- A high-throughput impurity-free process for gatifloxacin
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An improved process to obtain gatifloxacin (1) through use of boron chelate intermediates has been developed. The methodology involves an initial activation step which accelerates the formation of the first chelate under low-temperature conditions and prevents demethylation of the starting material. To increase the overall yield and to avoid the isolation and manipulation of the resulting intermediates, the process has been designed to be carried out in one pot. As a result, we present here an easy, scaleable and substantially impurity-free process to obtain gatifloxacin (1) in high yield.
- Villasante, F. Javier,Gude, Lourdes,Fernandez, Sara P.,Alonso, Olga,Garcia, Elena,Cosme, Antonio
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Read Online
- Gatifloxacin and synthesis method thereof
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The invention relates to a gatifloxacin and a synthesis method thereof. The synthesis method comprises the following steps: uniformly mixing N,N-dimethylaminoethyl acrylate, 2,4,5-trifluoro-3-methoxybenzoylchloride, ethyl acetate and triethylamine, and carrying out a complete reaction so as to obtain a first intermediate; uniformly mixing the first intermediate with acetic acid and cyclopropylamine, and carrying out a complete reaction to obtain a second intermediate; uniformly mixing the second intermediate with a strong base, and carrying out a complete reaction to obtain gatifloxacin cyclization ester; carrying out an ester exchange reaction on the gatifloxacin cycliztion ester to so as to obtain a third intermediate; uniformly mixing the third intermediate with 2-methylpiperazine, carrying out a complete reaction, and hydrolyzing and acidifying the obtained reaction product to obtain the gatifloxacin, wherein the strong base is selected from at least one of sodium hydroxide and potassium hydroxide. The synthesis method of gatifloxacin adopts the sodium hydroxide and potassium hydroxide to carry out the cyclization reaction, so that the cyclization reaction time is greatly shortened, and the time cost for synthesizing gatifloxacin is reduced.
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Paragraph 0061; 0063-0064; 0065; 0067-0068; 0069; 0071-0072
(2020/03/23)
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- STREAMLINED SYNTHESES OF FLUOROQUINOLONES
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Methods of synthesizing fluoroquinolones such as ciprofloxacin are provided. The methods utilize affordable materials, reduce the number of synthesis steps and provide high yields.
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- METHOD FOR PRODUCING QUINOLONE CARBOXYLIC ACID DERIVATIVE
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The present invention relates to a method for producing a quinolone compound having high antibacterial activity and high safety, at high yield and in a simple manner. A quinolonecarboxylic acid derivative (1) of interest is produced through a one-pot manner by reacting a compound (2) with a salt of a cyclic amine (3) and with a boron derivative in a solvent in the presence of a base.
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Page/Page column 12
(2009/12/24)
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- PROCESS FOR THE PREPARATION OF GATIFLOXACIN AND REGENERATION OF DEGRADATION PRODUCTS
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The subject of the present invention are an improved synthesis process comprising a process for regeneration of a side product of gatifloxacin and an analysis method for process control in the synthesis of gatifloxacin (Formula I).
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Page/Page column title page; 4; 10-11
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF GATIFLOXACIN
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The present invention relates to a process for the preparation of Gatifloxacin by reacting ethvl 1-cyclopropyl-6,7-difluoro-8- methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylate with aqueous hydrofluoroboric acid followed by condensation with 2-methyl piperazine in polar organic solvent resulting in an intermediate Cyclopropyl-7-(3-methylpiperazin-1-yl)-6-fluoro-8-methoxy-4-oxo- 1,4-dihydro-3-quinoline carboxylic acid boron difluoride chelate which upon hydrolysis yields Gatifloxacin.
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Page/Page column 9-11
(2008/06/13)
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- PROCESS FOR PREPARING GATIFLOXACIN
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This invention relates to a simplified process for preparing gatifloxacin. In said process the compound (II) is used as the starting compund, which is then made to react with 2-methylpiperazine after being silyated and activated in the form of boron chelate.Finally, the boron chelate is eliminated by treatment with a C1-C4 alkyl chain alcohol. One characteristic of the process described is that all the reactions are carried out without isolating the intermediate compounds formed ("one pot" process).
