WO2020065668A1 - Forme cristalline de l'ozénoxacine et procédés de préparation associés - Google Patents

Forme cristalline de l'ozénoxacine et procédés de préparation associés Download PDF

Info

Publication number
WO2020065668A1
WO2020065668A1 PCT/IN2019/050697 IN2019050697W WO2020065668A1 WO 2020065668 A1 WO2020065668 A1 WO 2020065668A1 IN 2019050697 W IN2019050697 W IN 2019050697W WO 2020065668 A1 WO2020065668 A1 WO 2020065668A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
methyl
crystalline form
oxo
Prior art date
Application number
PCT/IN2019/050697
Other languages
English (en)
Inventor
Nagaraju Chakilam
Ramprasad Achampeta Kodanda
Pradeep Rebelli
Tavitayya Kondaka
Original Assignee
Maithri Drugs Pvt Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Maithri Drugs Pvt Ltd filed Critical Maithri Drugs Pvt Ltd
Publication of WO2020065668A1 publication Critical patent/WO2020065668A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to a crystalline form of l-cyclopropyl-8-methyl-7-(5- methyl-6-(methylamino)pyridin-3-yl)-4-oxo- 1 ,4-dihydroquinoline-3-carboxylic acid compound of formula- 1, which is represented by the following structural formula:
  • the present invention also relates to process for the preparation crystalline form of the compound of formula- 1 and processes for the preparation of compound of formula- 1.
  • l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid is known as Ozenoxacin. It is a novel fluorine-free quinolone antibacterial agent, developed by Ferrer Internation SA under the brand name of XEPITMas 1 % topical cream for the treatment of impetigo due to Staphylococcus aureus or Strepto coccus pyogenes. The drug is approved in USA in December 2017 and September 2015 in Japan.
  • the patent US8507684B2 discloses various acid addition salts of l-cyclopropyl-8- methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid, such as citrate salt, hemifumarate salt, maleate salt, L-tartarate salt, mesylate salt, hydrochloride salt, potassium salt and sodium salt and their processes.
  • Polymorphism the occurrence of different crystal forms, is a property of some molecules and molecular complexes.
  • a single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis - "TGA”, or differential scanning calorimetry - “DSC”), X-ray diffraction pattern, infrared absorption fingerprint, and solid state NMR spectrum.
  • TGA thermogravimetric analysis -
  • DSC differential scanning calorimetry -
  • Discovering new salts and new polymorphic forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms.
  • New polymorphic forms and solvates of a pharmaceutically useful compound or salts thereof can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional salts and solid state forms of ozenoxacin.
  • the present invention provides a crystalline form of l-cyclopropyl-8-methyl-7-(5- methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula- 1 and processes for their preparation.
  • the first aspect of the present invention is to provide a crystalline form of 1- cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l,4-dihydroquinoline -3-carboxylic acid of formula- 1, herein after designated as crystalline form-M.
  • the second aspect of the present invention is to provide a process for the preparation of crystalline form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)- 4-oxo- 1 ,4-dihydro quinoline-3-carboxylic acid.
  • the third aspect of the present invention is to provide process for the preparation of 1 - cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l,4-dihydroquinoline -3-carboxylic acid compound of formula-l.
  • Figure 1 Illustrates the PXRD pattern of Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5- methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula-l obtained according to example- 16
  • Figure 2 Illustrates the PXRD pattern of Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5- methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula-l obtained according to example- 12.
