56 results about "Doripenem" patented technology

Disclosed are a doripenem hydrate crystal and preparation method therefor. The X-ray diffraction spectrogram of the crystal powder is basically as represented in figure 1, and the measured water content is 4.4 to 5.5%. The doripenem hydrate crystal of the present invention has high purity, low residual solvent, good stability, and application safety. Additionally, the preparation method for the doripenem hydrate crystal of the present invention has simple techniques and low preparation cost, and is suitable for industrial production.

The invention relates to the technical field of medicines and particularly provides a preparation process of the intermediate I of doripenem. In the process, a reagent which is environmentally-friendly and low in cost is used in place of a high-cost and high-toxicity reagent in the prior art, the synthesis route is optimized, the product purity is improved, and the preparation method is simple, reliable, easy to operate, high in yield and low in cost, reduces emission to the environment to the lowest degree and contributes to industrial production. The structure of the intermediate I of the doripenem is shown below.

The invention discloses a methanol solvate of a doripenem intermediate as shown by a formula I and a preparation method thereof, wherein PNB in an intermediate I represents para-nitrobenzyl, and PNZ represents para-nitro-carbobenzoxygroup. The methanol solvate has the advantages of high purity, good stability, and easy operation and storage; and the preparation method is simple and reliable, and is suitable for industrial implementation.

The invention discloses a process for synthesizing a doripenem lateral chain. According to the process disclosed by the invention, L-hydroxyproline is taken as a starting raw material, and the doripenem lateral chain is obtained through the following steps of: amino protection, carboxyl protection, hydroxyl activation, reduction reaction, acetyl vulcanization reaction and condensation reaction. The process provided by the invention has the advantages of simple and easily-obtained raw materials, no high-temperature and high-pressure reactions and no super-low-temperature reactions; the 'three wastes' generated in the production process mainly comprise waste liquid and the wastewater in the waste liquid is neutralized by appropriate acid and alkali and then is discharged after achieving the discharging standard; and the organic solvents in the waste liquid comprises dichloromethane, dichloromethane and alcohols and can be recycled to be reutilized so that the pollution on the environment is small.

The invention relates to a purification method of pyrrolidine carbapenem antibiotics, and in particular to a method for purifying Doripenem through crystallization or re-crystallization. In the method, the Doripenem is separated out from aqueous solution containing Doripenem and proline.

The present invention relates to preparing carbapenem intermediates that are useful to produce Ertapenem, Meropenem and Doripenem.

Disclosed is a process for detecting and/or identifying, in a biological sample, bacteria exhibiting a resistance to carbapenems, including: a) contacting said sample with a reaction medium including at least one chromogenic agent and faropenem and/or doripenem; b) incubating the whole so as to allow the bacteria to grow; and c) detecting the strains exhibiting a resistance to carbapenems. The medium employed in step a) also contains cloxacillin and/or a combination of cloxacillin and PAbetaN.

The invention discloses a process for preparing (2S, 4S)-1-p-nitro benzyloxycarbonyl-2-(N-tert-butoxycarbonyl amine-N-sulfonyl amino) methyl-4-mercapto-pyrrolidine which is an important intermediate used during preparation of doripenem and further discloses a novel process for preparing the doripenem by carrying out reaction on the intermediate which is used as a starting raw material and (1R, 5S, 6S)-6-[(1R)-1-hydroxy ethyl]-2-diphenylphosphine oxide acyloxy-1-methyl-1-carbon substituted-2-penem-3-carboxylic acid p-nitro benzyl ester with diisopropylethylamine used as the alkaline and removing protecting groups by adopting Pd/C. in the method, the readily available raw materials are adopted, other reagents are adopted to replace the traditional volatile reagents and the recrystallization method is adopted to purify the important intermediate, the high yield is ensured and the process is suitable for industrial production.

The present invention provides a doripenem intermediate compound shown by formula (XIV), wherein PNB is p-nitrobenzyl, and HX is an acid; and when HX is a monobasic acid, n=1; and when HX is a polybasic acid, n=2. The present invention also provides a process for preparing the doripenem intermediate compound (XIV). In addition, the present invention provides a process for preparing doripenem (I) from the doripenem intermediate compound (XIV) in a simple manner, with a high yield and low production costs. The new mono-protected doripenem intermediate compound provided in the present invention contains only one protecting group, reducing the difficulty and complexity in the subsequent de-protection step by catalytic hydrogenation, increasing the yield of the catalytic hydrogenation reaction, and thus reducing the production cost of the final product. The process is easy to operate and suitable for industrialized production.

