EP2867206A2 - Sels de saxagliptine - Google Patents

Sels de saxagliptine

Info

Publication number
EP2867206A2
EP2867206A2 EP13762566.1A EP13762566A EP2867206A2 EP 2867206 A2 EP2867206 A2 EP 2867206A2 EP 13762566 A EP13762566 A EP 13762566A EP 2867206 A2 EP2867206 A2 EP 2867206A2
Authority
EP
European Patent Office
Prior art keywords
saxagliptin
acetate
process according
bicarbonate
bisulphate
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP13762566.1A
Other languages
German (de)
English (en)
Inventor
Ram Chander Aryan
Ashwani Kumar Singh
Amit Sharma
Ramendra Singh Rathore
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ranbaxy Laboratories Ltd
Original Assignee
Ranbaxy Laboratories 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 Ranbaxy Laboratories Ltd filed Critical Ranbaxy Laboratories Ltd
Publication of EP2867206A2 publication Critical patent/EP2867206A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention provides saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, and saxagliptin carbonate, their polymorphic forms, processes for their preparation, and pharmaceutical compositions thereof.
  • Saxagliptin of Formula A an orally-active inhibitor of the dipeptidyl peptidase IV enzyme, chemically designated as (lS,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxytricyclo [3.3.1.1 3 ' 7 ]dec- l-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • U.S. Patent No. 6,395,767 (hereinafter "the '767 patent") provides a process for the preparation of the saxagliptin trifluoroacetate salt.
  • the '767 patent also provides the hydrochloride salt of saxagliptin.
  • U.S. Patent No. 7,943,656 provides a process for the preparation of crystalline forms of saxagliptin free base, hydrochloride, hydrobromide, hydroiodide, fumarate (2: 1), tartrate, benzoate, trifluoroacetate, ammonium sulfate complex, and nitrate.
  • PCT Publication No. WO 2010/1 15974 provides a process for the preparation of anhydrous crystalline forms of saxagliptin hydrochloride.
  • PCT Publication No. WO 2012/017028 provides a process for the preparation of crystalline forms of saxagliptin phosphate.
  • PCT Publication No. WO 2012/017029 provides a process for the preparation of a crystalline compound comprising a mixture of saxagliptin and an organic C 4 -diacid, wherein the organic C4-diacid is selected from maleic acid, malic acid, L-malic acid, D- malic acid, and succinic acid.
  • PCT Publication No. WO 2012/047871 provides a process for the preparation of crystalline Form K, Form Z, Form D, and amorphous saxagliptin hydrochloride.
  • Chinese Publication No. CN 102086172 provides a process for the preparation of mesylate, maleate, malate, succinate, and citrate salts of saxagliptin.
  • the present inventors have prepared saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, and saxagliptin carbonate salts.
  • the salts of the present invention are easy to prepare and isolate in solid forms, particularly, in crystalline forms. Further, they can be prepared by an efficient, economical, and reproducible process, which is particularly suited to large scale preparation.
  • a first aspect of the present invention provides saxagliptin bisulphate.
  • a second aspect of the present invention provides a crystalline form of saxagliptin bisulphate.
  • a third aspect of the present invention provides saxagliptin acetate.
  • a fourth aspect of the present invention provides a crystalline form of saxagliptin acetate.
  • a fifth aspect of the present invention provides saxagliptin oxalate.
  • a sixth aspect of the present invention provides a crystalline form of saxagliptin oxalate.
  • a seventh aspect of the present invention provides a process for the preparation of a compound of Formula I
  • HA is selected from sulphuric acid, acetic acid, and oxalic acid.
