206446-48-2

Upstream product

• 51934-41-9 4-iodobenzoic acid ethyl ester 
• 301673-14-3 tert-butyl 4-iodopiperidine-1-carboxylate 
• 5798-75-4 Ethyl 4-bromobenzoate 
• 180695-79-8 tert-butyl 4-bromo-1-piperidinecarboxylate 
• 4334-88-7 p-ethoxycarbonylphenylboronic acid 
• 159503-91-0 tert-butyl 4-bromo-5,6-dihydropyridine-1(2H)-carboxylate 
• 375853-82-0 tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate 
• 1240969-31-6 4-(4-ethoxycarbonylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 

Relevant academic research and scientific papers

Nickel-catalyzed cross-electrophile coupling of aryl bromides and cyclic secondary alkyl bromides with spiro-bidentate-pyox ligands

The cross-electrophile coupling of aryl bromides and cyclic secondary alkyl bromides catalyzed by nickel/spiro-bidentate-pyox ligands with lithium chloride as the additive for the Csp2-Csp3bond formation was reported. The reaction could tolerate functional groups such as sulfonamide, ester, aldehyde, ketone, protected indolyl, tert-butoxycarbonyl, aryl nitriles and aryl chloride. Various aryl-cyclic secondary alkyl Csp2-Csp3bond products were synthesized under optimal reaction conditions (19 examples).

Micelle enabled C(sp2)-C(sp3) cross-electrophile coupling in waterviasynergistic nickel and copper catalysis

A robust and sustainable C(sp2)-C(sp3) cross-electrophile coupling was developedvianickel/copper synergistic catalysis under micellar conditions. This protocol provided a general method to access alkylated arenes with good to excellent yields on a very large scale.

General C(sp2)-C(sp3) Cross-Electrophile Coupling Reactions Enabled by Overcharge Protection of Homogeneous Electrocatalysts

Cross-electrophile coupling (XEC) of alkyl and aryl halides promoted by electrochemistry represents an attractive alternative to conventional methods that require stoichiometric quantities of high-energy reductants. Most importantly, electroreduction can readily exceed the reducing potentials of chemical reductants to activate catalysts with improved reactivities and selectivities over conventional systems. This work details the mechanistically-driven development of an electrochemical methodology for XEC that utilizes redox-active shuttles developed by the energy-storage community to protect reactive coupling catalysts from overreduction. The resulting electrocatalytic system is practical, scalable, and broadly applicable to the reductive coupling of a wide range of aryl, heteroaryl, or vinyl bromides with primary or secondary alkyl bromides. The impact of overcharge protection as a strategy for electrosynthetic methodologies is underscored by the dramatic differences in yields from coupling reactions with added redox shuttles (generally >80%) and those without (generally 20%). In addition to excellent yields for a wide range of substrates, reactions protected from overreduction can be performed at high currents and on multigram scales.

Nickel-Catalyzed Cross-Electrophile Reductive Couplings of Neopentyl Bromides with Aryl Bromides

5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed cross-electrophile couplings by screening a diverse set of pharmaceutical compound library. A strategic screening approach led to the discovery of this novel ligand, which was successfully applied in the preparation of various alkylated arene products with good to high yields. Furthermore, the properties of this ligand allowed expanding the scope of reductive couplings to challenging substrates, such as sterically hindered neopentyl halides, which are known to generate motifs that are prevalent in biologically active molecules.

Metal-Reductant-Free Electrochemical Nickel-Catalyzed Couplings of Aryl and Alkyl Bromides in Acetonitrile

While reductive cross-electrochemical coupling is an attractive approach for the synthesis of complex molecules at both small and large scale, two barriers for large-scale applications have remained: the use of stoichiometric metal reductants and a need for amide solvents. In this communication, new conditions that address these challenges are reported. The nickel-catalyzed reductive cross-coupling of aryl bromides with alkyl bromides can be conducted in a divided electrochemical cell using acetonitrile as the solvent and diisopropylamine as the sacrificial reductant to afford coupling products in synthetically useful yields (22-80%). Additionally, the use of a combination of the ligands 4,4′,4″-tri-tert-butyl-2,2′:6′,2′-terpyridine and 4,4′-di-tert-butyl-2,2′-bipyridine is essential to achieve high yields.

Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists

Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Soluble Guanylate Cyclase Activators

This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Direct synthesis of 4-arylpiperidines via palladium/copper(I)-cocatalyzed negishi coupling of a 4-piperidylzinc iodide with aromatic halides and triflates

A general procedure for the synthesis of 4-arylpiperidines via the coupling of 4-(N-BOC-piperidyl)zinc iodide with aryl halides and triflates is presented. The reaction requires cocatalysis with both Cl2Pd(dppf) and a copper(I) species. An impr

Synthesis of C-substituted cyclic amines using azacycloalkyl organozinc reagents

Azetidine and piperidine derived organozinc species have been prepared from the corresponding azacycloalkyl iodides by direct Zn insertion. They have been shown to readily undergo Pd(0) mediated cross-coupling reactions and to transmetallate with CuCN.2LiCl.