CN106478658A - Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof - Google Patents
Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof Download PDFInfo
- Publication number
- CN106478658A CN106478658A CN201510522362.1A CN201510522362A CN106478658A CN 106478658 A CN106478658 A CN 106478658A CN 201510522362 A CN201510522362 A CN 201510522362A CN 106478658 A CN106478658 A CN 106478658A
- Authority
- CN
- China
- Prior art keywords
- crystal formation
- preparation
- good solvent
- crystalline solid
- powder diffraction
- 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
- 239000013078 crystal Substances 0.000 title claims abstract description 42
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- -1 benzoxazoles oxazines ketone compounds Chemical class 0.000 title claims abstract description 7
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 16
- 239000007787 solid Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 3
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 3
- 238000005352 clarification Methods 0.000 claims description 2
- 238000005755 formation reaction Methods 0.000 abstract description 34
- 238000001228 spectrum Methods 0.000 abstract description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 4
- 230000003292 diminished effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 150000000183 1,3-benzoxazoles Chemical class 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 206010003084 Areflexia Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000010431 corundum Substances 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 238000007416 differential thermogravimetric analysis Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000004893 oxazines Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000007575 pulmonary infarction Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical class NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- 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 present invention relates to crystal formation D of a kind of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof.At 5.46,11.00,15.85,16.56,17.06,17.39,19.15,19.85,21.63,23.91,24.27,25.98,28.19,28.55,29.07,29.59,30.14,31.69,32.32,32.98 and 34.48 ± 0.2 ° of 2 θ, there is X-ray powder diffraction peak in the X-ray powder diffraction spectrum of this crystal formation.Crystal formation D disclosed by the invention has good performance, not hygroscopic deliquescence, the features such as 10 days crystal formations keep constant under the conditions of 40 DEG C/75%RH.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology.Specifically related to benzoxazoles the crystal formation D of oxazines ketone compounds WA1-089 and preparation method thereof.
Background technology
A kind of brand-new Xa factor inhibitor benzoxazoles oxazines ketone compounds WA1-089（Abbreviation WA1-089）By structural formula（I）Represent, chemical name is that 5- is chloro-N-(((3S,3aS) -1- ketone -7- (3- ketone morpholine) -1,3,3a, 4- tetrahydro benzo [b] oxazole simultaneously [3,4-d] [Isosorbide-5-Nitrae] oxazines -3- base) methyl) thiophene-2-carboxamide derivatives, can be used for prevention of postoperative venous thrombosis（DVT）And pulmonary infarction（PE）, the apoplexy in atrial fibrillation for the prevention, treat acute coronary syndrome（ADS）Deng.
Crystal formation is an important physicochemical property of compound, and the different crystal formation of same medicine may have significant difference due to the difference of crystal formation type and purity, some of physicochemical property, thus affecting the performance of the stability of medicine, bioavailability and curative effect.The crystal formation of compound can by ripe technology such as：X-ray diffraction spectrum method, infrared spectrometry, differential scanning calorimetry, thermogravimetric analysiss and melting point analysis are being distinguished by and to characterize.This product is currently without related crystal formation document announcement.
Content of the invention
An object of the present invention is to provide a kind of WA1-089 of good stability to be formula（I）The crystal formation D of compound.
The second object of the present invention is to provide previously described formula（I）The preparation method of the crystal formation D of compound.
Formula disclosed by the invention（I）Compound crystal form D has following feature：
Crystal formation D can be described by comprising the XRPD collection of illustrative plates at 2 θ angles about 5.46,11.00,15.85,16.56,17.06,17.39,19.15,19.85,21.63,23.91,24.27,25.98,28.19,28.55,29.07,29.59,30.14,31.69,32.32,32.98,34.48.The general precision of 2 θ values is about in the range of ± 0.2 °.
Preferably, described X-ray powder diffraction figure is basically identical with Fig. 1.
Crystal formation D can also pass through means of differential scanning calorimetry（DSC）Characterizing, described DSC trace includes at about 201 DEG C trace, preferably at about 201.7 DEG C（All ± 2 DEG C）The means of differential scanning calorimetry of the endothermic peak at place（DSC）Trace is characterizing.
Preferably, the figure of described DSC trace is substantially consistent with Fig. 2.
Or crystal formation D can be by having thermogravimetric analysiss as shown in Figure 3（TGA）Trace, to characterize, shows that this crystal formation does not contain water of crystallization.
Or crystal formation D can be characterized by the total reflection infrared spectrum of decay, including in about following ripple
The absorption band of number：635th, 686,740,808,886,938,964,999,1024,1044,1087,1123,1137,1187,1239,1290,1322,1348,1385,1426,1473,1546,1626,1664 and 1759cm-1.The general precision of wave number value is about ± 2cm-1In the range of.
Preferably, the total reflection infrared spectrogram of described decay is that Fourier is infrared（FT-IR）Collection of illustrative plates, substantially consistent with Fig. 4.