  • An eighth aspect of the present invention provides saxagliptin bicarbonate of Formula II.
  • a ninth aspect of the present invention provides a crystalline form of saxagliptin bicarbonate.
  • a tenth aspect of the present invention provides a process for the preparation of saxagliptin bicarbonate, which comprises contacting saxagliptin or its salt with a suitable carbonate source.
  • An eleventh aspect of the present invention provides saxagliptin carbonate of Formula III.
  • a twelfth aspect of the present invention provides a crystalline form of saxagliptin carbonate.
  • a thirteenth aspect of the present invention provides a process for the preparation of saxagliptin carbonate, which comprises heating saxagliptin bicarbonate, optionally in the presence of water.
  • a fourteenth aspect of the present invention provides the use of saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate for the preparation of saxagliptin or salts, solvates, or polymorphs thereof.
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate for the preparation of saxagliptin or salts, solvates, or polymorphs thereof.
  • a fifteenth aspect of the present invention provides a pharmaceutical composition
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate, and a
  • a sixteenth aspect of the present invention provides a method of treating type 2 diabetes mellitus which comprises administering to a patient in need thereof a
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate, and a pharmaceutically acceptable carrier.
  • a first aspect of the present invention provides saxagliptin bisulphate.
  • a second aspect of the present invention provides a crystalline form of saxagliptin bisulphate.
  • the crystalline form of saxagliptin bisulphate of the present invention may be characterized by an XRPD pattern substantially the same as depicted in Figure 1 , exhibiting interplanar spacing (d) values at about 3.63, 3.39, 3.27, and 3.20 (A), and further exhibiting interplanar spacing (d) values at about 4.22, 3.89, 3.09, 3.05, 2.98, 2.91, 2.79, and 2.63 (A).
  • the crystalline form of saxagliptin bisulphate has an XRPD pattern with characteristic peak values (2 ⁇ ) at about 24.50, 26.26, 27.25, and 27.84 ⁇ 0.2°, and additional characteristic peak values (2 ⁇ ) at about 21.04, 22.82, 28.89, 29.26, 29.98, 30.71, 32.05, and 34.06 ⁇ 0.2°.
  • the crystalline form of saxagliptin bisulphate of the present invention may be characterized by FTIR as depicted in Figure 2.
  • the crystalline form of saxagliptin bisulphate of the present invention may be characterized by DSC as depicted in Figure 3, with a characteristic endothermic peak value at about 100.90°C in the DSC thermogram.
  • a third aspect of the present invention provides saxagliptin acetate.
  • a fourth aspect of the present invention provides a crystalline form of saxagliptin acetate.
  • the crystalline form of saxagliptin acetate of the present invention may be characterized by an XRPD pattern substantially the same as depicted in Figure 4, exhibiting interplanar spacing (d) values at about 1 1.97, 9.84, 5.98, 4.96, and 4.91 (A), and further exhibiting interplanar spacing (d) values substantially at about 6.27, 5.16, 4.71, 4.68, 4.50, 4.45, 3.99, and 3.87 (A).
  • the crystalline form of saxagliptin acetate has an XRPD pattern with characteristic peak values (2 ⁇ ) at about 7.38, 8.98, 14.79, 17.85, and 18.03 ⁇ 0.2°, and additional characteristic peak values (2 ⁇ ) at about 14.12, 17.17, 18.82, 18.92, 19.70, 19.94, 22.26, and 22.97 ⁇ 0.2°.
  • the crystalline form of saxagliptin acetate of the present invention may be characterized by FTIR as depicted in Figure 5.
  • the crystalline form of saxagliptin acetate of the present invention may be characterized by DSC as depicted in Figure 6, with characteristic endothermic peak values at about 68.12, 79.62, 152.38, and 161.14°C in the DSC thermogram.