  • Figure 3 Illustrates IR spectrum of Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5- methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula-l obtained according to example- 12.
  • Figure 4 Illustrates the DSC thermogram of Crystalline Form-M of l-cyclopropyl-8-methyl- 7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula-l obtained according to example- 12.
  • suitable solvent refers to “hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane, cycloheptane, methyl cyclohexane, m-, o-, or p-xylene and the like;“ether solvents” such as dimethoxymethane, tetrahydrofuran, l,3-dioxane, l,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, l,2-dimethoxy ethane and the like;“ester solvents” such as methyl acetate,
  • suitable base refers to inorganic or organic base.
  • Inorganic base refers to“alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate and the like; “alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate and the like;“alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like;“alkali metal alkoxides” such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium tert.butoxide, potassium tert.butoxide, lithium tert.butoxide and the like; alkali metal hydrides such as sodium hydride, potassium hydride, lithium hydride and the like; alkali metal amides such as sodium amide, potassium amide, lithium amide and the like; and organic bases like dimethylamine, diethylamine, diisopropyl amine, diiso
  • the term“acid” used in the present invention refers to inorganic acids selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid etc; organic acids such as acetic acid, maleic acid, malic acid, tartaric acid, oxalic acid, trifluoroacetic acid, methane sulfonic acid, p-toluene sulfonic acid etc.; Lewis acids and like.
  • the first aspect of the present invention provides Crystalline Form-M of l-cyclo propyl-8-methyl-7-(5-methyl- 6-(methylamino) pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3- carboxylic acid of formula- 1.
  • the crystalline form-M of the present invention is characterized by its powder X-Ray diffraction pattern having peaks at about 7.28, 9.33, 11.27, 13.97, 15.52, 16.8, 19.19, 22.59, 23.84, 24.94, 26 and 28.29 ⁇ 0.2° 2Q.
  • the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino) pyri din-3 -yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l is further characterized by its powder X-Ray diffraction pattern substantially in accordance with figure- 1.
  • the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino) pyri din-3 -yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l is further characterized by its IR spectrum substantially in accordance with figure-3.
  • Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino) pyri din-3 -yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l is further characterized by its DSC thermogram substantially in accordance with figure-4.
  • the second aspect of the present invention is to provide a process for the preparation of the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3- yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid of formula-l, comprising of:
  • step-a) adding a suitable acid to the solution of step-a) and stirring at suitable temperature, isolating the compound
  • step-b) adjusting the p H of the solution obtained in step-b) with a suitable base
  • step-c) filtering the solid obtained in step-c) provides the crystalline form-M of l-cyclopropyl-8- methyl-7-(5-methyl-6-(methylamino)pyri din-3 -yl)-4-oxo-l,4-dihydroquinoline-3-carboxy licacid compound of formula-l .
  • the suitable solvent is selected from polar protic, polar aprotic, alcohol, ether, ketone, water and mixture thereof.
  • suitable acid is citricacid, tataricacid, methane sulphonic acid, para toluenesulfonicacid, maleicacid, fumaricacid, camphorsulfonic acid, hydrobromicacid, aceticacid, trifluoroaceticacid;
  • suitable temperature is 0°C to l00°C, preferably 20-85°C;
  • the suitable base is potassium hydroxide, sodium hydroxide, lithium hydroxide, bariumhydroxide, aq. ammonia, triethylamine, diisopropylamine, diiso propyl ethylamine ; in Step-c) suitable p H range is 5.0 to 7.0;
