EP2598147A1 - Solvate de n-méthylformamide du dasatinib - Google Patents

Solvate de n-méthylformamide du dasatinib

Info

Publication number
EP2598147A1
EP2598147A1 EP11751946.2A EP11751946A EP2598147A1 EP 2598147 A1 EP2598147 A1 EP 2598147A1 EP 11751946 A EP11751946 A EP 11751946A EP 2598147 A1 EP2598147 A1 EP 2598147A1
Authority
EP
European Patent Office
Prior art keywords
dasatinib
solvate
methylformamide
crystalline
methylformamide solvate
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Withdrawn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
EP11751946.2A
Other languages
German (de)
English (en)
Inventor
Jagdev Singh Jaryal
Sudhir Singh Sanwal
Saridi Madhava Dileep Kumar
Swargam Sathyanarayana
Rajesh Kumar Thaper
Mohan Prasad
Sudershan Kumar Arora
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 EP2598147A1 publication Critical patent/EP2598147A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a N-Methylformamide solvate of dasatinib and a process for its preparation.
  • Dasatinib monohydrate of Formula A is a cyclic protein tyrosine kinase inhibitor.
  • Dasatinib monohydrate marketed under the brand name Sprycel®, is indicated for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib.
  • Sprycel® is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
  • U.S. Patent No. 6,596,746 provides a process for the preparation of dasatinib.
  • U.S. Patent No. 7,491,725 provides for the crystalline monohydrate, butanol solvate form, crystalline ethanol solvates and neat forms of dasatinib. It also provides a process for the preparation of crystalline monohydrate, butanol solvate form, crystalline ethanol solvate and neat form of dasatinib.
  • U.S. Publication No. 2009/0118297 provides for the anhydrous form, amorphous form, iso-propanol solvate, a n-propanol-dimethylsulfoxide (“DMSO”) solvate, a DMSO solvate, a hemi tetrahydrofuran (“THF”) solvate, a 2-methyl-tetrahydrofuran (“2-methyl THF”) solvate, a hemi 1,4-dioxane solvate, a pyridine solvate, a toluene solvate, a methyl isobutyl ketone (“MIBK”) solvate, a mono acetone solvate, an iso-propanol (“IPA”)- DMSO solvate, a 2-butanol-DMSO solvate, an IPA-DMF solvate, an IPA solvate, an n- propanol-DMF solvate, an n-
  • dimethoxyethane solvate dimethoxyethane solvate, a methylethylketone (“MEK”) solvate, a monochlorobenzene solvate, a propylene glycol monoethyl ether (“PGME”) solvate, a glycerol solvate, a cyclopentyl methyl ether solvate, a methyl tert butyl ether (“MTBE”) solvate, an amylalcohol solvate, a glycerol formal solvate of dasatinib and processes for their preparation.
  • MEK methylethylketone
  • PGME propylene glycol monoethyl ether
  • glycerol solvate glycerol solvate
  • MTBE methyl tert butyl ether
  • amylalcohol solvate a glycerol formal solvate of dasatinib and processes for their preparation.
  • WO 2010/062715 discloses an isosorbide dimethyl ether solvate of dasatinib, a ⁇ , ⁇ '-dimethylethylene urea solvate of dasatinib, and a N,N'-dimethyl-N,N'-propylene urea solvate of dasatinib and processes for their preparation.
  • WO 2010/067374 discloses a dimethylformamide solvate, dimethyl sulfoxide solvate, toluene solvate, isopropyl acetate solvate, crystalline Form I of dasatinib characterized by their X-ray powder diffractogram and processes for their preparation.
  • Polymorphism is defined as the ability of a substance to exist as two or more crystalline phases that have different arrangements and/or conformations of the molecule in the crystal lattice. Different polymorphs may differ in their physical properties, such as, melting point, solubility, X-ray diffraction patterns, and the like.
  • Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray Diffraction (XRD) powder as well as single crystal, DSC, IR, Solid state NMR, or Raman spectroscopy.
  • XRD X-ray Diffraction
  • the present inventors have now surprisingly found a N-Methylformamide solvate of dasatinib.
  • the novel N-Methylformamide solvate of dasatinib of the present invention is suitable for preparing pharmaceutical compositions.
  • the present invention provides for N-Methylformamide solvate of dasatinib of Formula B.
  • the present invention provides for crystalline N- Methylformamide solvate of dasatinib characterized by an X-Ray Powder Diffractogram (XRPD) substantially as depicted in Figure 1.
  • XRPD X-Ray Powder Diffractogram
  • the present invention provides for crystalline N- Methylformamide solvate of dasatinib characterized by an X-ray Powder Diffractogram which includes interplanar distances at approximately 14.21 , 7.1 1 , 5.80, 4.74, and 3.65 A.
  • Embodiments of this aspect may include one or more of the following features.
  • the crystalline N-Methylformamide solvate of dasatinib may be further characterized by an X-ray Powder Diffractogram which includes interplanar distance at approximately 7.45, 4.83, 4.29, 3.82, 3.73 and 3.49 A.
  • the crystalline N-Methylformamide solvate of dasatinib may further be characterized by a DSC thermogram substantially as depicted in Figure 2.
  • the crystalline N-Methylformamide solvate of dasatinib may have characteristic DSC endothermic peaks at about 160°C and about 287°C.
  • the crystalline N-Methylformamide solvate of dasatinib may also be further characterized by a TGA substantially as depicted in Figure 3.
  • the present invention provides for a process for the preparation of N-Methylformamide solvate of dasatinib.
  • the process includes:
  • Embodiments of this aspect may include one or more of the following features.
  • step a) is carried out at a temperature of 20°C to 50°C and the amount of N- Methylformamide is 3 to 10 times the amount of dasatinib.
