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WO2017191620A1 - Forme cristalline d'un sel de sacubitril et procédé pour le préparer - Google Patents

Forme cristalline d'un sel de sacubitril et procédé pour le préparer Download PDF

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Publication number
WO2017191620A1
WO2017191620A1 PCT/IB2017/052673 IB2017052673W WO2017191620A1 WO 2017191620 A1 WO2017191620 A1 WO 2017191620A1 IB 2017052673 W IB2017052673 W IB 2017052673W WO 2017191620 A1 WO2017191620 A1 WO 2017191620A1
Authority
WO
WIPO (PCT)
Prior art keywords
sodium
sacubitril
process according
group
crystalline form
Prior art date
Application number
PCT/IB2017/052673
Other languages
English (en)
Inventor
Siddamal Reddy PUTAPATRI
Bhushan Balasaheb KHAIRNAR
Ashok Kumar
Gyanendra Pandey
Kaptan Singh
Mohan Prasad
Original Assignee
Sun Pharmaceutical Industries Limited
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 Sun Pharmaceutical Industries Limited filed Critical Sun Pharmaceutical Industries Limited
Publication of WO2017191620A1 publication Critical patent/WO2017191620A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/22—Separation; Purification; Stabilisation; Use of additives
    • C07C231/24—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present invention provides a process for the preparation of a salt of sacubitril. Specifically, the present invention provides a process for the preparation of a sodium salt of sacubitril. The present invention further provides a crystalline Form I of sodium salt of sacubitril and its process of preparation.
  • the present invention provides a simple, industrially viable, and cost effective process for the preparation of a salt of sacubitril. Specifically, the present invention provides a process for the preparation of a sodium salt of sacubitril.
  • the sodium salt of sacubitril produced by following the process disclosed herein is non-hygroscopic, has better yield, purity, and flowability.
  • the sodium salt of sacubitril produced by following the process disclosed herein is also easy to handle and is found to be stable.
  • the present invention further provides a crystalline Form I of sodium salt of sacubitril and its process of preparation.
  • Figure 1 depicts an X-ray Powder Diffraction (XRPD) pattern of a crystalline Form I of the sodium salt of sacubitril as prepared according to Example 1(a).
  • XRPD X-ray Powder Diffraction
  • Figure 2 depicts an X-ray Powder Diffraction (XRPD) pattern of a crystalline Form I of the sodium salt of sacubitril as prepared according to Example 1(a) after 1 month of storage at 30°C ⁇ 2°C at a relative humidity of 75% ⁇ 5%.
  • XRPD X-ray Powder Diffraction
  • FIG. 3 depicts a Differential Scanning Calorimetry (DSC) pattern of a crystalline Form I of the sodium salt of sacubitril as prepared according to Example 1(a).
  • DSC Differential Scanning Calorimetry
  • ambient temperature refers to the temperature in the range of25°C to 35°C.
  • treating includes combining, mixing, triturating, suspending, contacting, or a combination thereof.
  • stable refers to a salt of sacubitril, which does not convert to any other polymorphic form upon storage at 30°C ⁇ 2°C and 75% ⁇ 5% relative humidity and for which the chromatographic purity does not decrease on storage.
  • a first aspect of the present invention provides a process for the preparation of a sodium salt of sacubitril, wherein the process comprises treating sacubitril with a sodium salt of an organic acid.
  • Sacubitril is prepared by any method known in the art, for example, according to the processes disclosed in U.S. Patent No. 5,217,996 or /. Med. Chem. 1995, 38, 1689- 1700.
  • the sodium salt of an organic acid is selected from the group consisting of sodium 2-ethyl hexanoate, sodium octanoate, sodium formate, sodium acetate, sodium propionate, sodium butyrate, sodium valerate, sodium caproate, sodium oxalate, sodium lactate, sodium malate, sodium citrate, sodium benzoate, sodium succinate and a mixture thereof.
  • the treatment of sacubitril with the sodium salt of an organic acid is carried out in a solvent.
  • the solvent is selected from the group consisting of water, aromatic hydrocarbons, ketones, esters, ethers, alkanols, halogenated hydrocarbons, aliphatic hydrocarbons, polar aprotic solvents, and mixtures thereof.
  • aromatic hydrocarbons include toluene or benzene.
  • ketones include acetone or methyl ethyl ketone.
  • esters include ethyl acetate, n-propyl acetate, isopropyl acetate, or n-butyl acetate.
  • ethers include methyl i-butyl ether or tetrahydrofuran.
  • alkanols include primary, secondary, and tertiary alcohols having from one to six carbon atoms. Suitable alkanols include methanol, ethanol, 1-propanol, 2-propanol, or butanol.
  • halogenated hydrocarbons include dichloromethane, chloroform, or 1,2- dichloroethane.
  • aliphatic hydrocarbons include n-pentane, n-hexane, n- heptane, cyclohexane, or cycloheptane.
  • polar aprotic solvents include N,N- dimethylformamide, N,N-dimethylacetamide, dimethylsulphoxide, acetonitrile, or N- methylpyrrolidone.
  • Sacubitril is treated with the sodium salt of an organic acid at a temperature of about 10°C to about 60°C, for example, at about 20°C to about 55°C.
  • Sacubitril is treated with the sodium salt of an organic acid for about 2 hours to about 15 hours, for example, for about 2 hours to about 14 hours.
  • the sodium salt of sacubitril may be isolated by methods including concentration, distillation, decantation, filtration, evaporation, centrifugation, or a combination thereof, and may further be dried.
  • a second aspect of the present invention provides crystalline Form I of the sodium salt of sacubitril characterized by an X-ray powder diffraction (XRPD) pattern having peaks at d-spacings of about 14.1, 4.4, and 3.7 A.
