135526-78-2Relevant articles and documents
Efficient multicomponent reaction synthesis of the schistosomiasis drug praziquantel
Cao, Haiping,Liu, Haixia,Doemling, Alexander
, p. 12296 - 12298 (2010)
Shorter than ever: A convergent, efficient, and scalable access based on a key Ugi four-component reaction (4CR) followed by a Pictet-Spengler reaction comprises the shortest known synthesis to the schistosomiasis drug praziquantel (see scheme).
Formation of pyrazinoisoquinoline ring system by the tandem amidoalkylation and N-acyliminium ion cyclization: An efficient synthesis of Praziquantel
Kim, Joong Hyup,Lee, Yong Sup,Park, Hokoon,Kim, Choong Sup
, p. 7395 - 7400 (1998)
An efficient synthesis of pyrazinoisoquinoline derivatives including Praziquantel has been accomplished by the tandem amidoalkylaion and N- acyliminium ion cyclization of amido-acetals.
Two approaches for the synthesis of levo-praziquantel
He, Zhaoting,Peng, Gang,Shou, Haowen,Su, Weike,Yu, Jingbo
, p. 4507 - 4514 (2021)
We report herein the development of two pathways for the preparation of levo-praziquantel (R-PZQ), which involves three-/four-step processes of a mechanochemical (asymmetric) aza-Henry/acylation reaction, a hydrogenation reaction, (chiral resolution) and a solvent-free acylation-ring closing reaction. The key intermediate (R)-1-aminomethyl tetrahydroisoquinoline could be obtained either by chiral resolution with a rational reuse of the S-isomer or by mechanochemical enantioselective synthesis that refrained from using a bulky toxic solvent. The efficiency and scalability of both the developed routes were demonstrated and desired target product was obtained in a satisfactory yield with excellent enantiopurity (>99%), offering practical, concise and environmentally friendly alternatives to access R-PZQ.
A 3D Homochiral MOF [Cd2(d-cam)3]?2Hdma?4dma for HPLC Chromatographic Enantioseparation
Zhang, Mei,Chen, Xinglian,Zhang, Junhui,Kong, Jiao,Yuan, Liming
, p. 340 - 346 (2016)
Up to now, some chiral metal-organic frameworks (MOFs) have been reported for enantioseparation in liquid chromatography. Here we report a homochiral MOF, [Cd2(d-cam)3]·2Hdma·4dma, used as a new chiral stationary phase for high-performance liquid chromatographic enantioseparation. Nine racemates of alcohol, naphthol, ketone, and base compounds were used as analytes for evaluating the separation properties of the chiral MOF packed column. Moreover, some effects such as mobile phase composition, column temperature, and analytes mass for separations on this chiral column also were investigated. The relative standard deviations for the resolution values of run-to-run and column-to-column were less than 2.1% and 3.2%, respectively. The experimental results indicate that the homochiral MOF offered good recognition ability, which promotes the application of chiral MOFs use as stationary phase for enantioseparation. Chirality 28:340-346, 2016.
Aza-Henry Reaction with Nitrones, an Under-Explored Transformation
Messire, Gatien,Massicot, Fabien,Vallée, Alexis,Vasse, Jean-Luc,Behr, Jean-Bernard
, p. 1659 - 1668 (2019)
Nitromethylation of nitrones occurred efficiently in CH3NO2 in the presence of tetramethylammonium fluoride or triazabicyclodecene as promoters. The obtained adducts might be conveniently transformed into vicinal diamines. The process was extended to nitroethane and nitropropane affording mixtures of syn and anti stereoisomers with low diastereoselectivity.
Preparation method of praziquantel
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, (2022/03/27)
The invention relates to the technical field of medical intermediates, and provides a praziquantel preparation method which comprises the following steps: S1, adding isoquinoline, cyanide, tetrabutylammonium bromide and dichloroethane into a reactor, and dropwise adding benzoyl chloride for reaction to obtain a first-step product; s2, performing catalytic hydrogenation on the first-step product to obtain a second-step product; and S3, adding ethyl acetate into the second-step product, stirring and dissolving, adding sodium bicarbonate, dropwise adding chloroacetyl chloride, stirring and reacting to obtain a praziquantel crude product, and recrystallizing to obtain praziquantel. Through the technical scheme, the problems of long reaction process, high energy consumption and low yield in the prior art are solved.
