57452-98-9

Usage

Uses

Used in Pharmaceutical Industry:
l-Praziquantel is used as an antiparasitic agent for the treatment of Schistosoma mansoni infestations. It is particularly effective against juvenile stages of the parasite, providing a targeted approach to combat the infection in both in vitro and in vivo settings. This application is crucial in the development of treatments for schistosomiasis, a disease caused by parasitic flatworms of the genus Schistosoma.

InChI:InChI=1S/C19H24N2O2/c22-18-13-20(19(23)15-7-2-1-3-8-15)12-17-16-9-5-4-6-14(16)10-11-21(17)18/h4-6,9,15,17H,1-3,7-8,10-13H2/t17-/m0/s1

Upstream product

• 60567-53-5 1-Cyclohexylcarbonylaminomethyl-2-chloracetyl-1,2,3,4-tetrahydro-isochinolin 
• 93255-08-4 Cyclohexanecarboxylic acid bicyclo[4.2.0]octa-1,3,5-trien-7-ylmethyl-[(methoxymethyl-carbamoyl)-methyl]-amide 
• 87693-75-2 4-(cyclohexylcarbonyl)-6-hydroxy-1-phenethylpiperazine-2-one 
• 32377-88-1 (cyclohexanecarbonyl-amino)-acetic acid 
• 17376-04-4 2-phenethyl iodide 
• 87693-73-0 4-(cyclohexylcarbonyl)-2,6-dioxopiperazine 
• 61196-40-5 2-acetyl-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one 
• 55375-91-2 (-)-2-Benzoyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline 
• 3230-65-7 3,4-dihydroisoquinoline 
• 1118640-91-7 (±)-tert-butyl 1-cyano-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1207175-15-2 2-methyl-2-propanyl 1-(aminomethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate 
• 1357103-92-4 t-butyl 1-(cyclohexanecarboxamidomethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 138350-92-2 tert-butyl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate 
• 850130-96-0 2-(4-methoxyphenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 134924-71-3 2-(4-trans-hydroxycyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino<2,1-a>isoquinolin-4-one 
• 134924-68-8 2-(4-cis-hydroxycyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino<2,1-a>isoquinolin-4-one 
• 1609979-51-2 C₂₃H₂₃N₃O₂ 
• 1609979-52-3 C₃₄H₄₀N₆O₄ 
• 99746-73-3 (S)-(-)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one 
• 55375-92-3 (R)-(-)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one 
• 135526-78-2 (-)-Praziquantel 
• 57452-97-8 (+)-Praziquantel 
• 1609986-43-7 C₁₉H₁₇N₃O₄ 
• 1609986-44-8 C₁₉H₁₉N₃O₂ 
• 1609979-49-8 C₂₈H₂₂F₃N₅O₃ 
• 1609979-50-1 C₃₁H₂₄F₃N₅O₃ 
• 135526-78-2 praziquantel 
• 135526-78-2 praziquantel 

Relevant academic research and scientific papers

Preparation method of praziquantel

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

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

Two approaches for the synthesis of levo-praziquantel

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 Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides

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

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

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.

A preparation method of praziquantel (by machine translation)

The invention discloses a method for preparation of praziquantel, comprises the following steps: S1, β - phenethylamine with chloroacetyl chloride in a polar aprotic solvent, under alkaline compound to promote the acylation reaction is carried out, to produce intermediate I: 2 - chloro - N - (2 - phenyl-ethyl) - acetamide; S2, intermediate I in ethanolamine in the condensation reaction, an intermediate II: 2 - (2 - hydroxy - ethylamino) - N - phenethyl - acetamide; S3, using the intermediate II and TEMPO as raw materials, after oxidation is carried out after the cyclization reaction to prepare the intermediate III: 4 - carbon yl - 1, 2, 3, 6, 7, 11b - hexahydro - 4 H - pyrazinyl [2, 1 - a] isoquinoline; S4, the intermediate III with the cyclohexyl chloride in a polar aprotic solvent, a basic compound for promoting the next, react to generate the target product pqt. The preparation method has the raw materials are easy, the price is cheap; the process is simple, the production safety; high yield, low cost and the like. (by machine translation)

Aza-Henry Reaction with Nitrones, an Under-Explored Transformation

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.

Cellulose type chiral stationary phase based on reduced graphene oxide@silica gel for the enantiomer separation of chiral compounds

The graphene oxide (GO) was covalently coupled to the surfaces of silica gel (SiO2) microspheres by amide bond to get the graphene oxide@silica gel (GO@SiO2). Then, the GO@SiO2 was reduced with hydrazine to the reduced graphene oxide@silica gel (rGO@SiO2), and the cellulose derivatives were physically coated on the surfaces of rGO@SiO2 to prepare a chiral stationary phase (CSP) for high performance liquid chromatography. Under the optimum experimental conditions, eight benzene-enriched enantiomers were separated completely, and the resolution of trans-stilbene oxide perfectly reached 4.83. Compared with the blank column of non-bonded rGO, the separation performance is better on the new CSP, which is due to the existence of rGO to produce special retention interaction with analytes, such as π-π stacking, hydrophobic effect, π-π electron-donor–acceptor interaction, and hydrogen bonding. Therefore, the obtained CSP shows special selectivity for benzene-enriched enantiomers, improves separation selectivity and efficiency, and rGO plays a synergistic effect with cellulose derivatives on enantioseparation.

PREPARATION METHOD FOR PRAZIQUANTEL AND INTERMEDIATE COMPOUNDS THEREOF

Disclosed is a preparation method for praziquantel and intermediates thereof. The method includes: obtaining a target product praziquantel by using β-phenethylamine as an initial raw material through a condensation reaction with chloroacetyl chloride, a substitution reaction with ethanolamine, and an acylation reaction with cyclohexanecarbonyl chloride, followed by an oxidation reaction and cyclization reaction. Also disclosed are two key intermediates, namely, a compound of formula IV and a compound of formula V for preparing praziquantel. The preparation method is reasonable and simple in its technological design, uses moderate reaction conditions, and is economical and environmentally friendly. Additionally, the raw materials are inexpensive and easy to obtain, the key intermediates are easy to prepare, and the total reaction yield and purity of the obtained target compound praziquantel is high, so that industrialized mass production is easy to achieve.