scholarly journals Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

2021 ◽  
Vol 17 ◽  
pp. 156-165
Author(s):  
Romain Pierre ◽  
Anne Brethon ◽  
Sylvain A Jacques ◽  
Aurélie Blond ◽  
Sandrine Chambon ◽  
...  
Keyword(s):  
Room Temperature ◽  
Kinase Inhibitor ◽  
Ionic Hydrogenation ◽  
Library Synthesis ◽  
Full Paper ◽  
Efficient Access

In our hands, efficient access to the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one kinase hinge-binder motif proved to be more challenging than anticipated requiring a significant investment in route scouting and optimization. This full paper focuses on the synthesis issues that we encountered during our route exploration and the original solutions we found that helped us to identify two optimized library-style processes to prepare our large kinase inhibitor library.

scholarly journals Efficient access to unprotected primary amines by iron-catalyzed aminochlorination of alkenes

Science ◽  
2018 ◽  
Vol 362 (6413) ◽  
pp. 434-439 ◽  
Author(s):  
Luca Legnani ◽  
Gabriele Prina-Cerai ◽  
Tristan Delcaillau ◽  
Suzanne Willems ◽  
Bill Morandi
Keyword(s):  
Room Temperature ◽  
Biologically Active ◽  
Primary Amines ◽  
General Strategy ◽  
Hydroxylamine Derivative ◽  
Homoallylic Amines ◽  
Efficient Access ◽  
Reaction Proceeds ◽  
Large Scope ◽  
Amphoteric Molecules

Primary amines are essential constituents of biologically active molecules and versatile intermediates in the synthesis of drugs and agrochemicals. However, their preparation from easily accessible alkenes remains challenging. Here, we report a general strategy to access primary amines from alkenes through an operationally simple iron-catalyzed aminochlorination reaction. A stable hydroxylamine derivative and benign sodium chloride act as the respective nitrogen and chlorine sources. The reaction proceeds at room temperature under air; tolerates a large scope of aliphatic and conjugated alkenes, including densely functionalized substrates; and provides excellent anti-Markovnikov regioselectivity with respect to the amino group. The reactivity of the 2-chloroalkylamine products, an understudied class of amphoteric molecules, enables facile access to linear or branched aliphatic amines, aziridines, aminonitriles, azido amines, and homoallylic amines.

Nitrogen-centered radical reaction leading to energetic materials: a mild and efficient access to N–N bridged compounds

2021 ◽  
Vol 9 (38) ◽  
pp. 21685-21688
Author(s):  
Zhiwei Zeng ◽  
Yuji Liu ◽  
Guangbin Cheng ◽  
Wei Huang ◽  
Hao Wei ◽  
...  
Keyword(s):  
Energetic Materials ◽  
Room Temperature ◽  
High Efficiency ◽  
Radical Reaction ◽  
Efficient Access ◽  
External Assistance

A novel nitrogen-centered radical reaction leading to the formation of an N–N coupled biheterocycle was discovered, which features high efficiency and greenness at room temperature without external assistance.

Responsiveness of canine bronchial vasculature to excitatory stimuli and to cooling

2001 ◽  
Vol 280 (5) ◽  
pp. L930-L937 ◽  
Author(s):  
Luke J. Janssen ◽  
Hwa Lu-Chao ◽  
Stuart Netherton
Keyword(s):  
Room Temperature ◽  
Vascular Tone ◽  
Kinase Inhibitor ◽  
Maximal Response ◽  
Airway Wall ◽  
Kinase C ◽  
Adrenergic Control ◽  
Intracellular Ca ◽  
Exercise Induced ◽  
Evoked Contractions

