiperidines by asymmetric deprotonation. The enantioenriched starting material was recovered with yields 39-48% and ers up to 97:3. On lithiation then electrophilic quench, 2,2-disubstituted piperidines were obtained with excellent yields and enantioselectivities.

SYNTHESIS OF ACYCLIC AND CYCLIC AMINES USING IRON-CATALYZED NITRENE GROUP TRANSFER

The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C-H groups, catalyzed by a FeII-dipyrromethene complex. The acyclic secondary amines are thought

An experimental and in situ IR spectroscopic study of the lithiation-substitution of N-Boc-2-phenylpyrrolidine and -piperidine: Controlling the formation of quaternary stereocenters

A general and enantioselective synthesis of 2-substituted 2-phenylpyrrolidines and -piperidines, an important class of pharmaceutically relevant compounds that contain a quaternary stereocenter, has been developed. The approach involves lithiation-substitution of enantioenriched N-Boc-2-phenylpyrrolidine or -piperidine (prepared by asymmetric Negishi arylation or catalytic asymmetric reduction, respectively). The combined use of synthetic experiments and in situ IR spectroscopic monitoring allowed optimum lithiation conditions to be identified: n-BuLi in THF at -50 °C for 5-30 min. Monitoring of the lithiation using in situ IR spectroscopy indicated that the rotation of the tert-butoxycarbonyl (Boc) group is slower in a 2-lithiated pyrrolidine than a 2-lithiated piperidine; low yields for the lithiation-substitution of N-Boc-2-phenylpyrrolidine at -78 °C can be ascribed to this slow rotation. For N-Boc-2-phenylpyrrolidine and -piperidine, the barriers to rotation of the Boc group were determined using density functional theory calculations and variable-temperature 1H NMR spectroscopy. For the pyrrolidine, the half-life (t1/2) for rotation of the Boc group was found to be ～10 h at -78 °C and ～3.5 min at -50 °C. In contrast, for the piperidine, t1/2 was determined to be ～4 s at -78 °C.

Alternative strategies for the stereoselective synthesis of enantioenriched 6-arylated piperidin-2-ones

Two alternative synthetic approaches to a variety of enantioenriched 6-arylated piperidin-2-ones have been developed. The first one is based on the hydrogenation of suitably arylated chiral cyclic enehydrazides. The second approach relies on the asymmetric catalytic hydrogenation of the corresponding N-alkylated precursors. 2012 Elsevier Ltd.