36600-71-2

Upstream product

• 141-97-9 ethyl acetoacetate 
• 18880-00-7 1-(bromomethyl)-4-(1,1-dimethylethyl)benzene 
• 6186-89-6 ethyl methyl malonate 

Downstream Products

• 1453097-24-9 4-[[4-(1,1-dimethylethyl)phenyl]methyl]-3-methyl-1-(5-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-5-ol 
• 944782-89-2 C₂₂H₂₄N₄O 
• 1272367-68-6 3-methyl-1-oxo-2-[(4-tert-butyl)benzyl]-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile 

Relevant academic research and scientific papers

Five Roads That Converge at the Cyclic Peroxy-Criegee Intermediates: BF3-Catalyzed Synthesis of β-Hydroperoxy-β-peroxylactones

We have discovered synthetic access to β-hydroperoxy-β-peroxylactones via BF3-catalyzed cyclizations of a variety of acyclic precursors, β-ketoesters and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals, with H2O2. Strikingly, independent of the choice of starting material, these reactions converge at the same β-hydroperoxy-β-peroxylactone products, i.e., the peroxy analogues of the previously elusive cyclic Criegee intermediate of the Baeyer-Villiger reaction. Computed thermodynamic parameters for the formation of the β-hydroperoxy-β-peroxylactones from silyl enol ethers, enol acetates, and cyclic acetals confirm that the β-peroxylactones indeed correspond to a deep energy minimum that connects a variety of the interconverting oxygen-rich species at this combined potential energy surface. The target β-hydroperoxy-β-peroxylactones were synthesized from β-ketoesters, and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals were obtained in 30-96% yields. These reactions proceed under mild conditions and open synthetic access to a broad selection of β-hydroperoxy-β-peroxylactones that are formed selectively even in those cases when alternative oxidation pathways can be expected. These β-peroxylactones are stable and can be useful for further synthetic transformations.

Development of coumarine derivatives as potent anti-filovirus entry inhibitors targeting viral glycoprotein

Filoviruses, including Ebolavirus (EBOV), Marburgvirus (MARV) and Cuevavirus, cause hemorrhagic fevers in humans with up to 90% mortality rates. In the 2014–2016 West Africa Ebola epidemic, there are 15,261 laboratory confirmed cases and 11,325 total deaths. The lack of effective vaccines and medicines for the prevention and treatment of filovirus infection in humans stresses the urgency to develop antiviral therapeutics against filovirus-associated diseases. Our previous study identified a histamine receptor antagonist compound CP19 as an entry inhibitor against both EBOV and MARV. The preliminary structure-activity relationship (SAR) studies of CP19 showed that its piperidine, coumarin and linker were related with its antiviral activities. In this study, we performed detailed SAR studies on these groups with synthesized CP19 derivatives. We discovered that 1) the piperidine group could be optimized with heterocycles, 2) the substitution groups of C3 and C4 of coumarin should be relatively large hydrophobic groups and 3) the linker part should be least substituted. Based on the SAR analysis, we synthesized compound 32 as a potent entry inhibitor of EBOV and MARV (IC50 = 0.5 μM for EBOV and 1.5 μM for MARV). The mutation studies of Ebola glycoprotein and molecular docking studies showed that the coumarin and its substituted groups of compound 32 bind to the pocket of Ebola glycoprotein in a similar way to the published entry inhibitor compound 118a. However, the carboxamide group of compound 32 does not have strong interaction with N61 as compound 118a does. The coumarin skeleton structure and the binding model of compound 32 elucidated by this study could be utilized to guide further design and optimization of entry inhibitors targeting the filovirus glycoproteins.

Interrupted Baeyer–Villiger Rearrangement: Building A Stereoelectronic Trap for the Criegee Intermediate

The instability of hydroxy peroxyesters, the elusive Criegee intermediates of the Baeyer–Villiger rearrangement, can be alleviated by selective deactivation of the stereoelectronic effects that promote the 1,2-alkyl shift. Stable cyclic Criegee intermediates constrained within a five-membered ring can be prepared by mild reduction of the respective hydroperoxy peroxyesters (β-hydroperoxy-β-peroxylactones) which were formed in high yields in reaction of β-ketoesters with BF3?Et2O/H2O2.

