WO2018173071A1 - Nouvelles formes cristallines de citrate d'ixazomib et son procédé de préparation - Google Patents

Nouvelles formes cristallines de citrate d'ixazomib et son procédé de préparation Download PDF

Info

Publication number
WO2018173071A1
WO2018173071A1 PCT/IN2018/050157 IN2018050157W WO2018173071A1 WO 2018173071 A1 WO2018173071 A1 WO 2018173071A1 IN 2018050157 W IN2018050157 W IN 2018050157W WO 2018173071 A1 WO2018173071 A1 WO 2018173071A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
solvents
ixazomib citrate
crystalline form
compound
Prior art date
Application number
PCT/IN2018/050157
Other languages
English (en)
Inventor
Thirumalai Rajan Srinivasan
Eswaraiah Sajja
Rajeshwar Reddy Sagyam
Srinivasulu Rangineni
Original Assignee
Msn Laboratories Private Limited, R&D Center
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 Msn Laboratories Private Limited, R&D Center filed Critical Msn Laboratories Private Limited, R&D Center
Publication of WO2018173071A1 publication Critical patent/WO2018173071A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • 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 pertains to crystalline forms of Ixazomib citrate and its process for preparation thereof.
  • the chemical structure of said compound represented by the following formula-I.
  • Ixazomib citrate The chemical name l,3,2-dioxaborolane-4,4-diacetic acid, 2-[(li?)-l-[[2-[(2,5- dichlorobenzoyl) amino] acetyl] amino] -3-methylbutyl]-5-oxo- or 4-(R,S)-(carboxymethyl)-2- ((R)-l-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)-6-oxo-l,3,2-dioxaborinane-4- carboxylic acid are generically known as Ixazomib citrate. Ixazomib citrate is a prodrug, rapidly hydrolyzes under physiological conditions to its biologically active form, boronic acid or Ixazomib which is shown in below chemical structure.
  • Ixazomib belongs to the chemical class of peptide boronic acid derivative compounds and inhibits the chymotrypsin-like subunit (beta 5) of the 20S proteasome reversibly.
  • Ixazomib citrate is a proteasome inhibitor used in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.
  • Ixazomib citrate was approved under the brand name of Ninlaro® by USFDA in November 2015 to Millennium Pharmaceuticals Inc.
  • Ninlaro® capsule was available with dosage strength of 2.3mg, 3mg and 4mg for oral administration.
  • WO 2016/155684 discloses a process for the preparation of Ixazomib citrate and its polymorph Form-3.
  • the process described in WO '684 is treating of the compound of formula-V with boric acid and citric acid to provide the Ixazomib citrate.
  • WO 2016/165677 discloses ethanol and isopropanol solvate forms of Ixazomib citrate.
  • polymorphism occurred because the difference in the physical properties of different crystalline forms results from the orientation and intermolecular interactions of adjacent molecules or complexes in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula yet having distinct advantageous physical properties compared to other crystalline forms of the same compound.
  • the first aspect of the present invention is to provide novel crystalline form of Ixazomib citrate of formula-I ((herein after designated as "crystalline Form-M”) and its process for preparation thereof.
  • the second aspect of the present invention is to provide another novel crystalline form of Ixazomib citrate of formula-I (herein after designated as "crystalline Form-S") and its process for preparation thereof.
  • the third aspect of the present invention is to provide solid dispersion of Ixazomib citrate of formula-I and its process for preparation thereof.
  • the fourth aspect of the present invention is to provide a novel crystalline form of Ixazomib citrate of formula-I (hereinafter referred as "crystalline Form-N") and process for preparation thereof.
  • the fifth aspect of the present invention is to provide a novel crystalline form of Ixazomib citrate of formula-I (hereinafter referred as "crystalline Form-L”) and process for preparation thereof.
  • the sixth aspect of the present invention is to provide a novel crystalline form of Ixazomib citrate of formula-I (hereinafter referred as "crystalline Form-R") and process for preparation thereof.
  • crystalline Form-R novel crystalline form of Ixazomib citrate of formula-I
  • the seventh aspect of the present invention is to provide a process for the preparation of Ixazomib citrate of formula-I.
  • FIG.l Illustrates the Powdered X-Ray Diffraction (PXRD) Pattern of the crystalline Form-M of Ixazomib citrate.
  • FIG.2 Illustrates the PXRD Pattern of the crystalline Form-S of Ixazomib citrate.
