- Synthesizing method of ofloxacin and levofloxacin
-
The invention relates to a novel method for preparing ofloxacin and levofloxacin. The method includes: using ofloxacin carboxylic acid (ester) or levofloxacin carboxylic acid (ester) as the raw material, allowing the ofloxacin carboxylic acid (ester) or levofloxacin carboxylic acid (ester) to have reaction with borate to generate intermediate 1A or intermediate 1, allowing the intermediate 1A or intermediate 1 to have reaction with N- methyl piperazine to generated intermediate 2A or intermediate 2, hydrolyzing the intermediate 2A or intermediate 2 under an acid condition to obtain levofloxacin/ofloxacin salt, and freeing and extracting the levofloxacin/ofloxacin salt under a corresponding alkaline condition to obtain levofloxacin/ofloxacin or hydrate thereof. The method has the advantagesthat the initial materials and reagents used by the method are easy to obtain, the method is simple to operate, mild in reaction conditions, high in yield, low in cost and suitable for industrial production, and the purity of the levofloxacin/ofloxacin or hydrate thereof prepared by the method reaches up to 99.9%.
- -
-
-
- Nano-Fe3 O4@ZrO2-SO3 H as highly efficient recyclable catalyst for the green synthesis of fluoroquinolones
-
Nano-Fe3 O4 @ZrO2-SO3 H (n-FZSA), was utilized as a magnetic catalyst for the synthesis of various fluoroquinolone compounds. These compounds were prepared by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b] pyridine in water. The results showed that n-FZSA exhibited high catalytic activity towards the synthesis of fluoroquinolone derivatives, giving the desired products in high yields. Furthermore, the catalyst was recyclable and could be used at least seven times without any discernible loss in its catalytic activity. Overall, this new catalytic method for the synthesis of fluoroquinolone derivatives provides rapid access to the desired compounds in refluxing water following a simple work-up procedure, and avoids the use of organic solvents.
- Nakhaei, Ahmad,Ramezani, Shirin,Shams-Najafi, Sayyed Jalal,Farsinejad, Sadaf
-
p. 739 - 746
(2018/09/26)
-
- Levofloxacin and ofloxacin preparation method
-
The invention discloses a preparing method for levofloxacin and ofloxacin. According to the preparing method, (S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyridino-[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid ethyl ester (or9,10- difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyridino-[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid ethyl ester) is taken as a raw material and subjected to a shrinkage piperazine reaction with N-methyl-piperazine or water or an organic solvent to obtain levofloxacin ethyl ester or a mixture of levofloxacin and levofloxacin ethyl ester (or levofloxacin ethyl ester or levofloxacin and levofloxacin ethyl ester); levofloxacin ethyl ester or the mixture of levofloxacin and levofloxacin ethyl ester is then hydrolyzed in an organic solvent 2 or water or a mixed solvent of the organic solvent 2 and water under the acid or alkaline condition to obtain levofloxacin (or ofloxacin). According to the preparing method, operation is easy and fast, the reaction cost is lowered, the production cycle is short, and pollution is greatly reduced. Furthermore, the yield and purity of obtained levofloxacin or ofloxacin are high.
- -
-
Paragraph 0039-0042
(2017/09/01)
-
- Ofloxacin preparation method (by machine translation)
-
The invention provides a preparation method of ofloxacin. The preparation method comprises the following steps of: reacting (N,N)-dimethylamino ethyl acrylate with aminopropanols in methylbenzene; directly adding lewis base serving as a catalyst and trimethylchlorosilane to protect hydroxyl and amido; after reaction is completely finished, dropwise adding (2,3,4,5)-tetrafluorobenzoyl chloride; preserving heat; performing acid washing; removing protecting groups; concentrating an organic layer to obtain an oil layer; adding a proper amount of dimethyl formamide (DMF); diluting and dropwise adding backflow DMF having anhydrous potassium fluoride; recovering DMF and adding water to centrifuge; adding acid water into a solid to hydrolyze to obtain difluorocarboxylic acid; and completely reacting difluorocarboxylic acid and N-methyl piperazine in dimethylsulfoxide (DMSO) by using triethylamine as an acid-binding agent at 90-100 DEG C to obtain ofloxacin. According to the process, hydroxyl and amido are protected by using trimethylchlorosilane, so that the utilization degree of (2,3,4,5)-tetrafluorobenzoyl chloride is effectively increased, and the generation of impurities is reduced to ensure that the reaction yield of intermediate difluorocarboxylic acid is increased by 10 percent.
