36 results about "Avibactam sodium" patented technology

The invention belongs to the technical field of medical chemistry and particularly relates to a preparation method of beta-lactamase inhibitor drug avibactam sodium and an intermediate of beta-lactamase inhibitor drug avibactam sodium. Triethyl-silane is adopted to realize benzyl removal, hydrogenation catalysis operation in the prior art is omitted, the reaction condition is milder, safety risk is reduced, the product yield and the purity are greatly improved, and the preparation method is more suitable for large-scale production.

The invention discloses a method for preparing amorphous avibactam sodium by spray-drying. According to the invention, solution of sodium iso-octoate is dropwise added into solution of avibactam tetrabutylammonium salt, after dropwise adding is completed, the reaction is performed for 3 to 4h, and purified water is added for extraction; after a water phase is subjected to spray-drying, the amorphous avibactam sodium is obtained. The method disclosed by the invention is simple in step and easy for industrial production, the purity of a product is greater than or equal to 98.0%, and yield is greater than or equal to 90.0%.

The invention discloses a preparation method of crystal form B avibactam sodium, which comprises the following steps: S100, adding methanol and water into avibactam sodium, stirring, heating and dissolving to obtain an avibactam sodium solution; and S200, adding an alcohol poor solvent into the avibactam sodium solution, cooling to a first temperature, stirring for growing crystals, and then continuously cooling to a second temperature for devitrification.

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.

The present invention relates to avibactam free acid, a method for preparing avibactam free acid and a method for preparing avibactam sodium by further reacting avibactam free acid. The invention further refers to a pharmaceutical composition comprising avibactam free acid, one or more alkaline sodium salt(s) and one or more beta-lactam antibiotic(s). The pharmaceutical composition of the present invention can be used as medicament, in particular for treatment and/or prevention of bacterial infections.

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.

The present invention relates to crystalline form C of avibactam sodium and to a process for its preparation. The invention also concerns a pharmaceutical composition comprising form C and one or more antibacterial agents, wherein at least one antibacterial agent is a beta-lactam antibiotic. The pharmaceutical composition of the present invention can be used as medicament, in particular for treatment and/or prevention of bacterial infections.

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.

Belonging to the technical field of medicinal chemistry, the invention particularly relates to a preparation method of a beta-lactamase inhibitor drug avibactam sodium intermediate. The method includes: adding a reaction solvent into a reaction container, then sequentially adding a compound II, a sulfur trioxide polymer, alkali and a catalyst, and stirring the substances uniformly; setting the reaction conditions of a micro-channel reactor, pumping the reaction materials into the micro-channel reactor for reaction, and collecting the reaction liquid; performing filtering and collecting the filtrate, adding an ammonium salt aqueous solution into the filtrate, and stirring the substances uniformly, finally adding an extraction agent for extraction, performing liquid separation, then collecting an organic phase and performing concentration to obtain a compound III crude product, and carrying out aftertreatment on the crude product to obtain a compound III. The method provided by the invention utilizes the micro-channel reactor to combine hydrogenation and sulfonation reactions into one, avoids decomposition of the reaction intermediate, and increases the yield; and the method also realizes safe, rapid and continuous reaction at the same time, greatly improves the productivity, and is more suitable for large-scale production.

The invention belongs to the technical field of pharmaceutical analysis detection, and more specifically relates to an avibactam sodium optical isomer high performance liquid chromatography detectionmethod. According to the invention, a celluloid IC column is taken as a chromatographic column, a mobile phase is a mixture of ethanol, diethylamine and trifluoroacetic acid with the volume ratio being 100: 0.15: 0.1, the column temperature is 25-40 DEG C, the flow velocity is 1ml/min, and the detection wavelength is 210 nm. The avibactam sodium optical isomer high performance liquid chromatography detection method has the advantages of good specialization, sensitivity and reappearance, can accurately detect the content of an optical isomer in avibactam sodium, and can guarantee good clinicaleffect.

The invention discloses a refining method of an avibactam sodium intermediate 1. The method comprises the step of refining a crude product of the avibactam sodium intermediate 1 in a good solvent dichloromethane and poor solvent methyl tert-butyl ether system to obtain the high-purity avibactam sodium intermediate 1. According to the refining method provided by the invention, the content of an isomer impurity A and a ring-opening impurity B can be effectively reduced, the purity is improved, the total purity of the refined avibactam sodium intermediate 1 is greater than 99.9%, the isomer impurity A and the ring-opening impurity B are both less than 0.05%, the other single impurities are all less than 0.10%, the reagents are conventional and easy to obtain, the operation is simple and safe and the method is very suitable for industrial amplification under conventional production conditions.