The second object of the present invention is realized in：
Prepare described formula（I）The method of the crystal formation D of compound, comprises the following steps：
1）By formula（Ⅰ）Compound adds in good solvent and dissolves, and obtains settled solution, described good solvent is isopropanol, dichloromethane, acetone, in ethyl acetate any one.
2）Using positive add or reverse add by the way of upper step settled solution is mixed with poor solvent, stirs, separates out crystalline solid, described poor solvent is water, in normal heptane, hexahydrotoluene, t-butyl methyl ether any one.
3）Separate from step 2）The crystalline solid of middle acquisition.
Wherein step 1）Make described solution dissolving clarification by ultrasonic.
Wherein step 1）Middle good solvent addition is every 10 milligrams of formulas（Ⅰ）Compound adds 0.5 ~ 5ml good solvent.
Wherein step 2）Middle poor solvent addition is the 0.4 ~ 4 of good solvent（v/v）Times.
Wherein step 3）In by filtering isolating crystalline solid.
Wherein step 3）In the crystalline solid isolated be dried under vacuum to constant weight.
Crystal formation D disclosed by the invention has good performance, such as good stability, not hygroscopic deliquescence the features such as；Crystal formation D 10 days crystal formations under the conditions of 40 DEG C/75%RH keep constant, crystal formation D is 0 day under the conditions of 40 DEG C/75%RH, 5 days, 10 days XRPD comparison diagrams as shown in Figure 5.
Brief description
The powder diffraction spectrum of Fig. 1 .WA1-089 crystal formation D（XRPD）
The DSC trace collection of illustrative plates of Fig. 2 .WA1-089 crystal formation D
The TGA trace collection of illustrative plates of Fig. 3 .WA1-089 crystal formation D
The Fourier of Fig. 4 .WA1-089 crystal formation D is infrared（FT-IR）Collection of illustrative plates
Fig. 5 .WA1-089 crystal formation D is 0 day under the conditions of 40 DEG C/70%RH, 5 days, the XRPD comparison diagram of 10 days
The dynamic water absorption collection of illustrative plates of Fig. 6 .WA1-089 crystal formation D
The adsorption isothermal curve of Fig. 7 .WA1-089 crystal formation D.
Specific embodiment：
Following embodiments are used merely to explain realizes the method for the present invention, should not be construed as limitation of the present invention.
Benzoxazoles used in the present invention oxazines ketone compounds WA1-089 are derived from North China Pharmacuetical Group New Drug Research ＆ Development Co., Ltd, and content is 99%.The high performance liquid chromatography that the present invention uses（HPLD）For 996 type detectors, 515 pumps（Waters company）.Powder diffractometer model used in the present invention is Bruker D8 Advance diffractometer, is the K α radiation of 1.54nm using copper target wavelength（40Kv, 40mA）, θ -2 θ clinometer, Mo monochromator and Lynxeye detector.Instrument was detected with corundum before use.Acquisition software is Diffrac Plus XRD Dommander, and analysis software shows MDI Jade 6.Sample is tested at ambient temperature, and the sample needing detection is placed on areflexia piece.Testing conditions in detail are as follows, angular range：3-40 ° of 2 θ, step-length：0.02 ° of 2 θ, speed：0.2 s.step-1.Except special instruction, sample is not ground before detection.Differential thermal analyses data is picked up from TA Instruments Q200 DSC, and instrument control software is Thermal Advantage, and analysis software is Universal
Analysis.Thermogravimetric analysis data picks up from TA Instruments Q500TGA, and instrument control software is Thermal Advantage, and analysis software is Universal
Analysis.Fourier is infrared（FT-IR）Data acquisition is in Bruker
Tensor 27, instrument control software data analysis software is all OPUS.Dynamic water is adsorbed（DVS）Analytical data picks up from TA Instruments
Q500TGA, instrument control software is Thermal Advantage, and analysis software is Universal Analysis.
Unless stated otherwise, the usual testing conditions of sample are as shown in table 1 below.
Table 1 DSV experiment parameter
Embodiment
1
The WA1-089 of 20mg is added in 9ml isopropanol, ultrasonic make it molten clear, obtain settled solution, stirring, 12ml water droplet is added in settled solution, continues stirring, separate out crystalline solid, solid to be crystallized separates out completely, filtration under diminished pressure, 40 DEG C are dried under vacuum to constant weight, must crystallize D product 17mg, yield 85%.Chemical purity ＞ 99%（Recorded by HPLC）.
The XRPD collection of illustrative plates of crystalline product is as shown in figure 1, DSC trace collection of illustrative plates is as shown in Fig. 2 TGA trace collection of illustrative plates is as shown in figure 3, Fourier is infrared（FT-IR）Collection of illustrative plates is as shown in Figure 4.XRPD collection of illustrative plates and Fourier are infrared（FT-IR）Collection of illustrative plates all confirms that the product of acquisition is the crystal formation D of WA1-089.DSC trace collection of illustrative plates proves that this crystalline product is non-solvated crystallization.TGA trace collection of illustrative plates illustrates that this crystalline product does not contain water of crystallization.
