CN107311993A - A kind of crystal formation II of canagliflozin and preparation method thereof - Google Patents
A kind of crystal formation II of canagliflozin and preparation method thereof Download PDFInfo
- Publication number
- CN107311993A CN107311993A CN201710675836.5A CN201710675836A CN107311993A CN 107311993 A CN107311993 A CN 107311993A CN 201710675836 A CN201710675836 A CN 201710675836A CN 107311993 A CN107311993 A CN 107311993A
- Authority
- CN
- China
- Prior art keywords
- canagliflozin
- crystal formation
- crystal
- bulk drug
- added
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of crystal formation II of canagliflozin, its X ray powder diffraction has characteristic peak at θ=3.8 ± 0.2,8.0 ± 0.2,10.9 ± 0.2,13.9 ± 0.2,15.5 ± 0.2,15.9 ± 0.2,20.3 ± 0.2,23.3 ± 0.2 degree of the angle of diffraction 2.The invention further relates to the crystal formation II of canagliflozin preparation method.Operating procedure of the present invention is simple, easy to operate；The product purity prepared is higher than 99%, and product yield is up to 85%, and product is under conditions of hot and humid, and its purity, content, outward appearance and crystal formation have no significant change, and stability preferably, is suitable for pharmaceutical manufacturing.
Description
Technical field
The invention belongs to fine chemistry industry and application, the novel crystal forms of more particularly to a kind of canagliflozin and its crystallization preparation side
Method.
Background technology
Canagliflozin (Canagliflozin), molecular formula is C24H25FO5S, molecular weight is 444.52, its structural formula (Formulas I)
It is as follows:
I
Its chemical entitled 1- (β- D- glycopyranosyls) -4- methyl -3- [5- (4- fluorophenyls) -2- thienyl methyls] benzene is FDA
White -2 (SGLT-2) inhibitor medicaments of the first sodium glucose co-transporter 2 of approval, by suppressing weight of the kidney to glucose
Absorb, increase glucose excretion, and then reduce the elevated blood sugar level of diabetic.Except good glycemic control, card
Lattice row it is net it is most noticeable be antiobesity action and seldom hypoglycemic event.
In general, medicinal crystal-form product should possess the good character of operation, the type for being easy to filtering and easily drying should be
Formula.In addition, preferable medicinal crystal-form product should be product that can be stable within the pot-life without special preservation condition.Card lattice
Row belong to slightly water-soluble compound only, typically use in solid form in the formulation, therefore have very to the research of its crystal formation
Important meaning.
CN101573368 discloses the semihydrate crystal formation and its method for crystallising of a kind of canagliflozin, and the crystal formation is in CuK α
There is 4.36 °, 13.54 °, 16.00 °, 19.32 ° and 20.80 ° ± 0.2 °, the crystal formation in the X-ray powder diffraction collection in source
TGA collection of illustrative plates shows 1.705% weightlessness.Its method for crystallising crystallization time is longer, typically in more than 20h.
CN101801371 discloses a kind of canagliflozin crystal formation and its method for crystallising, and is characterized by XRPD, should
Method for crystallising step described in document is more, and needs to carry out under conditions of argon gas protection.
CN103936726 is disclosed in a kind of canagliflozin crystal formation IV, its X-ray powder diffraction figure
17.40 °, 15.35 °, 14.91 ° ± 0.2 °, the crystal formation is anhydride, and fusing point is at 120 DEG C or so.
CN104530023 disclose in another crystal formation I, its X-ray powder diffraction figure at least 2 θ values be 4.4 °,
8.4 °, 16.8 °, 17.5 °, 18.0 °, 22.8 ° ± 0.2 of position to that should have characteristic diffraction peak, its DSC scanning figure is at 90-95 DEG C
Between have an endothermic peak；Its TGA scanning figure is when being heated to 180 DEG C, with about 3.97% weightlessness.
WO2015139386 discloses canagliflozin monohydrate, and its thermogravimetric analysis (TGA) collection of illustrative plates is shown：100 DEG C it
Preceding weightless 4.1%, it is roughly equal to per molecule monohydrate containing a molecular water.
Therefore, the crystal formation for studying the new more preferable canagliflozin of stable in physicochemical property has great importance.