  • a fifth aspect of the present invention provides saxagliptin oxalate.
  • a sixth aspect of the present invention provides a crystalline form of saxagliptin oxalate.
  • the crystalline form of saxagliptin oxalate of the present invention may be characterized by an XRPD pattern substantially the same as depicted in Figure 7, exhibiting interplanar spacing (d) values substantially at about 12.99, 6.28, 4.96, 4.91, and 4.67 (A), and further exhibiting interplanar spacing (d) values at about 5.99, 5.93, 5.69, 4.59, 4.32, 4.01, and 3.08 (A).
  • the crystalline form of saxagliptin oxalate has an XRPD pattern with characteristic peak values (2 ⁇ ) at about 6.80, 14.06, 17.88, 18.06, and 18.98 ⁇ 0.2°, and additional characteristic peak values (2 ⁇ ) at about 14.76, 14.93, 15.56, 19.30, 20.54, 22.15, and 28.97 ⁇ 0.2°.
  • the crystalline form of saxagliptin oxalate of the present invention may be characterized by FTIR as depicted in Figure 8.
  • the crystalline form of saxagliptin oxalate of the present invention may be characterized by DSC as depicted in Figure 9, with a characteristic endothermic peak value at about 61.67°C, and a characteristic exothermic peak value at about 186.24°C in the DSC thermogram.
  • a seventh aspect of the present invention provides a process for the preparation of a compound of Formula I
  • HA is selected from sulphuric acid, acetic acid, or oxalic acid.
  • the saxagliptin or its salt used as the starting material may be prepared by any of the methods known in the art including those described in, for example, U.S. Patent Nos. 6,395,767, and 7,943,656; PCT Publications WO 2004/052850, WO 2005/1 15982, WO 2005/10601 1, WO 2005/094323, WO 2010/1 15974, WO 2012/017028, WO 2012/017029, and WO 2012/047871.
  • saxagliptin or its salt prepared by any of the methods known in the art may be isolated or directly treated with HA.
  • saxagliptin or its salt prepared by any of the methods known in the art may be optionally purified prior to treatment with HA to remove foreign particulate matter.
  • saxagliptin or its salt may be optionally concentrated to reduce the amount of solvent.
  • the saxagliptin salt may optionally be converted to saxagliptin base before treatment with HA.
  • Treating saxagliptin or its salt with HA may include adding, dissolving, slurrying, stirring, or a combination thereof. Saxagliptin or its salt may be treated with HA directly, or in the presence of a suitable solvent at a suitable temperature.
  • solvent includes any solvent, or a solvent mixture, including for example, water, esters, alkanols, halogenated hydrocarbons, ketones, ethers, polar aprotic solvents, or mixtures thereof.
  • esters include ethyl acetate, n-propyl acetate, isopropyl acetate, and n- butyl acetate.
  • alkanols include those primary, secondary, and tertiary alcohols having from one to six carbon atoms. Examples of suitable alkanols include methanol, ethanol, n-propanol, isopropanol, and butanol. Examples of halogenated hydrocarbons include dichloromethane, chloroform, and 1 ,2-dichloroethane. Examples of ketones include acetone and methyl ethyl ketone. Examples of ethers include diethyl ether and tetrahydrofuran. Examples of polar aprotic solvents include NN-dimethylformamide, NN-dimethylacetamide, dimethylsulphoxide, acetonitrile, and N-methylpyrrolidone.
  • Saxagliptin or its salt is treated with HA at a temperature of from about - 10°C to about 10°C, preferably, from about -5°C to about 5°C.
  • the formation of the saxagliptin salt may be accelerated by stirring the reaction mixture for about 10 minutes to about 4 hours at a temperature of from about -5°C to about 40°C, preferably from about 0°C to about 25°C.
  • the saxagliptin salt of Formula I may be isolated by filtration, decantation, solvent precipitation, trituration, evaporation, distillation, or combinations thereof.