  • FIG.3 Illustrates a characteristic Powdered X-Ray Diffraction (PXRD) pattern of crystalline Form-N of Ixazomib citrate.
  • PXRD Powdered X-Ray Diffraction
  • FIG.4 Illustrates a characteristic Powdered X-Ray Diffraction (PXRD) pattern of crystalline Form-L of Ixazomib citrate.
  • PXRD Powdered X-Ray Diffraction
  • FIG.5 Illustrates a characteristic Powdered X-Ray Diffraction (PXRD) pattern of crystalline Form-R of Ixazomib citrate.
  • PXRD Powdered X-Ray Diffraction
  • FIG.6 Illustrates the PXRD Pattern of the solid dispersion of Ixazomib citrate with polyvinylpyrrolidone (PVP K-30).
  • FIG.7 Illustrates the PXRD Pattern of the solid dispersion of Ixazomib citrate with hydroxy propyl methyl cellulose (HPMC) and hydroxy propyl cellulose (HPC).
  • FIG.8 Illustrates the PXRD Pattern of the solid dispersion of Ixazomib citrate with hydroxypropyl beta cyclodextrin.
  • suitable solvent refers to the solvent selected from “alcoholic solvents” such as methanol, ethanol, n-propanol, isopropanol, n-butanol, teri-butanol and isobutanol; “chloro solvents” such as to methylene chloride, chloroform, ethylene dichloride and carbon tetra chloride; “ketone solvents” such as acetone, methyl ethyl ketone, methyl isobutyl ketone; “hydrocarbon solvents” such as n-hexane, heptane, cyclohexane, benzene, toluene, cycloheptane, methylcyclohexane, m-, o-, or p- xylene and the like; “nitrile solvents” such as acetonitrile; “ester solvents” such as ethyl acetate
  • suitable base refers to the bases selected from alkali metal hydroxides such as sodium hydroxide, potassium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate and alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate; organic bases such as alkali metal alkoxides such as sodium tertiary butoxide, potassium tertiary butoxide; methylamine, ethylamine, isopropylamine, diisopropyl ethylamine, triethylamine / and ammonia or their aqueous solution.
  • alkali metal hydroxides such as sodium hydroxide, potassium hydroxide
  • alkali metal carbonates such as sodium carbonate, potassium carbonate and alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate
  • organic bases such as alkali metal alkoxides such as sodium tertiary butoxide, potassium tertiary butoxide
  • suitable condensing agent or suitable coupling agent refers to ⁇ , ⁇ -dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide(DIC), carbonyldiimidazole (CDI), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1), (l-[bis(dimethylamino)methylene]-lH-l ,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluoro phosphate (HATU), alkyl or aryl chloroformates such as ethyl chloroformate, benzylchloroformate, diphenylphosphoryl azide (DPPA), benzotriazol-l-yl-oxytripyrrolidino phosphonium hexafluorophosphate (PyBOP)
  • the first aspect of the present invention provides crystalline Form-M of Ixazomib citrate of formula-I and it is characterized by its PXRD pattern substantially in accordance with figure- 1.
  • the further embodiment of the present invention provides a process for the preparation of crystalline Form-M of Ixazomib citrate, comprising:
  • step-a) adding suitable anti-solvent to the reaction mixture obtained in step-a) at a suitable temperature
  • step a) isolating crystalline Form-M of Ixazomib citrate of formula-I.
  • the suitable solvent is selected from hydrocarbon solvents, chloro solvents, ester solvents, polar aprotic solvents, ether solvents, alcoholic solvents, polar solvents and/or mixtures thereof and the suitable temperature is 0°C to reflux temperature of a solvent used;
  • the suitable anti-solvent is selected from the hydrocarbon solvents such as n- hexane, heptane, benzene, toluene, xylene, cyclohexane and the like and the suitable temperature is 0-5°C; in step-e) isolation may be affected by removing the solvent and then dried for morethan 7 hours.
  • Suitable techniques which may be used for the removal of solvent include filtration, using a rotational distillation device such as a Buchi Rotavapor, spray drying, agitated thin film drying (“ATFD”), freeze drying (lyophilization), and the like or any other suitable technique.
  • a rotational distillation device such as a Buchi Rotavapor
  • spray drying agitated thin film drying
  • freeze drying lyophilization
  • the preferred embodiment of the present invention provides a process for the preparation of crystalline Form-M of Ixazomib citrate of formula-I, comprising:
  • step-d) isolating the product obtained in step-d) and drying for about 7 hours to get crystalline Form-M of Ixazomib citrate.
