766-85-8Relevant academic research and scientific papers
Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases
Bach, Stéphane,Baratte, Blandine,Bazin, Marc-Antoine,Brachet-Botineau, Marie,Dao, Viet Hung,Denevault-Sabourin, Caroline,Gouilleux, Fabrice,Logé, Cédric,Marchand, Pascal,McCarthy, Florence O.,Ourliac-Garnier, Isabelle,Robert, Thomas,Thiéfaine, Jér?me,da Silva, Teresinha Gon?alves
, (2021/12/10)
Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b, d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.
Palladium-Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand-Assisted Halide Exchange
Boehm, Philip,Cacherat, Bastien,Lee, Yong Ho,Martini, Tristano,Morandi, Bill
supporting information, p. 17211 - 17217 (2021/07/02)
We report an efficient and broadly applicable palladium-catalyzed iodination of inexpensive and abundant aryl and vinyl carboxylic acids via in situ activation to the acid chloride and formation of a phosphonium salt. The use of 1-iodobutane as iodide source in combination with a base and a deoxychlorinating reagent gives access to a wide range of aryl and vinyl iodides under Pd/Xantphos catalysis, including complex drug-like scaffolds. Stoichiometric experiments and kinetic analysis suggest a unique mechanism involving C?P reductive elimination to form the Xantphos phosphonium chloride, which subsequently initiates an unusual halogen exchange by outer sphere nucleophilic substitution.
Direct Pd(II)-Catalyzed Site-Selective C5-Arylation of 2-Pyridone Using Aryl Iodides
Maity, Saurabh,Das, Debapratim,Sarkar, Souradip,Samanta, Rajarshi
supporting information, p. 5167 - 5171 (2018/09/13)
A straightforward Pd(II)-catalyzed general strategy was developed for the C5-selective arylation of the 2-pyridone core with easily available aryl iodides. The transformation was highly regioselective and accomplished with a wide scope and functional group tolerance. Silver nitrate played a crucial role in this direct site-selective arylation. The method was extended to synthesize biologically active molecules.
Visible-Light-Induced Decarboxylative Iodination of Aromatic Carboxylic Acids
Jiang, Min,Yang, Haijun,Jin, Yunhe,Ou, Lunyu,Fu, Hua
supporting information, p. 1572 - 1577 (2018/06/26)
A convenient, efficient and practical visible-light-induced decarboxylative iodination of aromatic carboxylic acids has been developed, and the corresponding aryl iodides were obtained in good yields. The method shows some advantages including the use of readily available aromatic carboxylic acids as the starting materials, simple and mild conditions, high efficiency, wide substrate scope and tolerance of various functional groups.
Electrochemical Synthesis of Aryl Iodides by Anodic Iododesilylation
M?ckel, Robert,Hille, Jessica,Winterling, Erik,Weidemüller, Stephan,Faber, Tabea Melanie,Hilt, Gerhard
supporting information, p. 442 - 445 (2018/02/21)
An electrochemical access to iodinated aromatic compounds starting from trimethylsilyl-substituted arenes is presented. By design of experiments, highly efficient and mild conditions were identified for a wide range of substrates. A functional group stability test and the synthesis of an important 3-iodobenzylguanidine radiotracer illustrate the scope of this process.
One-Pot, Metal-Free Conversion of Anilines to Aryl Bromides and Iodides
Leas, Derek A.,Dong, Yuxiang,Vennerstrom, Jonathan L.,Stack, Douglas E.
supporting information, p. 2518 - 2521 (2017/05/24)
A metal-free synthesis of aryl bromides and iodides from anilines via halogen abstraction from bromotrichloromethane and diiodomethane is described. This one-pot reaction affords aryl halides from the corresponding anilines in moderate to excellent yields without isolation of diazonium salts. The transformation has short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. DFT calculations support a SRN1 mechanism. This method represents a convenient alternative to the classic Sandmeyer reaction.
Copper-catalysed aromatic-Finkelstein reactions with amine-based ligand systems
Jin, Xiaodong,Davies, Robert P.