  • XRPD X-ray powder diffraction
  • the crystalline Form I of sodium salt of sacubitril is further characterized by an XRPD pattern having additional peaks at d-spacings of about 7.4, 6.9, 5.4, 4.1, 3.4 and 3.3
  • the crystalline Form I of sodium salt of sacubitril is further characterized by an XRPD pattern as depicted in Figure 1.
  • Table 1 provides XRPD peak values (2 ⁇ ), their corresponding d-spacing values (A), and the relative intensities of the crystalline Form I of the sodium salt of sacubitril as prepared according to Example 1(a).
  • the crystalline Form I of the sodium salt of sacubitril prepared by the present invention is found to be stable after storing at 30°C ⁇ 2°C/ 75% ⁇ 5% RH for 1 month as depicted in Figure 2.
  • the crystalline Form I of the sodium salt of sacubitril is characterized by a differential scanning calorimetry (DSC) thermogram as depicted in Figure 3.
  • the crystalline Form I of the sodium salt of sacubitril is characterized by a DSC thermogram having endothermic peaks at about 161.8°C and 247.2°C.
  • a third aspect of the present invention provides a process for the preparation of a crystalline Form I of the sodium salt of sacubitril, wherein the process comprises treating sacubitril with a sodium containing reagent.
  • Sacubitril is prepared by any method known in the art, for example, according to methods disclosed in U.S. Patent No. 5,217,996 or J. Med. Chem. 1995, 38, 1689-1700.
  • the sodium containing reagent is selected from the group consisting of sodium methoxide, sodium carbonate, sodium bicarbonate, sodium chloride, sodium bromide, sodium 2-ethyl hexanoate, sodium octanoate, sodium formate, sodium acetate, sodium propionate, sodium butyrate, sodium valerate, sodium caproate, sodium oxalate, sodium lactate, sodium malate, sodium citrate, sodium benzoate, sodium succinate and a mixture thereof.
  • the treatment of sacubitril with a sodium containing reagent is carried out in a solvent.
  • the solvent is selected from the group consisting of water, aromatic hydrocarbons, ketones, esters, ethers, alkanols, halogenated hydrocarbons, aliphatic hydrocarbons, polar aprotic solvents, and mixtures thereof.
  • aromatic hydrocarbons include toluene or benzene.
  • ketones include acetone or methyl ethyl ketone.
  • esters include ethyl acetate, n-propyl acetate, isopropyl acetate, or n-butyl acetate.
  • ethers include methyl i-butyl ether or tetrahydrofuran.
  • alkanols include primary, secondary, and tertiary alcohols having from one to six carbon atoms. Suitable alkanols include methanol, ethanol, 1-propanol, 2-propanol, or butanol.
  • halogenated hydrocarbons include dichloromethane, chloroform, or 1,2- dichloroethane.
  • aliphatic hydrocarbons include n-pentane, n-hexane, n- heptane, cyclohexane, or cycloheptane.
  • polar aprotic solvents include N,N- dimethylformamide, ⁇ , ⁇ -dimethylacetamide, dimethylsulphoxide, acetonitrile, or N- methylpyrrolidone .
  • Sacubitril is treated with the sodium containing reagent at a temperature of about 10°C to about 60°C, for example, at about 20°C to about 55°C.
  • Sacubitril is treated with the sodium containing reagent for about 2 hours to about
  • the crystalline Form I of the sodium salt of sacubitril may be isolated by methods including concentration, distillation, decantation, filtration, evaporation, centrifugation, or a combination thereof, and may further be dried.
  • a fourth aspect of the present invention provides use of a crystalline Form I of the sodium salt of sacubitril for the preparation of a pharmaceutical active agent.
  • a fifth aspect of the present invention provides use of a crystalline Form I of the sodium salt of sacubitril for the preparation of a pharmaceutical composition comprising solid forms of valsartan and sacubitril.
  • a sixth aspect of the present invention provides use of a crystalline Form I of the sodium salt of sacubitril for the preparation of a medicament for treating or preventing a cardiovascular or renal condition or a medical condition responsive to valsartan and/or sacubitril in a patient in need thereof.
  • a seventh aspect of the present invention provides use of a crystalline Form I of the sodium salt of sacubitril for the preparation of a medicament comprising a solid form of sacubitril and valsartan for treating or preventing a cardiovascular or renal condition or a medical condition responsive to valsartan and/or sacubitril in a patient in need thereof.
  • XRPD of the samples was determined by using a PANalytical ® instrument; Model X'pert PRO; Detector: X'celerator ® .
  • Sacubitril 50 g was added to methyl i-butyl ether (500 mL) at 20°C to 25°C and the mixture was stirred for 15 minutes.
  • Sodium-2-ethyl hexonoate (21.6 g) was added to the mixture.
  • the reaction mixture was heated to 50°C to 55°C for 14 hours.
  • the reaction mixture was cooled to 35°C to 40°C.
  • the reaction mixture was filtered under nitrogen atmosphere.
  • the reaction mixture was washed with methyl i-butyl ether (400 mL) under nitrogen atmosphere.
  • the product obtained was dried under 650 mm Hg to 680 mm Hg of pressure for 16 hours at 40°C to 45°C to obtain the title compound.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Cardiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé de préparation d'un sel de sacubitril. Spécifiquement, la présente invention concerne un procédé de préparation d'un sel de sodium de sacubitril. La présente invention concerne en outre une forme cristalline I du sel de sodium de sacubitril et son procédé de préparation.
PCT/IB2017/052673 2016-05-06 2017-05-08 Forme cristalline d'un sel de sacubitril et procédé pour le préparer WO2017191620A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201611015863 2016-05-06
IN201611015863 2016-05-06