Copper-Mediated Deuterotrifluoromethylation of α?Diazo Esters

A copper-mediated deuterotrifluoromethylation of α?diazo esters under the promotion of deuterium oxide (D2O) has been developed for the synthesis of deuterium-labeled trifluoromethyl compounds. This deuterotrifluoromethylation reaction is of broad scope and can afford the deuterated products with higher than 99% isotopic purity. Moreover, the results of this investigation also provide some experimental evidences to support our previously proposed trifluoromethylation mechanism.

NOVEL BENZIMIDAZOLE DERIVATIVE AND USE THEREOF

The present invention aims to provide a compound capable of inhibiting PCA-1 that can be a target for a novel treatment method of various diseases, and pharmaceutical use of the compound. A compound represented by the formula (I): wherein each symbol is a

gem-Difluoroolefination of Diazo Compounds with TMSCF3 or TMSCF2Br: Transition-Metal-Free Cross-Coupling of Two Carbene Precursors

A new olefination protocol for transition-metal-free cross-coupling of two carbene fragments arising from two different sources, namely, a nonfluorinated carbene fragment resulting from a diazo compound and a difluorocarbene fragment derived from Ruppert-Prakash reagent (TMSCF3) or TMSCF2Br, has been developed. This gem-difluoroolefination proceeds through the direct nucleophilic addition of diazo compounds to difluorocarbene followed by elimination of N2. Compared to previously reported Cu-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3, which possesses a narrow substrate scope due to a demanding requirement on the reactivity of diazo compounds and in-situ-generated CuCF3, this transition-metal-free protocol affords a general and efficient approach to various disubstituted 1,1-difluoroalkenes, including difluoroacrylates, diaryldifluoroolefins, as well as arylalkyldifluoroolefins. In view of the ready availability of diazo compounds and difluorocarbene reagents and versatile transformations of 1,1-difluoroalkenes, this new gem-difluoroolefination method is expected to find wide applications in organic synthesis.

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3: The important role of water as a promoter

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3 reagent has been developed as a new method to prepare α-trifluoromethyl esters. This trifluoromethylation reaction represents the first example of fluoroalkylation of a non-fluorinated carbene precursor. Water plays an important role in promoting the reaction by activating the "CuCF3" species prepared from CuI/TMSCF3/CsF (1.0:1.1:1.1). The scope of this trifluoromethylation reaction is broad, and its efficiency is demonstrated in the synthesis of a variety of aryl-, benzyl-, and alkyl-substituted 3,3,3-trifluoropropanoates.

2-OXO-2H-CHROMENE COMPOUNDS

Compounds of structural formula (1) modulate CRTH2 activity and are of utility in, for example, respiratory diseases formula (1): in which: A represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene; B represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene or (optionally substituted)alkylene-Z; Z represents an oxygen atom, an NH or N-alkyl group, or a group of formula S(O)n, in which n = 0 to 2; X represents a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, sulfonic acid or a group of formula C(=O)NHSO2W or SO2NHC(=O)W; W represents an optionally substituted aryl or heteroaryl group or an optionally substituted alkyl or cycloalkyl group; Y represents an optionally substituted phenyl or 5- or 6-membered heteroaryl group, Ra, Rb, and Rc independently represent hydrogen, acyl, alkoxy, alkoxycarbonyl, alkylamino, alkylsulfinyl, alkylsulfonyl, alkylthio, -NH2, aminoalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, cyano, dialkylamino, halo, haloalkoxy, haloalkyl, alkyl, alkenyl, -OH, optionally substituted aryl, optionally substituted heteroaryl, heterocycloalkyl, aminoacyl, aminosulfonyl, acylamino, sulfonylamino, heteroarylalkyl, cyclic amino, aryloxy, heteroaryloxy, arylalkyloxy or heteroarylalkyloxy.