![({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt](/Databaselist/images/loading.webp)
1192491-61-4Relevant academic research and scientific papers
Orally Absorbed Derivatives of the β-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs
Gordon, Eric M.,Duncton, Matthew A. J.,Gallop, Mark A.
, p. 10340 - 10344 (2018)
Only one FDA-approved β-lactamase inhibitor has ever been orally available: clavulanic acid, approved in 1984. Avibactam, approved by FDA in 2015, is the first of a new class of BLIs called diazabicyclooctanes, or "DBOs". This class has much broader coverage than clavulanic acid but can only be administered by intravenous injection. Herein, we describe the synthesis and testing of the first approved BLI to be rendered orally bioavailable since clavulanic acid (1984).
Understanding the Role of Water in Different Solid Forms of Avibactam Sodium and Its Affecting Mechanism
Cheng, Xiaowei,Ding, Zhiyong,Hao, Hongxun,Huang, Xin,Li, Guiping,Liu, Han,Mao, Yafei,Su, Wei,Tian, Beiqian
, p. 1150 - 1161 (2020)
Hydrates are common in pharmaceutical development, and the formation of hydrates affects the performance of the final product. However, the role that water plays in crystal packing remains unclear. In this study, Avibactam sodium, which has one dihydrate (Form E), one monohydrate (Form A), and two anhydrous forms (Form B and D), was chosen as the model compound to understand this subject. Single crystal structures of four solid forms were obtained and characterized by single X-ray diffraction. The dynamic vapor sorption experiments revealed the moisture-dependent stability increased in the order: Form B A w). The results indicated that both water activities and temperature are vital factors to determine the amount of water molecules existing in crystal lattice. Moreover, to probe the disintegration of water molecules, the dehydration of dihydrate was investigated in detail by solid-state transformation and solvent-mediated transformation experiments. Finally, two-step dehydration and one-step dehydration + recrystallization mechanisms of these different pathways were proposed by analyzing the transformation experiment results and the crystal structure of various solid forms.
RETRACTED ARTICLE: A New Synthetic Route to Avibactam: Lipase Catalytic Resolution and the Simultaneous Debenzylation/Sulfation
Wang, Tao,Du, Liang-Dong,Wan, Ding-Jian,Li, Xiang,Chen, Xin-Zhi,Wu, Guo-Feng
, p. 267 - 272 (2018)
An efficient synthesis of avibactam starting from commercially available ethyl-5-hydroxypicolinate was completed in 10 steps and 23.9% overall yield. The synthesis features a novel lipase-catalyzed resolution, in the preparation of (2S,5S)-5-hydroxypiperidine-2-carboxylate acid, which is a valuable precusor of the key intermediate ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate. An optimized one-pot debenzylation/sulfation reaction, followed by cation exchange, gave the avibactam sodium salt on a 400.0 g scale.
Preparation method of avibactam sodium
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, (2021/03/06)
The invention discloses a synthesis method of avibactam sodium. (2S,5R)-benzyloxyamino piperidine-2-ethyl formate oxalate (I) is used as an initial raw material; and the method comprises the followingsteps: reacting the raw material with a protecting group, carrying out carbonylation cyclization, carrying out hydrolysis of ester, ammoniating, sulfonating with a sulfur trioxide complex, salifyingwith an ammonium ion source, and salifying with a sodium salt to obtain avibactam sodium, and has the advantages of simple operation, easily controlled conditions, easy industrial production and wideapplication prospect.
Recovery and preparation method of avibactam sodium
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Paragraph 0044-0045, (2020/06/09)
The invention belongs to the technical field of medical chemistry, and particularly relates to a method for recycling, purifying and preparing a beta-lactamase inhibitor drug avibactam sodium. The method for recycling and preparing the sterile powder product is simple to operate and mild in condition, avoids hydrogenation catalytic operation for preparing a compound II from a starting material, reduces the safety risk, greatly improves the product purity, and is suitable for large-scale production.
Preparation method of avibactam intermediate compound
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, (2020/05/30)
The invention relates to medical compounds and organic chemical synthesis, in particular to an avibactam intermediate compound and a preparation method thereof. The preparation method of the avibactamintermediate compound comprises the following steps: (1) carrying out a hydrogenation sulfonation reaction on (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide; (2) after the reactionin the previous step is completed, carrying out washing once, and adding quaternary ammonium bromide for a reaction; and (3) after the reaction is finished, performing extracting, and then carrying out rotary evaporation and crystallizing. Compared with the prior art, the method of the invention has the advantages that operation is simple, raw materials are easy to obtain, cost is low, the purityof an obtained sulfonic acid quaternary ammonium salt is high, and the purity of avibactam sodium generated by sodium salt exchange of the sulfonic acid quaternary ammonium salt is 99.5T, so the method is suitable for large-scale production.
