14372-12-4

Upstream product

• 62-53-3 aniline 
• 2759-52-6 N-phenylcyclopropanecarboxamide 
• 1516-60-5 4-nitrophenyl azide 
• 100-01-6 4-nitro-aniline 
• 1489-69-6 Cyclopropanecarboxaldehyde 
• 4023-34-1 cyclopropanecarboxylic acid chloride 

Downstream Products

• 13691-26-4 1-(4-nitrophenyl)pyrrolidin-2-one 
• 74617-73-5 N-(4-aminophenyl)cyclopropanecarboxamide 
• 113286-64-9 {triphenylphosphinegold(p-nitrophenyl)carbamoyl}cyclopropane 

Relevant academic research and scientific papers

Tozasertib Analogues as Inhibitors of Necroptotic Cell Death

Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or type III kinase inhibitors. This opened up some interesting perspectives for the discovery of novel inhibitors that target the active site of RIPK1. Tozasertib, a type I pan-aurora kinase (AurK) inhibitor, was found to show a very high affinity for RIPK1. Because tozasertib presents the typical structural elements of a type I kinase inhibitor, the development of structural analogues of tozasertib is a good starting point for identifying novel type I RIPK1 inhibitors. In this paper, we identified interesting inhibitors of mTNF-induced necroptosis with no significant effect on AurK A and B, resulting in no nuclear abnormalities as is the case for tozasertib. Compounds 71 and 72 outperformed tozasertib in an in vivo TNF-induced systemic inflammatory response syndrome (SIRS) mouse model.

PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS

The present invention provides kinase inhibitors with anti-proliferative activity comprising substituted pyrimidine derivatives and pharmaceutically-acceptable formulations thereof. In addition, the invention provides methods for making novel compounds and methods for using the compounds.

Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under electron ionization and in the condensed phase

Rationale: Mass spectrometry is known as an excellent method to predict the behavior of organic compounds in solution. The behavior of organic compounds in the gas phase inside the ion source of a mass spectrometer allows their intrinsic properties to be defined, avoiding the influence of intermolecular interactions, counter ions and solvent effects. Methods: Arylpyrrolidin-2-ones were obtained by condensed-phase synthesis from the corresponding N-arylcyclopropanecarboxamides. Electron ionization (EI) with accurate mass measurements by high-resolution time-of-flight mass-spectrometry and quantum chemical calculations were used to understand the behavior of the molecular radical cations of N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones in the ion source of a mass spectrometer. The geometries of the molecules, transition states, and intermediates were fully optimized using DFT-PBE calculations. Results: Fragmentation schemes, ion structures, and possible mechanisms of primary isomerisation were proposed for isomeric N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones. Based on the fragmentation pattern of the N-arylcyclopropanecarboxamides, isomerisation of the original M+? ions into the M+? ions of the N-arylpyrrolidin-2-ones was shown to be only a minor process. In contrast, this cyclization proceeds easily in the condensed phase in the presence of Br?nsted acids. Conclusions: Based on the experimental data and quantum chemical calculations the principal mechanism of decomposition of the molecular ions of N-arylcyclopropanecarboxamides involves their direct fragmentation without any rearrangements. An alternative mechanism is responsible for the isomerisation of a small portion of the higher energy molecular ions into the corresponding N-arylpyrrolidin-2-one ions. Copyright

Effective nitration of anilides and acrylamides by tert-butyl nitrite

Nitro compounds are important intermediates in synthetic organic chemistry and the chemical industry. Herein, the efficient copper-catalyzed [10% Cu(NO3)2·3H2O] nitration of anilides was developed by using TBN (tert-butyl nitrite) as a nitrating reagent to give the corresponding nitro-substituted aromatic products in good to excellent yields. The use of TBN also led to the selective nitration of acrylamides at room temperature to afford only the (E) isomer of the nitration product. A series of anilides and acrylamides with a broad array of functional groups were well-tolerated by this procedure. This synthetic method has many advantages, which include inexpensive starting materials, mild reaction conditions, a fast reaction rate, and high yields. A mechanistic investigation indicates that a nitro radical, which is generated from the thermal homolysis of TBN, is involved in the two nitration processes. The efficient nitration of both anilides and acrylamides was achieved by using TBN (tert-butyl nitrite) as a metal-free nitrating reagent. This synthetic method has many advantages such as mild reaction conditions, a fast reaction rate, good to excellent yields, and a broad substrate scope. Our investigation indicates that a nitro radical is involved in the reaction mechanism.

A catalytic and tert-butoxide ion-mediated amidation of aldehydes with para-nitro azides

We report here a new catalytic reaction in which, para-nitro azides are acylated by aldehydes to produce amides and molecular nitrogen in a single step. The transformation is believed to proceed via an electron transfer process mediated by the tert-butoxide ion, and catalysed by a thiazolium salt derived species. The Royal Society of Chemistry 2013.

Ring-expanding reaction of cyclopropyl amides with triphenylphosphine and carbon tetrahalide

We succeeded in activating cyclopropyl amides (monoactivated cyclopropane) through the corresponding imidoyl halides prepared in situ in the presence of 2 equiv of PPh3 and 1 equiv of CX4, and the ring-expanding products (N-substituted pyrrolidin-2-ones) were obtained in good yields. The reaction mechanism was investigated on the basis of oxygen-18 tracer experiment.

Gold-containing derivatives of cyclopropanecarboxylic acid amides

The interaction of substituted cyclopropanecarboxylic acid amides with BF4 (I) has been studied.The reaction of I with cyclopropanecarboxylic acid p-nitroanilide leads to the gold derivative with the Au-N bond, the small cycle being unaltered.The interactions between lithiated cyclopropanecarboxylic acid N,N-diethylamides and I afford the organogold derivatives of the amides with gold bonded to the carbon of the small cycle.The compounds obtained were characterized by IR, 1H and 13C NMR spectral data.An X-ray structural study of cyclopropane and 1-triphenylphosphinegold-1-diethylcarbamoylcyclopropane was carried out.The interaction of lithiated derivatives of cyclopropanecarboxylic acid amides, in excess, with I gives unexpectedly stable anionic complexes of gold(I), (e.g. 1-diethylcarbamoylcyclopropyl)aurate.The potassium salt is stable in air, and it was isolated after treatment of the lithium salt of bis(diethylcarbamoylcyclopropyl)aurate with potassium carbonate.Its dimeric nature was confirmed by an RDF study, the Au2K2 fragment being a distorted tetrahedron.