  • An eighth aspect of the present invention provides a saxagliptin bicarbonate of Formula II.
  • a ninth aspect of the present invention provides a crystalline form of saxagliptin bicarbonate.
  • the crystalline form of saxagliptin bicarbonate of the present invention may be characterized by an XRPD pattern substantially the same as depicted in Figure 10, exhibiting interplanar spacing (d) values at about 3.70, 2.99, and 2.86 (A), and further exhibiting interplanar spacing (d) values at about 7.45, 3.17, 3.12, 2.64, 2.39, and 2.30 (A).
  • the crystalline form of saxagliptin bicarbonate has an XRPD pattern with characteristic peak values (2 ⁇ ) at about 24.05, 29.84, and 31.18 ⁇ 0.2°, and additional characteristic peak values (2 ⁇ ) at about 1 1.86, 28.13, 28.60, 33.88, 37.55, and 39.01 ⁇ 0.2°.
  • the crystalline form of saxagliptin bicarbonate of the present invention may be characterized by FTIR as depicted in Figure 1 1.
  • the crystalline form of saxagliptin bicarbonate of the present invention may be characterized by DSC as depicted in Figure 12, with a characteristic endothermic peak value at about 76.94°C in the DSC thermogram.
  • a tenth aspect of the present invention provides a process for the preparation of saxagliptin bicarbonate, which comprises contacting saxagliptin or its salt with a suitable carbonate source.
  • saxagliptin or its salt prepared by any of the methods known in the art may be isolated or directly treated with a suitable carbonate source.
  • the saxagliptin or its salt prepared by any of the methods known in the art, before treatment with a suitable carbonate source, may be optionally purified to remove foreign particulate matter or treated with activated charcoal to remove coloring and other related impurities in a suitable solvent.
  • the solution of saxagliptin or its salt may be optionally concentrated to reduce the amount of solvent.
  • the saxagliptin salt may optionally be converted to saxagliptin base before treatment with a suitable carbonate source, optionally in the presence of a base.
  • carbonate source includes carbon dioxide gas, dry ice, and carbonic acid prepared in situ by dissolving carbon dioxide gas in water.
  • base includes hydroxides, carbonates, and bicarbonates of alkali and alkaline earth metals; ammonia; alkyl amines; hydrazine; and the like.
  • hydroxides, carbonates, and bicarbonates of alkali and alkaline earth metals may include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate.
  • alkyl amines may include diethyl amine, triethyl amine, or methyl diethyl amine.
  • Treating saxagliptin or its salt with a suitable carbonate source may include adding, dissolving, slurrying, stirring, or combinations thereof. Saxagliptin or its salt may be treated with a suitable carbonate source directly or in the presence of a suitable solvent at a suitable temperature.
  • solvent includes any solvent, or a solvent mixture, including for example, water, alkanols, esters, ketones, polar aprotic solvents, or mixtures thereof.
  • alkanols include primary, secondary and tertiary alcohols having from one to six carbon atoms.
  • suitable alkanols include methanol, ethanol, n-propanol, isopropanol, and butanol.
  • esters include ethyl acetate, n-propyl acetate, isopropyl acetate, and n-butyl acetate.
  • ketones include acetone and methyl ethyl ketone.
  • polar aprotic solvents include NN-dimethylformamide, NN- dimethylacetamide, dimethylsulphoxide, acetonitrile, and N-methylpyrrolidone.
  • saxagliptin is treated with dry ice at a temperature of from about 20°C to about 30°C, in ethanol while stirring for about 30 minutes to about 1 hour, preferably, from about 35 minutes to about 45 minutes. Ethanol is removed by distillation under vacuum, followed by the addition of ethyl acetate while stirring. Saxagliptin bicarbonate of Formula II may be isolated by filtration, decantation, solvent precipitation, trituration, evaporation, distillation, or combinations thereof.
