16606-00-1

Upstream product

• 93-58-3 benzoic acid methyl ester 
• 186581-53-3 diazomethane 
• 716-76-7 3-phenylbenzoic acid 
• 87360-24-5 3-amino-benzoic acid methyl ester hydrochloride 
• 71-43-2 benzene 
• 369-57-3 benzenediazonium tetrafluoroborate 
• 22099-28-1 dibenzothiophene-2-carboxylic acid methyl ester 
• 126314-09-8 methyl 5-phenylcyclohexa-1,4-dienecarboxylate 
• 126314-10-1 methyl 5-phenylcyclohexa-1,5-dienecarboxylate 
• 25991-27-9 methyl 2-oxo-2H-pyrane-3-carboxylate 
• 536-74-3 phenylacetylene 
• 94-36-0 dibenzoyl peroxide 
• 98-80-6 phenylboronic acid 
• 100-42-5 styrene 

Downstream Products

• 42498-44-2 3-phenylbenzoyl chloride 
• 38580-82-4 3-biphenylylmethyl chloride 
• 729-01-1 4'-nitrobiphenyl-3-carboxylic acid 
• 897446-31-0 biphenyl-3-carboxylic acid (2-aminophenyl)amide 
• 1421511-72-9 N'-(3,5-dibromo-2,4-dihydroxybenzylidene)biphenyl-3-carbohydrazide 
• 709653-55-4 3-biphenylcarboxylic acid hydrazide 

Relevant academic research and scientific papers

Palladium-catalyzed Suzuki cross-coupling of phenylhydrazine or (phenylsulfonyl)hydrazine

The palladium-catalyzed Suzuki cross-coupling of phenylhydrazine or (phenylsulfonyl)hydrazine was developed for the preparation of biaryl compound in high yields. Moreover, these hydrazines were also used in other cross-coupling reactions, and a possible pathway of this reaction was examined. Copyright

A family of simple amide-derived air-stable P,O-ligands for Suzuki cross-coupling of unactivated aryl chlorides

A family of air-stable amide-derived phosphine (Aphos) ligands engineered on simple N,N-dialkyl aryl amide scaffolds has been designed and prepared by one-pot synthesis from the amides in high yields. The Aphos ligands have been used, in analogous to their atropisomeric variations, as hemilabile bidentate P,O-ligands in various Pd-catalyzed C-N and C-C bond forming reactions. We present here our results on the highly efficient Suzuki cross-coupling reactions of unactivated and/or sterically hindered aryl chlorides with arylboronic acids and a relationship of Aphos structures with catalytic efficacy.

Synthesis of palladium-bidentate complex and its application in Sonogashira and Suzuki coupling reactions

A new palladium-bidentate complex [m-C6H4(CH 2ImMe)2(PdCl2)] (III) was prepared in two steps. In the first step, [m-C6H4(CH2ImMeAgCl) 2] (II) (Im = imidazole moiety) was obtained by reacting imidazolium salt [m-C6H4(CH2ImMe)2]Cl 2 (I) (prepared by quaternisation of Nmethylimidazole with 1,3-bis(chloromethyl)benzene) and Ag2O in CH2Cl 2. In the next step, treatment of (II) with Pd(CH3CN) 2Cl2 afforded complex III which was evaluated for its catalytic activity for C-C bond-formation reactions by examining the coupling reaction of 3-iodoanisole with phenylacetylene in the Sonogashira reaction. In addition, 3-methoxybiphenyls were obtained with good to excellent yields by Suzuki coupling reactions of 3-iodoanisole with phenylboronic acids or phenylborates salts in the presence of this complex.

'Awaken' aryl sulfonyl fluoride: a new partner in the Suzuki-Miyaura coupling reaction

An example of the activation of the -SO2F group, which is traditionally considered a stable group even in the presence of a transition metal, is described using a novel partner in the Suzuki-Miyaura coupling reaction catalyzed by Pd(OAc)2 and Ruphos as ligands. The products showed good to outstanding yields and broad functional group compatibility under optimal conditions. The sequential synthesis of non-symmetric terphenyls and the gram grade process highlight the approach's synthetic utility. DFT calculations have shown that Pd0 prefers to insert between C-S bonds rather than S-F bonds. This journal is

GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes

GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 μM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.

