- Design and synthesis of novel active phosphonate esters and their application in preparation of ceftriaxone
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For a series of active phosphonate esters, the anhydride abbreviated as ANPTA (6a) exhibits the highest reactivity in the preparation of ceftriaxone. The synthesis of ceftriaxone was optimized with the pilot-scale yield reaching 95.7%. The results were explained from the structural viewpoint and supported by analysis of the calculated Mulliken atomic charge distribution.
- Ren, Hui-Xue,Sun, You-Min,Wu, Dao-Ji,Ma, Yong-Shan,Ying, Han-Jie,Ma, Yan
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p. 155 - 159
(2014/07/07)
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- IMPROVED PROCESS FOR THE PREPARATION OF CEPHALOSPORIN ANTIBIOTICS
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Abstract The present invention more particularly relates to a process for the preparation of cephalosporin antibiotics of the Formula (I) wherein R1 represents hydrogen, trityl, alkyl like CH3, CRaRbCOORc where Ra and Rb independently represent hydrogen or methyl and Rc represents hydrogen or (C1-C6) alkyl; R2 is carboxylate ion or COORd, where Rd represents hydrogen, ester or a counter ion which forms a salt; R3 represents hydrogen, CH3, CH2OCH3, CH2OCOCH3, CH=CH2, Formula (II).
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Page/Page column 11-12
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF CEPHALOSPORIN ANTIBIOTIC
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A process for the preparation of cephalosporin antibiotic of the formula (I) wherein R1 represents hydrogen, trityl, etc,; R3 is carboxylate ion or COORd, where Rd represents hydrogen, ester or a counter ion which forms a salt; R4 represents H, OCH3, OCOCH3, =CH2, OCONH2, etc, which comprises: (i) condensing the activated derivative of the formula (III) where X represents halogen atom, with 7-amino cephalosporin derivative of the formula (XV) wherein R represents hydrogen, lower alkyl, etc, in the presence of a solvent at a temperature in the range of -50 °C to +50 °C to produce a compound of formula (XVI) ii) maintaining the pH in the range 5.0-10.0 using an inorganic base, iii) cyclizing the compound of formula (XVI) with thiourea to produce compound of formula (I).
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Page/Page column 10
(2010/02/11)
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- Method for manufacture of ceftriaxone sodium
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An improved process for preparation of ceftriaxone sodium of formula (II), is disclosed.
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Page/Page column 20-21
(2008/06/13)
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- Method for manufacture of ceftriaxone sodium
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An improved process for preparation of ceftriaxone sodium of formula (II), is disclosed.
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- IMPROVED PROCESS FOR THE MANUFACTURE OF CEFTRIAXONE SODIUM
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A process for the production of (6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-syn-methoxyimino)acetamido]-3-[[2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid (Ceftriaxone acid) in water is discussed. The synthesis is effected by condensing (7R)-7-Amino-3-deacetoxy-3-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]cephalosporanic acid (7-ACT) with 2-(2-chloroacetamido-4-thiazolyl)-2-syn-methoxyiminoacetyl chloride followed be deblocking amino function. Finally, (6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-syn-methoxyimino)acetamido]-3-[[2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid (Ceftriaxone acid) is converted into Ceftriaxone disodium hemiheptahydrate in aqueous acetone using sodium-2-ethylhexanoate as sodium source. Isolation steps at every stage are quite short. The purity of the final product is obtained in more than 99 % by HPLC profile.
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Page/Page column 8
(2010/02/14)
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- Process for preparing cephalosporins with salified intermediate
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Cephalosporins may be conveniently prepared by a process in which 7-ACA is silylated, acylated, desilylated and then salified to give an intermediate which is eventually cyclized with thiourea.
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Page/Page column 6
(2010/02/11)
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- A PROCESS FOR THE PREPARATION OF A CEPHALOSPORIN ANTIBIOTIC
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An improved process for the preparation of ceftriaxone sodium comprising the steps of : i) reacting the 3-cephem derivative of formula (II) with halo acid derivative of formula (III) wherein X represents halogen and Y represent halogen in the presence of silylating agent and methylene chloride at -25 to 10 °C, to produce (IV), ii) quenching the reaction by pouring the reaction mixture into water or in a aqueous solution of sodium carbonate, iii) preparing sodium salt solution of (IV) by adding sodium carbonate and separating the organic layer, iv) cyclizing the sodium salt of (IV) in the aqueous solution with thiourea at a temperature in the range of 0 to 30 °C, v) adjusting the pH to 1.5 to 2.5 to precipitate the ceftriaxone free acid, vi) converting the ceftriaxone free acid to sodium salt using sodium-2-ethyl hexanoate in water and vii) precipitating and isolating the ceftriaxone sodium.
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Page/Page column 6-8
(2010/02/10)
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- NOVEL INTERMEDIATES FOR SYNTHESIS OF CEPHALOSPORINS AND PROCESS FOR PREPARATION OF SUCH INTERMEDIATES
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A novel 4-halo-2-oxyimino-3-oxo butyric acid-N, N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics, wherein X is chlorine or bromine; R is hydrogen, C1-4 alkyl group, an easily removable hydroxyl protective group, -CH2COOR5, or -C(CH3)2COOR5, wherein R5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV1), wherein X, R and R5 are as defined above, with N, N-dimethylformiminium chloride chlorosulphate of formula (VII), in an organic solvent at a temperature ranging from -30 °C to -15 °C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.
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- Beta-lactam production
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The present invention provides processes for the production of a compound of formula I wherein X, R1 and R2 are substituents conventional in cephalosporin chemistry; especially a compound of formula I is ceftrixone, cefotaxime; e.g., in the form of a salt.
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- Tricyclic carbacephems
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The present invention is concerned with compounds of formula where A is a group of formula (b1) or (b2) where R3 is unsubstituted aryl or aryl substituted by one or two substituents defined herein, and R is as defined herein, together with the pharmaceutically compatible, readily hydrolyzable esters and salts of these compounds. These compounds have valuable antibacterial properties.
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- Dimethyl formiminium chloride chlorosulphate derivatives useful as intermediates for producing cephalosporins
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This invention relates to reactive derivatives of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid and 1H-tetrazol-1-acetic acid of the following general formula I, STR1 wherein R3 = STR2 as well as to use thereof in the manufacture of cephalosporin antibiotics such as cefotaxime, ceftriaxone and cefazolin.
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- Method for manufacture of cephalosporins and intermediates thereof
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This invention relates to reactive derivatives of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid and 1H-tetrazol-1-acetic acid of the following general formula I, whereinR3= as well as to use thereof in the manufacture of cephalosporin antibiotics such as cefotaxime, ceftriaxone and cefazolin.
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