  • the present invention provides for the use of N- Methylformamide solvate of dasatinib for the preparation of other polymorphic forms or solvates of dasatinib.
  • the present invention provides for a pharmaceutical composition which includes a therapeutically effective amount of N-Methylformamide solvate of dasatinib and one or more pharmaceutically acceptable excipients.
  • the present invention provides for a method for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib and for the treatment of adults with Philadelphia chromosome-positive acute
  • the method includes administering to a mammal in need thereof a therapeutically effective amount of N-Methylformamide solvate of dasatinib.
  • Figure 1 and Figure la depicts X-Ray Powder Diffractogram (XRPD) of N- Methylformamide solvate of dasatinib and the associated values, respectively.
  • XRPD X-Ray Powder Diffractogram
  • FIG. 2 depicts Differential Scanning Calorimetry (DSC) thermogram of N- Methylformamide solvate of dasatinib.
  • Figure 3 depicts Thermogravimetric Analysis (TGA) of N-Methylformamide solvate of dasatinib.
  • the XRPD was determined by using PANalytical X' Pert Pro X-Ray Powder Diffractometer in the range 0°C to 40°C 2 ⁇ and under tube voltage and current of 45 Kv and 40 mA, respectively. Copper radiation of wavelength 1.54 angstrom and Xceletor detector was used.
  • the present invention provides for the N-Methylformamide solvate of dasatinib of Formula B
  • the present invention may be in the form of crystalline N-Methylformamide solvate of dasatinib.
  • the crystalline N-Methylformamide solvate of dasatinib has an X-Ray Powder Diffractogram (XRPD) substantially as depicted in Figure 1 of the accompanied drawings.
  • the crystalline N-Methylformamide solvate of dasatinib has an X-ray Powder Diffractogram which shows characteristic peaks expressed as interplanar distance at approximately 14.21, 7.11, 5.80, 4.74, and 3.65 A.
  • the crystalline N- Methylformamide solvate of dasatinib may be further characterized by peaks expressed as interplanar distance at approximately 7.45, 4.83, 4.29, 3.82, 3.73 and 3.49 A.
  • the crystalline N-Methylformamide solvate of dasatinib has a DSC thermogram substantially as depicted in Figure 2 of the accompanied drawings.
  • the DSC thermogram shows characteristic endothermic peaks at about 160°C and about 287°C.
  • the crystalline N-Methylformamide solvate of dasatinib has a TGA
  • the present invention also provides for a process for the preparation of N- Methylformamide solvate of dasatinib.
  • the process includes: a) treating dasatinib with N-Methylformamide; and b) isolating N-Methylformamide solvate of dasatinib.
  • Dasatinib in any previously known crystalline or amorphous form prepared by methods known in the art can be used as the starting material.
  • Step a) of the process involves adding dasatinib to N-Methylformamide or adding N-Methylformamide to dasatinib in optional order of succession at a suitable temperature of between 20°C to 50°C; preferably under stirring.
  • the addition may be performed at a temperature of between 20°C to 35°C.
  • N-Methylformamide may be used in an amount of 3 to 10 times the amount of dasatinib.
  • the resultant mixture is heated to a temperature of between about 50°C to 80°C for about 15 minutes to 3 hours. For example, it may be heated at about 60°C to 70°C.
  • Step b) of the process involves isolating N-Methylformamide solvate of dasatinib through common isolation techniques, such as one or more of washing, crystallization, precipitation, cooling, filtration, filtration under vacuum, decantation and centrifugation, or a combination thereof.
  • step b) involves filtration of the reaction mass obtained in step a) to remove foreign particulate matter or treated with activated charcoal to remove coloring and other related impurities.
  • the filtrate is maintained at about 10°C to 40°C for a time period of 2 hours to 24 hours to allow the N-Methylformamide solvate of dasatinib to crystallize.
  • the isolated crystalline N-Methylformamide solvate of dasatinib may be dried at 40°C to 60°C under vacuum for about 12 hours to 28 hours.
  • N-Methylformamide solvate of dasatinib may also be used for the preparation of other polymorphic forms or solvates of dasatinib.
  • the present invention also provides for a pharmaceutical composition that includes a therapeutically effective amount of N-Methylformamide solvate of dasatinib and one or more pharmaceutically acceptable excipient.
  • the present invention also provides for a method for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib and for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
  • the method includes administering to a mammal in need thereof a therapeutically effective amount of N- Methylformamide solvate of dasatinib.
  • Dasatinib (3.24 g) was charged in a round bottom flask. N-methyl formamide (20 ml) was added to it. The reaction mixture was heated at 70°C for 30 minutes and filtered. The filtrate was collected in a beaker and kept at a temperature of 20°C to 35°C overnight for crystallization. The solid was filtered and suck dried for 30 minutes. Solid was unloaded and dried under a vacuum at 55°C to 60°C for 24 hours to obtain the title compound.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention porte sur le solvate de N-méthylformamide du dasatinib, et sur un procédé pour sa préparation.
EP11751946.2A 2010-07-30 2011-07-25 Solvate de n-méthylformamide du dasatinib Withdrawn EP2598147A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1807DE2010 2010-07-30
PCT/IB2011/053318 WO2012014149A1 (fr) 2010-07-30 2011-07-25 Solvate de n-méthylformamide du dasatinib