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Page/Page column 7-9
(2010/02/11)
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- CRYSTALLINE FORM OF GATIFLOXACIN
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The present invention relates to a crystalline form of gatifoxacin (formula I) obtainable by process that comprises recrystallisation of the crude gatifloxacin in methanol and which is stable with a water content ranging between 2.5 and 4.5% by weight, to a process for preparing it and to the use thereof as an active substance in the preparation of pharmaceutical formulations.
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Page/Page column 7-8
(2010/02/11)
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- Antimicrobial drug reduced in effect on heart
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An antimicrobial drug containing a compound represented by the following formula (I): a salt of the compound, or a hydrate of the compound or the salt.
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Page/Page column 5
(2008/06/13)
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- SYNTHESIS OF GATIFLOXACIN
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Provided is a method for making (±)-1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolenecarboxylic acid, commonly known as gatifloxacin, in very high purity, in a suspension in a dipolar aprotic solvent.
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- PROCESS FOR PREPARING OMEGA-ANHYDROUS GATIFLOXACIN
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Novel process to manufacture omega form and form-II of anhydrous Gatifloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-l-piperazinyl)-3-guinodine carboxylic acid) having structural formula (I) is disclosed. The invention does not require high temperature or use of column chromatography for purification. Moreover the solvents being used in the process can be recovered and recycled. These factors make the process industrially efficient.
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- Novel crystalline forms of gatifloxacin
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Provided are novel crystalline forms of gatifloxacin denominated forms A, B, C, D, E1, F, G, H, I, and J, and methods for their preparation. Also provided are methods for making known crystalline forms of gatifloxacin, in particular forms omega and T2RP.
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Page/Page column 12
(2008/06/13)
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- Sulfate salt of quinolonecarboxylic acid derivatives and the use thereof
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To provide novel sulfate or its hydrate useful for efficiently recycling 1-cyclopropyl-7-(3-methyl-1- piperazinyl)-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3- quinolinecarboxylic acid, the sulfate of 1-cyclopropyl-7- (3-methyl-1-piperazinyl)-6-fluoro-8-methoxy-1,4-dihydro- 4-oxo-3-quinolinecarboxylic acid or its hydrate is provided and yet its industrially useful application is provided.
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- The Synthesis, Structure-Activity, and Structure-Side Effect Relationships of a Series of 8-Alkoxy- and 5-Amino-8-alkoxyquinolone Antibacterial Agents
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A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methoxy and 8-ethoxy)-quinoline-3-carboxylic acids and 1-cyclopropyl-5-amino-6-fluoro-8-alkoxyquinoline-3-carboxylic acids has been prepared and evaluated for antibacterial activity.In addition, they were also compared to quinolones with classic substitution at C8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxiciry assay.The series of 8-methoxyquinolones had antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria equivalent to that most active 8-substituted compounds (8-F and 8-Cl).There was also a concomitant reduction in several of the potential side effects (i.e., phototoxicity and clonogenicity) compared to the most active quinolones with classic substitution at C-8.The 8-ethoxy derivatives had an even better safety profile but were significantly less active (2-3 dilutions) in the antibacterial assay.
- Sanchez, Joseph P.,Gogliotti, Rocco D.,Domagala, John M.,Gracheck, Stephen J.,Huband, Michael D.,et al.
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p. 4478 - 4487
(2007/10/03)
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- (6,7)-substituted-8-alkoxy-1-cyclopropyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid-03,04) bis (acyloxy-0) borate and the salt thereof, and the preparing method of the same
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The invention relates to novel compounds of the formula: STR1 useful as an intermediate in the preparation of quinoline carboxylic acid medicaments.
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- 8-alkoxyquinolonecarboxylic acid and salts thereof
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Quinolonecarboxylic acid derivatives of the following formula: STR1 wherein R indicates a hydrogen atom or lower alkyl group, R1 indicates a lower alkyl group, R2 indicates a hydrogen atom, amino group or nitro group, X indicates a halogen atom, and Z indicates a halogen atom, piperazino group, N-methylpiperazino group, 3-methylpiperazino group, 3-hydroxypyrrolidino group, or pyrrolidino group of the following formula, STR2 (here, n is 0 or 1, R3 indicates a hydrogen atom or lower alkyl group, R4 indicates a hydrogen atom, lower alkyl group and R5 indicates a hydrogen atom, lower alkyl group, acyl group or alkoxycarbonyl group), the hydrates and pharmaceutically acceptable salts thereof are useful as antibacterial agents.
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