108168-88-3

Usage

Synthesis Reference(s)

Synthetic Communications, 20, p. 3235, 1990 DOI: 10.1080/00397919008051551

Upstream product

• 131297-21-7 5-(Bis-tert-butylamino-methylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione 
• 75-64-9 tert-butylamine 
• 105-56-6 ethyl 2-cyanoacetate 
• 75-05-8 acetonitrile 
• 1609-86-5 Tert-butyl isocyanate 
• 16130-58-8 cyanoacetic acid chloride 
• 109-77-3 malononitrile 
• 75-65-0 tert-butyl alcohol 
• 36140-83-7 1-cyanoacetyl-3,5-dimethylpyrazole 
• 119072-55-8 tert-butylisonitrile 
• 590-17-0 cyanomethyl bromide 
• 15678-99-6 N-tert-butylchloroacetamide 

Relevant academic research and scientific papers

Visible-Light Photocatalytic Functionalization of Isocyanides for the Synthesis of Secondary Amides and Ketene Aminals

A new visible light-induced photocatalytic protocol enabling the formation of secondary amides from electron-poor organic bromides and isocyanides was developed. In addition, the in situ interception of ketenimine intermediates with nitrogen nucleophiles such as amines, hydrazines, and TMSN3 afforded, in a one-pot two-step procedure, valuable scaffolds such as ketene aminals, pyrazolones, and tetrazoles. Mechanistic evidence confirmed a radical pathway where isocyanides acted as radical geminal acceptors generating key imidoyl radical species.

Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides

The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM).

Transformations of Isonitriles with Bromoalkanes Using Photoredox Gold Catalysis

Isonitriles have excellent electronic compatibility to react with free radicals. Recently, photoredox catalysis has emerged as a powerful tool for the construction of C-C bonds with few protocols for alkylative heterocycle synthesis through isonitrile addition. Herein, we describe the photocatalytic generation of alkyl radicals from unactivated bromoalkanes as part of an efficient cross-coupling strategy for the diversification of isonitriles using a dimeric gold(I) photoredox catalyst, [Au2(dppm)2]Cl2.

KINASE INHIBITORS

Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.

Application of SiO2-Pr-SO3H as an efficient catalyst in the Ritter reaction

Sulfonic-acid-functionalized silica was applied as an efficient heterogeneous acid catalyst in the Ritter reaction to prepare amides by reaction of various benzylic, allylic, and tertiary alcohols with various nitriles in good to excellent yields under solvent-free conditions. The simplicity of the reaction, recovery of catalyst without loss of reactivity, high yield of products, and short reaction time represent improvements over many existing methods.

KAl(SO4)2.12H2O as an eco-friendly and reusable catalyst for the synthesis of amides by the Ritter reaction

KAl(SO4)2.12H2O (Alum) is an eco-friendly, inexpensive, readily available and reusable and was applied as catalyst to the synthesis of N-alkyl amides from nitriles and alcohols by the Ritter reaction. This solvent-free procedure is very simple with excellent yields and easy work-up.

3-hydroxy-2-cyanoalk-2-enamides, and 2-cyano-2-(tetrahydrofuran2- ylidene)- and 2-cyano-2-(tetrahydropyran-2-ylidene)acetamides: Synthesis, structure, and solvent-dependent (Z)/(E)-isomerism

3-Hydroxy-2-cyanoalk-2-enamides, and 2-cyano-2-(tetrahydrofuran-2- ylidene)- and 2-cyano-2-(tetrahydropyran-2-ylidene)acetamides with N-alkyl and N-aryl substituents have been synthesized in three steps from cyanoacetic acid. Their conformations were investigated by X-ray crystallography and 1H- NMR ROESY spectroscopy at room temperature. The enolic compounds 1-3 adopt an extended conformation stabilized by a strong intramolecular O-H O=C bond both in the solid state and in (D6)DMSO solution. In contrast, the structure of the cyclic derivatives 5a,b-8a,b is solvent-dependent. In the solid state and in CDCI3 solution, the compounds adopt an extended conformation of type I or III, while, in (D6)DMSO solution, their structures undergo time-dependent (Z)/(E)-isomerization structures (of type II or IV). This observation is compatible with a dipolar transition state of rotation. The kinetics of the isomerization are controlled by the N-substituent, the N-(t-Bu) derivatives 7a and 71) having the highest barrier of rotation around the C=C bond. The whole body of experimental evidence together with the results of molecular- mechanics calculations with I-IV, indicate that, in DMSO, two (E)/(Z)- isomers with two conformations are present, and that they undergo interconversion at room temperature with four different constants. The very fast exchange rates k(I.II) and k(III.IV) in the NMR time-scale might be responsible for the detection of only two isomers.

Synthesis of α-Cyano Carbonyl Compounds by Flash Vacuum Thermolysis of (Alkylamino)methylene Derivatives of Meldrum's Acid. Evidence for Facile 1,3-Shifts of Alkylamino and Alkylthio Groups in Imidoylketene Intermediates

The syntheses and flash vacuum thermolyses of 5--2,2-dimethyl-1,3-dioxane-4,6-diones (Meldrum's acid derivatives) 13a - i are described.Thermolysis of 13a as well as of ethyl 3-(tert-butylamino)acrylate (22) gives a tautomeric mixture of cyanoacetaldehyde (14) and 3-hydroxypropenenitrile (15).Thermolysis of 13b gives iminoacrolein 26 and not cyanoacetone (29).Thermolysis of 13c, d gives S-methyl cyanothioacetate (30), and 13f - h give cyanoacetamides 31 in high yields. 2-Cyanopent-4-enoic acid derivatives 32 are obtained from Meldrum's acids 13e, i.The results are discussed in terms of facile 1,3-shifts of methylthio and alkylamino groups in imidoylketenes, interconverting imidoylketenes and acylketene imines.

Rapid, Low-Temperature Amidation of Ethyl Cyanoacetate with Lithium Amides Derived from Primary and Secondary Amines

A facile, rapid method for amidating ethyl cyanoacetate with lithium amides derived from various primary and secondary amines, including sterically demanding amines is described.

Anodic Oxidation of Alkyl Isocyanates and Their Thio Derivatives in Acetonitrile

Seven alkyl isocyanates (RNCO), five alkyl isothiocyanates (RNCS), and two aromatic cyanato derivatives (ArNCO) were electrochemically investigated by cyclic voltammetry and anodic controlled-potential electrolysis in acetonitrile at platinum anodes.It was found that RNCS compounds exhibited considerably lower anodic potentials than RNCO derivatives.The preparative electrochemical oxidation of RNCS was dependent on the nature of the alkyl group.Primary RNCS afforded mainly five-membered heterocyclic products while tertiary ones gave largery amides due to α-cleavage or isocyanates due to substitution of sulfur for oxygen processes.RNCO compounds were oxidized at the onset of the solvent electrolyte region and yielded amides and carbonyl products due to nucleophilic involvement of either acetonitrile or water, respectively, or formed products due to radical reactions (mono-, di-, and tricyanomethyl derivatives).ArNCO gave mostly polymeric products.Mechanistic routes for the formation of the various products are discussed.