- PROCESS FOR THE DEPROTECTION OF A CARBAPENEM BY HETEROGENEOUS CATALYTIC HYDROGENATION WITH HYDROGEN IN THE PRESENCE OF AN ORGANIC AMINE
-
201600080 17 Process for preparing a carbapenem Abstract Process for preparing a carbapenem or precursors thereof (I) by cleaving one or more protecting groups of a substance (II) 5 comprising the steps of: a) hydrogenating with hydrogen a reaction mixture (1) comprising the substance (II), at least 10 one organic solvent and at least one aromatic amine in the presence of a heterogeneous hydrogenation catalyst to form a product mixture (1), b) removing the heterogeneous catalyst from the product mixture (1) to form a product mixture (2), c) adding water to the product mixture (2), wherein the ratio by weight of water added to the 15 product mixture (2) is from 0.1 to 10, d) thermal treatment of the product mixture (2) to form a product mixture (3) comprising substance (I).
- -
-
Page/Page column 9-12
(2018/03/28)
-
- Method for preparing medicine and medicine intermediate by continuous solid-liquid-gas three-phase reaction
-
The invention provides a method for preparing meropenem or a 10,11-dihydro-5H-dibenzo[b, f] azepine by a continuous solid-liquid-gas three-phase reaction. A reactant in which acatalyst is dissolved ispumped into a microchannel reactor by using a diaphragm pump, and the hydrogen is bubbled into the reactor by using the pressure of a steel cylinder. The method uses the microchannel reactor to realize the continuous production of the meropenem or the 10,11-dihydro-5H-dibenzo[b, f] azepine. The technical effects of short reaction time, thorough reaction and high product yield are achieved.
- -
-
Paragraph 0035; 0036; 0037; 0041; 0049; 0050; 0053; 0054
(2018/07/30)
-
- Method for synthesizing meropenem trihydrate
-
The invention relates to a method for synthesizing meropenem trihydrate and belongs to the technical field of synthesis of carbapenem antibiotics. The method for synthesizing meropenem trihydrate provided by the invention comprises the following steps: using protected meropenem (I) as a raw material, using a single solvent water as a reaction solvent, performing deprotection reaction with a non-hydrogen reducing agent in the presence of an alkali and a catalyst, and obtaining a target product meropenem trihydrate (II). The method provided by the invention is low in cost, not only solves the problem of dissolution of the catalyst by the reaction solvent, but also has advantages of less equipment investment, simple operation, mild reaction conditions, good selectivity, stable process, high yield and the like, and is suitable for industrial production.
- -
-
Paragraph 0028; 0029
(2017/07/19)
-
- A kind of preparation method of meluopeinan
-
The invention relates to a method for preparing meropenem. The method provided by the invention comprises the following steps of: respectively adding (1R,5R,6S)-6-[(1R)-1-hydroxy]-1-methyl-2-diphenylphosphoacyloxy-carbapenicill-2-ene-3-p-nitryl phenyl carboxylate, (2R,4S)-4-sulfydryl-2-dimethylaminoformoxyl-1-p-nitryl phenyl carbonyl pyrrolidine and alkaline quaternary ammonium salt into a reaction bottle, and agitating for reaction; tracking by utilizing TLC (Thin-Layer Chromatography) and adding 5 wt% Pd (Palladium)/C (Carbon) catalyst after the reaction is finished; importing hydrogen gas for reduction, and tracking by utilizing the TLC; after the reaction is finished, extracting by utilizing toluene to separate out an organic layer; then drying and concentrating; and crystallizing by utilizing isopropanol to obtain a solid product. Compared with the prior art, the method provided by the invention has the advantages as follows: a quaternary ammonium alkali catalyst and a homogeneous catalysis one-pot method reaction technology are used in the reaction process, the technological operation is simplified and no pollution is generated to the environment.
