[go: up one dir, main page]

WO2025146653A1 - Procédé de préparation de n-[4(chlorodifluorométhoxy)phényl]-6-[(3r)-3-hydroxy pyrrolidin-l-yl]-5-(1h-pyrazol-3-yl) pyridine-3-carboxamide et ses sels pharmaceutiquement acceptables - Google Patents

Procédé de préparation de n-[4(chlorodifluorométhoxy)phényl]-6-[(3r)-3-hydroxy pyrrolidin-l-yl]-5-(1h-pyrazol-3-yl) pyridine-3-carboxamide et ses sels pharmaceutiquement acceptables Download PDF

Info

Publication number
WO2025146653A1
WO2025146653A1 PCT/IB2025/050064 IB2025050064W WO2025146653A1 WO 2025146653 A1 WO2025146653 A1 WO 2025146653A1 IB 2025050064 W IB2025050064 W IB 2025050064W WO 2025146653 A1 WO2025146653 A1 WO 2025146653A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
asciminib
formula
compound
sodium
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.)
Pending
Application number
PCT/IB2025/050064
Other languages
English (en)
Inventor
Manik Reddy Pullagurla
Kiran Kumar Kothakonda
Bhaskar Reddy Pitta
Jagadeesh Babu Rangisetty
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.)
Biophore India Pharmaceuticals Pvt Ltd
Original Assignee
Biophore India Pharmaceuticals 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 Biophore India Pharmaceuticals Pvt Ltd filed Critical Biophore India Pharmaceuticals Pvt Ltd
Publication of WO2025146653A1 publication Critical patent/WO2025146653A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • C07D401/14—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 three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

