40877-19-8Relevant academic research and scientific papers
A Facile Total Synthesis of Mubritinib
Wang, Rong,Cui, Menghan,Yang, Qing,Kuang, Chunxiang
supporting information, p. 978 - 982 (2021/02/03)
A five-step, practical, and concise total synthesis of mubritinib is described. The synthesis utilized Friedel-Crafts acylation, click reaction, reduction, and demethylation for the construction of the triazole ring system as key steps. Another important feature of this synthesis is the Bredereck oxazole synthesis. The main advantages of this process are the improved yield and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of mubritinib.
Synthesis of Pyrrolidines by a Csp3-Csp3/Csp3-N Transition-Metal-Free Domino Reaction of Boronic Acids with γ-Azido-N-Tosylhydrazones
Florentino, Lucía,López, Lucía,Barroso, Raquel,Cabal, María-Paz,Valdés, Carlos
supporting information, p. 1273 - 1280 (2020/12/01)
The reaction between γ-azido-N-tosylhydrazones and boronic acids leads to the obtention of 2,2-disubstituted pyrrolidines in a domino process that includes 1) diazoalkane formation, 2) intermolecular carboborylation of the diazocompound, and 3) intramolecular carborylation of the azide, and comprises the formation of a Csp3?Csp3 and a Csp3?N bonds on the same carbon atom. The reaction proceeds without the need of any transition-metal catalyst under microwave activation and features wide scope in both reaction partners. It can be applied to both alkyl and arylboronic acids with equal efficiency. With N-tosylhydrazones derived from 2-(2-azidoethyl)-cyclopentanone and cyclohexanone the reactions are highly diastereoselective leading to the cis-fused bicyclic systems as unique diastereoisomers. The scope of the process is illustrated by over sixty examples, including scaffolds present in natural alkaloids, and the mechanistic proposal is suppported by DFT-based computations.
Synthesis method of mubritinib triazole intermediate
-
Paragraph 0028-0033; 0048-0119, (2020/12/06)
The invention discloses a method for synthesizing a mubritinib triazole intermediate by taking propiolic acid as a raw material through a Click reaction. The method comprises the following steps: 1, taking anisole as a raw material, and carrying out a Friedel-Crafts acylation reaction with 4-chlorobutyryl chloride to obtain gamma-chloro-4-methoxyphenylbutanone, 2, enabling the gamma-chloro-4-methoxyphenylbutanone to react with sodium azide, propiolic acid, a copper catalyst, sodium ascorbate, an alkali and a solvent, so as to obtain 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone,3, reducing carbonyl into methylene by 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone in a trifluoroacetic acid/triethylsilane system, and 4, carrying out demethylation on the 1-[4-(4-methoxyphenyl)butyl]-1H-1, 2, 3-triazole by using 40% hydrobromic acid to obtain the mubritinib intermediate 4-[4-(1H-1, 2, 3-triazole-1-yl)butyl]phenol. The method greatly shortens the reaction path, and has the advantages of accessible raw materials, mild reaction conditions, high yield and the like, and is simple to operate.
The synthesis of ω-(2-aryl-1,3-dioxolan-2-yl)alkyl purine derivatives and their activity towards HIV reverse transcriptase
Komissarov,Valuev-Elliston,Ivanova,Kochetkov,Kritzyn
, p. 37 - 45 (2015/02/05)
Novel derivatives of 6-substituted purines were synthesized by alkylation of 6-substituted purines with various 2-(chloroalkyl)-2-aryl-1,3-dioxolanes and related compounds. Their inhibitory properties toward HIV reverse transcriptase were studied. The structure-activity relationship within the synthesized compounds was found.
Synthesis of nitrogenated heterocycles by asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines
Pablo, Oscar,Guijarro, David,Yus, Miguel
, p. 9181 - 9189 (2013/10/08)
Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl) haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.
Azido carbonyl compounds as DNA cleaving agents
Chowdhury, Nilanjana,Dutta, Sansa,Karthick,Anoop, Anakuthil,Dasgupta, Swagata,Pradeep Singh
, p. 25 - 34 (2012/11/07)
Irradiation of azido carbonyl compounds using UV light (≥310 nm) produced triplet alkyl nitrenes and aroyl radicals, which resulted in efficient cleavage of single strand DNA at pH 7.0. DNA cleaving ability of azido carbonyl compounds was found to be dependent on its concentration and substituents on its aromatic ring. Further, newly synthesized naphthalene based azido carbonyl compounds showed DNA cleavage ability at longer wavelength of UV light (≥350 nm) and also binding studies revealed that they bind to ct-DNA by weak intercalation mode.
Pyrazole-based sulfonamide and sulfamides as potent inhibitors of mammalian 15-lipoxygenase
Ngu, Khehyong,Weinstein, David S.,Liu, Wen,Langevine, Charles,Combs, Donald W.,Zhuang, Shaobin,Chen, Xing,Madsen, Cort S.,Harper, Timothy W.,Ahmad, Saleem,Robl, Jeffrey A.
scheme or table, p. 4141 - 4145 (2011/08/06)
A series of inhibitors of mammalian 15-lipoxygenase (15-LO) based on a 3,4,5-tri-substituted pyrazole scaffold is described. Replacement of a sulfonamide functionality in the lead series with a sulfamide group resulted in improved physicochemical properties generating analogs with enhanced inhibition in cell-based and whole blood assays.
Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: Highly enantioselective synthesis of valuable alcohols
Yu, Feng,Zhou, Ji-Ning,Zhang, Xi-Chang,Sui, Yao-Zong,Wu, Fei-Fei,Xie, Lin-Jie,S. C. Chan, Albert,Wu, Jing
supporting information; experimental part, p. 14234 - 14240 (2012/01/12)
In the presence of PhSiH3 as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)2·H 2O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9 % enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10 000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98 % ee) and exceedingly high turn-over rates (up to 50 000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.
2-Phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors: A study on the importance of modifications at the side chain on the activity
Shen, Yanhong,Sheng, Rong,Zhang, Jing,He, Qiaojun,Yang, Bo,Hu, Yongzhou
, p. 7646 - 7653 (2008/12/23)
As a part of our project aimed at developing new agents of potential application in AD, a new series of 2-phenoxy-indan-1-one derivatives which possess alkylamine side chain were designed, synthesized, and evaluated for their inhibitory activity against AChE and BuChE. Most of the compounds were found to inhibit AChE in the nanomolar range. The optimum inhibitor 3g exhibited 34-fold increase in AChE inhibition than donepezil and displayed neuroprotective effect against H2O2-induced cell death.
Atom-efficient cross-coupling reactions of triarylbismuths with acyl chlorides under Pd(0) catalysis
Rao, Maddali L.N.,Venkatesh, Varadhachari,Banerjee, Debasis
, p. 12917 - 12926 (2008/03/28)
The atom-efficient cross-coupling reaction of triarylbismuths with a variety of aliphatic, aromatic, and hetero-aromatic acyl chlorides was demonstrated to afford high yields of cross-coupled ketones under palladium catalysis. The corresponding cross-coupling reaction with diacid chlorides also furnished bis-coupled ketones in good yields.