The content of the invention
The technical problems to be solved by the invention are that there is provided a kind of new canagliflozin is brilliant in view of the shortcomings of the prior art
Type II.
Another technical problem solved by the invention is to provide foregoing canagliflozin crystal formation II preparation method.
Technology to be solved by this invention, which is asked, to be realized by following technical scheme.The present invention is a kind of Ka Gelie
Net crystal formation II, is characterized in：Its X-ray powder diffraction collection θ=3.8 ± 0.2 of the angle of diffraction 2,8.0 ± 0.2,
10.9 ± 0.2,13.9 ± 0.2,15.5 ± 0.2,15.9 ± 0.2,20.3 ± 0.2, at 23.3 ± 0.2 degree
There is characteristic peak.
The canagliflozin crystal formation II that more preferably present invention is provided has X-ray powder diffraction substantially as described in Figure 1
Figure.
The more preferably canagliflozin crystal formation II that the present invention is provided fusing point is about 99.5 DEG C, its means of differential scanning calorimetry
（DSC）Collection of illustrative plates is as shown in Fig. 2 there is the endothermic peak of a feature at 99.5 ± 2 DEG C.
The more preferably thermogravimetric analysis for the canagliflozin crystal formation II that the present invention is provided（TGA）Figure is in 80-100 DEG C of weightlessness
1.33%。
On the other hand the present invention also provides a kind of preparation method for preparing canagliflozin crystal formation II, and step is as follows：By card lattice
Arrange net bulk drug and be dissolved in organic solvent, add appropriate purified water, the card separated out is dried in rising temperature for dissolving, cooling stirring and crystallizing, filtering
Lattice arrange net II.
Mixing plant used has the reactor or reactor of mixing effect from this area.
One or more of the organic solvent in esters solvent；More preferably isopropyl acetate and acetic acid second
One or more in ester；More preferably isopropyl acetate.
The w/v of the canagliflozin bulk drug and organic solvent is 1g：（1~20）mL；More preferably 1g：
（1~10）mL；Most preferably 1g：5mL.
The canagliflozin bulk drug and the w/v of purified water are（1~50）g：1mL；More preferably（10~
25）g：1mL；More preferably（10~20）g：1mL；Most preferably 20g：1mL.
Seeding can be carried out during described cooling stirring and crystallizing by the way of being not added with or adding crystal seed；Further preferably
Seeding is carried out to add crystal seed, the amount for adding crystal seed is the 0 ~ 10% of canagliflozin bulk drug weight；More preferably add crystal seed
Amount be 0.1 ~ 1%.
The solution temperature is 30 ~ 70 DEG C；It is further preferred for 50 ~ 70 DEG C.Described is cooled to 20 ~ 55 DEG C, enters one
Step is preferably 45 ~ 55 DEG C.Described drying temperature is 25 ~ 60 DEG C；More preferably 35 ~ 50 DEG C.
The inventive method has the advantages that：Operating procedure of the present invention is simple, easy to operate, high income, favorable reproducibility；
The features such as canagliflozin novel crystal forms prepared have stable in physicochemical property, purity is high, product purity is higher than 99%, product yield
More than 85%, product is under conditions of hot and humid, and its purity, content, outward appearance and crystal formation have no significant change, and stability is preferable,
It is suitable for pharmacy life, is more suitable for pharmaceuticals industry and uses, it is easier to the big production of commercialization.
Brief description of the drawings
The X-ray powder diffraction figure for the canagliflozin crystal formation II that Fig. 1 is prepared for the present invention.
The means of differential scanning calorimetry figure for the canagliflozin crystal formation II that Fig. 2 is prepared for the present invention.
The thermogravimetric analysis figure for the canagliflozin crystal formation II that Fig. 3 is prepared for the present invention.
Embodiment
The present invention is expanded on further below by specific embodiment and with reference to accompanying drawing.It should be appreciated that following examples
Simply to further illustrate the features and advantages of the present invention, to those skilled in the art, the present invention is not being departed from
On the premise of design, various modifications and improvements can be made.These belong to protection scope of the present invention.