  • An eleventh aspect of the present invention provides saxagliptin carbonate of Formula III.
  • a twelfth aspect of the present invention provides a crystalline form of saxagliptin carbonate.
  • the crystalline form of saxagliptin carbonate of the present invention may be characterized by FTIR as depicted in Figure 13.
  • the crystalline form of saxagliptin carbonate of the present invention may be characterized by DSC as depicted in Figure 14.
  • the crystalline form of saxagliptin carbonate has a characteristic endothermic peak value at about 1 13.45°C in the DSC thermogram.
  • a thirteenth aspect of the present invention provides a process for the preparation of saxagliptin carbonate, which comprises heating saxagliptin bicarbonate, optionally in the presence of water.
  • saxagliptin bicarbonate is dissolved in water and stirred at a temperature of from about 50°C to about 100°C, preferably, from about 65°C to about 70°C, for about 3 hours to about 6 hours, preferably, for about 4 hours to about 5 hours. Water is then removed by distillation under vacuum. The residue obtained is stirred with ethyl acetate and then removed by distillation under vacuum to obtain the solid. The solid may be washed with ethyl acetate, and is then isolated by filtration, decantation, solvent precipitation, trituration, evaporation, distillation, or combinations thereof to obtain the saxagliptin carbonate.
  • a fourteenth aspect of the present invention provides the use of saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate for the preparation of saxagliptin or salts, solvates, or polymorphs thereof.
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate for the preparation of saxagliptin or salts, solvates, or polymorphs thereof.
  • Saxagliptin salts may be used for the preparation of saxagliptin by contacting with a base or heating, optionally in the presence of water.
  • the base may be selected from the group comprising of hydroxides, carbonates, and bicarbonates of alkali and alkaline earth metals; ammonia; alkyl amines; hydrazine; and the like.
  • hydroxides, carbonates, and bicarbonates of alkali and alkaline earth metals include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate.
  • alkyl amines may include diethyl amine, triethyl amine, or methyl diethyl amine. Saxagliptin thus obtained may be converted to salts, solvates, or polymorphs thereof.
  • a fifteenth aspect of the present invention provides a pharmaceutical composition
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate, and a
  • a sixteenth aspect of the present invention provides a method of treating type 2 diabetes mellitus which comprises administering to a patient in need thereof a therapeutically effective amount of saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate, and a pharmaceutically acceptable carrier.
  • saxagliptin salts selected from saxagliptin bisulphate, saxagliptin acetate, saxagliptin oxalate, saxagliptin bicarbonate, or saxagliptin carbonate, and a pharmaceutically acceptable carrier.
  • Figure 1 and Figure 1 a depict the X-Ray Powder Diffractogram (XRPD) of saxagliptin bisulphate and the associated values, respectively, prepared as per Example 1.
  • XRPD X-Ray Powder Diffractogram
  • Figure 2 depicts the Fourier-Transform Infra-red (FTIR) spectrum of saxagliptin bisulphate prepared as per Example 1.
  • FTIR Fourier-Transform Infra-red
  • FIG. 3 depicts the Differential Scanning Calorimetry (DSC) of saxagliptin bisulphate prepared as per Example 1.
  • Figure 4 and Figure 4a depict the XRPD of saxagliptin acetate and the associated values, respectively, prepared as per Example 2.