Avibactam intermediate compound disulfonic acid gemini quaternary ammonium salt and preparation method thereof
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, (2020/10/14)
The invention discloses an avibactam intermediate compound, disulfonic acid gemini quaternary ammonium salt, and a preparation method thereof, and relates to medical compounds and organic chemical synthesis, and the preparation method of the avibactam intermediate compound disulfonic acid gemini quaternary ammonium salt comprises the following steps: (1) carrying out hydrogenolysis sulfonation reaction on (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide; (2) after the reaction in the previous step is completed, performing suction filtration, washing filtrate once, and adding gemini quaternary ammonium salt for reaction; and (3) after the reaction in the previous step is completed, carrying out extraction, rotary evaporation and crystallization. Compared with the prior art,the method has the advantages that the operation is simple, the raw materials are easy to obtain, the cost is lower, the dosage of the gemini quaternary ammonium salt is lower, the purity of the obtained disulfonic acid gemini quaternary ammonium salt is higher, and the HPLC relative purity of avibactam sodium generated by sodium salt exchange of the disulfonic acid gemini quaternary ammonium salt is greater than 99.5%, so that the process is suitable for large-scale production.
Stable crystal form of avibactam sodium and preparation method thereof
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Paragraph 0021-0023, (2020/10/04)
The invention discloses an effective stable crystal form of avibactam sodium ((1R, 2S, 5R)-7-oxo-6-sulfonyloxy-1, 6-diazabicyclo(3, 2, 1)octane-2-formamide sodium salt) and a preparation method. The crystal form compound is a drug stable crystal form and has a wide application prospect.
Simple and convenient production method of avibactam
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Paragraph 0089; 0109-0113; 0115; 0126-0128; 0129; 0160-0164, (2019/07/16)
The invention provides a simple and convenient production method of avibactam. The simple and convenient production method of the avibactam comprises the steps of using piperidyl-5-keto-2S-formate IIas a raw material, making the piperidyl-5-keto-2S-formate II and O-protecting group hydroxylamine hydrochloride subjected to condensation reaction, and then obtaining 5R-substituted oxyaminopiperidyl-2S-formic acid V through reduction, chiral resolution and hydrolysis under an alkaline condition; and then making the 5R-substituted oxyamino piperidyl-2S-formic acid V and phosgene or triphosgene ordiphosgene subjected to cyclic urea reaction reaction, acylating chlorination reaction and amidation reaction through a one-pot method, obtaining {[(2S,5R)-2-formamyl-7-oxo-1,6-diazetidine[3.2.1]octane-6-yl]oxy}sulfonyl tetra-n-butylammonium salt VII through protecting group take-off, sulphating and tetrabutyl amination salification, and producing the avibactam I finally through ion exchange. Thesimple and convenient production method of the avibactam is simple and convenient in production route, easy to operate, low in raw material price, low in cost, small in three waste discharge, high inatom utilization rate, economical and environmentally friendly, and the yields of the various steps are high, so that the simple and convenient production method of the avibactam benefits industrial production of the avibactam.
Avibactam intermediate, and preparation method and application of avibactam intermediate
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Paragraph 0037; 0045-0046; 0048-0049; 0051-0052, (2019/09/17)
The invention discloses an avibactam intermediate, and a preparation method of the avibactam intermediate. The preparation method comprises the steps of allowing a compound II to react with a sulfonation reagent in the presence of an alkaline agent and then react with the alkaline agent to form the avibactam intermediate, wherein the alkaline agent is trialkylamine, pyridine, alkylpyridine, N-alkylpiperidine, dialkyl phenylamine or dialkyl benzylamine; alkyl in trialkyl amine is C5-8 alkyl; alkyl in alkyl pyridine in C1-4 alkyl; alkyl in N-alkylpiperidine is C1-4 alkyl; alkyl in dialkyl phenylamine is C1-4 alkyl; and alkyl in dialkyl benzylamine is C1-4 alkyl. Compared with the traditional method, the method adopts the alkaline agent with appropriate alkalinity to substitute the traditional alkaline agent; the alkaline agent can react with the compound II in a step directly with the sulfonation reagent; the post-treatment is simple; and the method is more suitable for industrial mass production.
