6829-41-0Relevant articles and documents
Isolation and characterization of a novel tetrahydro-[2,2′]bipyrrolyl dimer as an impurity from a Knorr reaction
Thompson, Alison,Alattar, Yousef,Beshara, Cory S.,Burley, Rodney K.,Cameron, T. Stanley,Robertson, Katherine N.
, p. 777 - 781 (2004)
A novel dimer, tetraethyl 2,2′,3,3′-tetramethyl-1,1′,2, 2′-tetrahydro-4H,4′H-2,2′-bipyrrolyl-5,5,5′, 5′-tetracarboxylate, has been isolated as an impurity (0.4% yield) from a Knorr reaction for the synthesis of ethyl 3,5-dimethylpyrrole-2-carboxylate from 2,4-pentanedione and diethyl oximinomalonate in a dissolving zinc reduction. The solid-state structure of this novel dimer was determined by X-ray crystallography. Knorr reactions typically rely upon the requisite pyrrole being the only water-insoluble crystalline material present in the reaction mixture, and so work-up and purification procedures for Knorr reactions should be monitored carefully given the water-insolubility of this dimer. Investigations regarding mechanistic implications and reductive dimerization are underway.
Preparation method of diethyl amino-malonate hydrochloride
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Paragraph 0023, (2021/12/07)
The preparation method comprises first steps of preparing diethyl malonate in acetic acid, subnitration with an aqueous solution of nitrous acid to obtain the oxime-based malonic acid diethyl ester. 2nd: The oxime-based malonate is subjected to catalytic hydrogenation reaction with a nickel-containing ternary catalyst in an alcohol solvent to obtain diethyl amino-malonate. 3rd-Step: After the catalyst is filtered off, the catalyst is salified with hydrogen chloride ethanol and then dissolved in acetone to obtain diethyl amino-malonate hydrochloride. The method has the characteristics of mild and safe reaction conditions, simple and convenient operation, high yield, low cost, good quality and the like, and has wide application prospects. In addition, the hydrogenation technology for the method not only avoids waste residues and waste acid generated by reduction of zinc powder, but also avoids the disadvantages of expensive price and easy poisoning inactivation of the palladium-carbon catalyst.
Scalable synthesis of favipiravir: Via conventional and continuous flow chemistry
Charoensetakul, Netnapa,Khamkhenshorngphanuch, Thitiphong,Srikun, Onsiri,Srimongkolpithak, Nitipol,Thongpanchang, Chawanee,Tiyasakulchai, Thanat,Yuthavong, Yongyuth
, p. 38691 - 38693 (2021/12/20)
Decagram scale synthesis of favipiravir was performed in 9 steps using diethyl malonate as cheap starting material. Hydrogenation and bromination steps were achieved by employing a continuous flow reactor. The synthetic process provided a total of 16% yield and it is suitable for larger-scale synthesis and production. This journal is
3, 5-dimethyl-4-sulfonyl-1H-pyrrole compound as well as preparation method and application thereof
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Paragraph 0019; 0049-0053, (2021/02/06)
The invention discloses a 3, 5-dimethyl-4-sulfonyl-1H-pyrrole compound as well as a preparation method and application thereof. The chemical structure of the 3, 5-dimethyl-4-sulfonyl-1H-pyrrole compound is shown, wherein R1 and R2 are H, methyl, ethyl or isopropyl; R3 is benzyl, 3-thienyl, 1-naphthyl, 2-pyridyl, cyclopentyl, cyclohexyl or -Ar, and Ar is 4-methylphenyl, 2, 6-dimethylphenyl, 3, 5-dimethylphenyl, 4-ethyl phenyl, 4-isopropyl phenyl, 4-tert-butyl phenyl, 4-biphenyl, 4-fluorophenyl, 4-chlorphenyl, 4-bromophenyl, 4-acetyl phenyl, 3-acetyl phenyl, 2-acetyl phenyl, 4-methoxy phenyl, 3-methoxy phenyl, 2-methoxy phenyl, 4-ethoxy phenyl, 4-phenoxy phenyl, 4-benzoyl, phenyl, 4-nitrophenyl, 4-aminophenyl, 4-carboxyphenyl, or other phenyl substituted by monohydroxyl at different positions. The compound has high inhibitory activity on Mcl-1.
Discovery of 3,5-Dimethyl-4-Sulfonyl-1 H-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability
Zhu, Peng-Ju,Yu, Ze-Zhou,Lv, Yi-Fei,Zhao, Jing-Long,Tong, Yuan-Yuan,You, Qi-Dong,Jiang, Zheng-Yu
, p. 11330 - 11353 (2021/08/24)
Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound 11 with primary Mcl-1 inhibition (52%@30 μM) led to the discovery of the most potent compound 40 with high affinity (Kd = 0.23 nM) and superior selectivity over other Bcl-2 family proteins (>40,000 folds). Mechanistic studies revealed that 40 could activate the apoptosis signal pathway in an Mcl-1-dependent manner. 40 exhibited favorable physicochemical properties and pharmacokinetic profiles (F% = 41.3%). Furthermore, oral administration of 40 was well tolerated to effectively inhibit tumor growth (T/C = 37.3%) in MV4-11 xenograft models. Collectively, these findings implicate that compound 40 is a promising antitumor agent that deserves further preclinical evaluations.
Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride
Liu, Jinxin,Li, Yaling,Ke, Miaolin,Liu, Minjie,Zhan, Pingping,Xiao, You-Cai,Chen, Fener
, p. 15360 - 15367 (2020/11/30)
The asymmetric synthesis of (-)-chloramphenicol, (-)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired trans-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of syn-vicinal amino alcohols in the amphenicol family.
PREPARATION OF SECONDARY AMINES WITH ELECTROPHILIC N-LINCHPIN REAGENTS
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Page/Page column 54, (2018/12/13)
In one aspect, the present disclosure provides methods of preparing a secondary amine. In some embodiments, the secondary amine comprises two different groups or two identifical groups. Also provided herein are compositions for use in the preparation of the secondary amine.
A phosphine-mediated synthesis of 2,3,4,5-tetra-substituted N-hydroxypyrroles from α-oximino ketones and dialkyl acetylenedicarboxylates under ionic liquid green-media
Shahvelayati, Ashraf S.,Ghazvini, Maryam,Yadollahzadeh, Khadijeh,Delbari, Akram S.
, p. 14 - 18 (2018/06/19)
Background: The development of multicomponent reactions (MCRs) in the presence of task-specific ionic liquids (ILs), used not only as environmentally benign reaction media, but also as catalysts, is a new approach that meet with the requirements of sustainable chemistry. In recent years, the use of ionic liquids as a green media for organic synthesis has become a chief study area. This is due to their unique properties such as non-volatility, non-flammability, chemical and thermal stability, immiscibility with both organic compounds and water and recyclability. Ionic liquids are used as environmentally friendly solvents instead of hazardous organic solvents. Objective: We report the condensation reaction between α-oximinoketone and dialkyl acetylene dicarboxylate in the presence of triphenylphosphine to afford substituted pyrroles under ionic liquid conditions in good yields. Result: Densely functionalized pyrroles was easily prepared from reaction of α-oximinoketones, dialkyl acetylene dicarboxylate in the presence of triphenylphosphine in a quantitative yield under ionic liquid conditions at room temperature. Conclusion: In conclusion, ionic liquids are indicated as a useful and novel reaction medium for the selective synthesis of functionalized pyrroles. This reaction medium can replace the use of hazardous organic solvents. Easy work-up, synthesis of polyfunctional compounds, decreased reaction time, having easily available-recyclable ionic liquids, and good to high yields are advantages of present method.
Practical Singly and Doubly Electrophilic Aminating Agents: A New, More Sustainable Platform for Carbon-Nitrogen Bond Formation
Kattamuri, Padmanabha V.,Yin, Jun,Siriwongsup, Surached,Kwon, Doo-Hyun,Ess, Daniel H.,Li, Qun,Li, Guigen,Yousufuddin, Muhammed,Richardson, Paul F.,Sutton, Scott C.,Kürti, László
supporting information, p. 11184 - 11196 (2017/08/21)
Given the importance of amines in a large number of biologically active natural products, active pharmaceutical ingredients, agrochemicals, and functional materials, the development of efficient C-N bond-forming methods with wide substrate scope continues to be at the frontier of research in synthetic organic chemistry. Here, we present a general and fundamentally new synthetic approach for the direct, transition-metal-free preparation of symmetrical and unsymmetrical diaryl-, arylalkyl-, and dialkylamines that relies on the facile single or double addition of readily available C-nucleophiles to the nitrogen atom of bench-stable electrophilic aminating agents. Practical single and double polarity reversal (i.e., umpolung) of the nitrogen atom is achieved using sterically and electronically tunable ketomalonate-derived imines and oximes. Overall, this novel approach represents an operationally simple, scalable, and environmentally friendly alternative to transition-metal-catalyzed C-N cross-coupling methods that are currently used to access structurally diverse secondary amines.
Synthesis and spectrophotometry study of the acid-base properties of nitro-substituted 5-phenyl-β-octaalkylporphines
Ivanova, Yu. B.,Plotnikova,Semeikin,Lyubimova,Mamardashvili, N. Zh.
, p. 1742 - 1751 (2017/09/25)
10,15-Dinitro-5-phenyl-2,3,7,8,12,13,17,18-octamethylporphine, 10,15,20-trinitro-5-phenyl-2,3,7,8,12,13,17,18-octamethylporphine, and 10,15,20-trinitro-5-(4-nitrophenyl)-2,3,7,8,12,13,17,18-octamethylporphine were synthesized and identified by electronic absorption, IR, and 1Н NMR spectroscopy. The acid–base properties of the synthesized compounds were studied by spectrophotometric titration in HClO4–acetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene–acetonitrile systems at 298 K. Parameters of the electronic absorption spectra and concentration ranges of existence of the mono- and diprotonated, as well as mono- and dideprotonated forms of the corresponding ligands and the acid and base dissociation constants of the latter were determined. Comparative analysis of the effect of nitro groups on the reactivity of the synthesized compounds was performed.