Changes in bronchial vascular tone, in part due to cooling during ventilation, may contribute to altered control of airflow during airway inflammation, asthma, and exercise-induced bronchoconstriction. We investigated the responses of canine bronchial vasculature to excitatory stimuli and cooling. Electrical stimulation evoked contractions in only some (8 of 88) tissues; these were phentolamine sensitive and augmented by N ω-nitro-l-arginine. However, sustained contractions were evoked in all tissues by phenylephrine [concentration evoking a half-maximal response (EC50) ≈2 μM] or the thromboxane A2 mimetic U-46619 (EC50 ≈5 nM) and less so by β,γ-methylene-ATP or histamine. Cooling to room temperature markedly suppressed (≈75%) adrenergic responses but had no significant effect against U-46619 responses. Adrenergic responses, but not those to U-46619, were accompanied by an increase in intracellular Ca2+concentration. Chelerythrine (protein kinase C antagonist) markedly antagonized adrenergic responses (mean maxima reduced 39% in artery and 86% in vein) but had no significant effect against U-46619, whereas genistein (a nonspecific tyrosine kinase inhibitor) essentially abolished responses to both agonists. We conclude that cooling of the airway wall dramatically interferes with adrenergic control of bronchial perfusion but has little effect on thromboxane-mediated vasoconstriction.

Catalyst- and solvent-free efficient access to N-alkylated amines via reductive amination using HBpin

2020 ◽  
Vol 18 (20) ◽  
pp. 3853-3857
Author(s):  
Vipin K. Pandey ◽  
Somnath Bauri ◽  
Arnab Rit
Keyword(s):  
Room Temperature ◽  
Reductive Amination ◽  
Solvent Free ◽  
Secondary Amines ◽  
One Pot ◽  
Efficient Access ◽  
Wide Range ◽  
General Method

A general method for catalyst- and solvent-free room temperature reductive amination has been developed and it efficiently delivers a wide range of sterically and electronically diverse secondary amines in one-pot.

Organocatalytic Regioselective [3+2] Annulation of Morita-Baylis-Hillman Carbonates with Azonaphthalenes: An Efficient Access to 3-Spiropyrazole- 2-oxindoles

2020 ◽  
Vol 7 (2) ◽  
pp. 134-139
Author(s):  
Yuyu Cheng ◽  
Zhongyue Lu ◽  
Pengfei Li
Keyword(s):  
Room Temperature ◽  
Mild Conditions ◽  
Efficient Access

Background: A cheap and commercially available organocatalyst, 4-dimethylaminopyridine was successfully employed in the regioselective [3+2] cycloaddition of isatin-derived Morita-Baylis- Hillman carbonates with azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles in excellent yields under mild conditions. Methods: In the presence of 4-dimethylaminopyridine with a loading of 10 mol%, a series of isatinderived Morita-Baylis-Hillman carbonates reacted smoothly with azonaphthalenes in dichloromethane at room temperature to furnish 3-spiropyrazole-2-oxindoles in 72-98% yield. Result and Conclusion: In summary, we have developed reasonably cheap and commercially available 4-dimethylaminopyridine-mediated regioselective [3+2] annulations between isatin-derived Morita- Baylis-Hillman carbonates and azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles under mild conditions.

Phosphine-Free [3+2] Cycloaddition of Propargylamines with Dialkyl Azodicarboxylates: An Efficient Access to Pyrazole Backbone

Synthesis ◽  
2018 ◽  
Vol 50 (17) ◽  
pp. 3499-3505 ◽  
Author(s):  
Jie Liu ◽  
Xueshun Jia ◽  
Yicheng Zhang
Keyword(s):  
Room Temperature ◽  
High Selectivity ◽  
Cycloaddition Reaction ◽  
New Approach ◽  
Efficient Access

A phosphine-free [3+2] cycloaddition reaction of the substituted propargylamines with dialkyl azodicarboxylates at room temperature is described. This reaction provides a new approach to functionalized pyrazoles in good yields and high selectivity.

Ti(iv)-catalyzed cascade synthesis of tetrahydrofuro[3,2-d]oxazole from arene-1,4-diones

2015 ◽  
Vol 13 (15) ◽  
pp. 4418-4421 ◽  
Author(s):  
Gang Li ◽  
Li Li ◽  
Haihong Huang ◽  
Dali Yin
Keyword(s):  
Intramolecular Cyclization ◽  
Room Temperature ◽  
Ionic Hydrogenation ◽  
Oxazole Derivatives

The tandem ionic hydrogenation, ketalization, and intramolecular cyclization of arene-1,4-diones with a combination of TiCl4/Et3SiH give facile access to tetrahydrofuro[3,2-d]oxazole derivatives in good yields at room temperature.