  • the other preferred embodiment of the present invention is to provide a process for the preparation of the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methyl amino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l, comprising of:
  • step-c) a) stirring the compound of formula-l in isopropanol and water, b) adding methane sulphonic acid to the solution of step-a)and stirring at 40-45°C, c) adjusting the p H of the solution obtained in step-b) with aq. sodium hydroxide solution, d) filtering the solid obtained in step-c) provides the crystalline form-M of l-cyclopropyl-8- methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid compound of formula- 1.
  • the other embodiment of the present invention is to provide a process for the preparation of the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methyl amino) pyri din-3 -yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l, comprising of:
  • step-b) stirring the compound obtained in step-a) in base solution at suitable temperature, c) isolating the compound obtained in step-b), purifying in suitable solvent,
  • step-e) optionally purifying the compound obtained in step-e) in suitable solvent to provide the crystalline form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4- oxo-l, 4-dihydro quinoline-3 -carboxylic acid compound of formula-l .
  • the suitable solvent is selected from polar aprotic, alcohol, ether, ketone, water and mixture thereof.
  • suitable base solvent is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide in alcoholic solution, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide; preferebly: alcoholic base, potassium hydroxide in ethanol; suitable temperature is 0°C to lOO°C, preferably 20-85°C;
  • the suitable solvent is alcohol, ketone, ester;
  • suitable solvent is water, alcohol ketone and mixture thereof;
  • suitable base is selected from potassium hydroxide, sodium hydroxide;
  • suitable acid is selected from hydrochloric acid; citric acid, acetic acid; preferably hydrochloric acid; p H range is 11-12 & 4-6; step-f) suitable solvent is selected from alcohol, ester, ketone, DMF, acetonitrile, polar a
  • the other embodiment of the present invention is to provide a process for the preparation of the Crystalline Form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methyl amino) pyri din-3 -yl)-4-oxo-l, 4-dihydro quinoline-3-carboxylic acid of formula-l, comprising of:
  • step-b) stirring the compound obtained in step-a) in ethanolic KOH, stirring at 25-35°C, c) isolating the compound obtained in step-b) and purifying in ethanol,
  • step-d) adjusting the p of the solution obtained in step-d) with potassium hydroxide and hydrochloric acid at suitable temperature and isolating the compound
  • step-e fjpurifying the compound obtained in step-e) in water to provide the crystalline form-M of 1 - cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline -3 -carboxylic acid compound of formula- 1.
  • the third aspect of the present invention is to provide processes for the preparation of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l, 4-dihydro quinoline -3- carboxylic acid compound of formula- 1, comprising of ;
  • step-a) reacting the compound obtained in step-a) using a suitable reagent to get the compound of formula- 1,
  • step-b) suspending the compound obtained in step-b) in an organic solvent
  • step-e) stirring the compound obtained in step-c) in base solution at suitable temperature, e) isolating the compound obtained in step-d) purifying in suitable solvent and isolating, f) suspending the compound obtained in step-e) in suitable solvent,
  • step-g or b) optionally purifying the compound obtained in step-g or b) in suitable solvent to provide the crystalline form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)- 4-oxo- 1, 4-dihydro quinoline-3 -carboxylic acid compound of formula- 1.
  • step-a) catalyst is selected from tetrakis(triphenylphosphine)palladium(0), palladium (II) acetate, tris(dibenzylideneacetone)dipalladium(0), Pd(dppf)Cl 2.
