70450-41-8

Upstream product

• 766-80-3 1-bromomethyl-3-chlorobenzene 
• 873-63-2 m-chlorobenzyl alcohol 
• 76950-81-7 1-(3-Chloro-benzyl)-2-methylsulfanyl-4,6-diphenyl-pyridinium; iodide 
• 27396-17-4 tert.-Butyl-m-chlorphenylperacetat 
• 4152-90-3 m-chlorobenzylamine 
• 108-41-8 1-chloro-3-methylbenzene 
• 620-20-2 1-Chloro-3-chloromethyl-benzene 
• 76950-88-4 1-(3-Chloro-benzyl)-4,6-diphenyl-1H-pyridine-2-thione 

Downstream Products

• 136794-80-4 4'-O-demethyl-4β-[(3''-chlorobenzyl)amino]-4-desoxypodophyllotoxin 
• 108-41-8 1-chloro-3-methylbenzene 
• 766-80-3 1-bromomethyl-3-chlorobenzene 
• 203808-37-1 3-Butyl-1-(3-chloro-benzyl)-5,6-dimethyl-1H-thieno[2,3-d]pyrimidine-2,4-dione 

Relevant academic research and scientific papers

CENTRALLY ACTIVE P38ALPHA INHIBITING COMPOUNDS

Compounds that are inhibitors of p38alpha and centrally available are described.

Iminophosphorane-mediated regioselective umpolung alkylation reaction of α-iminoesters

Umpolung reactions of imines, especially the asymmetric reactions, have been extensively studied as they provide access to important chiral amines in an efficient manner. The reactions studied range from simple Michael reactions to several kinds of other reactions such as the aza-benzoin reaction, aza-Stetter reaction, addition with MBH carbonate, and Ir-catalysed allylation. Herein, we report the first umpolung alkylation reaction of α-iminoesters with alkyl halides mediated by iminophosphorane as an organic superbase. The desired products were obtained in up to 82% yield with almost perfect regioselectivities. The key to the regioselectivity of this reaction was the use of 4-trifluoromethyl benzyl imines as a substrate. The products were successfully derivatised into the more functionalised molecules in good yields.

Bioisosteric Replacement of Arylamide-Linked Spine Residues with N-Acylhydrazones and Selenophenes as a Design Strategy to Novel Dibenzosuberone Derivatives as Type i 1/2 p38α MAP Kinase Inhibitors

The recent disclosure of type I 1/2 inhibitors for p38α MAPK demonstrated how the stabilization of the R-spine can be used as a strategy to greatly increase the target residence time (TRT) of inhibitors. Herein, for the first time, we describe N-acylhydrazone and selenophene residues as spine motifs, yielding metabolically stable inhibitors with high potency on enzymatic, NanoBRET, and whole blood assays, improved metabolic stability, and prolonged TRT.

Rhodium-Catalyzed Generation of Anhydrous Hydrogen Iodide: An Effective Method for the Preparation of Iodoalkanes

The preparation of anhydrous hydrogen iodide directly from molecular hydrogen and iodine using a rhodium catalyst is reported for the first time. The anhydrous hydrogen iodide generated was proven to be highly active in the transformations of alkenes, phenyl aldehydes, alcohols, and cyclic ethers to the corresponding iodoalkanes. Therefore, the present methodology not only has provided convenient access to anhydrous hydrogen iodide but also offers a practical preparation method for various iodoalkanes in excellent atom economy.

Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine

We recently reported 1a (skepinone-L) as a type I p38α MAP kinase inhibitor with high potency and excellent selectivity in vitro and in vivo. However, as a type I inhibitor, it is entirely ATP-competitive and shows just a moderate residence time. Thus, the scope was to develop a new class of advanced compounds maintaining the structural binding features of skepinone-L scaffold like inducing a glycine flip at the hinge region and occupying both hydrophobic regions I and II. Extending this scaffold with suitable residues resulted in an interference with the kinase's R-Spine. By synthesizing 69 compounds, we could significantly prolong the target residence time with one example to 3663 s, along with an excellent selectivity score of 0.006 and an outstanding potency of 1.0 nM. This new binding mode was validated by cocrystallization, showing all binding interactions typifying type I1/2 binding. Moreover, microsomal studies showed convenient metabolic stability of the most potent, herein reported representatives.

Catalytic Halogen Bond Activation in the Benzylic C-H Bond Iodination with Iodohydantoins

This letter presents the side-chain iodination of electron-deficient benzylic hydrocarbons at rt using N-hydroxyphthalimide (NHPI) as radical initiator and 1,3-diiodo-5,5-dimethylhydantoin and 3-iodo-1,5,5-trimethylhydantoin (3-ITMH) as iodine source. Addition of a carboxylic acid increased the reactivity due to complex formation with and activation of 3-ITMH by proton transfer and halogen bond formation. No SEAr reactions were observed under the employed reaction conditions. Our method enables convenient product isolation and gives 50-72% yields of isolated products.

Application of "click" chemistry in solid phase synthesis of alkyl halides

A convenient and highly selective microwave assisted procedure for the conversion of allylic, benzylic and aliphatic alcohols to their corresponding halides using polymer-bound triphenylphosphine and iodine is presented. In case of symmetrical diols, mono-iodination product is obtained in very high yield. Additionally, highly regioselective behavior is observed in our procedure. Simplicity in operation, no column chromatography required for the purification of the products, recyclability of the reagents used, short reaction times and good to excellent yields are the advantages of our protocol. Most functional groups remain unaffected under our reaction condition.

Uranyl Schiff base complexes as new heterogeneous catalysts for halogen exchange reactions between alkyl halides and elemental halogens

Mild and effective procedure for the halogen exchange reaction of alkyl halides with elemental iodine and bromine catalyzed with uranyl Schiff base complexes in various aprotic solvents was developed. Corresponding alkyl bromides and iodides were obtained with high yields within 20—70 min. The structures of the target products were confirmed by physical and spectroscopic data.

Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity

p38α mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38α MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.

Efficient and selective iodination of benzylic alcohols using NaI/bronsted ionic liquid system at room temperature

A simple, chemoselective, and effective procedure for the conversion of benzylic and allylic alcohols into corresponding iodides using NaI in the presence of a catalytic amount of 3-methylimidazolium hydrogensulfate ([Hmim]+[image omitted]) at room temperature is reported.