Dependence of Intergranular Fracture on Boundary Topography and Cohesion

1973 ◽  
Vol 31 ◽  
pp. 150-151
Author(s):  
J. E. Doherty ◽  
A. F. Giamei ◽  
B. H. Kear ◽  
C. W. Steinke
Keyword(s):  
Grain Boundary ◽  
Room Temperature ◽  
Nickel Base Superalloy ◽  
Boundary Shear ◽  
Room Temperature Ductility ◽  
Solid Solution Matrix ◽  
Nickel Base ◽  
Solution Matrix ◽  
Different Levels ◽  
Base Superalloy

Recently we have been investigating a class of nickel-base superalloys which possess substantial room temperature ductility. This improvement in ductility is directly related to improvements in grain boundary strength due to increased boundary cohesion through control of detrimental impurities and improved boundary shear strength by controlled grain boundary micros true tures.For these investigations an experimental nickel-base superalloy was doped with different levels of sulphur impurity. The micros tructure after a heat treatment of 1360°C for 2 hr, 1200°C for 16 hr consists of coherent precipitates of γ’ Ni3(Al,X) in a nickel solid solution matrix.

Hepatocyte Alterations in Guinea Pigs FED Polychlorinated Biphenyls (PCBs), Dibenzodioxins (PCDD), AND DIBENZOFURANS (PCDF)

1982 ◽  
Vol 40 ◽  
pp. 56-57
Author(s):  
J. N. Turner ◽  
D. N. Collins
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Dose Group ◽  
Methyl Cellulose ◽  
Uranyl Acetate ◽  
Target Organ ◽  
Office Building ◽  
Lead Citrate ◽  
Control Groups ◽  
Cooling Fluid

A fire involving an electric service transformer and its cooling fluid, a mixture of PCBs and chlorinated benzenes, contaminated an office building with a fine soot. Chemical analysis showed PCDDs and PCDFs including the highly toxic tetra isomers. Guinea pigs were chosen as an experimental animal to test the soot's toxicity because of their sensitivity to these compounds, and the liver was examined because it is a target organ. The soot was suspended in 0.75% methyl cellulose and administered in a single dose by gavage at levels of 1,10,100, and 500mgm soot/kgm body weight. Each dose group was composed of 6 males and 6 females. Control groups included 12 (6 male, 6 female) animals fed activated carbon in methyl cellulose, 6 males fed methyl cellulose, and 16 males and 10 females untreated. The guinea pigs were sacrificed at 42 days by suffocation in CO2. Liver samples were immediately immersed and minced in 2% gluteraldehyde in cacadylate buffer at pH 7.4 and 4°C. After overnight fixation, samples were postfixed in 1% OsO4 in cacodylate for 1 hr at room temperature, embedded in epon, sectioned and stained with uranyl acetate and lead citrate.

Domain Formation in Synthetic Quartz

1971 ◽  
Vol 29 ◽  
pp. 156-157
Author(s):  
Joseph J. Comer
Keyword(s):  
Electron Beam ◽  
Room Temperature ◽  
Domain Formation ◽  
Synthetic Quartz ◽  
Transmission Electron ◽  
Black Spots ◽  
Diffraction Mode ◽  
Domain Boundaries ◽  
Kikuchi Lines ◽  
Straight Lines

Domains visible by transmission electron microscopy, believed to be Dauphiné inversion twins, were found in some specimens of synthetic quartz heated to 680°C and cooled to room temperature. With the electron beam close to parallel to the [0001] direction the domain boundaries appeared as straight lines normal to <100> and <410> or <510> directions. In the selected area diffraction mode, a shift of the Kikuchi lines was observed when the electron beam was made to traverse the specimen across a boundary. This shift indicates a change in orientation which accounts for the visibility of the domain by diffraction contrast when the specimen is tilted. Upon exposure to a 100 KV electron beam with a flux of 5x 1018 electrons/cm2sec the boundaries are rapidly decorated by radiation damage centers appearing as black spots. Similar crystallographio boundaries were sometimes found in unannealed (0001) quartz damaged by electrons.

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