  • Another aspect of the present invention is to provide process for the preparation of 1- cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l,4-dihydroquinoline -3- carboxylic acid compound of formula- 1, comprising of ;
  • step-a) reacting the compound obtained in step-a) with hydrochloric acid to get the compound of formula- 1,
  • step-e) stirring the compound obtained in step-c) in ethanolic KOH, at 25-35°C, e) isolating the compound obtained in step-d) and purifying in ethanol, isolating, f) suspending the compound obtained in step-e) in water,
  • step-f) adjusting the p H of the solution obtained in step-f) with potassium hydroxide, hydrochloric acid at suitable temperature and isolating the compound of ofrmula-l,
  • step-g) purifying the compound obtained in step-g) in water to provide the crystalline form-M of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-l,4-di hydro quinoline-3-carboxylic acid compound of formula-l .
  • the obtained compound is reduced with sodium borohydride in tetrahydrofuran to get N-(5-bromo-3-methyl-2-pyridinyl)-N- methylamine, in situ the obtained compound reacting with benzoyl chloride in presence of tri ethylamine to get N-(5-bromo-3-methylpyridin-2-yl)-N-methylbenzamide.
  • the obtained compound is reacted with triisopropyl borate in presence n-butyl lithium in tetrahydrofuran to get the 5-methyl-6(N-methylbenzamido)pyridin-3-ylboronic acid.
  • the obtained compound is reacted with dimethylformamide dimethylacetal (DMF-DMA) to obtain ethyl-2-(2,4-dichloro -3-methylbenzoyl)-3-(dimethylamino)acrylate.
  • the obtained compound is reacted with cyclo propylamine in toluene to get ethyl-3-(cyclopropyl)-2-(2,4-dichloro-3-methyl benzoyl) acrylate.
  • the obtained compound is cyclized with potassium carbonate in DMSO to get ethyl- 7-chloro-l-cyclopropyl-8-methyl-4-oxo-l,4-dihydroquinoline-3-carboxylate.
  • the particle size of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3- yl)-4-oxo-l, 4-dihydro quinoline-3 -carboxylic acid compound of formula- 1 produced by the present invention can be reduced by micronization or milling to get the desired particle size to achieve desired solubility profile.
  • Techniques that may be used for particle size reduction include, but not limited to ball, roller and hammer mills, and jet mills. Milling or micronization may be performed before drying, or after the completion of drying of the product.
  • Particle size of l-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4- oxo-l, 4-dihydroquinoline-3-carboxylicacid produced according to the present process is D90 ⁇ 100 microns, Preferably D90 ⁇ 50 microns, more preferably D90 ⁇ 20 microns.
  • the precipitated compound was filtered, washed with water (100 ml).
  • the wet compound was charged in RBF with n-heptane (400 ml), heated to 60-70°C and for 1 hr.
  • the reaction mixture was cooled to 0-10°C and stirred for 1 hr, the obtained solid was filtered and washed with n- heptane (100 ml) to get the title compound.
  • the reaction mixture was cooled to 25-35°C, charged with cyclo propylamine (30.6gm) stirred for 4 hr.
  • the precipitated compound was filtered, washed with toluene (100 ml).
  • the obtained compound was charged with water (500 ml), stirred for 2 hr.
  • the obtained solid was filtered and washed with water (100 ml), dried to get the title compound.
  • a round bottom flask was charged with compound of formula-6a (100 gr), DMSO (300 ml) and potassium carbonate (80 gr), heated to 95-105°C and stirred for 4 hr.
  • the reaction mixture was cooled to 25-30°C, diluted with hydrochloric acid (100 ml) and water (800 ml) stirred for 1.5 hr.
  • the precipitated solid was filtered and washed with water (100 ml).
  • the wet compound was stirred in isopropanol (200 ml) for 1 hr, filtered the obtained solid and washed with isopropanol (100 ml) dried to get the title compound.
  • the obtained compound was charged in RBF with ethyl acetate (250 ml), heated to 75-85°C stirred for 2 hr and cooled the solution to 25-35° stirred for 2 hr.