- -
-
Paragraph 0021;0022
(2017/02/24)
-
- A raw meluopeinan, method for preparing the same and pharmaceutical composition containing the same
-
The invention discloses a meropenem raw medicine which is characterized in that the content of meropenem in the raw medicine is 98.0-101.0% by weight based on anhydride; the content of the impurity A and impurity B in the related substances of the raw medicine is not greater than 0.25% respectively; the content of any unknown single impurity is not greater than 0.05%; the total content of other impurities except the A and B is not greater than 0.25%; the acetone residue is not greater than 300ppm. The invention also discloses a meropenem pharmaceutical composition for injection, and the pharmaceutical composition takes the meropenem raw medicine provided by the invention as an active ingredient and has excellent stability. The meropenem raw medicine provided by the invention has the advantages of high purity, clear impurity condition, low solvent residue, good solubility and good long-term storage stability, and can guarantee the effectiveness and safety of the medicine.
- -
-
Paragraph 0154-0157
(2016/10/08)
-
- PROCESS FOR PREPARING A CARBAPENEM ANTIBIOTIC
-
The present invention provides a process for the preparation of a carbapenem, said process comprising the step of treating a solution of a protected carbapenemwith hydrogen gas in the presence of a heterogeneous catalystto form the carbapenem, wherein the heterogeneous catalyst comprises at least two platinum group metals.
- -
-
Page/Page column 13
(2016/01/16)
-
- PROCESS FOR THE PREPARATION OF CARBAPENEM ANTIBIOTIC
-
The present invention provides an improved process for the preparation Ertapenem monosodium of formula (I) having purity greater than 98.5% and having pharmaceutically acceptable level of palladium and residual solvent. (I)
- -
-
Paragraph 0071; 0072
(2015/02/19)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF CARBAPENEM ANTIBIOTIC
-
The present invention provides an improved process for the preparation Ertapenem monosodium of formula (I) having purity greater than 98.5% and having pharmaceutically acceptable level of palladium and residual solvent. (I)
- -
-
Page/Page column 19
(2013/10/22)
-
- Synthesis, pH-dependent, and plasma stability of meropenem prodrugs for potential use against drug-resistant tuberculosis
-
Meropenem, a broad-spectrum parenteral β-lactam antibiotic, in combination with clavulanate has recently shown efficacy in patients with extensively drug-resistant tuberculosis. As a result of meropenem's short half-life and lack of oral bioavailability, the development of an oral therapy is warranted for TB treatment in underserved countries where chronic parenteral therapy is impractical. To improve the oral absorption of meropenem, several alkyloxycarbonyloxyalkyl ester prodrugs with increased lipophilicity were synthesized and their stability in physiological aqueous solutions and guinea pig as well as human plasma was evaluated. The stability of prodrugs in aqueous solution at pH 6.0 and 7.4 was significantly dependent on the ester promoiety with the major degradation product identified as the parent compound meropenem. However, in simulated gastrointestinal fluid (pH 1.2) the major degradation product identified was ring-opened meropenem with the promoiety still intact, suggesting the gastrointestinal environment may reduce the absorption of meropenem prodrugs in vivo unless administered as an enteric-coated formulation. Additionally, the stability of the most aqueous stable prodrugs in guinea pig or human plasma was short, implying a rapid release of parent meropenem.
- Teitelbaum, Aaron M.,Meissner, Anja,Harding, Ryan A.,Wong, Christopher A.,Aldrich, Courtney C.,Remmel, Rory P.
-
p. 5605 - 5617
(2013/09/02)
-
- METHOD FOR PREPARING MEROPENEM USING ZINC POWDER
-
The present invention relates to an improved method for synthesizing meropenem trihydrate [(1R,5S,6S)-2-[((2′S,4′S)-2′-dimethylaminocarbozyl)pyrrolidin-4′-ylthio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid, trihydrate], which is a novel carbapenem antibiotic.
