82467-84-3Relevant academic research and scientific papers
Preparation method of rocuronium bromide intermediate
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Paragraph 0029-0041, (2021/11/26)
The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of a rocuronium bromide intermediate. To the preparation method, androsterone as shown I is used as a raw material, dehydration reaction is carried out under catalysis of an ecton reagent, and then washing is carried out. To the preparation method, the reaction temperature is reduced -2 - to -17 - 5 α - the byproduct of high-temperature reaction is reduced 40 °C, the reaction liquid is subjected to simple water washing, extraction and concentration to obtain a white solid, and the loss of the main product caused by the recrystallization of the by-product is reduced. The process is simpler, the yield is lower, and the three-waste discharge is less.
Vecuronium bromide and its advanced intermediates: A crystallographic and spectroscopic study
Ciceri, Samuele,Colombo, Diego,Ferraboschi, Patrizia,Grisenti, Paride,Iannone, Marco,Mori, Matteo,Meneghetti, Fiorella
, (2021/10/25)
Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the 1H, 13C, and 15N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
Preparation method of 5alpha-androstane-2-ene-17 ketone
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Paragraph 0025-0030, (2021/11/14)
The invention discloses a preparation method of a skeletal muscle relaxant drug intermediate 5 alpha-androstane-2-ene-17 ketone, and belongs to the technical field of synthesis. According to the method disclosed by the invention, epiandrosterone is taken as a raw material and reacts with p-dodecyl benzene sulfonyl chloride under the action of a catalyst to generate sulfonate, and the 5alpha-androstane-2-ene-17 ketone is generated by elmination. The synthesis method provided by the invention can effectively reduce a double-bond position isomer 5 [alpha]-androstane-3-ene-17 ketone of the target product 5 [alpha]-androstane-2-ene-17 ketone, greatly improves the product quality, and reduces the production cost at the same time.
Preparation method of rocuronium bromide intermediate 5alpha-sterane-2-ene-17-one
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Paragraph 0009; 0020-0031, (2020/04/02)
The invention discloses a preparation method of a rocuronium bromide intermediate 5alpha-sterane-2-ene-17-one. The specific steps include: sequentially adding epiandrosterone TS, a solvent and a phasetransfer catalyst into a reaction bottle, performing heating to a reaction temperature of 90-120DEG C, carrying out stirring reaction, and conducting post-treatment purification to obtain the 5alpha-sterane-2-ene-17-one. The method provided by the invention greatly shortens the reaction time, reduces byproducts, enhances the yield, reduces three wastes, lowers the production cost, is suitable forindustrial production, and has obvious social and economic benefits.
Preparation method of 5 alpha-androstane-2-ethylene-17-ketone
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Paragraph 0021-0024; 0025-0026; 0027-0028; 0029-0044, (2019/05/08)
The invention discloses a preparation method of 5 alpha-androstane-2-ethylene-17-ketone. The preparation method comprises the steps of taking epiandrosterone (formula I as shown in the specification)as a raw material to give a dehydration reaction by joint catalysis of protonic acid and trifluoromethanesulfonate, and performing post-treatment, recrystallization and separation on a reaction product to form 5 alpha-androstane-2-ethylene-17-ketone (formula II as shown in the specification). The preparation method avoids the use of much organic base compound in the traditional method, has the advantages of high reaction yield, short procedure, good selectivity, low cost, less waste gas, waste water and industrial residue and the like and is a synthesis method suitable for industrial production.
Rapid Deoxyfluorination of Alcohols with N-Tosyl-4-chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature
Guo, Junkai,Kuang, Cuiwen,Rong, Jian,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
supporting information, p. 7259 - 7264 (2019/05/10)
The deoxyfluorination of alcohols is a fundamentally important approach to access alkyl fluorides, and thus the development of shelf-stable, easy-to-handle, fluorine-economical, and highly selective deoxyfluorination reagents is highly desired. This work describes the development of a crystalline compound, N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor), as a novel deoxyfluorination reagent that possesses all of the aforementioned merits, which is rare in the arena of deoxyfluorination. Endowed by the multi-dimensional modulating ability of the sulfonimidoyl group, SulfoxFluor is superior to 2-pyridinesulfonyl fluoride (PyFluor) in fluorination rate, and is also superior to perfluorobutanesulfonyl fluoride (PBSF) in fluorine-economy. Its reaction with alcohols not only tolerates a wide range of functionalities including the more sterically hindered alcoholic hydroxyl groups, but also exhibits high fluorination/elimination selectivity. Because SulfoxFluor can be easily prepared from inexpensive materials and can be safely handled without special techniques, it promises to serve as a practical deoxyfluorination reagent for the synthesis of various alkyl fluorides.
Steroid compound 3-site hydroxyl configuration inversion method
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, (2018/12/14)
The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.
NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF
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, (2015/02/02)
Described herein are neuroactive steroids of the Formula (I): (Formula (I)) or a pharmaceutically acceptable salt thereof; wherein R1a and R1b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.
In vitro metabolism studies of desoxy-methyltestosterone (DMT) and its five analogues, and in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses
Kwok, Wai Him,Kwok, Karen Y.,Leung, David K. K.,Leung, Gary N. W.,Wong, Colton H. F.,Wong, Jenny K. Y.,Wan, Terence S. M.
, p. 994 - 1005 (2015/11/10)
The positive findings of norbolethone in 2002 and tetrahydrogestrinone in 2003 in human athlete samples confirmed that designer steroids were indeed being abused in human sports. In 2005, an addition to the family of designer steroids called 'Madol' [also known as desoxy-methyltestosterone (DMT)] was seized by government officials at the US-Canadian border. Two years later, a positive finding of DMT was reported in a mixed martial arts athlete's sample. It is not uncommon that doping agents used in human sports would likewise be abused in equine sports. Designer steroids would, therefore, pose a similar threat to the horseracing and equestrian communities. This paper describes the in vitro metabolism studies of DMT and five of its structural analogues with different substituents at the 17α position (R￡H, ethyl, vinyl, ethynyl and 2H3-methyl). In addition, the in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses will be presented. The in vitro studies revealed that the metabolic pathways of DMT and its analogues occurred predominantly in the A-ring by way of a combination of enone formation, hydroxylation and reduction. Additional biotransformation involving hydroxylation of the 17α-alkyl group was also observed for DMT and some of its analogues. The oral administration experiment revealed that DVT was extensively metabolised and the parent drug was not detected in urine. Two in vivo metabolites, derived respectively from (1) hydroxylation of the A-ring and (2) di-hydroxylation together with A-ring double-bond reduction, could be detected in urine up to a maximum of 46 h after administration. Another in vivo metabolite, derived from hydroxylation of the A-ring with additional double-bond reduction and di-hydroxylation of the 17α-vinyl group, could be detected in urine up to a maximum of 70 h post-administration. All in vivo metabolites were excreted mainly as glucuronides and were also detected in the in vitro studies.
PyFluor: A low-cost, stable, and selective deoxyfluorination reagent
Nielsen, Matthew K.,Ugaz, Christian R.,Li, Wenping,Doyle, Abigail G.
supporting information, p. 9571 - 9574 (2015/08/18)
We report an inexpensive, thermally stable deoxyfluorination reagent that fluorinates a broad range of alcohols without substantial formation of elimination side products. This combination of selectivity, safety, and economic viability enables deoxyfluorination on preparatory scale. We employ the [18F]-labeled reagent in the first example of a no-carrier-added deoxy-radiofluorination.