  • the second aspect of the present invention provides crystalline Form-S of Ixazomib citrate of formula-I and it is characterized by its PXRD pattern substantially in accordance with figure-2.
  • the further embodiment of the present invention provides a process for the preparation of crystalline Form-S of Ixazomib citrate, comprising:
  • step-a) adding suitable anti-solvent to the reaction mixture obtained in step-a) at a suitable temperature
  • step e) isolating the product obtained in step-d) and then drying for about 5 hours to get crystalline Form-S of Ixazomib citrate of formula-I.
  • the suitable solvent is selected from hydrocarbon solvents, chloro solvents, ester solvents, polar aprotic solvents, ether solvents, alcoholic solvents, polar solvents and/or mixtures thereof and the suitable temperature is 25°C to reflux temperature of a solvent used
  • step-b) the suitable anti-solvent is selected from the hydrocarbon solvents such as n- hexane, heptane, benzene, toluene, xylene, cyclohexane and the like and the suitable temperature is 0-5°C
  • step-e) isolation may be affected by removing the solvent and then drying for about 5 hours; suitable techniques which may be used for the removal of solvent including filtration, using a rotational distillation device such as a Buchi Rotavapor, spray drying, agitated thin film drying ("
  • the preferred embodiment of the present invention provides a process for the preparation of crystalline Form-S of Ixazomib citrate, comprising the steps of: a) dissolving Ixazomib citrate of formula-I in a mixture of tetrahydrofuran and ethanol at 60-65°C,
  • step-d) isolating the product obtained in step-d) and drying for about 5 hours to get crystalline Form-S of Ixazomib citrate.
  • the third aspect of the present invention provides crystalline Form-N of Ixazomib citrate.
  • Crystalline Form-N of the present invention is characterized by its powder X-ray diffraction (PXRD) pattern having characteristic peaks at about 7.7, 13.1, 14.1, 18.1 and 22.6 ⁇ 0.2 degrees of two-theta.
  • PXRD powder X-ray diffraction
  • the crystalline Form-N of Ixazomib citrate is further characterized by its powder X- ray diffraction (PXRD) pattern having characteristic peaks at about 7.7, 8.4, 11.4, 13.1, 14.1 18.1, 18.8, 21.0, 22.6, 30.2 and 31.3 ⁇ 0.2 degrees of two-theta.
  • PXRD powder X- ray diffraction
  • the crystalline Form-N of Ixazomib citrate is further characterized by its PXRD pattern as illustrated in figure-3.
  • said crystalline Form-N is stable under stress conditions at 60°C for 24 hours, 10 tons of pressure, hygroscopic conditions at 75% RH for 24 hours and under UV light at 254nm for 24 hours.
  • step-a) the suitable organic acid is selected from C1-C5 carboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid or mixtures thereof; the suitable temperature is ranges between 25°C to the reflux temperature of the acid which is used; in step-c) the suitable solvent is selected from "ether solvents” such as methyl tert -butyl ether, dimethyl ether, diisopropyl ether, diethyl ether, 1,3-dioxane, 1,4-dioxane tetrahydrofuran; "hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, petroleum ether, benzene, toluene,
  • the preferred embodiment of the present invention provides a process for the preparation of crystalline Form-N of Ixazomib citrate, comprising:
  • step-c) combining the reaction mixture obtained in step-c) with methyl tert-butyl ether, e) filtering the precipitated solid and drying at about 100°C to provide the crystalline Form-N of Ixazomib citrate.
  • the another embodiment of the present invention provides crystalline Form-N of Ixazomib citrate can be prepared from any other crystalline forms of Ixazomib citrate known in the art or treating the compound of formula-V with isobutyl boronic acid, citric acid and optionally in presence of crystalline Form-N seed crystal.
  • the fourth aspect of the present invention provides crystalline Form-L of Ixazomib citrate.
  • Crystalline Form-L of the present invention is characterized by its powder X-ray diffraction (PXRD) pattern having characteristic peaks at about 7.2, 7.6, 11.1, 16.7, 19.7, 21.6 and 29.8 ⁇ 0.2 degrees of two-theta.
  • the crystalline Form-L of Ixazomib citrate is further characterized by its PXRD pattern as illustrated in figure-4.
  • the other embodiment of the present invention provides a process for the preparation of crystalline Form-L of Ixazomib citrate, comprising:
  • step-b) combining the reaction mixture obtained in step-b) with a suitable solvent at a suitable temperature