Definitions

  • the present invention provides a process for the preparation of N- [4(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-l-yl]-5-(lH- pyrazol-3-yl) pyridine-3-carboxamide represented by compound of formula (1) and pharmaceutically acceptable salts thereof.
  • N-[4(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-l-yl]-5-(lH- pyrazol-3-yl) pyridine-3-carboxami dehydrogen chloride (1/1) is commonly known as Asciminib hydrochloride. It is having a molecular formula of C20H18CIF2N5O3.HCI. Asciminib hydrochloride is a white to slightly yellow powder.
  • US8829195 discloses preparation of Asciminib free base and isolation using silica gel column chromatography which is not feasible at industrial scale.
  • W02020230100 Al discloses a process for the reparation of compound N-[4- (Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-l-yl]-5-(lH-pyrazol- 5-yl)pyridine-3-carboxamide (Asciminib) or its salt comprising reaction of (R)-methyl 5-bromo-6-(3-hydroxypyrrolidin-l-yl)nicotinate (D2) with 1-1 - (tetrahydro-2H- pyran-2-yl)-l H-pyrazole-5-boronic acid, pinacol ester (D3) using K2CO3 in toluene in the presence of PdCl2(dtbpf) to provide methyl 6-((R)-3- hydroxypyrrolidin-1 -yl)-5- (1 -(tetrahydro-2H-pyran-2-yl)-l H-pyrazol-5-yl)nico
  • Figure 1 Illustrates characteristic Powdered X-Ray Diffraction (PXRD) pattern of amorphous solid dispersion of Asciminib hydrochloride (1) with HPMC-E3
  • Figure 2 Illustrates characteristic Powdered X-Ray Diffraction (PXRD) pattern of amorphous form of Asciminib free base of formula (2).
  • suitable base used herein the present invention until unless specified is selected from inorganic bases like “alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and the like; “alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, cesium bicarbonate and the like; “alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide and the like; “alkali metal alkoxides” such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, lithium methoxide, lithium ethoxide, sodium tert- butoxide, potassium tert-butoxide, lithium tert-butoxide and the like; organic bases like dimethylamine, diethylamine, diisopropyl amine, diisopropylethylamine (DIPEA), di isobutyl amine, tri
  • Coupler used herein the present invention until unless specified is selected from the group consisting of carbonyl-diimidazole (CDI), carbonyl-di (1,2,4- triazole), 1 -(3 -dimethylaminopropyl)-3 -ethylcarbodiimide hydrochloride (EDC-HC1), di cyclohexyl carbodiimide (DCC) and propane phosphonic acid cyclic anhydride (PPA).
  • CDI carbonyl-diimidazole
  • EDC-HC1 1 -(3 -dimethylaminopropyl)-3 -ethylcarbodiimide hydrochloride
  • DCC di cyclohexyl carbodiimide
  • PPA propane phosphonic acid cyclic anhydride
  • the present invention provides a process for the preparation of Asciminib salts (1), is having a purity greater than 99.5% by HPLC, as illustrated in Scheme 2.
  • Step a) of the foregoing process involves reacting methyl 5-bromo-6-chloronicotinate (10) with (R)-pyrrolidin-3-ol (9) in the presence of a base selected from organic bases, such as dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine (DIPEA), di isobutyl amine, trimethylamine, triethylamine, tri isopropyl amine, tributylamine, tert-butylamine, pyridine, piperidine, 4-dimethylamino pyridine (DMAP), or mixtures thereof, with Diisopropylethylamine (DIPEA) being particularly preferred.
  • organic bases such as dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine (DIPEA), di isobutyl amine, trimethylamine, triethylamine, tri isopropyl amine,
  • the reaction is carried out in a suitable solvent, such as ester solvents including ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec butyl acetate, isopropyl acetate, and the like, with ethyl acetate being most preferred.
  • a suitable solvent such as ester solvents including ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec butyl acetate, isopropyl acetate, and the like, with ethyl acetate being most preferred.
  • the reaction is performed under appropriate conditions, at a temperature from about 70°C to about 80°C, and maintained for a sufficient period of time to ensure the completion of the reaction, yielding the compound of formula (8).