- -
-
Page/Page column 5
(2012/03/27)
-
- IMPROVED METHOD FOR PREPARING MEROPENEM USING ZINC POWDER
-
The present invention relates to an improved method for synthesizing meropenem trihydrate [(1R,5S,6S)-2-[((2'S,4'S)-2'-dimethylaminocarbozyl)pyrrolidin-4'-ylthio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid, trihydrate], which is a novel carbapenem antibiotic.
- -
-
Page/Page column 6
(2012/02/04)
-
- Improved process for the preparation of carbapenem using carbapenem intermediates and recovery of carbapenem
-
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.
- -
-
Page/Page column 12-13
(2011/12/03)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF MEROPENEM
-
The present invention provides an improved process for the preparation of methyl carbapenem derivative of formula (I) or its pharmaceutically acceptable salts or hydrates thereof in a pure form.
- -
-
Page/Page column 12-13
(2011/12/02)
-
- Preparation of Carbapenem Intermediate and Their Use
-
The present invention relates to preparing carbapenem intermediates that are useful to produce Ertapenem, Meropenem and Doripenem.
- -
-
Page/Page column 7
(2011/12/12)
-
- PROCESS FOR THE PREPARATION OF CARBAPENEM COMPOUNDS
-
The present invention relates to a process for the preparation of carbapenem compound of Formula (I), wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is C1-3 alkyl, and A is selected from a group consisting of a) Formula (II), b) Formula (III), c) Formula (IV), d) Formula (V), e) Formula (VI), f) Formula (VII), wherein P2 is hydrogen or an amino protecting group, R2 and R3 may be same or different and are hydrogen, C1-5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl, and X1 is O or S, or its stereoisomers, or salts thereof.
- -
-
-
- PROCESS FOR SYNTHESIZING CARBAPENEM USING RANEY NICKEL
-
Convenient method for obtaining carbapenem by hydrogenation with Raney Nickel, as an alternative to the known catalytic hydrogenation conducted under hydrogen overpressure in the presence of Palladium, starting from corresponding protected intermediates such as p-nitrobenzylesters and with optional suitable protections of any primary and secondary amino functions structurally present.
- -
-
Page/Page column 3
(2010/02/16)
-
- PROCESS FOR THE PREPARATION OF CARBAPENEM COMPOUNDS
-
The present invention relates to a process for the preparation of carbapenem compound of Formula (I), wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is C1-3 alkyl, and A is selected from a group consisting of a) Formula (II), b) Formula (III), c) Formula (IV), d) Formula (V), e) Formula (VI), f) Formula (VII), wherein P2 is hydrogen or an amino protecting group, R2 and R3 may be same or different and are hydrogen, C1-5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl, and X1 is O or S, or its stereoisomers, or salts thereof.
- -
-
Page/Page column 24
(2010/04/03)
-
- Process for The Preparation of Beta-Lactam Antibiotic
-
The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
- -
-
Page/Page column 5-6
(2009/10/30)
-
- MEROPENEM INTERMEDIATE IN NOVEL CRYSTALLINE FORM AND A METHOD OF MANUFACTURE OF MEROPENEM
-
The present invention specially relates to the crystalline form of (4-Nitrobenzyl (4R,5S,6S)-(3-{(3S,5S)-5-[(dimethylamino)carbonyl]-1-[(4-nitrophenoxy)carbonxyl]pyrrolidin-3-yl}thio-6-[(1R)-1-hydorxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0].hept-2-ene-2-carboxylate) of compound Formula I as well as an improved process for preparation of meropenem trihydrate of compound Formula II wherein PNB represents a P-nitro benzyl group and PNZ represents a P-nitrobenzyloxycarbonyl group.
- -
-
Page/Page column 5
(2009/12/23)
-
- IMPROVED PROCESS FOR PRODUCING CARBAPENEM COMPOUND
-
The present invention has its object to provide an easy process for producing (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylaminocarbonyl)-3-pyrrolid inyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicy clo[3.2.0]hept-2-ene-2-carboxylic acid, excellent in antimicrobial activity. The present invention relates to a process for continuously producing (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylaminocarbonyl)-3-pyrrolid inyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicy clo[3.2.0]hept-2-ene-2-carboxylic acid without isolating/purifying the reaction intermediate.