  • step-a) the suitable organic acid is selected from C1-C5 carboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid or mixtures thereof; the suitable temperature is ranges between 25°C to the reflux temperature of the acid which is used; in step-c) the suitable solvent is selected from "ether solvents" such as methyl tert -butyl ether, dimethyl ether, diisopropyl ether, diethyl ether, 1,3-dioxane, 1,4-dioxane tetrahydrofuran; "hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, petroleum ether, benzene, toluene, xylene; ester solvents such as methyl acetate, ethyl acetate, is
  • the preferred embodiment of the present invention provides a process for the preparation of crystalline Form-L of Ixazomib citrate, comprising:
  • step-c) combining the reaction mixture obtained in step-c) with methyl tert-butyl ether, e) filtering the precipitated solid to provide crystalline Form-L of Ixazomib citrate.
  • the fifth aspect of the present invention provides Ixazomib citrate crystalline Form-R.
  • Crystalline Form-R of the present invention is characterized by its powder X-ray diffraction (PXRD) pattern having characteristic peaks at about 6.0, 10.4 and 14.1 ⁇ 0.2 degrees of two-theta.
  • the crystalline Form-R of Ixazomib citrate is further characterized by its PXRD pattern as illustrated in figure-5.
  • the another embodiment of the present invention provides a process for the preparation of Ixazomib citrate crystalline Form-R, comprising: a) providing Ixazomib citrate in a mixture of benzoyl alcohol, acetic acid and isobutyl acetate at 25-30°C,
  • the sixth aspect of the present invention provides a solid dispersion of Ixazomib citrate of formula-I in combination with one or more pharmaceutically acceptable carrier.
  • the composition of the solid dispersion consist of a ratio of the amount of the compound of formula-I to the amount of the pharmaceutically acceptable carrier therein ranges from about 1 : 0.1 to 1 : 10 (w/w).
  • the composition of Ixazomib citrate with pharmaceutically acceptable carrier preferably microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC), hydroxypropylcellulose (HPC), hydroxy propyl beta cyclodextrin, hypromellose acetate succinate (HPMCAS) is about 1 :0.1 to 1: 10 (w/w).
  • the further embodiment of the present invention provides a process for the preparation of a solid dispersion of Ixazomib citrate of formula-I, comprising:
  • the suitable solvent is selected from alcoholic solvents, chloro solvents, ester solvents, polar aprotic solvents, ketone solvents, hydrocarbon solvents and polar solvent like water or mixture thereof;
  • the suitable pharmaceutically acceptable carrier is selected from cellulose derivatives such as cellulose acetate, cellulose nitrate, cellulose xanthate, carboxy methyl cellulose, micro crystalline cellulose, methyl cellulose, ethyl cellulose and hydroxy ethyl cellulose, hydroxy propyl methyl, hydroxy propyl beta cyclodextrin; polyvinylpyrrolidone;
  • the suitable temperature is ranging from 25°C to reflux temperature of the solvent which is used; in step-b) isolation may be affected by removing the solvent; suitable techniques which may be used for the removal of solvent include filtration, using a rotational distillation device such as a Buchi Rotavapor, spray drying,
  • the seventh aspect of the present invention provides a process for the preparation of Ixazomib citrate of the formula-I, comprising: a) reacting the compound of formula-II with glycine in presence of a base in a suitable solvent to provide the compound of formula-Ill,
  • Formula-II Glycine Formula-Ill b) reacting the compound of formula-Ill with the compound of formula-IV in presence of suitable coupling agent, suitable base in a suitable solvent to provide the compound of
  • step-a) step-b) and step-c) the suitable solvent is selected from alcoholic solvents such as methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol and isobutanol; chloro solvents such as methylene chloride, chloroform; ketone solvents such as acetone, methyl ethyl ketone; hydrocarbon solvents such as n-hexane, heptane, toluene, benzene; nitrile solvents” such as acetonitrile; "ester solvents” such as ethyl acetate, methyl acetate, isopropyl acetate, butyl acetate and tert -butyl acetate; ether solvents such as tetrahydrofuran, diethyl ether and methyl tert-butyl ether; polar solvents such as water; polar solvents such
  • the preferred embodiment of the present invention provides a process for the preparation of Ixazomib citrate of the formula-I, comprising: a) reacting the compound of formula-II with glycine in presence of sodium hydroxide or its aqueous solution in water and tetrahydrofuran to provide the compound of formula- Ill,
