WO2012014149A1 - N-methylformamide solvate of dasatinib - Google Patents
N-methylformamide solvate of dasatinib Download PDFInfo
- Publication number
- WO2012014149A1 WO2012014149A1 PCT/IB2011/053318 IB2011053318W WO2012014149A1 WO 2012014149 A1 WO2012014149 A1 WO 2012014149A1 IB 2011053318 W IB2011053318 W IB 2011053318W WO 2012014149 A1 WO2012014149 A1 WO 2012014149A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dasatinib
- solvate
- methylformamide
- crystalline
- methylformamide solvate
- Prior art date
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.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2806820A CA2806820A1 (en) | 2010-07-30 | 2011-07-25 | N-methylformamide solvate of dasatinib |
AU2011284341A AU2011284341A1 (en) | 2010-07-30 | 2011-07-25 | N-Methylformamide solvate of dasatinib |
EP11751946.2A EP2598147A1 (en) | 2010-07-30 | 2011-07-25 | N-methylformamide solvate of dasatinib |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1807DE2010 | 2010-07-30 | ||
IN1807/DEL/2010 | 2010-07-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012014149A1 true WO2012014149A1 (en) | 2012-02-02 |
Family
ID=44545784
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2011/053318 WO2012014149A1 (en) | 2010-07-30 | 2011-07-25 | N-methylformamide solvate of dasatinib |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP2598147A1 (en) |
AU (1) | AU2011284341A1 (en) |
CA (1) | CA2806820A1 (en) |
WO (1) | WO2012014149A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013186726A3 (en) * | 2012-06-15 | 2014-02-20 | Basf Se | Multicomponent crystals comprising dasatinib and selected cocrystal formers |
WO2017108605A1 (en) | 2015-12-22 | 2017-06-29 | Synthon B.V. | Pharmaceutical composition comprising amorphous dasatinib |
WO2017134615A1 (en) * | 2016-02-03 | 2017-08-10 | Dr. Reddy's Laboratories Limited | Solid state forms of dasatinib and processes for their preparation |
WO2018078392A1 (en) | 2016-10-29 | 2018-05-03 | Cipla Limited | Polymorphs of dasatinib |
WO2019209908A1 (en) | 2018-04-25 | 2019-10-31 | Johnson Matthey Public Limited Company | Crystalline forms of dasatinib |
US10799459B1 (en) | 2019-05-17 | 2020-10-13 | Xspray Microparticles Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6596746B1 (en) | 1999-04-15 | 2003-07-22 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
US7491725B2 (en) | 2004-02-06 | 2009-02-17 | Bristol-Myers Squibb Company | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
US20090118297A1 (en) | 2007-10-23 | 2009-05-07 | Ondrej Simo | Polymorphs of dasatinib and process for preparation thereof |
WO2010062715A2 (en) | 2008-11-03 | 2010-06-03 | Teva Pharmaceutical Industries Ltd. | Polymorphs of dasatinib and process for preparation thereof |
WO2010067374A2 (en) | 2008-12-08 | 2010-06-17 | Hetero Research Foundation | Polymorphs of dasatinib |
-
2011
- 2011-07-25 WO PCT/IB2011/053318 patent/WO2012014149A1/en active Application Filing
- 2011-07-25 EP EP11751946.2A patent/EP2598147A1/en not_active Withdrawn
- 2011-07-25 CA CA2806820A patent/CA2806820A1/en not_active Abandoned
- 2011-07-25 AU AU2011284341A patent/AU2011284341A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6596746B1 (en) | 1999-04-15 | 2003-07-22 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
US7491725B2 (en) | 2004-02-06 | 2009-02-17 | Bristol-Myers Squibb Company | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
US20090118297A1 (en) | 2007-10-23 | 2009-05-07 | Ondrej Simo | Polymorphs of dasatinib and process for preparation thereof |
WO2010062715A2 (en) | 2008-11-03 | 2010-06-03 | Teva Pharmaceutical Industries Ltd. | Polymorphs of dasatinib and process for preparation thereof |
WO2010067374A2 (en) | 2008-12-08 | 2010-06-17 | Hetero Research Foundation | Polymorphs of dasatinib |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2650524C2 (en) * | 2012-06-15 | 2018-04-16 | Басф Се | Multicomponent crystals comprising dasatinib and selected cocrystal formers |
JP2015525227A (en) * | 2012-06-15 | 2015-09-03 | ビーエーエスエフ ソシエタス・ヨーロピアBasf Se | Multi-component crystals comprising dasatinib and a selected co-crystal former |
US9340536B2 (en) | 2012-06-15 | 2016-05-17 | Basf Se | Multicomponent crystals comprising dasatinib and selected co-crystal formers |
AU2013276138B2 (en) * | 2012-06-15 | 2017-02-23 | Basf Se | Multicomponent crystals comprising Dasatinib and selected cocrystal formers |
WO2013186726A3 (en) * | 2012-06-15 | 2014-02-20 | Basf Se | Multicomponent crystals comprising dasatinib and selected cocrystal formers |