  • the obtained solid was filtered and washed with ethyl acetate (50 ml). The same purification process was repeated to get pure title compound.
  • the obtained compound was charged in RBF with dil. hydrochloric acid (750 ml), washed with dichloromethane (3x150 ml) and separated both layers.
  • the aqueous layer was taken, heated to 90-l00°C stirred for 6 hr.
  • the reaction mixture was cooled to 25-35°C, washed with dichloromethane (5x150 ml) and separated the both layers.
  • the aqueous layer was diluted with ethanol (375 ml) and the solution p was adjusted to 11.3 with sodium hydroxide solution (300 gr in 600 ml), stirred for 6 hr at 25-35°C.
  • the reaction mass p H was adjusted to 5.2 with dil.HCl and stirred for 45 min.
  • the obtained solid was filtered and washed with water (100 ml).
  • the obtained wet compound was again slurred in water (750 ml) and stirred for 45 min, filtered the obtained solid and dried to get the
  • the obtained compound was charged in RBF with water (550 ml), methanesufonicacid (116.3 gr) and washed with dichloromethane (3x150 ml), separated the both layers.
  • the aqueous layer was heated to 90-100°C stirred for 6 hr.
  • the reaction mixture was cooled to 25-35°C, washed with dichloromethane (5x150 ml) and separated the both layers.
  • the aqueous layer was diluted with ethanol (375 ml) and the solution p was adjusted to 11.8 with sodium hydroxide solution (300 gr in 600 ml), stirred for 6 hr at 25-35°C.
  • the reaction mass p H was adjusted to 5.3 with dil. hydrochloric acid and stirred for 45 min.
  • the obtained solid was filtered and washed with water (100 ml).
  • the obtained compound was charged with water (750 ml) and stirred for 45 min, filtered the obtained solid and dried to get the
  • the obtained compound was charged in RBF with water (900 ml) adjusted the p H to 11.6 with potassium hydroxide solution (10 ml) and stirred for 2 hr.
  • the reaction mass was filtered through hyflow bed to remove solid particles and washed with water (900 ml).
  • the filtrate layer p H was adjusted to 5.2 with hydrochloric acid (15 ml) stirred for 1 hr. Filtered the obtained compound and washed with water (100 ml) to get wet compound.
  • the obtained wet compound was charged in RBF with water (1 lit), heated to 70- 80°C and stirred for 1 hr.
  • the reaction mixture was cooled to 50-60°C stirred for 45 min and filtered the obtained compound and washed with water (100 ml).
  • the same purification process was repeated with water and dried the obtained compound to get the tilted compound. Yield: 32 gr.
  • the PXRD of the obtained compound is depicted in figure-2
  • Example-18 Preparation of crystalline form-M of compound of formula-1.
  • the obtained compound was charged in RBF with water (450 ml) adjusted the p H to 11.4 with potassium hydroxide solution (5 ml) and stirred for 2 hr.
  • the reaction mass was filtered through hyflow bed to remove solid particles and washed with water (450 ml).
  • the filtrate layer p H was adjusted to 5.3 with hydrochloric acid (8 ml) stirred for 1 hr. Filtered the obtained compound and washed with water (50 ml) to get wet compound.
  • the obtained compound was suspended in DMF (250 ml) stirred for 4-5 hr.
  • the reaction mixture was cooled to 25-35°C stirred for 30 min.
  • the obtained solid was filtered and washed with DMF to get the title compound.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une forme cristalline de l'acide 1-cyclopropyl-8-méthyl-7-(5-méthyl-6-(méthylamino)pyridin-3-yl)-4-oxo-1,4-dihydroquinoléine-3-carboxylique, composé de formule-1, représentée par la formule structurale suivante-1. La présente invention concerne également un procédé de préparation de la forme cristalline du composé de formule-1 et un procédé de préparation du composé de formule-1.
PCT/IN2019/050697 2018-09-26 2019-09-24 Forme cristalline de l'ozénoxacine et procédés de préparation associés WO2020065668A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201841036343 2018-09-26
IN201841036343 2018-09-26

