7103-46-0Relevant academic research and scientific papers
Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
, p. 4623 - 4661 (2021/05/07)
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides
Connell, Timothy U.,Forni, José A.,Micic, Nenad,Polyzos, Anastasios,Weragoda, Geethika
supporting information, p. 18646 - 18654 (2020/08/21)
We report a new visible-light-mediated carbonylative amidation of aryl, heteroaryl, and alkyl halides. A tandem catalytic cycle of [Ir(ppy)2(dtb-bpy)]+ generates a potent iridium photoreductant through a second catalytic cycle in the presence of DIPEA, which productively engages aryl bromides, iodides, and even chlorides as well as primary, secondary, and tertiary alkyl iodides. The versatile in situ generated catalyst is compatible with aliphatic and aromatic amines, shows high functional-group tolerance, and enables the late-stage amidation of complex natural products.
IrIII-Catalyzed direct syntheses of amides and esters using nitriles as acid equivalents: A photochemical pathway
Talukdar, Ranadeep
supporting information, p. 5303 - 5308 (2020/04/17)
An unprecedented IrIII[df(CF3)ppy]2(dtbbpy)PF6-catalyzed simple photochemical process for direct addition of amines and alcohols to the relatively less reactive nitrile triple bond is described herein. Various amides and esters are synthesized as the reaction products, with nitriles being the acid equivalents. A mini-library of different types of amides and esters is made using this mild and efficient process, which uses only 1 mol% of photocatalyst under visible light irradiation (λ = 445 nm). The reaction strategy is also efficient for gram-scale synthesis.
Frustrated Lewis Pair Catalyzed Hydrogenation of Amides: Halides as Active Lewis Base in the Metal-Free Hydrogen Activation
Sitte, Nikolai A.,Bursch, Markus,Grimme, Stefan,Paradies, Jan
supporting information, p. 159 - 162 (2019/01/04)
A method for the metal-free reduction of carboxylic amides using oxalyl chloride as an activating agent and hydrogen as the final reductant is introduced. The reaction proceeds via the hydrogen splitting by B(2,6-F2-C6H3)3 in combination with chloride as the Lewis base. Density functional theory calculations support the unprecedented role of halides as active Lewis base components in the frustrated Lewis pair mediated hydrogen activation. The reaction displays broad substrate scope for tertiary benzoic acid amides and α-branched carboxamides.
Cross-Dehydrogenating Coupling of Aldehydes with Amines/R-OTBS Ethers by Visible-Light Photoredox Catalysis: Synthesis of Amides, Esters, and Ureas
Pandey, Ganesh,Koley, Suvajit,Talukdar, Ranadeep,Sahani, Pramod Kumar
supporting information, p. 5861 - 5865 (2018/09/21)
A straightforward synthesis of amides, ureas, and esters is reported by visible-light cross-dehydrogenating coupling (CDC) of aldehydes (or amine carbaldehydes) and amines/R-OTBS ethers by photoredox catalysis. The reaction is found to be general and high yielding. A plausible mechanistic pathway has been proposed for these transformations and is supported by appropriate controlled experiments.
Mild Amide-Cleavage Reaction Mediated by Electrophilic Benzylation
Yamada, Kohei,Karuo, Yukiko,Tsukada, Yuichi,Kunishima, Munetaka
supporting information, p. 14042 - 14047 (2016/09/21)
An extremely mild method for amide-cleavage by using the triazine-based benzylating reagent 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4-benzylmorpholinium trifluoromethanesulfonate (DPT-BM), which spontaneously releases benzyl cation species when being dissolved at room temperature, has been developed. O-Benzylation of the amide with DPT-BM and the subsequent hydrolysis of the resulting intermediate benzyl imidate salt afford the corresponding amine and benzyl ester, which can be converted by hydrogenolysis into a carboxylic acid under neutral conditions. O-Benzylation proceeds depending on both steric and electronic factors around the amide group. Thus, some amides have been selectively cleaved over other amides. Furthermore, intramolecular chemoselective cleavage of an amide group in the presence of an ester group was achieved. Such selective hydrolytic reactions cannot be performed with Meerwein reagents as well as under acidic or basic hydrolytic conditions.
PROCESSES USING MOLECULAR SIEVE SSZ-101
-
, (2016/04/20)
This disclosure is directed to uses for a new crystalline molecular sieve designated SSZ-101. SSZ-101 is synthesized using a N-cyclohexylmethyl-N-ethylpiperidinium cation as a structure directing agent.
Metal–Organic Framework Based on Copper and Carboxylate-Imidazole as Robust and Effective Catalyst in the Oxidative Amidation of Carboxylic Acids and Formamides
Albert-Soriano, María,Pastor, Isidro M.
supporting information, p. 5180 - 5188 (2016/10/26)
A metal–organic framework (MOF) based on copper and 1,3-bis(carboxymethyl)imidazole (bcmim) was prepared on a gram scale by using a precipitation method at room temperature. The Cu(bcmim)2MOF was shown to be an efficient catalyst for the preparation of amides through an oxidative coupling between carboxylic acids and formamides in the presence of an oxidant, such as tert-butyl hydroperoxide (TBHP). The method for the preparation of the amides is robust regardless of the carboxylic acid and gives good conversions with good selectivity. The heterogeneous catalyst was recovered unaltered after the reaction, was easily separated from the reaction mixture, and subsequently reactivated by suitable treatment. Moreover, the coupling reaction was scaled up to a gram scale, which allowed for the preparation of valuable products, such as fatty acid amides (i.e., 1-palmitoylpiperidine).
Low-Pressure Radical11C-Aminocarbonylation of Alkyl Iodides through Thermal Initiation
Chow, Shiao Y.,Odell, Luke R.,Eriksson, Jonas
, p. 5980 - 5989 (2016/12/26)
A radical11C-aminocarbonylation protocol characterized by excellent substrate compatibility was developed to transform alkyl iodides into11C-labelled amides, including the 11β-HSD1 inhibitor [carbonyl-11C]adamantan-1-yl(piperidin-1-yl)methanone. This protocol serves as a complementary extension of palladium-mediated11C-aminocarbonylation, which is limited to the preparation of11C-labelled compounds lacking beta-hydrogen atoms. The use of AIBN as a radical initiator and a low-pressure xenon–[11C]CO delivery unit represents a simple and convenient alternative to previous radical11C-carbonylation methodologies burdened with the need for a proprietary high pressure reactor connected to a light source.
Mild and Low-Pressure fac-Ir(ppy)3-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis
Chow, Shiao Y.,Stevens, Marc Y.,?kerbladh, Linda,Bergman, Sara,Odell, Luke R.
supporting information, p. 9155 - 9161 (2016/07/14)
A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3-catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3, amines, reductants, and CO gas (released ex situ from Mo(CO)6), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields.
