56 results about "Doripenem" patented technology

The invention provides a novel crystal form of a carbapenem antimicrobial medicament, namely, (+)-(4R,5S,6S)-3-[[(3S,5S)-5-(aminosulfonyl)aminomethyl]-3-pyrrolidine]sulfur]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclic[3,2,0]heptyl-2-ene-2-carboxylic acid-hydrate (doripenem). The X-ray powder diffraction pattern of the crystal powder shows main peaks when 2theta is equal to 15.20 degrees, 16.06 degrees, 16.83 degrees, 19.40 degrees, 21.29 degrees, 23.68 degrees, 24.08 degrees, 24.70 degrees, 26.28 degrees, 28.43 degrees, 29.17 degrees and 34.35 degrees. The novel crystal form has the advantages of easiness in preparation and industrial production, low cost, high solubility and high stability.

The invention provides a method for measuring Doripenem and / or relevant substances by utilizing a high performance liquid chromatography. The method comprises the following steps of: measuring by utilizing an ultraviolet detector with the detection wavelength of 230nm; with silane-bonded silica gel bonded with polar groups as a stationary phase, with a mixture compounded of a sodium salt or sylvite aqueous solution of phosphoric acid with the pH of 4.7-6.0 and the concentration of 0.01-0.2mol / L and acetonitrile as a mobile phase, carrying out isocratic or gradient elution. Compared with the prior art, the method provided by the invention has the advantages that more impurities can be detected, good separation degree and peak shape of the Doripenem and / or relevant substances can be realized, and good base line separation can be realized between the Doripenem and the impurities as well as between the impurities and the impurities; and the method has good reproducibility between batches and between columns and is suitable for industrial production.

The invention discloses a method of detecting the content of doripenem with high performance liquid chromatography, which adopts an ultraviolet detector for detecting. The invention is characterized in that: the method adopts an octyl chemically bonded silica chromatographic column as the chromatographic column, and acetonitrile and solium salt aqueous solution of phosphoric acid as the mobile phase, and the pH of the solium salt aqueous solution of phosphoric acid is 5.0-6.0. The invention has simple operation, high sensitivity and good peak form, and can detect the doripenem in the range of pH 5.0-6.0.

The invention discloses a method for preparing a doripenem intermediate compound (I), which comprises the following step: under the protection of inert gas, in a polar aprotic solvent, reacting a compound (II) with a compound (III) at the temperature of between -60 and 25 DEG C under the action of organic base, wherein AOC is allyloxycarbonyl group. The preparation method has the advantages of high yield and high purity of the product, simple operation, simple posttreatment, cost conservation and easy realization of industrialization.

The invention relates to a preparation method of doripenem as shown in the formula 1. The method comprises the following steps of: using a doripenem intermediate II 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 a series of problems caused by the use of an organic solvent in the reaction solvent, 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 Doripenem intermediate alcoholate shown as a formula 2 and a preparation method and application of the Doripenem intermediate alcoholate. Doripenem intermediate alcoholate is stable in property, easy to preserve, and high in purity, and establishes a foundation for a following hydrogenating deprotection reaction. The preparation method of the alcoholate is simple in operation, and a used crystallization reagent is ethanol which is less harmful to human health and environment, and the preparation method is suitable for industrial production.

A (1R, 5S, 6S)-6-((1R)-1-ethoxyl)-2-((3S, 5S)-5-sulfonamide-amino-methyl-pentazane-3-base) sulfur-1-methyl-1-carbon-2-penicillic vinyl-3-carboxylic acid or its hydrate, its medicinal composite containing multi-nipenan crystal, its production and use in preparation of anti-infectious medicine are disclosed. In the crystallizing powdery X-ray diagram, it has main peak at diffraction angle (2 theta)=6.46, 15.27, 16.41, 17.49, 20.72, 23.05 and 25.38 deg. minus or plus 0.1. It's simple and cheap, and has excellent thermodynamic stability and dissolubility.

The invention discloses a method for preparing high purity doripenem. The method comprises the following steps: (1) conducting a contact reaction on carbapenem bicyclic nucleus and (2S,4S)-1-p-nitrocarbobenzoxy-4-sulfenyl-2-(N-sulfamoyl amino)methylpyrrolidine in a water and 1,4-dioxane mixed solvent in the presence of copper salt and triethylamine; adding water and ethyl acetate, stirring, standing for layering, concentrating the ethyl acetate layer; recrystallizing a dichloromethane and petroleum ether mixed solvent to obtain (1R,5S,6S)-2-[(3S,5S)-1-nitrophenyl formate-5-sulfamoyl amino methylpyrrolidine-3-sulfenyl]-6-[(1R)-1-ethoxyl]-1-methyl-1-carba-2-penem-3-p-nitrobenzyl carboxylate; and (2) adding the product obtained in the step (1), tetrabutyl ammonium chloride and 0.2M of phosphate buffered solution having a pH value of 8 into a reaction kettle which is filled with water, replacing three times with hydrogen, adding hydrogen to react, filtering, concentrating the filtrate, and recrystallizing in methanol to obtain doripenem.