  • Figure 5 depicts the FTIR spectrum of saxagliptin acetate prepared as per Example
  • Figure 6 depicts the DSC of saxagliptin acetate prepared as per Example 2.
  • Figure 7 and Figure 7a depict the XRPD of saxagliptin oxalate and the associated values, respectively, prepared as per Example 4.
  • Figure 8 depicts the FTIR spectrum of saxagliptin oxalate prepared as per Example
  • Figure 9 depicts the DSC of saxagliptin oxalate prepared as per Example 4.
  • Figure 10 and Figure 10a depict the XRPD of saxagliptin bicarbonate and the associated values, respectively, prepared as per Example 5.
  • Figure 1 1 depicts the FTIR spectrum of saxagliptin bicarbonate prepared as per Example 5.
  • Figure 12 depicts the DSC of saxagliptin bicarbonate prepared as per Example 5.
  • Figure 13 depicts the FTIR spectrum of saxagliptin carbonate prepared as per Example 6.
  • Figure 14 depicts the DSC of saxagliptin carbonate prepared as per Example 6.
  • the XRPD of the samples were determined by using Instrument: PANalytical; Mode: Expert PRO; Detector: Xcelerator; ScanRange: 3-40; Step size: 0.02; Range: 3-40 degree 2 theta; CuKa radiation at 45kV.
  • DSC of the samples was determined by using Instrument: Perkin Elmer, Diamond DSC. Data collection parameters: Scanning rate: 10°C/min; Temperature: 30°C - 300°C.
  • a mixture of saxagliptin (1.13 g) and isopropanol (10 mL) was stirred, and cooled to 5°C, followed by the addition of acetic acid (0.22 g) at 5°C to 10°C, and then stirred for 1 hour while gradually raising the temperature to about 20°C to 25°C.
  • the reaction mixture was cooled to 0°C to 5°C, and then stirred for 4 hours, maintaining the same temperature, to obtain a white solid.
  • the solid was filtered through a sintered funnel under vacuum in a nitrogen environment, washed with isopropanol (10 mL), and dried under vacuum at 40°C to 45°C for 12 hours to 14 hours to obtain the title compound.
  • Saxagliptin hydrochloride (5 g) was dissolved in water (50 mL) at 22°C, stirred, and cooled to 1°C in 15 minutes, followed by drop-wise addition of 10% aqueous potassium carbonate solution (20 mL) at 0°C to 5°C over 10 minutes to adjust the pH to 8.3.
  • the reaction mixture was stirred for 10 minutes at 5°C and the pH was checked and adjusted to 8.3.
  • the water in the reaction mixture was distilled off under vacuum at 25°C in 2 hours, followed by the addition of ethanol (60 mL).
  • the inorganic substances in the reaction mixture were filtered under vacuum.
  • the inorganic substances were washed with ethanol (15 mL) and filtered to obtain filtrate.
  • the obtained filtrates were distilled off under vacuum at 25°C in 1 hour to obtain an oily mass.
  • Saxagliptin bicarbonate (300 mg) obtained as per Example 5 was dissolved in water (30 mL) and stirred for 4 hours at 65°C to 70°C.
  • the water in the reaction mixture was recovered at 65°C to 70°C under vacuum to obtain a residue.
  • ethyl acetate (20 mL) was added, stirred for 10 minutes at 55°C, and the solvent was recovered under vacuum at 50°C to 55°C to obtain a solid mass.
  • ethyl acetate (10 mL) was added, and stirred for 15 minutes.
  • the solid obtained was filtered, then dried under vacuum at 65°C for 14 hours to obtain the title compound.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne du bisulfate de saxagliptine, de l'acétate de saxagliptine, de l'oxalate de saxagliptine, du bicarbonate de saxagliptine et du carbonate de saxagliptine, leurs formes polymorphes, leurs procédés de préparation et leurs compositions pharmaceutiques.
EP13762566.1A 2012-07-02 2013-07-02 Sels de saxagliptine Withdrawn EP2867206A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN2061DE2012 2012-07-02
IN3917DE2012 2012-12-19
PCT/IB2013/055429 WO2014006569A2 (fr) 2012-07-02 2013-07-02 Sels de saxagliptine