- -
-
-
- LEVO-ofloxacin and oxfloxacin synthetic method
-
The invention provides a levofloxacin and ofloxacin synthesis method. S-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-delta]-[1,4]-benzoxazinyl-6-carboxylate or 9,10-difluoro-2,3-dihydro-3- methyl-7-oxo-7H-pyrido[1,2,3-delta]-[1,4]-benzoxazinyl-6?-carboxylate is adopted as a raw material, two steps of hydrolysis and N-methylpiperazine replacement are improved, and one-pot process is carried out to synthesize. The method is a simple, economical and efficient one-step synthesis method Specific impurities generated in relevant operations are separated, identified and prepared. The method has the advantages of high raw material utilization rate, high yield and purity, original step simplification, reaction period shortening and convenience for the industrial production. The invention also provides a detection method of the relevant purities to discriminate products obtained through the synthesis method from products obtained through other synthesis methods.
- -
-
Paragraph 0062-0063
(2017/02/24)
-
- Conventional and microwave-assisted synthesis of quinolone carboxylic acid derivatives
-
Various antibacterial fluoroquinolone compounds are synthesized by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with a variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b]pyridine using microwave under different reaction conditions. Solvent free high yield microwave synthesis of antibacterial fluoroquinolone compounds is convenient, rapid and environmentally friendly method.
- Mirzaie,Lari,Vahedi,Hakimi
-
p. 2865 - 2869
(2017/03/22)
-
- PROCESS FOR THE PREPARATION OF BENZOXAZINE DERIVATIVES AND INTERMEDIATES THEREFOR
-
A processes which is industrially advantageous in producing antibacterial agents. An industrially advantageous process for producing an intermediate useful in producing antibactrial agents is provided by producing compound (VI-a) in accordance with the following reaction schema. A process for producing the compound represented by the above formulae and production intermediates thereof.
- -
-
-
- An efficient synthesis of ofloxacin and levofloxacin from 3,4- difluoroaniline
-
The functionalization at either C-2 or C-3 of N-(tert-butoxycarbonyl)- 3,4-difluoroaniline based on its ortho-deprotonation under different experimental conditions is described. This kind of products can be readily applied to the synthesis of ofloxacin, levofloxacin and related compounds.
- Adrio, Javier,Carretero, Juan C.,Garcia Ruano, Jose L.,Pallares, Antonio,Vicioso, Mercedes
-
p. 1563 - 1572
(2007/10/03)
-
- Regioselective nucleophilic substitution of halogen derivatives of 1-substituted 4-oxo-1,4-dihydroquinoline-3-carboxylic acids
-
The rate of the nucleophilic displacement of the fluoro atom of 7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate could be enhanced either by the introduction of further fluoro atom(s) into position(s) 6 and/or 8, or by the formation of a boron chelate (e.g. 3). The regioselectivity of the nucleophilic substitution of the chloro atom in 1-substituted 6-fluoro-7-chloro-4-oxo-1,4dihydroquinoline-3-carboxylic acids could also be enhanced by the formation of a boron chelate (e.g. 7).
