- Synthesis method of 2, 4, 5-trifluoro-3-methoxybenzoyl chloride
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The invention discloses a synthesis method of 2, 4, 5-trifluoro-3-methoxybenzoyl chloride. The method comprises the following steps of: (1) using a metal halide as a catalyst, putting N-methyltetrafluorophthalimide in an alkaline environment, and carrying out hydroxylation reaction to obtain a sodium salt of 4-hydroxy-3, 5, 6-trifluorophthalic acid; (2) adding acid into the reaction system, and carrying out decarboxylation reaction to obtain 2, 4, 5-trifluoro-3-hydroxybenzoic acid; (3) sequentially adding a methylation reagent and acid into the reaction system under an alkaline condition, andcarrying out methylation reaction and acidification reaction to obtain 2, 4, 5-trifluoro-3-methoxybenzoic acid; and (4) mixing the 2, 4, 5-trifluoro-3-methoxybenzoic acid with thionyl chloride, and carrying out acylation reaction so as to obtain the 2, 4, 5-trifluoro-3-methoxybenzoyl chloride. The synthesis method disclosed by the invention is short in route, small in alkali dosage and few in sidereaction, the total molar yield of the reaction reaches 82.5%, and the purity of the product reaches 99.6% or above.
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Paragraph 0053; 0063-0066; 0073; 0079-0080; 0083; 0089-0090
(2020/09/16)
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- One-pot process for preparing 2,trifluoro -3 - methoxybenzoic acid (by machine translation)
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The method comprises the following steps: obtaining -3 - hydroxyl salt 4 - and -3 trifluoroortho-phthalate; and the method comprises the following steps: taking a metal halide as a catalyst, putting N - methyltetrafluoro phthalimide into a basic environment, and obtaining the 5,6 -hydroxy salt 4 - and -3 trifluoroortho-benzoate through hydrolysis defluorination and hydroxylation reaction 5,6 . The raw material cost is low, the process route is short, 4 - hydroxyl salt -3 and 5,6 -trifluoroortho-phthalate are synthesized only by about 8 - 10 hours, the base is reduced by 50% or more, the side reaction is less or complete, 85%, and the product purity can reach above 99.8%. (by machine translation)
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- Preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride and intermediate thereof
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The invention discloses a preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride and intermediate thereof. The preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride comprises the following steps: by taking tetrafluorophthalic acid as a raw material, carrying out defluorination hydroxylation and acidification decarboxylation to obtain 2,4,5-trifluoro-3-hydroxybenzoic acid, thenreacting with dimethyl carbonate to obtain 2,4,5-trifluoro-3-methoxybenzoic acid, and finally carrying out acylating chlorination to obtain 2,4,5-trifluoro-3-methoxybenzoyl chloride. The preparation process is simple, the total reaction yield is high, the product quality is good, the process route is environment-friendly, and the method has a good industrial application prospect.
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Paragraph 0045; 0047; 0065-0094
(2020/07/02)
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- Synthesis method of gatifloxacin cyclic ester
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The invention belongs to a production process of a pharmaceutical intermediate, and particularly discloses a synthesis method of gatifloxacin cyclic ester. The synthesis method comprises the followingsteps: performing hydrolysis, decarboxylation and methylation on 3, 4, 5, 6-tetrafluoro-N-methylphthalimide serving as a starting material to obtain 2,4,5-trifluoro-3-methoxybenzoyl chloride, coupling the 2,4,5-trifluoro-3-methoxybenzoyl chloride with N,N-ethyl dimethylaminoacrylate, then replacing with cyclopropylamine, and finally performing cyclization to produce the gatifloxacin cyclic esterunder the action of DMF and potassium fluoride. The reaction route is short, the raw materials are wide in source; furthermore, the reaction conditions are mild and easy to operate and control, whichreduces the consumption of the raw materials, facilitates the post-treatment and reduces the cost; potassium fluoride used instead of potassium carbonate in the reaction can not only reduce productionof exhaust gas, but also make the used potassium fluoride used continuously through adjustment by potassium hydroxide, and the cost is further reduced.
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Paragraph 0031; 0039; 0042; 0045; 0048; 0051; 0054;0072-0075
(2019/11/04)
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- Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids
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Thirty-four newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids were synthesized from 1,2,3,4-tetrafluoro benzene and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase. Among the synthesized compounds, 7-(1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinolin-2(1H)-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylic acid (13n) was found to be the most active compound in vitro with MIC of 0.16 and 0.33 μM against MTB and MDR-TB, respectively. In the in vivo animal model 13n decreased the bacterial load in lung and spleen tissues with 2.54 and 2.92 - log10 protections, respectively, at the dose of 50 mg/kg body weight. Compound 13n also inhibited the supercoiling activity of mycobacterial DNA gyrase with IC50 of 30.0 μg/ml.
- Senthilkumar, Palaniappan,Dinakaran, Murugesan,Banerjee, Debjani,Devakaram, Ruth Vandana,Yogeeswari, Perumal,China, Arnab,Nagaraja, Valakunja,Sriram, Dharmarajan
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p. 2558 - 2569
(2008/09/21)
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- A prodrug approach toward the development of water soluble fluoroquinolones and structure-activity relationships of quinoline-3-carboxylic acids
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A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine g) at C-7 resulted in some of the most active analogues.
- Baker, William R.,Cai, Shaopei,Dimitroff, Martin,Fang, Liming,Huh, Kay K.,Ryckman, David R.,Shang, Xiao,Shawar, Ribhi M.,Therrien, Joseph H.
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p. 4693 - 4709
(2007/10/03)
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- Processes for producing tetrafluorophthalic anhydride and fluorobenzoic acids
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A process for producing tetrafluorophthalic anhydride, which comprises chlorinating tetrachlorophthalic anhydride to obtain 3,3,4,5,6,7-hexachloro-1-[3H]-isobenzofuranone, then fluorinating it to obtain 3,4,5,6-tetrafluorophthaloyldifluoride and/or 3,3,4,5,6,7-hexafluoro-1-[3H]-isobenzofuranone, and further reacting the tetrafluorophthalolyldifluoride and/or the hexafluoro-1-[3H]-isobenzofuranone with an inorganic base or an organic acid to obtain tetrafluorophthalic anhydride.
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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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- Quinoline-3-carboxylic acid derivatives
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Compounds of formula (I): STR1 (in which R1 is alkoxy, R is alkyl, haloalkyl, alkylamino, cycloalkyl or optionally substituted phenyl, X is chlorine or fluorine and Y is selected from certain specific heterocycles) have excellent antibacterial activity. They may be prepared by introducing the group represented by Y into the corresponding compound in which Y is replaced by a halogen atom.
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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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