6148-64-7Relevant articles and documents
Kinetic study of the Ce(III)-, Mn(II)- or Fe(phen)32+-catalyzed Belousov-Zhabotinsky reaction with ethyl hydrogen malonate
Hsu,Jwo,Jwo
, p. 52 - 61 (2000)
In a stirred batch reaction, Fe(phen)32+ ion behaves differently from Ce(III) or Mn(II) ion in catalyzing the bromate-driven oscillating reaction with ethyl hydrogen malonate [CH2COOHCOOEt, ethyl hydrogen malonate (EHM)]. The effects of N2 atmosphere, concentrations of bromate ion, EHM, metal ion catalyst, sulfuric acid, and additive (bromide ion or bromomalonic acid) on the pattern of oscillations were investigated. The kinetic study of the reaction of EHM with Ce(IV), Mn(III), or Fe(phen)33+ ion indicates that under aerobic or anaerobic conditions the order of reactivity toward reacting with EHM is Mn(III)>Ce(IV)?Fe(phen)33+, which follows the same trend as that of the malonic acid system. The presence of the ester group in EHM lowers the reactivity of the two methylene hydrogen atoms toward bromination or oxidation by Ce(IV), Mn(III), or Fe(phen)33+ ion. No good oscillations were observed for the BrO3-CH2(COOEt)2 reaction catalyzed by Ce(III), Mn(II), or Fe(phen)32+ ion. A discussion of the effects of oxygen on the reactions of malonic acid and its derivatives (RCHCOOHCOOR′) with Mn(III), Fe(phen)33+ ion is also presented.
Continuous Flow Electrochemical Oxidative Cyclization and Successive Functionalization of 2-Pyrrolidinones
Quertenmont, Mathilde,Toussaint, Frédéric C.,Defrance, Thierry,Lam, Kevin,Markó, István E.,Riant, Olivier
supporting information, p. 2631 - 2638 (2021/11/24)
2-Pyrrolidinones are important scaffolds found in numerous pharmacologically active compounds, such as brivaracetam and levetiracetam (antiepileptic drugs) or piracetam and pramiracetam (age-related memory impairment drugs). Among the numerous targets, nootropic agents represent an attractive class of compounds since they selectively improve cognitive functions. In this study, we report the successful translation of an electrochemical batch oxidative cyclization/functionalization of 2-pyrrolidinones, using the Kolbe reaction, from a batch type cell to a continuous flow electrochemical reactor. Combining organic electrosynthesis with continuous flow chemistry offers numerous advantages over batch electrolysis such as a faster reaction time and better mixing of the heterogeneous reaction. Moreover, due to the use of continuous flow electrochemical cells, which have a precise geometry, a small interelectrode gap, and large electrode surface area to reactor volume ratio, the productivity of organic electrosynthesis can be easily improved. Additionally, the translation of a batch electrochemical transformation to a continuous flow reactor is a critical step in the development of an electrochemical process given that flow chemistry is the most straightforward approach for the scale-up of this type of reactions. In this study, the application of continuous flow electrochemistry in our process allowed for an excellent productivity of 0.40 g/(h·mL) and an up to 81% yield of 2-pyrrolidinone within a loop-reactor setup (equipped with a 5 mL container).
Structure-based linker optimization of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
Li, Daxiong,Zhang, Chunsheng,Ding, Wei,Huang, Siming,Yu, Le,Lu, Nan,Pan, Wenkai,Li, Yiming,De Clercq, Erik,Pannecouque, Christophe,Zhang, Hongbing,Wang, Yueping,He, Yanping,Chen, Fener
supporting information, p. 1020 - 1024 (2020/10/12)
In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with diverse structures, a series of novel S-DACO analogues of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)pyrimidin-4(3H)-ones were designed, synthesized and evaluated for their antiviral activities in MT-4 cells. Most of these new compounds showed moderate to good activities against wild type HIV-1 with IC50 values ranging from 7.55 μmol/L to 0.018 μmol/L. Among them, compound 5c was identified as the most promising inhibitor against HIV-1 replication with an IC50 = 0.018 μmol/L, CC50 = 194 μmol/L, and SI = 12791, which was much more potent than the reference drugs NVP and DLV and comparable to AZT and EFV. In addition, 5c also exhibited improved activity against double mutant HIV-1 strain RES056 compared to that of the reference drugs NVP/DLV and DB02. The preliminary structure-activity relationship (SAR) and molecular modeling studies were also discussed, which provides some useful indications for guiding the further rational design of new S-DACO analogues.
Kolbe Anodic Decarboxylation as a Green Way to Access 2-Pyrrolidinones
Goodall, Iain,Lam, Kevin,Markó, István,Quertenmont, Mathilde,Riant, Olivier
supporting information, (2020/03/04)
Nootropic compounds are a group of pharmacologically active pyrrolidones. These molecules, which enhance cognition properties and possess a large prescription field, are particularly interesting synthetic targets for the pharmaceutical industry. In this Article, we disclose an effective and environmentally friendly pyrrolidinone synthesis using electrosynthesis. The newly developed methodology includes a Kolbe decarboxylation, followed by an intramolecular radical cyclization and a radical-radical cross-coupling.