  • Formula-II Glycine Formula-Ill b) reacting the compound of formula-Ill with the compound of formula-IVa in presence of 0-(lH-benzotriazol-l-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), diisopropylethylamine (DIPEA) in dimethylformamide to provide the compound of formula-V,
  • TBTU 0-(lH-benzotriazol-l-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate
  • DIPEA diisopropylethylamine
  • the oral pharmaceutical composition may contain crystalline Form-M, crystalline Form-S, crystalline Form-N, crystalline Form-L, crystalline Form-R and solid dispersion of amorphous Ixazomib citrate obtained by the present invention and one or more additional ex- cipients such as diluents, binders, disintegrants and lubricants.
  • diluents include lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, microcrystalline cellulose, magnesium stearate and mixtures thereof.
  • Exemplary binders are selected from L-hydroxy propyl cellulose, povidone, hydroxypropyl methyl cellulose, hydroxylethyl cellulose and pre- gelatinized starch.
  • Exemplary disintegrants are selected from croscarmellose sodium, cros -povidone, sodium starch glycolate and low substituted hydroxylpropyl cellulose.
  • Exemplary lubricants are selected from sodium stearyl fumarate, magnesium stearate, zinc stearate, calcium stearate, stearic acid, talc, glyceryl behenate and colloidal silicon dioxide.
  • Example-2 Preparation of 2,5-dichloro-N-(2-(((R)-3-methyl-l-((3aS,4S,6S,7aR)-3a,5,5- trimethylhexahydro-4,6-methanobenzo[d][l,3,2]dioxaborol-2-yl)butyl)amino)-2-oxoethyl )benzamide compound of formula (V).
  • Example-3 Preparation of Ixazomib citrate.
  • the compound of formula- V (10 gms) was added to toluene (150 ml) at 25-30°C.
  • Methanol (50 ml) was added to the reaction mixture at 25-30°C.
  • Isobutyl boronic acid (2.47 gms) and citric acid (4.65 gms) were added to the reaction mixture at 25-30°C. Heated the reaction mixture to 70-75 °C and filtered the reaction mixture through hiflow bed, washed with methanol. Stirred the obtained filtrate for 5 hours at 70-75°C. Distilled off the solvent completely from the reaction mixture under reduced pressure, co-distilled with methanol and again co-distilled with ethyl acetate.
  • Example-4 Preparation of Ixazomib citrate.
  • the compound of formula- V (20.0 gms) was added to ethyl acetate (400 ml) at 25- 30°C.
  • Example-5 Preparation of crystalline Form-M of Ixazomib citrate
  • Example-6 Preparation of crystalline Form-S of Ixazomib citrate
  • Ixazomib citrate (1.0 gm) was dissolved in a mixture of tetrahydrofuran/ethanol solution (10 ml, (1: 1)) at 60-65°C.
  • n-Heptane (30 ml) was added to the reaction mixture at 25- 30°C. Cooled the reaction mixture to 0-5°C and stirred for 1 hour at same temperature. Filtered the precipitated solid, washed with n-heptane and then dried for about 5 hours to get the title compound. (Yield: 800 mgs).
  • Example 7 Preparation of crystalline Form-N of Ixazomib citrate.
  • Ixazomib citrate (5 gm) was added to formic acid (75 ml) at 25-30°C and stirred the reaction mixture for 10 min at same temperature. Reaction mixture was cooled to 0-5°C and stirred for 1 hour. Methyl tert-butyl ether (MTBE) (150 ml) was added to the reaction mixture at 0-5°C and stirred for 7 hours at same temperature. Filtered the precipitated solid and dried at 100°C for about 3 hours to afford crystalline Form-N of Ixazomib citrate.
  • MTBE Methyl tert-butyl ether
  • Example 8 Preparation of crystalline Form-L of Ixazomib citrate.
  • Ixazomib citrate (5 gm) was added to formic acid (75 ml) at 25-30°C and stirred the reaction mixture for 10 min at same temperature. Reaction mixture was cooled to 0-5°C and stirred for 1 hour. Methyl tert-butyl ether (MTBE) (150 ml) was added to the reaction mixture at 0-5°C and stirred for 7 hours at same temperature. Filtered the precipitated solid and dried for 15 min to afford crystalline Form-L of Ixazomib citrate.
  • MTBE Methyl tert-butyl ether
  • Ixazomib citrate (1 gr) was added to a mixture of acetic acid, benzoyl alcohol and isobutyl acetate (25 ml, 1: 1: 1) at 25-30°C. Heated the reaction mixture to 75-80°C and stirred for 1 hour at the same temperature. Cooled the reaction mixture to 0-5°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid, washed with isobutyl acetate and then dried to afford the title compound. (Yield: 600 mg).
  • Ixazomib citrate 1.0 gms
  • PVP K-30 polyvinylpyrrolidone
  • Example-13 Preparation of solid dispersion of Ixazomib citrate