, p. 2110 - 2117 (2017/07/22)
A new efficient and low-cost ligand, diethylenetriamine, has been utilised to promote the iodination of 16 different bromo-substrates via the copper catalysed Finkelstein halogen exchange reaction under mild conditions. In contrast to earlier methods, the use of inert atmosphere conditions was not required to obtain high yields and purity. Studies on the speciation of the catalyst in solution indicate rapid disproportionation of copper(i) in the presence of diethylenetriamine to give copper(0) and a bis-ligated copper(ii) complex which is characterised by X-ray diffraction. This copper(ii) complex was also shown to be catalytically active in the halogen exchange reaction. In contrast, no significant disproportionation was observed using dimethylethylenediamine as the ligand, and the solid-state structures of a copper(i) dimeric complex and a 2D polymeric network of copper(i) iodide tetramers are reported. The catalytic activity of diethylenetriamine and dimethylethylenediamine with both copper(i) and copper(ii) salts are compared, and possible mechanistic implications discussed.
Orbital Crossings Activated through Electron Injection: Opening Communication between Orthogonal Orbitals in Anionic C1-C5 Cyclizations of Enediynes
Peterson, Paul W.,Shevchenko, Nikolay,Breiner, Boris,Manoharan, Mariappan,Lufti, Forat,Delaune, Jess,Kingsley, Margaret,Kovnir, Kirill,Alabugin, Igor V.
, p. 15617 - 15628 (2016/12/16)
Generally, the long-range electronic communication between spatially orthogonal orbitals is inefficient and limited to field and inductive effects. In this work, we provide experimental evidence that such communication can be achieved via intramolecular electron transfer between two degenerate and mutually orthogonal frontier molecular orbitals (MOs) at the transition state. Interaction between orthogonal orbitals is amplified when the energy gap between these orbitals approaches zero, or at an “orbital crossing”. The crossing between two empty or two fully occupied MOs, which do not lead to stabilization, can be “activated” when one of the empty MOs is populated (i.e., electron injection) or one of the filled MOs is depopulated (i.e., hole injection). In reductive cycloaromatization reactions, such crossings define transition states with energies defined by both the in-plane and out-of-plane π-systems. Herein, we provide experimental evidence for the utility of this concept using orbital crossings in reductive C1-C5 cycloaromatization reactions of enediynes. Communication with remote substituents via orbital crossings greatly enhances regioselectivity of the ring closure step in comparison to the analogous radical cyclizations. We also present photophysical data pertaining to the efficiency of electron injection into the benzannelated enediynes.
Copper-mediated aerobic iodination and perfluoroalkylation of boronic acids with (CF3)2CFI at room temperature
Liu, Xi-Hai,Leng, Jing,Jia, Su-Jiao,Hao, Jian-Hong,Zhang, Fanglin,Qin, Hua-Li,Zhang, Cheng-Pan
, p. 59 - 67 (2016/08/09)
The copper-mediated aerobic reactions between the branched (CF3)2CFI and boronic acids (R-B(OH)2) are described. Different from the linear perfluoroalkyl analogs CF3(CF2)nI (n?=?2, 3, 5, 7), (CF3)2CFI reacting with R-B(OH)2at room temperature under air in the presence of catalytic Cu powder provided exclusively the corresponding iodides (R-I), while the aerobic reactions of arylboronic acids with (CF3)2CFI at room temperature in the presence of Cu(OAc)2gave the perfluoroalkylation products (R-CF(CF3)2) in acceptable to moderate yields. The iodination reaction could be further promoted by hydroquinone, the addition of which improved the oxidation ability of (CF3)2CFI and provided the ipso-iodination products in high yields. The perfluoroalkylation was facilitated by the copper carboxylates since the addition of these salts into the reaction mixtures could successfully give rise to Ar-CF(CF3)2.
Rapid and efficient copper-catalyzed finkelstein reaction of (hetero)aromatics under continuous-flow conditions
Chen, Mao,Ichikawa, Saki,Buchwald, Stephen L.
supporting information, p. 263 - 266 (2015/02/05)
A general, rapid, and efficient method for the copper-catalyzed Finkelstein reaction of (hetero)aromatics has been developed using continuous flow to generate a variety of aryl iodides. The described method can tolerate a broad spectrum of functional groups, including N-H and O-H groups. Additionally, in lieu of isolation, the aryl iodide solutions were used in two distinct multistep continuous-flow processes (amidation and Mg-I exchange/nucleophilic addition) to demonstrate the flexibility of this method.