Cobalt-Catalyzed Coupling of Aryl Chlorides with Aryl Boron Esters Activated by Alkoxides

The cobalt-catalyzed Suzuki biaryl cross-coupling of aryl chloride substrates with aryl boron reagents, activated with more commonly used bases, remained a significant unmet challenge in the race to replace platinum group metal catalysts with Earth-abundant metal alternatives. We now show that this highly desirable process can be realized using alkoxide bases, provided the right counterion is employed, strict stoichiometric control of the base is maintained with respect to the aryl boron reagent, and the correct boron ester is selected. Potassium tert-butoxide works well, but any excess of the base first inhibits and then poisons the catalyst. Lithium tert-butoxide performs very poorly, while even catalytic amounts of lithium additives also poison the catalyst. Meanwhile, a neopentane diol-based boron ester is required for best performance. As well as delivering this sought-after transformation, we have undertaken detailed mechanistic and computational investigations to probe the possible mechanism of the reaction and help explain the unexpected experimental observations.

Palladium-Catalyzed, Copper(I)-Promoted Methoxycarbonylation of Arylboronic Acids with O-Methyl S-Aryl Thiocarbonates

Here, we report O-methyl S-aryl thiocarbonates as a versatile esterification reagent for palladium-catalyzed methoxycarbonylation of arylboronic acid in the presence of copper(I) thiophene-2-carboxylate (CuTC). The reaction condition is mild, and a variety of substituents including sensitive-Cl,-Br, and free-NH2 could be tolerated. Further applications in the late-stage esterification of some pharmaceutical drugs demonstrate the broad utility of this method.

Discovery of acylsulfonohydrazide-derived inhibitors of the lysine acetyltransferase, kat6a, as potent senescence-inducing anti-cancer agents

A high-throughput screen designed to discover new inhibitors of histone acetyltransferase KAT6A uncovered CTX-0124143 (1), a unique aryl acylsulfonohydrazide with an IC50 of 1.0 μM. Using this acylsulfonohydrazide as a template, we herein disclose the results of our extensive structure-activity relationship investigations, which resulted in the discovery of advanced compounds such as 55 and 80. These two compounds represent significant improvements on our recently reported prototypical lead WM-8014 (3) as they are not only equivalently potent as inhibitors of KAT6A but are less lipophilic and significantly more stable to microsomal degradation. Furthermore, during this process, we discovered a distinct structural subclass that contains key 2-fluorobenzenesulfonyl and phenylpyridine motifs, culminating in the discovery of WM-1119 (4). This compound is a highly potent KAT6A inhibitor (IC50 = 6.3 nM; KD = 0.002 μM), competes with Ac-CoA by binding to the Ac-CoA binding site, and has an oral bioavailability of 56% in rats.

Cobalt-catalyzed C(sp2)?CN bond activation: Cross-electrophile coupling for biaryl formation and mechanistic insight

Herein, we report a cross-electrophile coupling of benzonitrile derivatives and aryl halides with a simple cobalt-based catalytic system under mild conditions to form biaryl compounds. Even though the cobalt catalyst is able to activate the C(sp2)?CN bond alone, the use of the AlMe3 Lewis acid enhances the reactivity of benzonitriles and improves the cross-selectivity with barely any influence on the functional group compatibility. X-ray structure determination of an original low-valent cobalt species combined with catalytic and stoichiometric reactions reveals a catalytically active cobalt(I) species toward the aryl halide partner. On the other hand, experimental insights, including cyclic voltammetry experiments, suggest the involvement of a cobalt complex of a lower oxidation state to activate the benzonitrile derivative. Finally, density functional theory calculations support the proposed mechanistic cycle involving two low-valent cobalt species of different oxidation states to perform the reaction.

Ni: Vs. Pd in Suzuki-Miyaura sp2-sp2 cross-coupling: A head-to-head study in a comparable precatalyst/ligand system

The Suzuki-Miyaura reaction is a cornerstone method for sp2-sp2 cross-coupling in industry. There has been a concerted effort to enable the use of Ni catalysis as an alternative to Pd in order to mitigate cost and improve sustainability. Despite significant advances, ligand development for Ni-catalyzed Suzuki-Miyaura cross-coupling remains underdeveloped when compared to Pd and, as a consequence, ligands for Ni-catalyzed processes are typically taken from the Pd arena. In this study we evaluate the effect of using a similar Ni and Pd precatalyst based on a common bidentate ligand (dppf) in a head-to-head format for the most common type of biaryl couplings, establishing the practical implications of direct replacement of Pd with Ni, and identifying the potential origins of these observations in a mechanistic context.