  • the step b) of the forgoing process involves reacting the compound of formula (8) with l-(tetrahydro-2H-pyran-2-yl)-lH-pyrazole-5-boronic acid, pinacol ester of formula (7) in the presence of metal complex catalyst selected from from [(o- tol) 3 P] 2 PdC12, [t-Bu3PPdBr]2/Pd-113, (dtbpf)PdC12/Pd-118, PEPPSI, PdCl 2 (PPh 3 ) 2 , Pd(tBu 2 PhP) 2 , Pd(dppf)C12.CH 2 C12, [(t-Bu) 3 P]Pd(0), CataCXium C, Pd(tBu 2 PhP) 2 (Pd-122), Pd(dppf)Cl 2 — CH 2 C1 2 (Pd-106), (2-MeOPh) 3 P/Pd 2 (dba) 3 , and PdC12(Amphos
  • the step d) of the forgoing process involves coupling compound of formula (5) with 4-(chloro difluoromethoxy)aniline (4) or its salt thereof in the presence of coupling agent selected from carbonyl-diimidazole (CDI), carbonyl-di(l,2,4-triazole), l-(3- dimethylaminopropyl)-3 -ethylcarbodiimide hydrochloride (EDC-HC1), di cyclohexyl carbodiimide (DCC) and propane phosphonic acid cyclic anhydride (PPA); additive selected from 1 -hydroxy benzotriazole (HOBt), l-hydroxy-7-azabenzotriazole (HO At), 6-chloro-l-hydroxy-lH-benzotriazole (Cl-HOBt), hydroxy pyridines (HOPy), Imidazole or its salts; a base selected from organic bases like dimethylamine, diethylamine, diisopropyl amine,
  • the step d) of the forgoing process also involves reacting the compound of formula (6) with 4-(chloro difluoromethoxy)aniline (4) or its salt thereof in the presence of a base selected from "alkali metal alkoxides" such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, lithium methoxide, lithium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide and the like, preferably potassium tert-butoxide; in a solvent selected from “ether solvents” such as tetrahydrofuran, diethyl ether, methyl tert-butyl ether, 2-methyl tetrahydrofuran, 1,4-di oxane and the like; preferably 2-methyl tetrahydrofuran to provide N-(4-(chlorodifluoromethoxy)phenyl)-6-((R)-3-hydroxypyr
  • the step e) of the forgoing process involves reacting the compound of formula (3) with an acid selected from sulfuric acid, hydrochloric acid, phosphoric acid, and the like; preferably hydrochloric acid; in a solvent selected from “alcoholic solvents” such as methanol, ethanol, isopropyl alcohol, n-propanol, butanol and the like; preferably methanol, followed by treated with (+)-Dibenzoyl-D-tartaric acid (DBTA) to provide Asciminib as DBTA salt of formula (2a).
  • DBTA (+)-Dibenzoyl-D-tartaric acid
  • the step f) of the forgoing process involves converting the compound of formula (2a) to Asciminib of formula (2) by treating with a base selected from alkali metal carbonates" such as sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and the like, preferably sodium carbonate.
  • a base selected from alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and the like, preferably sodium carbonate.
  • Asciminib free base obtained in step f) is amorphous in nature.
  • the step g) of the forgoing process involves optionally converting the Asciminib of formula (2) to Asciminib salt (1) in presence of hydrochloric acid in a suitable solvent, to the reaction mixture, pharmaceutically acceptable excipient was added.
  • the pharmaceutically acceptable excipient selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone K-30, (PVP K-30), Copovidone, povidone, magnesium stearate, polyvinyl acetate hydroxyethyl cellulose (HEC), hydroxy propyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy propyl methyl cellulose acetate succinate (HPMC-AS), hydroxy propyl methyl cellulose -E3, (HPMC-E3), Soluplus, Neusilin, Salcaprozate sodium, Sodium caprylate, Eudragit, Eudragit-EPO, Dicalcium phosphate (DCP), croscarmellose, sodium croscarmel
  • the compound of formula (6), (5), and (2a) can be prepared in-situ and proceeds to next steps without further purification. wherein the preparation of solid dispersion of Asciminib hydrochloride does not involves isolation of Asciminib hydrochloric acid salt. In another embodiment, wherein the solid dispersion of Asciminib hydrochloride so obtained according to the present invention could be amorphous or crystalline.
  • the present invention provides a process for the purification of Asciminib (2) and its salts (1), which involves dissolving Asciminib (1) and its salts in a suitable solvent, followed by cooling the solution to a suitable temperature.
  • the final step of the process is the isolation of pure Asciminib (1) and its salts.