The invention provides a Doripenem side-chain compound shown by the formula (IX), wherein R represents hydrogen, p-nitrobenzyloxycarbonyl or p-methoxyl carbobenzoxy. The compound does not contain a protective group or only contains one protective group, and can be directly connected with a mother nucleus compound to prepare Doripenem, so that the utilization efficiency of a mother nucleus is improved, the operation is simplified, the hydrogenation reaction efficiency is improved, the manufacture cost of a product is reduced, in addition, the side-chain compound is a crystal so as to have better material attributes including stability, separability or purity, the crystal is reacted with the mother nucleus compound to obtain the Doripenem with high quality, and the advantages of convenience in purification, low cost and convenience in direct use are provided. In addition, the invention provides a preparation method of the Doripenem side-chain compound, which has the advantages of simpleness in operation, and the like, and is suitable to be applied in factories in a large scale. The invention also provides application of the Doripenem side-chain compound in the preparation of Doripenem.

The invention provides a novel crystal form of a carbapenem antimicrobial medicament, namely, (+)-(4R,5S,6S)-3-[[(3S,5S)-5-(aminosulfonyl)aminomethyl]-3-pyrrolidine]sulfur]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclic[3,2,0]heptyl-2-ene-2-carboxylic acid-hydrate (doripenem). The X-ray powder diffraction pattern of the crystal powder shows main peaks when 2theta is equal to 15.20 degrees, 16.06 degrees, 16.83 degrees, 19.40 degrees, 21.29 degrees, 23.68 degrees, 24.08 degrees, 24.70 degrees, 26.28 degrees, 28.43 degrees, 29.17 degrees and 34.35 degrees. The novel crystal form has the advantages of easiness in preparation and industrial production, low cost, high solubility and high stability.

The invention relates to a method for detecting and / or identifying, in a biological sample, bacteria having a resistance to carbapenems. The method comprises the following steps consisting in: a) bringing the sample into contact with a reaction medium containing at least one chromogenic agent and faropenem and / or doripenem; b) incubating the sample and reaction medium brought into contact in step(a), such as to allow the growth of bacteria; and c) detecting the strains having a resistance to carbapenems. The medium used in step (a) also contains cloxacillin and / or a combination of cloxacillinand PAbetaN.

The invention belongs to the field of medicine synthesis and particularly relates to a doripenem preparation method. The method includes the steps that a compound 5 reacts with concentrated sulfuric acid in methanol to obtain a compound 4; the compound 4 and p-Nitrobenzyl-6-(1-hydroxyethyl)-1-azabicyclo(3.2.0)heptane-3,7-dione-2-carboxylate (a compound 3) are subjected to a condensation reaction under the condition that N,N-diisopropylethylamine exists, water and ethyl acetate are added and stirred after the reaction, an ethyl acetate layer is collected, alcohol is added in ethyl acetate collection liquid, crystallization is carried out, and a compound 2 is obtained; the product is dissolved through ethyl acetate; after a monopotassium phosphate solution and a phase transfer reagent of triethylbenzylammonium chloride are added, zinc powder is added into the ethyl acetate / monopotassium phosphate solution in batches to react and obtain doripenem. According to the method, reaction conditions are moderate, the technology is simple, and the conversion rate and the yield are high. Two-phase reaction is used in deprotection reaction, and the after-treatment process is simplified. The zinc powder which is cheap is used, so that the method is economical, and a new concept and a new method are provided for doripenem preparation.

The invention relates to a chiral pyrrolidine compound and a preparation method thereof, in particular to a preparation method of a compound (IX). The chiral pyrrolidine compound is used as a Doripenem intermediate. According to the compound, sulfydryl is protected by adopting aroyl, amino is protected by using allyloxycarbonyl, bromide is prepared, a sulfamide group is used for substitution, the prepared compound is feasible in process route, and industrial production can be realized. The chiral pyrrolidine compound is high in quality, is a tabular crystal, and is easily purified; and the purity can be accurately measured by using HPLC (High Performance Liquid Chromatography), and the defects of content measured by using a titration or derivation method, and the like are avoided. When the Doripenem is synthesized by connecting with a Doripenem mother nucleus, the utilization rate of the mother nucleus is increased, the purification process of the Doripenem bulk pharmaceutical chemicals is simplified, the consumption of a hydrogenation catalyst is reduced, byproducts are prevented from being introduced due to deprotection of aluminum trichloride, protecting groups are finally transformed into gas which is completely removed, so that the Doripenem bulk pharmaceutical chemicals are high in yield and good in purity, and are reduced in manufacture cost. The compound is shown in the description, wherein Ar=Ph, PhCH2, 4-NO2Ph and 4CH3Ph.