Landscapes

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

Abstract

La présente invention concerne de nouvelles formes cristallines de citrate d'ixazomib de formule I et son procédé de préparation. La structure chimique du composé de l'invention est représentée par la formule I suivante. La présente invention concerne également un procédé de préparation de citrate d'ixazomib de formule I ainsi que ses dispersions solides.
PCT/IN2018/050157 2017-03-20 2018-03-20 Nouvelles formes cristallines de citrate d'ixazomib et son procédé de préparation WO2018173071A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN201741009635 2017-03-20
IN201741009635 2017-03-20
IN201741044474 2017-12-11
IN201741044474 2017-12-11

Publications (1)

Publication Number Publication Date
WO2018173071A1 true WO2018173071A1 (fr) 2018-09-27

Family

ID=63585067

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2018/050157 WO2018173071A1 (fr) 2017-03-20 2018-03-20 Nouvelles formes cristallines de citrate d'ixazomib et son procédé de préparation

Country Status (1)

Country Link
WO (1) WO2018173071A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117964650A (zh) * 2024-03-28 2024-05-03 成都硕德药业有限公司 一种枸橼酸伊沙佐米的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009154737A1 (fr) * 2008-06-17 2009-12-23 Millennium Pharmaceuticals, Inc. Composés de borates esters et compositions pharmaceutiques contenant des composés
WO2016155684A1 (fr) * 2015-04-03 2016-10-06 Zentiva, K.S. Procédé de préparation de citrate d'ixazomib

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009154737A1 (fr) * 2008-06-17 2009-12-23 Millennium Pharmaceuticals, Inc. Composés de borates esters et compositions pharmaceutiques contenant des composés
WO2016155684A1 (fr) * 2015-04-03 2016-10-06 Zentiva, K.S. Procédé de préparation de citrate d'ixazomib