  • the suitable solvent used in the first step is selected from alcohol solvents or hydrocarbon solvents, with methanol or n-heptane being particularly preferred.
  • the present invention provides a process for preparing solid dispersion of Asciminib hydrochloride with at least one pharmaceutically acceptable excipient from Asciminib salt, comprising the following steps: i. dissolving Asciminib salt in a suitable solvent; ii. adjusting the pH of the solution using a suitable base; iii. adding a suitable solvent to the reaction mixture; iv. adding hydrochloric acid to the reaction mixture; v. adding at least one pharmaceutically acceptable excipient to the reaction mixture; and vi. isolating the solid dispersion of Asciminib hydrochloride.
  • the suitable solvent used in the first step is selected from ester solvents and water and/or mixture thereof, with ethyl acetate and water being particularly preferred.
  • the salt used in step i. is selected from oxalic acid, succinic acid, malonic acid, malic acid, maleic acid, mandelic acid, tartaric acid, lactic acid, acetic acid, ‘fumaric acid, benzoic acid, benzenesulfonic acid, citric acid, camphor sulfoicacid, ethane sulfonic acid, gluconic acid, glutamic acid, methanesulfonic acid, para toluene sulfonic acid, with (+)-dibenzoyl-D-tartaric acid being used.
  • Asciminib (+) DBTA salt used in step i) is amorphous in nature and X-Ray powder diffractogram as shown in figure-3.
  • the suitable base used in the second step is selected from “alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide and the like, with sodium hydroxide being particularly preferred.
  • pharmaceutically acceptable excipient selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone K-30, (PVP K-30), Copovidone, povidone, magnesium stearate, polyvinyl acetate hydroxyethyl cellulose (HEC), hydroxy propyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy propyl methyl cellulose acetate succinate (HPMC-AS), hydroxy propyl methyl cellulose -E3, (HPMC-E3), Soluplus, Neusilin, Salcaprozate sodium, Sodium caprylate, Eudragit, Eudragit-EPO, Dicalcium phosphate (DCP), croscarmellose, sodium croscarmellose, a-cyclodextrin, P-Cyclodextrin, y-cyclodextrin, hydroxypropyl beta cyclodextrin (HPBCD), Sulfobutylether-P
  • the present invention provides a process for preparing solid dispersion of Asciminib hydrochloride from Asciminib (2), comprising the following steps:
  • the pharmaceutically acceptable excipient is selected from the list as defined above, preferably Hydroxypropyl methylcellulose-E3.
  • isolating involve removal of solvent is carrying out by suitable techniques which includes but not limited to decantation, evaporation under reduced pressure, flash evaporation, vacuum drying, concentrating the reaction mixture, atmospheric distillation, distillation under reduced pressure, distillation by using a rotational distillation device such as Buchi rotavapor, agitated thin film drying (ATFD), melt extrusion, spray drying, freeze drying (lyophilization), spray-freeze drying, cooling the clear solution to lower temperatures to precipitate the solid followed by filtration by gravity or suction, thin film drying, centrifugation or any other suitable techniques known in the art.
  • suitable techniques which includes but not limited to decantation, evaporation under reduced pressure, flash evaporation, vacuum drying, concentrating the reaction mixture, atmospheric distillation, distillation under reduced pressure, distillation by using a rotational distillation device such as Buchi rotavapor, agitated thin film drying (ATFD), melt extrusion, spray drying, freeze drying (lyophilization), spray-freeze drying, cooling the clear solution to lower temperatures to
  • drying solid dispersion of Asciminib hydrochloride by a suitable drying equipment such as tray dryer, vacuum oven, rotatory cone dryer, air oven, fluidized bed dryer, spin flash dryer, flash dryer, or the like.
  • the drying can be carried out at atmospheric pressure or under reduced pressures at temperatures of less than about 100°C, less than about 60°C, less than about 40°C, or any other suitable temperatures.
  • the drying can be carried out for any period required to obtain the desired quality, such as from about 15 minutes to 10 hours or longer.