Method for preparing urea-based pyrimidone precursor
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Paragraph 0017, (2019/04/06)
The invention discloses a urea-based pyrimidone precursor compound and a synthetic method thereof. The urea-based pyrimidone precursor is an isoheptyl substituted isocytosine compound. The specific synthetic method comprises the following steps: synthesizing diethyl potassium malonate, synthesizing 2-ethylhexanoyl chloride, synthesizing beta-keto ester from the diethyl potassium malonate and 2-ethylhexanoyl chloride, and synthesizing the urea-based pyrimidone precursor from the beta-keto ester and guanidine carbonate. The urea-based pyrimidone precursor compound and the synthetic method thereof disclosed by the invention have the beneficial effects that the urea-based pyrimidone precursor provides a basic raw material for preparation of a multiple hydrogen bonding supra-molecular material,and the method is controllable in synthetic process and capable of saving resources and improving the yield, and has excellent application prospects.
Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia
Li, Xingjian,Payne, Daniel T.,Ampolu, Badarinath,Bland, Nicholas,Brown, Jane T.,Dutton, Mark J.,Fitton, Catherine A.,Gulliver, Abigail,Hale, Lee,Hamza, Daniel,Jones, Geraint,Lane, Rebecca,Leach, Andrew G.,Male, Louise,Merisor, Elena G.,Morton, Michael J.,Quy, Alex S.,Roberts, Ruth,Scarll, Rosanna,Schulz-Utermoehl, Timothy,Stankovic, Tatjana,Stevenson, Brett,Fossey, John S.,Agathanggelou, Angelo
supporting information, p. 1379 - 1390 (2019/08/20)
Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from feverfew and protocols for growing, extracting and derivatising it are reported. A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on in vitro anti-leukaemic activity and calculated "drug-likeness" properties, in vitro and in vivo pharmacokinetics studies and hERG liability testing. In vitro studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative. The newly identified compound was shown to have pro-oxidant activity and in silico molecular docking studies indicate a prodrug mode of action. A synthesis scheme is presented for the production of amine 7 used in the generation of 5f.
Method for preparing potassium monoethyl malonate
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Paragraph 0025, (2019/02/27)
The invention provides a method for preparing potassium monoethyl malonate. According to the method, a compound in a malonate monoester series is used as a raw material to react with potassium bicarbonate to obtain the potassium monoethyl malonate. The invention opens up a new way to prepare potassium monoethyl malonate series under a very mild condition in a safe and environment-friendly mode, and the method is suitable for industrial production and meets the market demands of the compound.
Pyrazole alcohol compound, pharmaceutical composition thereof and application thereof to drugs
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Paragraph 0119; 0127, (2018/10/19)
The invention discloses a 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound, a tautomer thereof, a pharmaceutical composition thereof and application thereof to drugs. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound has double effects of resisting platelet aggregation and protecting nerve cells, and comprises a compound as shown in the formula (I), a tautomer (Ia) thereof, or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound and the pharmaceutical composition thereof provided by the invention can be used for preparing drugs for prevention and/or treatment and/or auxiliary treatment of cerebral apoplexy, cardiovascular and cerebrovascular diseases, senile dementia and complications thereof caused by thrombosis and excessive free radicals.
Preparation method for polyfluoromethylpyrazole compound, and intermediate of compound and preparation method thereof
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Paragraph 0126; 0127; 0128, (2017/06/30)
The invention discloses a preparation method for a polyfluoromethylpyrazole compound, and an intermediate of the compound and a preparation method thereof. The invention provides a preparation method for a compound 1 as defined in the specification. The preparation method comprises a step of subjecting a compound 2 as defined in the specification and methylhydrazine to a ring-closure reaction in an organic solvent so as to obtain the compound 1, wherein R is a C1-4 alkyl group, R is a methyl or ethyl group and x is 2 or 3. The preparation method provided by the invention uses cheap and easily available raw materials and is mild in reaction conditions, safe to operate, environment friendly, low in production cost, high in reaction conversion rate, low in the content of isomer in by-products, high in reaction yield and product purity and suitable for industrial production.
Silver-Catalyzed Cyclization of Propargylic Amides to Oxazolines
Wong, Valerie H. L.,White, Andrew J. P.,Hor,Hii
supporting information, p. 3943 - 3948 (2016/01/25)
A ligand-accelerated effect is observed in the cyclization of propargylic amides catalyzed by bis(pyridyl)silver(I) complexes, with an unexpected reversal of electronic demand to the analogous NH addition reaction. The catalyst was found to be effective for internal alkyne substrates, offering exclusive selectivity for the 5-exo-dig product. Differences in selectivity profile between gold- and silver-catalyzed processes are highlighted and discussed.
