CN104761546A - Novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form and preparation method thereof - Google Patents
Novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form and preparation method thereof Download PDFInfo
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- CN104761546A CN104761546A CN201410281048.4A CN201410281048A CN104761546A CN 104761546 A CN104761546 A CN 104761546A CN 201410281048 A CN201410281048 A CN 201410281048A CN 104761546 A CN104761546 A CN 104761546A
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- gelie
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- beta crystal
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- 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
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- 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
Abstract
The invention provides a novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form (shortened as canagliflozin beta crystal form), and the crystal form has good stability and is applicable to large scale production. The invention also provides a preparation method of the crystal form.
Description
Technical field
The invention belongs to field of medicine and chemical technology, be specifically related to a kind of new crystalline form of Remedies for diabetes (1S)-1,5-dehydrogenation-1-[3-[[5-(4-fluorophenyl)-2-thienyl] methyl]-4-aminomethyl phenyl]-D-Glucose alcohol and preparation method thereof.
Background technology
Ka Gelie is clean, i.e. (1S)-1,5-dehydrogenation-1-[3-[[5-(4-fluorophenyl)-2-thienyl] methyl]-4-aminomethyl phenyl]-D-Glucose alcohol, and its structure is:
Ka Gelie is sodium-glucose co-transporters body (sodium-glucose linked transporter only, SGLT) inhibitor, this medicine, by suppressing SGLT2, makes the glucose in uriniferous tubules heavily not absorb smoothly and enters blood and discharge with urine, thus reduces blood sugar concentration.Be used for the treatment of the type ii diabetes (type 2 diabetes mellitus) of adult patients.
Patent WO2013064909 reports the clean cocrystallizing type of Ka Gelie and comprises the clean and L-PROLINE of Ka Gelie, and the clean and D-PROLINE of Ka Gelie and Ka Gelie are only and the cocrystallizing type of phenylalanine.Report the amorphous article that Ka Gelie is clean simultaneously.Above-mentioned eutectic adds composition invalid in treatment, is not suitable for medicinal.And amorphous substance is also not suitable for medicinal due to poor stability.
Patent CN200780043154.7 reports the clean semihydrate crystal formation of Ka Gelie, and this crystal formation efficiently avoid the problems referred to above, but this crystal formation is in drying course, should guarantee to remove dissolvent residual, guarantees again not lose crystal water, therefore higher to drying requirement.
Summary of the invention
The present inventor finds a kind of clean crystal formation of new Ka Gelie (the clean beta crystal of Ka Gelie) that is stable, that be easy to large-scale production in research process, and the present invention effectively can solve the deficiencies in the prior art.
The invention provides the clean beta crystal of a kind of Ka Gelie, use Cu-Ka radiation, the X-ray powder diffraction represented with 2 θ angles 6.5 ± 0.2,13.0 ± 0.2,19.5 ± 0.2,21.3 ± 0.2,24.7 ± 0.2 have characteristic peak.
Further, the clean beta crystal of Ka Gelie provided by the invention, use Cu-Ka radiation, the X-ray powder diffraction represented with 2 θ angles is 6.5 ± 0.2,12.1 ± 0.2,13.0 ± 0.2,17.9 ± 0.2,19.5 ± 0.2,21.3 ± 0.2,24.7 ± 0.2,28.5 ± 0.2 have characteristic peak.
The X-ray powder diffraction of the clean beta crystal of Ka Gelie of the present invention as shown in Figure 1.
The present invention also provides a kind of Ka Gelie preparation method of clean beta crystal, and step is as follows:
Clean for Ka Gelie crude product is joined backflow in ethylene glycol monomethyl ether to dissolve, be down to room temperature crystallization, filtration, drying, the clean beta crystal of get Ka Gelie.
The mass volume ratio of the clean crude product of described Ka Gelie and ethylene glycol monomethyl ether is 1:1 ~ 1:5, and unit is g/ml.
Cooling of the present invention can adopt Temperature fall, circulating water cooling or other equipment that can lower the temperature.
In sum, the clean beta crystal suitability for industrialized of Ka Gelie provided by the invention is produced, stable crystal form, and has the mass uniformity of good guarantee preparation, and clinical application is safer.
Accompanying drawing explanation
Fig. 1 is the Ka Gelie clean beta crystal X-ray powder diffraction of embodiment 1.
Embodiment
Further illustrate the present invention below by concrete preparation embodiment, these embodiments are only used for the use specifically described more in detail, and should not be construed as limiting the present invention in any form.
The inspection apparatus that the present invention is used:
X-ray powder diffractometer
Source of radiation: Cu target K α radiation.
Sample preparation: after sample porphyrize, is placed in standard model frame and measures.
embodiment 1
Clean for 10kg Ka Gelie crude product is joined backflow in 20L ethylene glycol monomethyl ether to dissolve, be down to room temperature, stirring and crystallizing, after separating out a large amount of crystal, filtration, drying, the clean beta crystal 8.1kg of get Ka Gelie, yield 81%, purity 99.89%, fusing point 102 ~ 104 DEG C.