WO2017108605A1 (en) | 2015-12-22 | 2017-06-29 | Synthon B.V. | Pharmaceutical composition comprising amorphous dasatinib |
US10464933B2 (en) | 2016-02-03 | 2019-11-05 | Dr. Reddy's Laboratories Limited | Solid state forms of dasatinib and processes for their preparation |
JP2019504090A (en) * | 2016-02-03 | 2019-02-14 | ドクター レディズ ラボラトリーズ リミテッド | Solid state forms of dasatinib and their preparation process |
WO2017134615A1 (en) * | 2016-02-03 | 2017-08-10 | Dr. Reddy's Laboratories Limited | Solid state forms of dasatinib and processes for their preparation |
WO2018078392A1 (en) | 2016-10-29 | 2018-05-03 | Cipla Limited | Polymorphs of dasatinib |
WO2019209908A1 (en) | 2018-04-25 | 2019-10-31 | Johnson Matthey Public Limited Company | Crystalline forms of dasatinib |
US11440908B2 (en) | 2018-04-25 | 2022-09-13 | Johnson Matthey Public Limited Company | Crystalline forms of dasatinib |
US10869836B1 (en) | 2019-05-17 | 2020-12-22 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10869837B1 (en) | 2019-05-17 | 2020-12-22 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10874613B1 (en) | 2019-05-17 | 2020-12-29 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10874614B1 (en) | 2019-05-17 | 2020-12-29 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10894018B1 (en) | 2019-05-17 | 2021-01-19 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10894017B1 (en) | 2019-05-17 | 2021-01-19 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US11344500B2 (en) | 2019-05-17 | 2022-05-31 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US10799459B1 (en) | 2019-05-17 | 2020-10-13 | Xspray Microparticles Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
US11833249B2 (en) | 2019-05-17 | 2023-12-05 | Xspray Pharma Ab | Rapidly disintegrating solid oral dosage forms containing dasatinib |
Also Published As
Publication number | Publication date |
---|---|
AU2011284341A1 (en) | 2013-02-21 |
CA2806820A1 (en) | 2012-02-02 |
EP2598147A1 (en) | 2013-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6081763B2 (en) | Dasatinib polymorph and its preparation process | |
US11149017B2 (en) | Solid state forms of apalutamide | |
EP3248983B1 (en) | Crystal form a of obeticholic acid and preparation method therefor | |
EP3180343A1 (en) | Solid state forms of ibrutinib | |
US20090298947A1 (en) | Polymorphic and amorphous forms of lacosamide and amorphous compositions | |
EP3337485B1 (en) | Crystalline forms of ibrutinib | |
EP2598147A1 (en) | N-methylformamide solvate of dasatinib | |
US20090076272A1 (en) | Polymorphs of eszopiclone malate | |
KR20190035680A (en) | Polymorphism of binalinostet and its production method | |
WO2013065063A1 (en) | Anhydrous form of dasatinib, process for its preparation and its use | |
WO2010144675A1 (en) | Polymorphs of bendamustine hcl and processes for preparation thereof | |
US20150183767A1 (en) | Novel polymorphs of azilsartan medoxomil | |
WO2017098391A1 (en) | Process for the preparation of dasatinib | |
TW201829420A (en) | New solid forms of [(1s)-1-[(2s,4r,5r)-5-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate | |
CN111094241B (en) | Crystal form of oxopyridine amide derivative and preparation method thereof | |
JP2011505416A (en) | Process for the preparation of chemically and chirally pure solifenacin base and its salts | |
WO2014195977A2 (en) | Novel polymorphs of vismodegib | |
WO2012125993A1 (en) | Solid state forms of rilpivirine base, and rilipivirine salts | |
CA2811912A1 (en) | Novel polymorphs of febuxostat | |
KR20200036867A (en) | Polymorphs of dasatinib | |
CN116997331A (en) | Quinolone compound in solid form and process for preparing same | |
WO2011114336A1 (en) | Process for the isolation of ganciclovir intermediate | |
US20150291574A1 (en) | Novel polymorphs of azilsartan | |
WO2015114479A1 (en) | Crystalline forms of darapladib oxalate, adipate, succinate, phosphate, sulphate, fumaratetartrate, nitrate and borate | |
US20090062546A1 (en) | Dolasetron trifluoroacetate, polymorphs of dolasetron trifluoroacetate and process for preparation thereof |
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: 11751946 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2806820 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011751946 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2011284341 Country of ref document: AU Date of ref document: 20110725 Kind code of ref document: A |