The present invention relates to preparing carbapenem intermediates that are useful to produce Ertapenem, Meropenem and Doripenem; and provides an effective process for recovering ertapenem compounds.

The invention relates to a method for preparing a ring-opening impurity of carbapenems. The ring-opening impurity is of a structure represented by formula I. In the formula I, R represents a meropenem side chain, an ertapenem side chain or a doripenem side chain. The method includes the following steps: (1) adding carbapenems into an alkaline solution, stirring and reacting for 1-4 hours; (2) adjusting the pH to 6.0-9.0; (3) freeze-drying the materials to obtain the ring-opening impurity of carbapenems. The method provided by the invention is simple to operate and short in reaction time; the product has the purity of 95% or above and can be directly used as a reference substance for quantitative and qualitative research on the ring-opening impurity of carbapenem products, so that the product quality can be effectively controlled. The formula I is shown in the description.

The invention relates to a method for preparing a carbapenem antibacterial medicament doripenem. The method comprises the following steps: dispersing a compound of a formula (I) as shown in the specification in a two-phase composite solvent so as to be subjected to hydrogenation deprotection, layering so as to obtain an enriched doripenem phase, and adjusting the pH value by using acid so as to obtain doripenem crystal. PNZ is p-nitryl benzyl oxygroup carbonyl; PNB is p-nitryl benzyl.

The invention relates to a composition containing Doripenem, in particular to a composition containing the Doripenem and amino acid, wherein the amino acid is selected from one ore some of aminopropionic acid, phenylalanine, aminocaproic acid and threonine.

The invention relates to the technical field of pharmacy, in particular to a process for preparing doripenem. The process comprises the following steps: taking tetrahydrofuran, a doripenem condensation compound, magnesium chloride hexahydrate, 10% Pd/C and distilled water as raw materials, carrying out a series of reactions; extracting an aqueous phase by using ethyl acetate and n-butyl alcohol; washing with propyl alcohol to obtain a crude product of doripenem, treating with activated carbon and propyl alcohol, thus obtaining sterile doripenem. The operation is simple, is favorable for the environment protection and health of workers, and the raw materials are readily available and low in price; therefore, the process is more suitable for industrial production of doripenem.

The invention relates to a preparation method of doripenem. The method comprises the following steps: removing an acetyl group and a tert-butyloxycarbonyl group from an acetylthiopyrrolidine derivative (SM-1) used as an initial raw material to prepare a thiopyrrolidine derivative (DN-1), carrying out a nucleophilic substitution reaction on the DN-1 and a doripenem parent nucleus (SM-2, MAP) to prepare protected doripenem, carrying out catalytic hydrogenation to remove PNZ and PNB protection, and purifying to obtain final doripenem. A solvent and a catalyst used in the method can be recycled, so the production cost is greatly saved, and the method is suitable for large-scale industrial production.

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 discloses a crystal of a doripenem intermediate compound (I). In an X-ray diffraction pattern of powder of the crystal, main peaks are present at a diffraction angle 2 theta which is equal to 10.27 degrees, 10.75 degrees, 12.28 degrees, 13.35 degrees, 17.33 degrees, 20.85 degrees, 21.24 degrees, 21.75 degrees or 22.31 degrees and an error range of a value of the 2 theta is +/-0.2 degree; and BOC is tert-butoxycarbonyl group. The invention also discloses two preparation methods for the crystal, which comprise the following steps: (1) dissolving a mixture of the compound (1) and triphenylphosphine oxide in a soluble solvent, adding water, and stirring to separate out the crystal of the compound (1); and (2) dissolving a mixture of the compound (1) and triphenylphosphine oxide in methanol, and stirring to separate out the crystal of the compound (I), wherein the volume/mass ratio of the methanol to the mixture is 0.5 to 2.0ml/g. The crystal has the advantages of easy storage, easy operation, good stability and high purity; and the preparation methods have the advantages of simpleness, reliability, cost conservation, simple separation, and suitability for industrial production.