Gained crystal formation measures through X-ray powder diffractometer, and result as shown in Figure 1.
embodiment 2
Clean for 100g Ka Gelie crude product is joined backflow in 100ml ethylene glycol monomethyl ether to dissolve, be down to room temperature, stirring and crystallizing, after separating out a large amount of crystal, filtration, drying, the clean beta crystal 89g of get Ka Gelie, yield 89%, purity 99.82%.
embodiment 3
Clean for 100g Ka Gelie crude product is joined backflow in 500ml ethylene glycol monomethyl ether to dissolve, be down to room temperature, stirring and crystallizing, after separating out a large amount of crystal, filtration, drying, the clean beta crystal 71g of get Ka Gelie, yield 71%, purity 99.95%.
Claims (5)
1. the clean beta crystal of Ka Gelie, is characterized in that, uses Cu-Ka radiation, the X-ray powder diffraction represented with 2 θ angles 6.5 ± 0.2,13.0 ± 0.2,19.5 ± 0.2,21.3 ± 0.2,24.7 ± 0.2 have characteristic peak.
2. the clean beta crystal of Ka Gelie according to claim 1, it is characterized in that, use Cu-Ka radiation, the X-ray powder diffraction represented with 2 θ angles 6.5 ± 0.2,12.1 ± 0.2,13.0 ± 0.2,17.9 ± 0.2,19.5 ± 0.2,21.3 ± 0.2,24.7 ± 0.2,28.5 ± 0.2 have characteristic peak.
3. the clean beta crystal of Ka Gelie according to claim 1 and 2, it has and X-ray diffracting spectrum identical in fact shown in Fig. 1.
4. a preparation method for the clean beta crystal of the Ka Gelie described in any one of claims 1 to 3, step is as follows:
Clean for Ka Gelie crude product is joined backflow in ethylene glycol monomethyl ether to dissolve, be down to room temperature crystallization, filtration, drying, the clean beta crystal of get Ka Gelie.
5. the preparation method of the clean beta crystal of Ka Gelie according to claim 4, the mass volume ratio of the clean crude product of described Ka Gelie and ethylene glycol monomethyl ether is 1:1 ~ 1:5, and unit is g/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410281048.4A CN104761546A (en) | 2014-06-21 | 2014-06-21 | Novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410281048.4A CN104761546A (en) | 2014-06-21 | 2014-06-21 | Novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form and preparation method thereof |
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| CN104761546A true CN104761546A (en) | 2015-07-08 |
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| CN201410281048.4A Pending CN104761546A (en) | 2014-06-21 | 2014-06-21 | Novel (1S)-1,5-dehydro-1-[3-[[5-(4-(4-fluorophenyl)-2-thiophene] methyl]-4-methyl phenyl)-D-glucitol crystal form and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108349927A (en) * | 2015-11-20 | 2018-07-31 | 赞蒂瓦有限合伙公司 | The crystal form and preparation method of canagliflozin |
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| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (belta-D-glucopyranosyl) -4 -methyl- 3- [5- (4 -fluorophenyl) -2-thienylmethyl] benzene hemihydrate |
| 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 |
| WO2013064909A2 (en) * | 2011-10-31 | 2013-05-10 | Scinopharm Taiwan, Ltd. | Crystalline and non-crystalline forms of sglt2 inhibitors |
| CN103554092A (en) * | 2013-11-11 | 2014-02-05 | 苏州晶云药物科技有限公司 | New crystal form B of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene and preparation method of new crystal form B |
| CN103588762A (en) * | 2013-11-27 | 2014-02-19 | 苏州晶云药物科技有限公司 | Novel crystal form of canagliflozin and its preparation method |
| 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 |
-
2014
- 2014-06-21 CN CN201410281048.4A patent/CN104761546A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (belta-D-glucopyranosyl) -4 -methyl- 3- [5- (4 -fluorophenyl) -2-thienylmethyl] benzene hemihydrate |
| 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 |
| WO2013064909A2 (en) * | 2011-10-31 | 2013-05-10 | Scinopharm Taiwan, Ltd. | Crystalline and non-crystalline forms of sglt2 inhibitors |
| 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 |
| CN103554092A (en) * | 2013-11-11 | 2014-02-05 | 苏州晶云药物科技有限公司 | New crystal form B of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene and preparation method of new crystal form B |
| CN103588762A (en) * | 2013-11-27 | 2014-02-19 | 苏州晶云药物科技有限公司 | Novel crystal form of canagliflozin and its preparation method |
| CN104356122A (en) * | 2013-11-27 | 2015-02-18 | 苏州晶云药物科技有限公司 | New crystal form of canagliflozin and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108349927A (en) * | 2015-11-20 | 2018-07-31 | 赞蒂瓦有限合伙公司 | The crystal form and preparation method of canagliflozin |
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