57 results about "Doripenem" patented technology

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.

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.