183950-95-0

Usage

Structure

Tertiary amine with a piperidine ring, a carboxylic acid group, and a 4-(4-fluorophenyl) substituent

Classification

Tertiary amine, piperidine derivative, carboxylic acid derivative

Usage

Building block in the synthesis of pharmaceuticals, agrochemicals, and other fine chemicals; reagent in organic chemical reactions; protected amino acid derivative in peptide synthesis

Other potential applications

Medicinal chemistry and drug discovery research

Upstream product

• 118811-07-7 tert-butyl 4-(tosyloxy)piperidin-1-carboxylate 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 180695-79-8 tert-butyl 4-bromo-1-piperidinecarboxylate 
• 225916-39-2 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane 
• 84358-13-4 N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid 
• 1765-93-1 4-fluoroboronic acid 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 352-13-6 4-flourophenylmagnesium bromide 
• 301673-14-3 tert-butyl 4-iodopiperidine-1-carboxylate 
• 375853-82-0 tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 133472-27-2 4-fluorophenylzinc chloride 

Downstream Products

• 37656-48-7 4-(4-fluorophenyl)piperidine 

Relevant academic research and scientific papers

Cobalt-Catalyzed C(sp2)-C(sp3) Suzuki-Miyaura Cross-Coupling Enabled by Well-Defined Precatalysts with L,X-Type Ligands

Cobalt(II) halides in combination with phenoxyimine (FI) ligands generated efficient precatalysts in situ for the C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling between alkyl bromides and neopentylglycol (hetero)arylboronic esters. The protocol enabled efficient C-C bond formation with a host of nucleophiles and electrophiles (36 examples, 34-95%) with precatalyst loadings of 5 mol %. Studies with alkyl halide electrophiles that function as radical clocks support the intermediacy of alkyl radicals during the course of the catalytic reaction. The improved performance of the FI-cobalt catalyst was correlated with decreased lifetimes of cage-escaped radicals as compared to those of diamine-type ligands. Studies of the phenoxyimine-cobalt coordination chemistry validate the L,X interaction leading to the discovery of an optimal, well-defined, air-stable mono-FI-cobalt(II) precatalyst structure.

Nickel-Catalyzed Cross-Coupling of Redox-Active Esters with Boronic Acids

A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross-coupling between alkyl-carboxylic acids and boronic acids is described. This Ni-catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox-active ester derivatives, specifically N-hydroxy-tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl2?6 H2O—$9.5 mol?1, Et3N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption.

Engaging nonaromatic, heterocyclic tosylates in reductive cross-coupling with aryl and heteroaryl bromides

A method has been developed for the introduction of nonaromatic heterocyclic structures onto aryl and heteroaryl bromides using alkyl tosylates in a reductive cross-coupling manifold. This protocol offers an improvement over previous methods by utilizing alkyl tosylate coupling partners that are bench-stable, crystalline solids that can be prepared from inexpensive, commercially available alcohols.

Cobalt-Catalyzed Cross-Coupling of 3- and 4-Iodopiperidines with Grignard Reagents

A cobalt-catalyzed cross-coupling between 3- and 4-iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)-preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates. Scaffold synthesis: A cobalt-catalyzed cross-coupling between iodopiperidines and Grignard reagents is reported (see scheme; PG=protecting group). A large variety of 3- and 4-substituted piperidines were synthesized and the method was applied to a short synthesis of (±)-preclamol. This work constitutes one of the rare examples of cross-couplings involving 3-halogeno piperidines.

Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with grignard reagents

Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.

Reductive cross-coupling of nonaromatic, heterocyclic bromides with aryl and heteroaryl bromides

Reductive cross-coupling allows the direct C-C bond formation between two organic halides without the need for preformation of an organometallic reagent. A method has been developed for the reductive cross-coupling of nonaromatic, heterocyclic bromides with aryl or heteroaryl bromides. The developed conditions use an air-stable Ni(II) source in the presence of a diamine ligand and a metal reductant to allow late-stage incorporation of saturated heterocyclic rings onto aryl halides in a functional-group tolerant manner.

PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME

Provided are picolinamide and pyrimidine-4-carboxamide compounds, a method for preparing the same, a pharmaceutical composition containing the same, and a medical use using the compound as an agent for preventing, regulating, and treating diseases related to regulation of glucocorticoids by using selective inhibitory activity of the compound for an 11β-HSD1 enzyme. The picolinamide and pyrimidine-4-carboxamide compounds of the present invention are selective inhibitors of human-derived 11β-HSD1 enzymes, and are useful in an agent for preventing, regulating, and treating diseases related to glucocorticoid regulation in which human- derived 11β-HSD1 enzymes are involved, for example, metabolic syndromes such as, type 1 and type 2 diabetes, diabetes later complications, latent autoimmune diabetes adult (LAD A), insulin tolerance syndromes, obesity, impaired glucose tolerane (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.

AZABENZIMIDAZOLYL COMPOUNDS

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I), as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

BENZIMIDAZOLYL COMPOUNDS AS POTENTIATORS OF MGLUR2 SUBTYPE OF GLUTAMATE RECEPTOR

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Efficient Solution-Phase Parallel Synthesis of 4-Substituted N-Protected Piperidines

Practical conditions for the synthesis of 4-substituted N-protected piperidines through CuCN·2LiBr-catalyzed organozinc additions to 1-acylpyridinium salts and subsequent hydrogen-transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4-substituted N-protected piperidines in excellent overall yields without the isolation of intermediate dihydropyridines, In those cases in which the organozinc addition results in mixtures of 2- and 4-substituted dihydropyridines, the 2-substituted isomers are efficiently scavenged with maleic anhydride and subsequently removed by a mild extractive workup with NaHCO3 (sat.). The N-acyl group can conveniently be exchanged from N-phenoxycarbonyl to N-tBoc, thus allowing orthogonal deprotection strategies. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.