Publications (1)

Publication Number Publication Date
EP2598147A1 true EP2598147A1 (fr) 2013-06-05

Family

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EP11751946.2A Withdrawn EP2598147A1 (fr) 2010-07-30 2011-07-25 Solvate de n-méthylformamide du dasatinib

Country Status (4)

Country Link
EP (1) EP2598147A1 (fr)
AU (1) AU2011284341A1 (fr)
CA (1) CA2806820A1 (fr)
WO (1) WO2012014149A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2650524C2 (ru) * 2012-06-15 2018-04-16 Басф Се Многокомпонентные кристаллы, содержащие дазатиниб и определенные сокристаллобразователи
WO2017108605A1 (fr) 2015-12-22 2017-06-29 Synthon B.V. Composition pharmaceutique comprenant du dasatinib amorphe
EP3411372A4 (fr) * 2016-02-03 2019-07-17 Dr. Reddy's Laboratories Ltd. Formes solides de dasatinib et leurs procédés de préparation
US20190270735A1 (en) 2016-10-29 2019-09-05 Cipla Limited Polymorphs of Dasatinib
WO2019209908A1 (fr) 2018-04-25 2019-10-31 Johnson Matthey Public Limited Company Formes cristallines de dasatinib
US10799459B1 (en) 2019-05-17 2020-10-13 Xspray Microparticles Ab Rapidly disintegrating solid oral dosage forms containing dasatinib

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Publication number Priority date Publication date Assignee Title
RU2260592C9 (ru) 1999-04-15 2017-04-07 Бристол-Маерс Сквибб Ко. Циклические ингибиторы протеинтирозинкиназ
US7491725B2 (en) 2004-02-06 2009-02-17 Bristol-Myers Squibb Company Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors
KR20100058660A (ko) 2007-10-23 2010-06-03 테바 파마슈티컬 인더스트리즈 리미티드 다사티닙 다형체 및 이의 제조 방법
WO2010062715A2 (fr) 2008-11-03 2010-06-03 Teva Pharmaceutical Industries Ltd. Polymorphes de dasatinib et leur procédé de préparation
WO2010067374A2 (fr) 2008-12-08 2010-06-17 Hetero Research Foundation Polymorphes de dasatinib

Non-Patent Citations (1)

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Title
See references of WO2012014149A1 *

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Publication number Publication date
WO2012014149A1 (fr) 2012-02-02
AU2011284341A1 (en) 2013-02-21
CA2806820A1 (fr) 2012-02-02

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