- -
-
Page/Page column 11
(2009/01/24)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF BETA-LACTAM ANTIBIOTIC
-
The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
- -
-
Page/Page column 14
(2008/06/13)
-
- A PROCESS FOR THE PREPARATION OF CARBAPENEM COMPOUNDS
-
The present invention relates to an improved process for the preparation of carbapenem compounds.
- -
-
Page/Page column 12
(2008/06/13)
-
- A PROCESS FOR THE PREPARATION OF THE INTERMEDIATE OF Β-METHYL CARBAPENEM
-
A process of preparation of the intermediate of β-methyl carbapenem is disclosed, in which 4-acetylazacyclobutanone as the raw material is firstly reacted with α-bromopropionamide having a big inductive group. Since this reaction is highly stereoselectivity, most of the product is the required parent nucleus of β-methyl carbapenem, a product of β-configuration. Compared with the prior art, the process of the present invention is highly-yielding, cost-effective and can be used for large scale production.
- -
-
Page/Page column 18
(2010/11/28)
-
- A PROCESS FOR THE PREPARATION OF MEROPENEM
-
The invention relates to a process for the preparation of meropenem, a β-methylcarbopenem. The said process comprises the following steps: preparing the compound of Formula (XI) from the compound of Formula (IV) through three steps "one-pot process"; then condensing the compound of Formula (XI) with the compound of Formula (XX) to form the compound of Formula (XXIV); finally preparing meropenam of Formula (I) from the compound of Formula (XXIV) by deprotection reaction by means of catalyst. The process of the invention is easily to carry out, the product is isolated in high content and yield, and the cost is reduced, thereby overcoming the shortage of the prior art.
- -
-
Page/Page column 14; 15
(2010/11/28)
-
- PROCESSES FOR THE PREPARATION OF CARBAPENEMS
-
The invention relates to processes for the preparation of carbapenems. More particularly, it relates to a process for the preparation of meropenem.
- -
-
Page/Page column 5-6
(2010/11/28)
-
- Carbapenems, their preparation and use the synthesis of carbapenems
-
Pyrrolidine compound (V), in free or salt form, is new. Pyrrolidine compound of formula (V), in free or salt form, is new. Independent claims aren also included for: (1) the preparation of (V); (2) the preparation of 3-[(3S,5S)-5-carbamido-3-pyrrolidinyl]-thio substituted carbapenem compound of formula (II) comprising reaction of (V) with an amine compound of formula (NH(R1)(R2)) to give a pyrrolidine compound of formula (III); and elimination of p-nitrobenzyl- and/or p-nitrobenzylcarbonyl-protection groups from (III); and (3) preparation of a pharmaceutical composition of (II) comprising mixing (II) with solvents or auxiliary materials. Either R1, R2alkyl, H, aryl or heterocyclyl; or NR1R25-8 membered optionally saturated heterocyclic group (optionally substituted). [Image] [Image].
- -
-
Page/Page column 9
(2008/06/13)
-
- A PROCESS FOR THE PREPARATION OF MEROPENEM
-
The present invention provides a one-pot process for the preparation of meropenem. The present invention further provides a process for the preparation of meropenem trihydrate.
- -
-
Page/Page column 10-11
(2008/06/13)
-
- MEROPENEM INTERMEDIATE IN CRYSTALLINE FORM
-
The present invention relates to the compound (4R, 5S, 6S)-(p-nitrobenzyl) 3-[[(3S, 5S)-1(-p-nitrobenzyloxycarbonyl)-5-(dimethylaminocarbonyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2carboxylate in crystalline form, as well as a process for the production of this crystalline compound in alkyl alkanoates, and its usage in a process for producing meropenem. Formula (I).
- -
-
Page/Page column 7-8
(2008/06/13)
-
