52 results about "Biapenem" patented technology

The invention is a synthesis method of the biapenem, with the MAP ((1R, 5R, 6R) 2-(drophenyl phosphate)-6-[(R)-1- hydroxyethyl]-1-methyl-1-1 - carbapenems-2-en-3-formic acid benzyl ester of p-nitrophenol)) and the 6, 7-dihydro-6-mercapto-5 H-pyrazol [1,2 - a] [1,2 , 4]-triazole chloride ( the intermediate III) as the starting materials; after the condensation, hydrolysis and the fine preparation reaction and synthesis, the biapenem is made.

The invention relates to a biapenem compound and a preparation method thereof, which comprises the following steps: 1) dissolving crude biapenem in water, then adding activated carbon, keeping warm, fully stirring, filtering the deactivated carbon, and collecting the filtrate; 2) dissolving The filtrate obtained in the previous step is separated and purified by column chromatography, and the eluent is collected; 3) the temperature is increased to concentrate the above-mentioned eluent solution, and then adding ethanol and acetone with a volume ratio of 1: 0.5~2 mixed solvent solvent, and control temperature for crystallization, the precipitated crystals are centrifuged, washed, and dried to obtain a refined biapenem compound; 4) Optionally, the crystallization mother liquor is returned to step 3), that is, added to the eluting solution obtained in step 2) together with a mixed solvent. By adopting the method of the invention, the purity of crude biapenem can be greatly improved, the quality of preparation products can be improved, and toxic and side effects can be reduced.

The invention discloses a biapenem crystalline solid and a preparation method thereof. X ray diffraction spectrogram of the biapenem crystalline powder has a peak at the position where an angle of 2theta is 16.228+/-0.2. The biapenem crystalline solid is prepared by means of crystallization, three kinds of reagents are used, operation is simple, cost is low, crystalline particles are uniform, solid-liquid separation and dying are convenient and the preparation method is suitable for industrial production. The biapenem crystalline solid prepared with the preparation method has the advantages that purity of crystalline solid is high, and the crystalline solid has good stability in bright, hot and humid environments.

The invention relates to a preparation method for a biapenem condensation compound shown in a formula II and a crystalline solid thereof. Impurities in reaction raw materials can be effectively removed by adding a lower alcohol solvent in a reaction system so as to obtain the crystalline solid of the biapenem condensation compound with high purity. Because particles of the obtained crystalline solid of the biapenem condensation compound are large, the crystalline solid is beneficial to solid-liquid separation and drying, and is more suitable for industrial production.

The invention relates to a synthesis method of biapenem ester, which comprises the steps of: 1) under the condition of air isolation, adding organic solvent, compound (II), compound (IV), R13P and alkali into a reactor, controlling the reaction temperature, and reacting for more than 15min; 2) carrying out HPLC monitoring, and using acid to adjust a system to acidity after reaction; and 3) crystallizing, cooling the reaction liquid, adding crystallization solvent for stirring and crystallization, filtering and obtaining the target compound (compound I). The invention has simple and convenient operation, can directly crystallize without needing purification in the reaction, and avoids using biapenem branched chain which is compound (III) and is easy in moisture absorption and difficult to prepare and store.

The invention relates to a preparation method of high-purity biapenem, which includes the steps of: (A) carrying out a condensation reaction with a compound represented as the formula V and a compound represented as the formula VI in an acetonitrile solvent in the presence of a less amount of N,N-dimethylformamide and an organic alkali to obtain a compound represented as the formula VII; (B) carrying out a catalytic hydrogenation to the reaction product in the step (A) in a mixed solution composed of an alcohol solvent and a non-proton polarity organic solvent in the presence of a catalyst and an organic alkali to remove a carboxylic acid protective group in the compound represented as the formula VII; and (C) filtering a reaction mixed solution to obtain a filter cake, adding the filter cake in water with stirring to obtain a filtrate, mixing the filtrates, adding an organic solvent under stirring, performing precipitation crystallization, and filtering and drying a product to obtain the biapenem.

The invention discloses a method for synthesizing biapenem medicine intermediates. The method has the advantages that the biapenem medicine intermediates 4-AA are prepared from (R)-3-polyhydroxybutyrate which is a raw material, and the raw material in the routes is inexpensive, is easily available and can be substantially purchased; the method includes simple steps, the various steps are high in yield, and reaction is simple; chiral reagents and chiral resolution are omitted, accordingly, the method is low in cost and high in yield, and reaction conditions are easily available.

The invention belongs to the technical field of medicines, and discloses a preparation method of biapenem. The method comprises the following steps: p-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-2-[(diphenylphosphono)oxy]-1-methylcarboxyl pen-2-em-3-carboxylate and 4-sulfydryl-N,N-bis(p-nitrobenzyloxycarbonyl)pyrazolidine are used as raw materials, substitution is performed, hydrogenation is performed and cyclization is performed to synthesize the biapenem. The method provided by the invention overcomes the defects of a long reaction route, easy degradation of raw materials in the reactionprocess, a low yield and the like in the prior art, and is more suitable for industrial production.

The invention discloses an HPLC detection method of biapenem side chain related substances. Linear gradient elution is carried out by using octadecylsilane chemically bonded silica as a filler and using a mixed solution of a buffer solution of which the pH value is 3.0-4.5 and an organic solvent as a mobile phase. The detection sensitivity of the detection method provided by the invention is obviously improved compared with that of related substances of the apixem side chain, the separation degree of each impurity and a main peak is very good, and the increase of hydrolyzed impurities can be effectively controlled.

The invention relates to a preparation method of biapenem as shown in the formula 1. The method comprises the following steps of: using a biapenem intermediate I as a raw material, using a single solvent--water as a reaction solvent and conducting a hydrogenated deprotection reaction in the presence of alkali and a catalyst. The single solvent water is used as a reaction solvent, thus solving the problem of dissolving the catalyst by the reaction solvent, simplifying post-treatment operational step, reducing product degradation and raising product purity. In addition, the preparation method is economical, safe and environmentally friendly, and is more suitable for industrial operation at large scale.

The invention relates to a biapenem dimer with a structure shown in the following formula and a preparation method and an application thereof. The preparation method comprises the steps of: weighing biapenem raw material, dissolving in acidic water solution as solvent to obtain a solution; standing at 25-100DEG C (at 25-50DEG C for 24 hours and at 51-100DEG C for 1-4 hours), and filtering to obtain filtrate; and separating the filtrate with reversed phase high performance liquid chromatography, and preparing the dimer. The biapenem dimer can be used as a reference substance of biapenem impurities to facilitate the control of the amount of biapenem and related preparations thereof.