Publications (1)

Publication Number Publication Date
EP2867206A2 true EP2867206A2 (fr) 2015-05-06

Family

ID=54193750

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13762566.1A Withdrawn EP2867206A2 (fr) 2012-07-02 2013-07-02 Sels de saxagliptine

Country Status (5)

Country Link
EP (1) EP2867206A2 (fr)
AU (1) AU2013285078A1 (fr)
CA (1) CA2879824A1 (fr)
SG (1) SG11201408619WA (fr)
WO (1) WO2014006569A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013175297A1 (fr) 2012-05-24 2013-11-28 Apotex Pharmachem India Pvt. Ltd Sels de saxagliptine avec des acides organiques
WO2015166466A1 (fr) * 2014-05-01 2015-11-05 Sun Pharmaceutical Industries Limited Forme cristalline d'acétate de saxagliptine

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6395767B2 (en) * 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
US7420079B2 (en) 2002-12-09 2008-09-02 Bristol-Myers Squibb Company Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof
TW200538122A (en) 2004-03-31 2005-12-01 Bristol Myers Squibb Co Process for preparing a dipeptidyl peptidase Ⅳ inhibitor and intermediates employed therein
US7741082B2 (en) 2004-04-14 2010-06-22 Bristol-Myers Squibb Company Process for preparing dipeptidyl peptidase IV inhibitors and intermediates therefor
US7214702B2 (en) 2004-05-25 2007-05-08 Bristol-Myers Squibb Company Process for producing a dipeptidyl peptidase IV inhibitor
PE20090696A1 (es) * 2007-04-20 2009-06-20 Bristol Myers Squibb Co Formas cristalinas de saxagliptina y procesos para preparar las mismas
KR20120006047A (ko) 2009-04-09 2012-01-17 산도즈 아게 삭사글립틴의 결정 형태
WO2012017028A1 (fr) 2010-08-06 2012-02-09 Sandoz Ag Nouveau composé cristallin comprenant de la saxagliptine et de l'acide phosphorique
WO2012017029A1 (fr) * 2010-08-06 2012-02-09 Sandoz Ag Nouveaux sels de saxagliptine comportant des diacides organiques
US8410288B2 (en) 2010-10-04 2013-04-02 Teva Pharmaceutical Industries Ltd. Polymorphs of Saxagliptin hydrochloride and processes for preparing them
CN102086172A (zh) * 2011-01-13 2011-06-08 廖国超 沙格列汀的药用盐及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2014006569A2 *

Also Published As

Publication number Publication date
AU2013285078A1 (en) 2015-01-29
WO2014006569A3 (fr) 2014-03-06
WO2014006569A2 (fr) 2014-01-09
SG11201408619WA (en) 2015-01-29
CA2879824A1 (fr) 2014-01-09

Similar Documents

Publication Publication Date Title
US20210371397A1 (en) Synthesis of omecamtiv mecarbil
WO2012025944A2 (fr) Sitagliptine, sels et polymorphes de celle-ci
JP2021105003A (ja) 多形体及びキナゾリニル誘導体の調製プロセス
US10464906B2 (en) Crystalline forms of a histone deacetylase inhibitor
JP2013525384A (ja) ニトロイミダゾール系化合物、その製造方法および用途
WO2018142327A1 (fr) Sels d'oxalate de ténéligliptine et solvates de ceux-ci, intermédiaires, procédé de préparation
EP2867206A2 (fr) Sels de saxagliptine
CN110655517A (zh) 一种多替拉韦开环杂质的制备方法及其杂质
EP2860180A1 (fr) Nouveaux sels gentisate d'inhibiteur de DPP-IV
CN112759545A (zh) 3-(二甲氨基甲基)哌啶-4-醇类衍生物及其制备方法和药物用途
WO2004067496A1 (fr) Forme cristalline de nateglinide
US20150329489A1 (en) Saxagliptin salts
US20150051213A1 (en) Novel salts of sitagliptin
US20040181089A1 (en) Polymorphic forms of nateglinide
WO2015092624A1 (fr) Mono-oxalate de nilotinib et sa forme cristalline
EP1467964A1 (fr) Formes polymorphes de nateglinide
ES2709110T3 (es) Un proceso mejorado para la preparación de sunitinib y sus sales de adición de ácido
WO2017213944A1 (fr) Formes solides de ceftolozane et procédés de préparation
US10793554B2 (en) Solid forms of 4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone
WO2015166466A1 (fr) Forme cristalline d'acétate de saxagliptine
EP3990091A1 (fr) Procédés et intermédiaires pour la préparation de sel de chlorhydrate de 5- [3-(3-hydroxyphénoxy)azétidine-1-yl]-5-méthyl-2,2-diphénylhexanamide
CN116239491A (zh) 一种西格列汀杂质化合物i及其制备方法
WO2015114479A1 (fr) Formes cristallines d'oxalate, d'adipate, de succinate, de phosphate, de sulphate, de fumaratetartrate, de nitrate et de borate de darapladib
US20070238889A1 (en) Process for preparing dc-cholesterol
WO2014118737A1 (fr) Sels d'erlotinib

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20150202

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20160108