Publications (1)

Publication Number Publication Date
WO2020065668A1 true WO2020065668A1 (fr) 2020-04-02

Family

ID=69952491

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2019/050697 WO2020065668A1 (fr) 2018-09-26 2019-09-24 Forme cristalline de l'ozénoxacine et procédés de préparation associés

Country Status (1)

Country Link
WO (1) WO2020065668A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6335447B1 (en) * 1998-04-06 2002-01-01 Toyama Chemical Co., Ltd. Quinolonecarboxylic acid derivatives or salts thereof
US8507684B2 (en) * 2010-04-06 2013-08-13 Ferrer Internacional S.A. 1-cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid salts

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6335447B1 (en) * 1998-04-06 2002-01-01 Toyama Chemical Co., Ltd. Quinolonecarboxylic acid derivatives or salts thereof
US8507684B2 (en) * 2010-04-06 2013-08-13 Ferrer Internacional S.A. 1-cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid salts

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAIRA M R: "CRYSTALLINE POLYMORPHISM OF ORGANIC COMPOUNDS", TOPICS IN CURRENT CHEMISTRY, vol. 198, 1 January 1998 (1998-01-01), BERLIN, DE, pages 163 - 208, XP001156954 *

Similar Documents

Publication Publication Date Title
EP1992626A1 (fr) Procédé de préparation de chlorure de moxifloxacine
KR101539561B1 (ko) 목시플록사신 염산염의 합성방법
WO2016063294A2 (fr) Procédé de préparation de phosphate de (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile et de ses polymorphes
WO2018008042A1 (fr) Nouveau procédé de préparation de 2-{4-[(5,6-diphényl pyrazin-2-yl)(isopropyl)amino]butoxy}-n-(méthylsulfonyl)acétamide et nouveaux polymorphes associés
US20210403431A1 (en) Process for the preparation of n-(4-(6,7-dimethoxyquinolin-4-yloxy) phenyl)-n'-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide, (2s)-hydroxybutanedioate and its polymorphs thereof
US20100029938A1 (en) Process for the preparation of an antibacterial quinolone compound
WO2006134491A2 (fr) Nouvelle forme cristalline d'hydrochlorure de moxifloxacine et procede de preparation de cette derniere
US11279696B2 (en) Processes for the preparation of 7-{4-[4-(1-benzothiophen-4-yl) piperazin-1-yl]butoxy}quinolin-2(1H)-one
WO2008059521A2 (fr) Nouveau procédé pour la préparation de chlorhydrate de moxifloxacine et nouveau polymorphe de moxifloxacine
WO2017021975A1 (fr) Procédé de préparation de formes cristallines de rifaximine
WO2014049612A2 (fr) Procédés et polymorphes de 5-[4-[4-(5-cyano-1h-indol-3-yl) butyl]-1-pipérazinyl]-2-benzofuran carboxamide et ses sels
US11236050B2 (en) Polymorphs of 4-[3-chloro-4-(n′-cyclopropyl ureido)phenoxy] -7-methoxyquinoline-6-carboxamide, its salts and process for the preparation thereof
WO2020065668A1 (fr) Forme cristalline de l'ozénoxacine et procédés de préparation associés
AU773722B2 (en) Process for production of naphthyridine-3-carboxylic acid derivatives
WO2016139677A1 (fr) Procédé amélioré pour la préparation de 2-({6- [(3r)-3-aminopipéridin-1-yl]-3-méthyl-2,4-dioxo -3,4-dihydropyrimidin-1 (2h)-yl} méthyl)benzonitrile et des sels pharmaceutiquement acceptables de celui-ci
WO2019058387A1 (fr) Procédé amélioré de préparation de (5α,6α)-17-allyl-6-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy) -4,5-époxymorphinane-3,14-diol et de ses sels pharmaceutiquement acceptables
EP0549857A1 (fr) Dérivés d'acides quinolone-carboxyliques comme agent antibactérien
US9115130B2 (en) Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives
EP1437354B1 (fr) Antimicrobiens 4-oxoquinolizine comportant un squelette 2-pyridone comme structure partielle
WO2017163258A1 (fr) Procédé de préparation de n-[6-(cis-2,6-diméthylmorpholin-4-yl)pyridine-3-yl]-2- méthyl-4'-(trifluorométhoxy) [1,1'-biphényl]-3-carboxamide et de ses polymorphes
CA2481217C (fr) Procede de preparation de sels acides de gemifloxacine
ES2232309B1 (es) Procedimiento simplificado para la obtencion de gatifloxacino.
JPH0564955B2 (fr)
EP2161269A1 (fr) Procédé de préparation de gémifloxacine amorphe
WO2018096550A1 (fr) Procédé de préparation de méthyle 4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(méthyl)carbamate et ses polymorphes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19865034

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19865034

Country of ref document: EP

Kind code of ref document: A1