1133931-74-4Relevant articles and documents
Recycling method of avibactam intermediate isomer
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, (2018/09/11)
The invention relates to a recycling method of an avibactam intermediate isomer, belonging to the technical fields of pharmaceutical synthesis and recycling. According to the pharmaceutical synthesis,the existing complex recycling problem is solved. The recycling method comprises the following steps: reacting by virtue of (2S,5S)-5-((benzyloxy)amino)piperidine-2-carboxylate and an amino protection group Boc2O in the presence of weakly alkaline substances, so as to generate an intermediate product; carrying out catalytic hydrogenation reduction reaction in the presence of a palladium-containing catalyst; carrying out oxidation reaction under the effect of an oxidant, so as to obtain a corresponding ketone intermediate product; and carrying out condensation reaction on a compound represented by a formula I (shown in the description) and benzyloxyamine hydrochloride in the presence of an acid-binding agent, and carrying out deprotection reaction, so as to obtain a final product, namely the compound of the formula I. The recycling method has the advantages that the recycling is efficient, the process route is simple, reaction conditions are mild, and the environmental pollution is low.
Convenient preparing methods for 5R-benzyloxyaminopiperidine-2S-formate and oxalate thereof
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Paragraph 0076; 0077, (2018/04/01)
The invention relates to convenient preparing methods for 5R-benzyloxyaminopiperidine-2S-formate and oxalate thereof. L-glutamic acid is adopted as an initial raw material and esterified under the existence of an acidic agent to prepare a compound III; the compound III and 2-halogen-acetate are reacted under an alkaline condition to obtain a compound IV; the compound IV is subjected to intramolecular condensation and cyclization under functions of a strong alkali to obtain piperidin-5-one-2S-formate; the piperidin-5-one-2S-formate and benzylhydroxylamine hydrochloride are subjected to a condensation reaction under the existence of an alkali to obtain 5-benzyloxy imino piperidine-2S-formate; the 5-benzyloxy imino piperidine-2S-formate is subjected to reduction and chiral resolution to obtain the 5R-benzyloxyaminopiperidine-2S-formate oxalate; and the 5R-benzyloxyaminopiperidine-2S-formate oxalate is neutralized to obtain the 5R-benzyloxyaminopiperidine-2S-formate. The invention also provides a method for preparing avibactam. Raw materials of the methods are easily available, the methods are simple to operate, a production process is environmentally friendly, yields are high, and a production cost of the avibactam can be reduced.
A method of recovering and utilizing avibactam intermediate production waste liquid
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Paragraph 0062; 0063, (2018/03/01)
The invention relates to a method of recovering and utilizing avibactam intermediate production waste liquid. The waste liquid produced in a production process of an avibactam intermediate that is 5R-benzyloxyaminopiperidine-2S-formateoxalate IIb is adopted as an initial raw material, and is oxidized to generate 5R-benzyloxyiminopiperidine-2S-formate III; the compound III is subjected to selectivereduction, chiral crystallization resolution and filtration to obtain the solid 5R-benzyloxyaminopiperidine-2S-formateoxalateoxalate IIb; and the obtained filtrate is subjected to the oxidation, reduction and resolution steps again. The compound IIb is neutralized to prepare 5R-benzyloxyaminopiperidine-2S-formate IIa, and the compound IIa or the compound IIb can be utilized to prepare avibactam I. The method is simple and convenient to operate, the atom utilization rate is increased, and the total yield of the compound IIb can be 99.0% or above, thus facilitating cost reduction, facilitatingreduction of avibactam waste liquid and facilitating environment protection.
B-LACTAMASE INHIBITOR AND APPLICATION THEREOF
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Paragraph 0177; 0178, (2018/03/07)
The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R1, R2, M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.
Development of a Manufacturing Route to Avibactam, a β-Lactamase Inhibitor
Ball, Matthew,Boyd, Alistair,Ensor, Gareth J.,Evans, Matthew,Golden, Michael,Linke, Simon R.,Milne, David,Murphy, Rebecca,Telford, Alex,Kalyan, Yuriy,Lawton, Graham R.,Racha, Saibaba,Ronsheim, Melanie,Zhou, Shao Hong
, p. 1799 - 1805 (2016/10/31)
Process development work to provide an efficient, robust, and cost-effective manufacturing route to avibactam, a β-lactamase inhibitor is presented herewith. Aspects of this optimization work include the counterintuitive introduction of a protecting group to effect a difficult urea formation and the use of controlled feed hydrogenation conditions to facilitate an elegant one pot debenzylation and sulfation reaction. Overall, the commercial process delivers avibactam in much improved yield with significant reduction in the environmental footprint.
PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF
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Page/Page column 14-15, (2013/02/27)
The present invention relates to compounds and processes for preparing compounds of Formula (I), including compounds such as trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof (e.g., NXL-104).