  • the present invention provides a process for the preparation of (R)-pyrrolidin-3-ol (8).
  • the process involves dissolving (2R, 4R)-4- hydroxypyrrolidine-2-carboxylic acid in cyclohexanone, resulting in the formation of (R)-pyrrolidin-3-ol (8).
  • the present invention provides a process for the preparation of l-(tetrahydro-2H-pyran-2-yl)-lH-pyrazole-5-boronic acid, pinacol ester of formula (6).
  • the process comprises two key steps: (a) converting IH-pyrazole to l-(tetrahydro- 2H-pyran-2-yl)-lH-pyrazole, and (b) further converting l-(tetrahydro-2H-pyran-2- yl)-lH-pyrazole to l-(tetrahydro-2H-pyran-2-yl)-lH-pyrazole-5-boronic acid, pinacol ester of formula (6).
  • the present invention is to provide a process for the preparation of 4-(chloro difluoromethoxy) aniline (3), which is illustrated in scheme
  • the present invention provides Asciminib hydrochloride (1) is purity greater than 99% by HPLC, preferably greater than 99.5% by HPLC, more preferably greater than 99.9% by HPLC with total impurities less than 1.0%, more preferably less than 0.5%.
  • the present invention provides Asciminib hydrochloride (1) obtained according to the present invention is having loss on drying less than 5.0% (w/w), preferably less than 3.0% (w/w).
  • the present invention provides Asciminib hydrochloride (1) obtained in the present invention is free of any degradation impurities preferably less than 0.15% and more preferably less than 0.10%(w/w).
  • the present invention provides Asciminib hydrochloride (1) obtained in the present invention have Acid impurity and THP impurity are less than
  • Methyl 5-bromo-6-chloronicotinate (10) (100 g) was dissolved in ethyl acetate (500 mL) with (R)-pyrrolidin-3-ol (9) (45 g) and diisopropylethylamine (110 g) at room temperature. The mixture was heated to 70-85°C and stirred. Upon completion, the reaction was cooled to room temperature, and IN hydrochloric acid (500 mL) was added. The organic layer was separated, and additional ethyl acetate was added to the aqueous layer, stirred, and separated again. The combined organic layers were washed with water and sodium chloride solution and the solvent was distilled off.
  • the reaction mixture was cooled to 10- 15°C, and concentrated hydrochloric acid (25 mL) in methanol (500 mL) was added. After stirring, the pH was adjusted to 4.0-5.0 with sodium hydroxide solution at 0- 5°C, then further adjusted to 7.5-8.5 with 1% sodium hydroxide solution. The solvent was distilled off, and the mixture was cooled to 25-35°C. Ethyl acetate (1000 mL) and water (1000 mL) were added and stirred. The organic layer was separated, and the aqueous layer was extracted with additional ethyl acetate.
  • Example 8 Preparation of amorphous solid dispersion of Asciminib hydrochloride (1) with Hydroxypropyl methylcellulose-E3 (HPMC-E3)
  • N-[4-(Chloro difluoromethoxy )phenyl]-6-[(3 R)-3-hy droxypyrrolidin- 1 -yl]-5-(lH- pyrazol-3-yl)pyridine-3 -carboxamide (2) was dissolved in methanol (3000 mL) at 25- 35°C. Concentrated hydrochloric acid (30 mL) was added, and the mixture was stirred. Hydroxypropyl methylcellulose-E3 (150 g) was then added, and the reaction mass was heated to 60-65°C while stirring.
  • Example 9 Preparation of Asciminib hydrochloride (la) N-(4-(chloro difluoromethoxy) phenyl)-6-((R)-3-hydroxypyrrolidin-l-yl)-5-(l- (tetrahydro-2H-pyran-2-yl)-lH-pyrazol-5-yl) nicotinamide (3) (2 gm) was dissolved in methanol (16 ml) at room temperature. To this 37% hydrochloric acid was added at the same temperature for 1-2 hours. On completion of the reaction, 30% sodium hydroxide (2 ml) solution and neutral carbon was added to the reaction mass at 50°C and stirred for 30 minutes.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne un procédé de préparation de N-[4(chlorodifluorométhoxy)phényl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-3-yl)pyridine-3-carboxamide représenté par le composé de formule (1) et des sels pharmaceutiquement acceptables de celui-ci. (1)
PCT/IB2025/050064 2024-01-04 2025-01-03 Procédé de préparation de n-[4(chlorodifluorométhoxy)phényl]-6-[(3r)-3-hydroxy pyrrolidin-l-yl]-5-(1h-pyrazol-3-yl) pyridine-3-carboxamide et ses sels pharmaceutiquement acceptables Pending WO2025146653A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN202441000659 2024-01-04
IN202441000659 2024-01-04