Raw material and universal testing method：
Canagliflozin bulk drug used is prepared with reference to Chinese patent literature CN101801371B in embodiment.
X-ray powder diffraction (XRD) instrument：Bruker D8 Advance X-ray diffractometers, test condition：40kv
40mA, slit：1.0/1.0/Ni/0.2, step-length：0.02 °, target type：Cu, Range:3.00-40.00 Deg, scan Rate：
10.00 Deg/min。
Differential scanning calorimetry analyzes (DSC) instrument：The type differential thermal analyzers of NETZSCH DSC 204, temperature range：40-
230 DEG C, heating rate：10℃/min.
Thermogravimetric analysis (TGA) instrument：The type thermogravimetric analyzers of NETZSCH TG 209, temperature range：30-300 DEG C, heating speed
Rate：10℃/min.
Embodiment 1
Take canagliflozin bulk drug 10.0g, add isopropyl acetate 50mL, add purified water 0.5mL, be warming up to 55 DEG C it is molten
Solution, slow cooling is to 45 DEG C, at a temperature of this after stirring and crystallizing 1h, continues slow cooling to 25 DEG C of crystallization 12h, filters, and 50 DEG C true
Empty dry canagliflozin II product 9.50g, yield is 95.0%, and purity is 99.93%.Gained canagliflozin crystal formation II is entered
Row XRD test, DSC test, TGA test and FTIR test, its XRD spectrum as shown in figure 1, its DSC collection of illustrative plates as shown in Fig. 2 its
TGA collection of illustrative plates is as shown in Figure 3.
Embodiment 2
Take canagliflozin bulk drug 10.0g, add isopropyl acetate 50mL, add purified water 0.5mL, be warming up to 60 DEG C it is molten
Solution, is cooled to 50 DEG C, adds after 0.05g crystal seed stirring and crystallizings 1h, slow cooling to 25 DEG C of crystallization 10h, filtering, and 40 DEG C of vacuum are done
Dry to obtain canagliflozin II product 9.38g, yield is 93.8%, and purity is 99.91%.Gained canagliflozin crystal formation II XRD
Spectrum, DSC collection of illustrative plates and TGA collection of illustrative plates and embodiment 1 are consistent.
Embodiment 3
Take canagliflozin bulk drug 10.0g, add isopropyl acetate 75mL, add purified water 0.5mL, be warming up to 60 DEG C it is molten
Solution, is cooled to 55 DEG C, adds after 0.1g crystal seeds, stirring and crystallizing 1h, slow cooling to 25 DEG C of crystallization 8h, filtering, and 45 DEG C of vacuum are done
Dry to obtain canagliflozin II product 9.03g, yield is 90.3%, and purity is 99.89%.Gained canagliflozin crystal formation II XRD
Spectrum, DSC collection of illustrative plates and TGA collection of illustrative plates and embodiment 1 are consistent.
Embodiment 4
Canagliflozin bulk drug 10.0g is taken, isopropyl acetate 50mL is added, adds purified water 1mL, be warming up to 60 DEG C of dissolvings,
55 DEG C are cooled to, is added after crystal seed, stirring and crystallizing 1h, slow cooling to 25 DEG C of crystallization 8h, filtering, 40 DEG C of vacuum drying get Ka Ge
Net II products 9.15g is arranged, yield is 91.5%, and purity is 99.89%.Gained canagliflozin crystal formation II XRD spectrum, DSC figures
Spectrum and TGA collection of illustrative plates are consistent with embodiment 1.
Embodiment 5
Canagliflozin bulk drug 10.0g is taken, ethyl acetate 50mL is added, adds purified water 0.5mL, be warming up to 60 DEG C of dissolvings,
Slow cooling is to 25 DEG C, and stirring and crystallizing 12h is filtered, 50 DEG C are dried in vacuo to obtain canagliflozin crystal type II 8.64g, and yield is
86.4%, purity is 99.91%.Gained canagliflozin crystal formation II XRD spectrum, DSC collection of illustrative plates and TGA collection of illustrative plates and embodiment 1 one
Cause.
The canagliflozin II stability studies of table 1：Purity is 99.91% before placing, and content is 99.5% before placing.