Publications (1)

Publication Number Publication Date
WO2017191620A1 true WO2017191620A1 (fr) 2017-11-09

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108530371A (zh) * 2017-12-27 2018-09-14 浙江天宇药业股份有限公司 一种沙库比曲钠盐、沙库比曲游离酸与乙酸的共晶物、其晶型、晶型的制备方法及用途
WO2019243799A1 (fr) * 2018-06-22 2019-12-26 Johnson Matthey Public Limited Company Forme cristalline de sacubitril, sa préparation et son utilisation

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4277601A (en) * 1979-02-15 1981-07-07 Glaxo Group Limited Preparation of sodium cefuroxime
US5217996A (en) * 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
WO2008083967A2 (fr) * 2007-01-12 2008-07-17 Novartis Ag Nouveau procédé
US20150057322A1 (en) * 2005-11-09 2015-02-26 Novartis Pharmaceuticals Corporation Compounds containing s-n-valeryl-n--valine and (2r,4s)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations
CN105461587A (zh) * 2014-08-27 2016-04-06 上海翰森生物医药科技有限公司 Ahu-377半钙盐晶型及其制备方法和应用
CN105461647A (zh) * 2014-09-28 2016-04-06 四川海思科制药有限公司 缬沙坦沙库比曲三钠盐复合物的固态形式及其制备方法和用途
WO2016051393A2 (fr) * 2014-12-26 2016-04-07 Crystal Pharmatech Inc. Forme cristalline iv de complexe supramoléculaire de trisodium comprenant du valsartan et ahu-377 ainsi que procédés associés
WO2017033212A1 (fr) * 2015-08-26 2017-03-02 Actavis Group Ptc Ehf. Préparation de sacubitril et de son sel et nouveau composés utilisés dans le procédé

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4277601A (en) * 1979-02-15 1981-07-07 Glaxo Group Limited Preparation of sodium cefuroxime
US5217996A (en) * 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
US20150057322A1 (en) * 2005-11-09 2015-02-26 Novartis Pharmaceuticals Corporation Compounds containing s-n-valeryl-n--valine and (2r,4s)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations
WO2008083967A2 (fr) * 2007-01-12 2008-07-17 Novartis Ag Nouveau procédé
CN105461587A (zh) * 2014-08-27 2016-04-06 上海翰森生物医药科技有限公司 Ahu-377半钙盐晶型及其制备方法和应用
CN105461647A (zh) * 2014-09-28 2016-04-06 四川海思科制药有限公司 缬沙坦沙库比曲三钠盐复合物的固态形式及其制备方法和用途
WO2016051393A2 (fr) * 2014-12-26 2016-04-07 Crystal Pharmatech Inc. Forme cristalline iv de complexe supramoléculaire de trisodium comprenant du valsartan et ahu-377 ainsi que procédés associés
WO2017033212A1 (fr) * 2015-08-26 2017-03-02 Actavis Group Ptc Ehf. Préparation de sacubitril et de son sel et nouveau composés utilisés dans le procédé

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108530371A (zh) * 2017-12-27 2018-09-14 浙江天宇药业股份有限公司 一种沙库比曲钠盐、沙库比曲游离酸与乙酸的共晶物、其晶型、晶型的制备方法及用途
WO2019127994A1 (fr) * 2017-12-27 2019-07-04 浙江天宇药业股份有限公司 Sel de sodium de sacubitril, eutectique de l'acide libre de sacubitril et de l'acide acétique, forme cristalline de celui-ci, procédé de préparation de la forme cristalline et utilisation associée
WO2019243799A1 (fr) * 2018-06-22 2019-12-26 Johnson Matthey Public Limited Company Forme cristalline de sacubitril, sa préparation et son utilisation

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