Publications (1)

Publication Number Publication Date
WO2025146653A1 true WO2025146653A1 (fr) 2025-07-10

Family

ID=96300153

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2025/050064 Pending WO2025146653A1 (fr) 2024-01-04 2025-01-03 Procédé de préparation de n-[4(chlorodifluorométhoxy)phényl]-6-[(3r)-3-hydroxy pyrrolidin-l-yl]-5-(1h-pyrazol-3-yl) pyridine-3-carboxamide et ses sels pharmaceutiquement acceptables

Country Status (1)

Country Link
WO (1) WO2025146653A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008107911A2 (fr) * 2007-03-05 2008-09-12 Lupin Limited Nouveau procédé de préparation du chlorhydrate de duloxétine
US8829195B2 (en) * 2012-05-15 2014-09-09 Novartis Ag Compounds and compositions for inhibiting the activity of ABL1, ABL2 and BCR-ABL1
WO2022068876A1 (fr) * 2020-09-29 2022-04-07 Shenzhen Pharmacin Co., Ltd. Compositions pharmaceutiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008107911A2 (fr) * 2007-03-05 2008-09-12 Lupin Limited Nouveau procédé de préparation du chlorhydrate de duloxétine
US8829195B2 (en) * 2012-05-15 2014-09-09 Novartis Ag Compounds and compositions for inhibiting the activity of ABL1, ABL2 and BCR-ABL1
WO2022068876A1 (fr) * 2020-09-29 2022-04-07 Shenzhen Pharmacin Co., Ltd. Compositions pharmaceutiques

Similar Documents

Publication Publication Date Title
RU2577331C2 (ru) Кристаллическое основание миноциклина и способы его получения
US9938283B2 (en) Crystalline form of baricitinib
US10376494B2 (en) Carboxamide derivative and its diastereomers in stable crystalline form
CA2694242C (fr) Procede d'introduction d'une chaine laterale hydroxyethoxy dans le bosentan
TWI750685B (zh) 二取代吡唑化合物
AU2013301156B2 (en) Process for the preparation of pemetrexed and lysin salt thereof
EP2545063A2 (fr) Procede perfectionne de preparation de tenofovir disoproxil fumarate
KR20230043910A (ko) 벨루모수딜 및 벨루모수딜 염의 고체 상태 형태
WO2016178150A1 (fr) Nouveaux polymorphes d'axitinib
WO2008135795A2 (fr) Nouvelles formes polymorphes
WO2020208592A1 (fr) Procédé de préparation d'erdafitinib, sa purification et dispersion solide amorphe
CN120247907A (zh) Iap拮抗剂化合物和中间体及其合成方法
WO2016005874A1 (fr) Procédé pour la préparation du régorafénib et ses formes cristallines
KR20110120941A (ko) 결정 다형성 형태 631
WO2019008520A1 (fr) Procédé de préparation d'alectinib ou d'un sel pharmaceutiquement acceptable de celui-ci
CZ2005679A3 (cs) Zpusob odstranování trifenylmethanové chránící skupiny u prekursoru antihypertensních léciv
WO2025146653A1 (fr) Procédé de préparation de n-[4(chlorodifluorométhoxy)phényl]-6-[(3r)-3-hydroxy pyrrolidin-l-yl]-5-(1h-pyrazol-3-yl) pyridine-3-carboxamide et ses sels pharmaceutiquement acceptables
CA2615345A1 (fr) Forme cristalline du rabeprozole sodique
EP2162434B1 (fr) Sels de périndopril
AU2010313521B2 (en) Methods of preparing 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone
WO2011096697A2 (fr) Procédé de préparation de voriconazole à l'aide de nouveaux intermédiaires
WO2022040111A2 (fr) Formes à l'état solide de sels de l'erdafitinib et procédés de préparation de l'erdafitinib
WO2022009235A1 (fr) Procédé de préparation de fumarate de giltéritinib
WO2017056031A1 (fr) Procédé de préparation de lumacaftor
WO2023157030A1 (fr) Procédé de préparation de 1-(4-(((6-amino-5-(4-phénoxyphényl)pyrimidin-4-yl) amino)méthyl)pipéridin-1-yl)prop-2-én-1-one

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: 25736362

Country of ref document: EP

Kind code of ref document: A1