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117964650A (zh) * 2024-03-28 2024-05-03 成都硕德药业有限公司 一种枸橼酸伊沙佐米的制备方法
CN117964650B (zh) * 2024-03-28 2024-06-07 成都硕德药业有限公司 一种枸橼酸伊沙佐米的制备方法

Similar Documents

Publication Publication Date Title
US20190321363A1 (en) Process for the preparation of elagolix sodium and its polymorph
US10703731B2 (en) Process for the preparation of Trisodium (4- {[1S,3R)-1-([1,1′-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoate)-(N-petanoyl-N-{[2′-(1H-tetrazol-1-1D-5-yl)[1,1′-biphenyl]-4-yl]methyl}- L-valinate) and its polymorphs thereof
WO2021001858A1 (fr) Procédé amélioré pour la préparation d'acide 2-(3,5-dichlorophényl)-1,3-benzoxazole-6-carboxylique ou de ses sels pharmaceutiquement acceptables et leurs polymorphes
WO2019026014A1 (fr) Procédés de préparation de lifitegrast et de ses intermédiaires
EP2539321A1 (fr) Intermédiaires de saxagliptine, formes polymorphiques de saxagliptine et leurs procédés de synthèse
CA3068522A1 (fr) Procede pour la preparation de lifitegrast et d'intermediaires de celui-ci
WO2019097547A1 (fr) Procédé amélioré pour la préparation de lifitegrast ou de sels de celui-ci
CA3165995A1 (fr) Formes solides de mavacamten et leur procede de preparation
WO2019016828A1 (fr) Nouveaux procédés pour la préparation de chlorhydrate de trans-n-{4-[2-[4-(2,3-dichlorophényl)pipérazine-1-yl]éthyl] cyclohexyl}-n',n'-diméthyl urée et polymorphes de celui-ci
US11498902B2 (en) Process for the preparation of Cabozantinib and its pharmaceutically acceptable salts thereof
WO2017070878A1 (fr) Dérivés d'acides aminés estérifiés à fonction c14-hydroxyle de triptolide, procédé pour leur préparation et utilisation correspondante
WO2018173071A1 (fr) Nouvelles formes cristallines de citrate d'ixazomib et son procédé de préparation
US20220306650A1 (en) Process and polymorphic forms of bictegravir and its pharmaceutically acceptable salts or co-crystals thereof
US20220356165A1 (en) Solid state forms of roluperidone and salts thereof
US20110039937A1 (en) Novel process for the preparation of vorinostat
WO2019142206A1 (fr) Procédé amélioré pour la préparation de succinate de ribociclib et de ses nouvelles formes cristallines associées
AU2011307346A1 (en) Solid state forms of a potent HCV inhibitor
US20240010632A1 (en) Solid state forms of erdafitinib salts and processes for preparation of erdafitinib
WO2018029699A1 (fr) Formes à l'état solide de (2e)-n-hydroxy-3-[3- (phénylsulfamoyl) phényl] prop-2-énamide et leur procédé de préparation
WO2018134843A1 (fr) Formes polymorphes de (e)-n-{4-[3-chloro-4-((pyridin-2-yl-méthoxy)-anilino]-3-cyano-7-éthoxyquinolin-6-yl)-4-(diméthylamino)-but-2-énamide, son sel de maléate et un procédé de préparation correspondant
US20220153744A1 (en) Solid state forms of acalabrutinib
US11465974B2 (en) Crystalline polymorphs of Pracinostat and Pracinostat salts
WO2022009235A1 (fr) Procédé de préparation de fumarate de giltéritinib
WO2021117062A1 (fr) Procédé de préparation de 4-[7-(6-cyano-5-trifluorométhylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-n-méthylbenzamide et de ses polymorphes
WO2018134842A1 (fr) Procédé de préparation d'acide carbamique, d'ester de n,n'-[[1,1'-biphényl] -4,4'-diylbis]- 1 h-imidazole-5,2 diyi-(2s)-2,1-pyrrolidinédiyl[(1 s)-1-(1-méthyléthyl)-2-oxo-2,1-éthanediyl]]] bis-,c,c'-diméthyl et ses sels et 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: 18770885

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: 18770885

Country of ref document: EP

Kind code of ref document: A1