Test result indicates that：
Under upper table experiment condition, the relevant materials of canagliflozin II, content, outward appearance and crystal formation obtained by the present invention etc. are without substantially
Change, has good stability.
Described above is only the citing for applying mode of the present invention, it is noted that for the ordinary skill people of the art
For member, to canagliflozin II of the present invention and its preparation on the premise of present invention, spirit and scope is not departed from
Method is modified or suitably change is with combining, and to realize the technology of the present invention, all similar improvement and modification are to this area
It is it will be apparent that these improvement and modification are considered as being included in present disclosure, spirit and scope for technical staff
In.
Claims (10)
1. a kind of crystal formation II of canagliflozin, it is characterised in that：Its X-ray powder diffraction collection θ=3.8 of the angle of diffraction 2 ±
0.2、8.0 ± 0.2、10.9 ± 0.2、13.9 ± 0.2、15.5 ± 0.2、15.9 ± 0.2、 20.3 ± 0.2、
There is characteristic peak at 23.3 ± 0.2 degree.
2. the crystal formation II of canagliflozin as claimed in claim 1, it is characterised in that the crystal formation II of described canagliflozin difference
Show scanning calorimetric DSC collection of illustrative plates, there is the endothermic peak of a feature at 99.5 ± 2 DEG C.
3. the crystal formation II of canagliflozin as claimed in claim 1, it is characterised in that the crystal formation II of canagliflozin thermogravimetric analysis
TGA curves, in 80 ~ 110 DEG C of dehydrations 1.33%.
4. the method that one kind prepares the canagliflozin crystal formation II any one of claim 1 ~ 3, it is characterised in that：It is to include
Following steps：
Canagliflozin bulk drug is added in esters solvent, suspension is configured to, purified water is added into system, heating stirring makes
Solid is completely dissolved, cooling, is not added with or adds canagliflozin crystal formation II crystal seeds, and insulated and stirred crystallization, filtering is blocked after drying
Lattice arrange net crystal formation II.
5. method as claimed in claim 4, it is characterised in that：Canagliflozin crystal formation II is added before insulated and stirred crystallization brilliant
Kind.
6. method as claimed in claim 5, it is characterised in that：The amount for adding crystal seed is canagliflozin bulk drug weight
0.1% ~ 10%, preferably 0.1 ~ 1%.
7. method as claimed in claim 4, it is characterised in that：Described esters class solvent is selected from isopropyl acetate and acetic acid second
The mixed solvent of one or both of ester.
8. method as claimed in claim 4, it is characterised in that：Described canagliflozin bulk drug and the weighing body of esters solvent
Product is than being 1g：1mL~ 20mL；It is preferred that 1g：1mL~ 10mL；Most preferably 1g：5mL.
9. method as claimed in claim 4, it is characterised in that：The w/v of the canagliflozin bulk drug and purified water
For 1g ~ 50g：1mL, preferably 10g ~ 25g：1mL；More preferably 10g ~ 20g：1mL；Most preferably 20g：1mL.