Preparation of a novel bridged bis(β-cyclodextrin) chiral stationary phase by thiol-ene click chemistry for enhanced enantioseparation in HPLC
Gong, Bolin,Guo, Siyu,Zhang, Ning
, p. 35754 - 35764 (2021/12/02)
A bridged bis(β-cyclodextrin) ligand was firstly synthesized via a thiol-ene click chemistry reaction between allyl-ureido-β-cyclodextrin and 4-4′-thiobisthiophenol, which was then bonded onto a 5 μm spherical silica gel to obtain a novel bridged bis(β-cyclodextrin) chiral stationary phase (HTCDP). The structures of HTCDP and the bridged bis(β-cyclodextrin) ligand were characterized by the 1H nuclear magnetic resonance (1H NMR), solid state 13C nuclear magnetic resonance (13C NMR) spectra spectrum, scanning electron microscope, elemental analysis, mass spectrometry, infrared spectrometry and thermogravimetric analysis. The performance of HTCDP in enantioseparation was systematically examined by separating 21 chiral compounds, including 8 flavanones, 8 triazole pesticides and 5 other common chiral drugs (benzoin, praziquantel, 1-1′-bi-2-naphthol, Tr?ger's base and bicalutamide) in the reversed-phase chromatographic mode. By optimizing the chromatographic conditions such as formic acid content, mobile phase composition, pH values and column temperature, 19 analytes were completely separated with high resolution (1.50-4.48), in which the enantiomeric resolution of silymarin, 4-hydroxyflavanone, 2-hydroxyflavanone and flavanone were up to 4.34, 4.48, 3.89 and 3.06 within 35 min, respectively. Compared to the native β-CD chiral stationary phase (CDCSP), HTCDP had superior enantiomer separation and chiral recognition abilities. For example, HTCDP completely separated 5 other common chiral drugs, 2 flavanones and 3 triazole pesticides that CDCSP failed to separate. Unlike CDCSP, which has a small cavity (0.65 nm), the two cavities in HTCDP joined by the aryl connector could synergistically accommodate relatively bulky chiral analytes. Thus, HTCDP may have a broader prospect in enantiomeric separation, analysis and detection. This journal is
A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels
supporting information, p. 7114 - 7123 (2021/03/03)
A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.
Synthetic method of praziquantel
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, (2020/05/08)
The invention provides a synthetic method of praziquantel. The method comprises the following steps: (1) subjecting beta-phenylethylamine and chloroacetyl chloride to an acylation reaction under an alkaline condition by adopting water as a solvent, then adding an amino compound shown as a formula I into the reaction mixture and reacting to obtain a compound shown as a formula II; (2) carrying outa cyclization reaction on the compound shown as the formula II under the action of a cyclizing agent, and reacting with cyclohexanecarbonyl chloride in an alkaline environment to obtain the praziquantel. The method has the advantages of low cost, mild reaction conditions, simple and controllable operation method, capability of avoiding the use of a large amount of organic solvents in the reactionprocess, greenness, environmental protection, good safety and stable product quality, and the obtained product meets the medicinal requirements.
Preparation method of (R)-praziquantel
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, (2020/06/17)
The invention provides a preparation method of (R)-praziquantel. The method for preparing (R)-praziquantel comprises the following steps: by taking dihydroisoquinoline and nitromethane as raw materials, carrying out solvent-free Henry reaction and nickel catalytic hydrogenation reduction reaction under mechanical ball milling to obtain a 1-aminomethyl-2-chloracetyl tetrahydroisoquinoline intermediate; carrying out salifying resolution reaction on the intermediate and an acidic resolving agent to obtain a (R)-praziquantel intermediate; and carrying out solvent-free amidation-cyclization reaction on the (R)-praziquantel intermediate and cyclohexanecarboxylic acid under mechanical ball milling to synthesize the (R)-praziquantel. According to the method, mother liquor left after crystallization and resolution can be subjected to racemization recovery and reutilization, so that the yield of the (R)-praziquantel intermediate is greatly increased; the method is easy and convenient to operate,mild in reaction condition and environmentally friendly, and the obtained (R)-praziquantel product is high in optical purity and has good application and popularization prospects.