- Hermecz, Istvan,Vasvari-Debreczy, Lelle,Podanyi, Benjamin,Kereszturi, Geza,Balogh, Maria,Horvath, Agnes,Varkonyi, Peter
-
p. 1111 - 1116
(2007/10/03)
-
- Process for making antimicrobial compounds
-
The present invention provides a process for making a compound having a structure according to Formula (I) STR1 wherein A1, A2 and A3 are independently carbon or nitrogen and R1, R3, R4 and R6 are known quinolone substituents; and wherein one of R1, R3 or R6 may be a lactam-containing moiety; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof; the process comprising reacting one or more organosilicon compounds with a compound having a structure according to Formula (II) STR2 wherein A1, A2 and A3, R1, R3, R4 and R6 as described above; wherein one of R1, R3 or R6 may be a lactam-containing moiety; and X is a leaving group; or a protected form, salt, biohydrolyzable ester, or solvate thereof. The compounds prepared according to the processes of the invention are themselves useful as antimicrobials, or they may be used as intermediates for making other quinolone-containing antimicrobials.
- -
-
-
- Process to obtain benzoxazines to be used for the synthesis of ofloxazine, levofloxazine and derivatives
-
A process to obtain benzoxazines useful for the synthesis of Ofloxazine, Levofloxazine and derivatives. The benzoxacines (I) where Xb is an halogen and R1 is H, alkyl or alkenyl of up to 6 atoms of C or aryl, can be obtained by means of cycling a compound of formula (II) through the reaction with triphenylphosphine and ethyl azodicarboxilate. The compounds of formula (II) can be obtained through the reaction of a compound (III) with an adequate epoxide. Through the use of the adequate chiral epoxide it is possible to obtain the enantiomerically desired intermediate and, therefore and selectively, it is possible to obtain the desired final product with the adequate enantiomeric form without the need to carry out a resolution stage. The Compounds (I) are useful and key intermediates for the synthesis of the antimicrobials Oflixazine and Levofloxazine. STR1
- -
-
-
- Synthesis and antipseudomonal activities of some ofloxacin esters as prodrugs
-
Three new ofloxacin esters have been synthesized as prodrug by the reaction of ofloxacin (CAS 82419-36-1) with chloromethylacetate, 1-chloroethylacetate and 1-chloroethyl-ethylcarbonate in acetonitrile. The structures of the compounds have been elucidated by UV, 1R, 1H-NMR, Mass spectra and elementary analysis. In vitro activities of these compounds against clinical isolates of various Pseudomonas aeruginosa species have been determined by microtiter tube dilution method, and octanol/water partition coefficients and pH dependent hydrolysis rates have been investigated in comparison with ofloxacin.
- Ertan,Palaska,Ertan,Yulug
-
-
- Process for preparing piperazinyl quinolone derivatives
-
A novel process for preparing piperazinyl quinolone derivatives of the formula (I) is disclosed. The process comprises reacting dihaloquinolones with piperazine derivatives and tetraalkyl ammonium halides in the presence of a polar solvent such as acetonitrile, dimethylformamide, pyridine, sulfolane and dimethyl sulfoxide. STR1
- -
-
-
- Synthesis and antibacterial activities of substituted 7-oxo-2,3-dihydro-7h-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acids
-
As part of a search for new synthetic antibacterial agents to combat systemic infection, various analogues of 7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acids were synthesized. Among the compounds newly synthesized, 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[ 1,2,3-de][1,4]benzoxazine-6-carboxylic acid (DL-8280) showed potent antibacterial activity against Gram-positive and -negative pathogens, including Psedomonas aeruginosa, and its metabolic disposition was shown in separate experimentals to be favorable.
- Hayakawa,Hiramitsu,Tanaka
-
p. 4907 - 4913
(2007/10/02)
-
- Benzoxazine derivatives
-
Pyrido[1,2,3-de][1,4]benzoxazine derivatives are described having the formula (I) STR1 wherein X is a halogen atom, R is a hydrogen atom or an alkyl group of 1 to 6 carbon atoms and Z represents mono-substituted, di-substituted or cyclic-substituted amino group which may contain a hetero atom and may have a substituent such as hydroxyl, alkyl having 1 to 6 carbon atoms, amino, hydroxyalkyl having 1 to 6 carbon atoms or mono- or di-alkylamino having 1 to 6 carbon atoms in each alkyl moiety and the pharmaceutically acceptable salt thereof, having antibacterial activity.
- -
-
-