125670-62-4Relevant academic research and scientific papers
Efficient palladium-catalyzed synthesis of 2-aryl propionic acids
Neumann, Helfried,Sergeev, Alexey G.,Spannenberg, Anke,Beller, Matthias
, (2020)
A flexible two-step, one-pot procedure was developed to synthesize 2-aryl propionic acids including the anti-inflammatory drugs naproxen and flurbiprofen. Optimal results were obtained in the presence of the novel ligand neoisopinocampheyldiphenylphosphine (NISPCPP) (9) which enabled the efficient sequential palladium-catalyzed Heck coupling of aryl bromides with ethylene and hydroxycarbonylation of the resulting styrenes to 2-aryl propionic acids. This cascade transformation leads with high regioselectivity to the desired products in good yields and avoids the need for additional purification steps.
Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids
Guan, Zheng-Hui,Ren, Zhi-Hui,Wang, Yuan,Yang, Hui-Yi,Yao, Ya-Hong,Zou, Xian-Jin
supporting information, p. 23117 - 23122 (2021/09/18)
Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.
Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists
Sun, Nannan,Huang, Yafei,Yu, Mingcheng,Zhao, Yunpeng,Chen, Ji-An,Zhu, Chenyu,Song, Meiqi,Guo, Huimin,Xie, Qiong,Wang, Yonghui
, (2020/07/21)
GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76percent inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.
Ni-Catalyzed Reductive C-O Bond Arylation of Oxalates Derived from α-Hydroxy Esters with Aryl Halides
Gao, Mengyu,Sun, Deli,Gong, Hegui
supporting information, p. 1645 - 1648 (2019/03/11)
A Ni-catalyzed reductive cross-coupling of α-hydroxycarbonyl compounds modified with oxalyl groups and aryl halides has been developed that furnishes α-aryl esters under mild conditions and tolerates a variety of functionalized aryl halides bearing electron-withdrawing and -donating groups. This work highlights C-O bond fragmentation on secondary alkyl carbon centers that generates α-carbonyl radicals.
BIARYL UREA DERIVATIVE OR SALT THEREOF, AND MANUFACTURING AND APPLICATION OF SAME
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Paragraph 0155, (2019/05/10)
The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.
Metallic reductant-free synthesis of α-substituted propionic acid derivatives through hydrocarboxylation of alkenes with a formate salt
Takaya, Jun,Miyama, Ko,Zhu, Chuan,Iwasawa, Nobuharu
supporting information, p. 3982 - 3985 (2017/04/11)
A PGeP-pincer palladium-catalyzed hydrocarboxylation of styrenes to obtain pharmaceutically important α-arylpropionic acid derivatives was achieved using a formate salt as both a reductant and a CO2 source. The reaction was also applicable to vinylsulfone and acrylates. Isotope labeling experiments demonstrated that a CO2-recycling mechanism is operative through generation and reaction of a benzylpalladium complex as a carbon nucleophile. This protocol has realized a mild and atom economical CO2-fixation reaction without the necessity of using strong metallic reductants.
Construction of a visible light-driven hydrocarboxylation cycle of alkenes by the combined use of Rh(i) and photoredox catalysts
Murata, Kei,Numasawa, Nobutsugu,Shimomaki, Katsuya,Takaya, Jun,Iwasawa, Nobuharu
supporting information, p. 3098 - 3101 (2017/03/17)
A visible light driven catalytic cycle for hydrocarboxylation of alkenes with CO2 was established using a combination of a Rh(i) complex as a carboxylation catalyst and [Ru(bpy)3]2+ (bpy = 2,2′- bipyridyl) as a photoredox catalyst. Two key steps, the generation of Rh(i) hydride species and nucleophilic addition of π-benzyl Rh(i) species to CO2, were found to be mediated by light.
Nickel-Catalyzed Carboxylation of Benzylic C-N Bonds with CO2
Moragas, Toni,Gaydou, Morgane,Martin, Ruben
, p. 5053 - 5057 (2016/04/26)
A user-friendly Ni-catalyzed reductive carboxylation of benzylic C-N bonds with CO2 is described. This procedure outperforms state-of-the-art techniques for the carboxylation of benzyl electrophiles by avoiding commonly observed parasitic pathways, such as homodimerization or β-hydride elimination, thus leading to new knowledge in cross-electrophile reactions.
Palladium-catalyzed α-arylation of zinc enolates of esters: Reaction conditions and substrate scope
Hama, Takuo,Ge, Shaozhong,Hartwig, John F.
, p. 8250 - 8266 (2013/09/24)
The intermolecular α-arylation of esters by palladium-catalyzed coupling of aryl bromides with zinc enolates of esters is reported. Reactions of three different types of zinc enolates have been developed. α-Arylation of esters occurs in high yields with i
Nickel-catalyzed reductive carboxylation of styrenes using CO2
Williams, Catherine M.,Johnson, Jeffrey B.,Rovis, Tomislav
supporting information; experimental part, p. 14936 - 14937 (2009/03/12)
A nickel-catalyzed reductive carboxylation of styrenes using CO2 has been developed. The reaction proceeds under mild conditions using diethylzinc as the reductant. Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. Importantly, the catalyst system is very robust and will fixate CO2 in good yield even if exposed to only an equimolar amount introduced into the headspace above the reaction. Copyright