10. method as claimed in claim 4, it is characterised in that：The solution temperature be 30 DEG C ~ 70 DEG C, preferably 50 ~
70℃；Described is cooled to 20 DEG C ~ 55 DEG C, preferably 45 ~ 55 DEG C；Described drying temperature is 25 DEG C ~ 60 DEG C, is preferably
35~50℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710675836.5A CN107311993A (en) | 2017-08-09 | 2017-08-09 | A kind of crystal formation II of canagliflozin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710675836.5A CN107311993A (en) | 2017-08-09 | 2017-08-09 | A kind of crystal formation II of canagliflozin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107311993A true CN107311993A (en) | 2017-11-03 |
Family
ID=60175646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710675836.5A Pending CN107311993A (en) | 2017-08-09 | 2017-08-09 | A kind of crystal formation II of canagliflozin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107311993A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111487266A (en) * | 2020-04-30 | 2020-08-04 | 江苏德源药业股份有限公司 | Quantitative determination method for monohydrate crystal form in medicinal crystal form of canagliflozin hemihydrate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101801371A (en) * | 2007-09-10 | 2010-08-11 | 詹森药业有限公司 | The preparation method of the chemical compound of useful as inhibitors of sglt |
| CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
| CN103936725A (en) * | 2014-04-01 | 2014-07-23 | 天津大学 | C crystal form of canagliflozin and crystal preparation method of canagliflozin |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | Crystal form I of Canagliflozin and preparation method thereof |
| CN105001214A (en) * | 2015-04-20 | 2015-10-28 | 华润赛科药业有限责任公司 | Canagliflozin crystal-type F and preparation method thereof |
-
2017
- 2017-08-09 CN CN201710675836.5A patent/CN107311993A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101801371A (en) * | 2007-09-10 | 2010-08-11 | 詹森药业有限公司 | The preparation method of the chemical compound of useful as inhibitors of sglt |
| CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
| CN103936725A (en) * | 2014-04-01 | 2014-07-23 | 天津大学 | C crystal form of canagliflozin and crystal preparation method of canagliflozin |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | Crystal form I of Canagliflozin and preparation method thereof |
| CN105001214A (en) * | 2015-04-20 | 2015-10-28 | 华润赛科药业有限责任公司 | Canagliflozin crystal-type F and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111487266A (en) * | 2020-04-30 | 2020-08-04 | 江苏德源药业股份有限公司 | Quantitative determination method for monohydrate crystal form in medicinal crystal form of canagliflozin hemihydrate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10662198B2 (en) | Polymorphic form of compound, preparation method and use thereof | |
| CN105801645B (en) | The method for preparing Suo Feibuwei crystal form 6 | |
| CN106854187A (en) | A kind of preparation method of AHU-377 and Valsartan trisodium salt eutectic hydrate crystal forms II | |
| CN111517980B (en) | N- [8- (2-hydroxybenzoyl) amino ] caprylic acid monopotassium crystal type compound, preparation method and application | |
| CN118525027A (en) | Polymorphic form of reduced beta-nicotinamide mononucleotide disodium salt, preparation method and application thereof | |
| CN103755723B (en) | A kind of preparation method of rifampicin I crystal form | |
| CN102875531A (en) | (R)-lansoprazole unhydrous crystal and preparation method thereof | |
| CN105985394A (en) | Novel sofosbuvir crystal form and preparation method thereof | |
| CN104829673B (en) | A kind of preparation method of rope fluorine cloth Wei crystal formation 6 | |
| CN107226826A (en) | Tenofovir Chinese mugwort draws phenol amine fumarate compound and its pharmaceutical composition | |
| CN111303097B (en) | Crystal form C of michelia lactone fumarate dimethylamine and preparation method thereof | |
| CN107311993A (en) | A kind of crystal formation II of canagliflozin and preparation method thereof | |
| CN107286220B (en) | 1,2, 4-triazole coupled dihydromyricetin derivative and preparation method and application thereof | |
| CN111171015A (en) | Berberine-cinnamic acid derivative monocrystal, and preparation method and application thereof | |
| CN105315266B (en) | The crystal form of 1- { the fluoro- 4- of 2- [5- (4- isobutyl phenenyl) -1,2,4- oxadiazoles -3- base]-benzyl } -3- azetidinecarboxylic acid | |
| CN105992769B (en) | A kind of L-PROLINE compound, its monohydrate and the crystal of white 2 inhibitor of sodium glucose co-transporter 2 | |
| CN109369757B (en) | Method for preparing Sofosbuvir crystal form 6 | |
| CN112225730A (en) | Crystal form of fused ring compound, composition, preparation method and application thereof | |
| CN110128305A (en) | The new salt form of melbine-orinase, preparation method and medical usage | |
| CN107056691A (en) | A kind of method for preparing Etoricoxib crystal formation V | |
| CN112028838B (en) | Preparation method of 2-ethoxy-5-fluorouracil impurity | |
| US11008357B2 (en) | Method for preparing canagliflozin amorphous form | |
| WO2023173561A1 (en) | Crystal form i of deuterated nirmatrelvir and method for preparing same | |
| CN107325043A (en) | A kind of crystal formation of left-handed Aranidipine and preparation method thereof | |
| CN105541818A (en) | Novel crystal form of canagliflozin hydrate and preparation method of novel crystal form |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171103 |
|
| RJ01 | Rejection of invention patent application after publication |