Embodiment
2
The WA1-089 of 20mg is added in 10ml ethyl acetate, ultrasonic make it molten clear, obtain settled solution, settled solution forward direction Deca is entered in the 10ml methyl tertiary butyl ether(MTBE) under stirring condition, separates out crystalline solid, solid to be crystallized separates out completely, filtration under diminished pressure, 35 DEG C are dried under vacuum to constant weight, must crystallize D product 16mg, yield 80%.Chemical purity ＞ 99%（Recorded by HPLC）.
The XRPD collection of illustrative plates of crystalline product is basically identical with Fig. 1, and DSC trace collection of illustrative plates is basically identical with Fig. 2, and TGA trace collection of illustrative plates is basically identical with Fig. 3, and Fourier is infrared（FT-IR）Collection of illustrative plates is basically identical with Fig. 4.
Embodiment
3
The WA1-089 of 40mg is added in 2ml dichloromethane, ultrasonic make it molten clear, obtain settled solution, settled solution forward direction Deca is entered in the 8ml normal heptane under stirring condition, separates out solid, solid to be crystallized separates out completely, filtration under diminished pressure, 30 DEG C are dried under vacuum to constant weight, must crystallize D product 35mg, yield 87.5%.Chemical purity ＞ 99%（Recorded by HPLC）.
The XRPD collection of illustrative plates of crystalline product is basically identical with Fig. 1, and DSC trace collection of illustrative plates is basically identical with Fig. 2, and TGA trace collection of illustrative plates is basically identical with Fig. 3, and Fourier is infrared（FT-IR）Collection of illustrative plates is basically identical with Fig. 4.
Embodiment
4
The WA1-089 of 50mg is added in 5ml acetone, ultrasonic make it molten clear, obtain settled solution, 2ml hexahydrotoluene Deca entered in settled solution, continue stirring, separate out crystalline solid, solid to be crystallized separates out completely, filtration under diminished pressure, 35 DEG C are dried under vacuum to constant weight, must crystallize D product 43mg, yield 86%.Chemical purity ＞ 99%（Recorded by HPLC）.
The XRPD collection of illustrative plates of crystalline product is basically identical with Fig. 1, and DSC trace collection of illustrative plates is basically identical with Fig. 2, and TGA trace collection of illustrative plates is basically identical with Fig. 3, and Fourier is infrared（FT-IR）Collection of illustrative plates is basically identical with Fig. 4.
Embodiment
5
Crystalline product is carried out study on the stability, the crystal formation D of WA1-089 is placed under the conditions of 40 DEG C/70%RH 0 day, 5 days, 10 days, and detect XRPD, as shown in figure 5, being found out by comparison diagram, crystal D is not changed in comparison diagram, stable crystal form.
Embodiment
6
The crystal formation D taking the WA1-089 of 10mg is positioned in the platinum crucible of TGA, weight change in humidity change procedure for the TA software records sample（As shown in Figure 6）, Fig. 7 is crystalline product weight change in 20% ~ 80% RH range, and as can be seen from Figure 7 in 20% ~ 80% RH range, weight change is 0.19%, and display crystal formation D is non-hygroscopic for result.
Embodiment
7
Product 9.48mg in Example 1, adds in 37 DEG C of water of 3 mL, and constant temperature 10 minutes filters to obtain clear liquid.Clear liquid carries out assay using HPLC, and recording dissolubility is 17.32
µg/ml.
Claims (8)
1. the crystal formation D of benzoxazoles oxazines ketone compounds WA1-089, this structure such as formula（Ⅰ）It is shown,
It is characterized in that, at 2 θ are 5.46,11.00,15.85,16.56,17.06,17.39,19.15,19.85,21.63,23.91,24.27,25.98,28.19,28.55,29.07,29.59,30.14,31.69,32.32,32.98 and 34.48 ± 0.2 °, there is X-ray powder diffraction peak in the X-ray powder diffraction figure of described crystal formation.
2. crystal formation D according to claim 1 is it is characterised in that described X-ray powder diffraction figure is basically identical with Fig. 1.
3. the preparation method of crystal formation D described in claim 1 or 2, comprises the steps of：
1）By formula（Ⅰ）Compound adds in good solvent and dissolves, and obtains settled solution, described good solvent is isopropanol, dichloromethane, acetone, in ethyl acetate any one；
2）Using positive add or reverse add by the way of upper step settled solution is mixed with poor solvent, stirs, separates out crystalline solid, described poor solvent is water, in normal heptane, hexahydrotoluene, t-butyl methyl ether any one；
3）Separate from step 2）The crystalline solid of middle acquisition.
4. preparation method according to claim 3, wherein step 1）Make described solution clarification by ultrasonic.
5. preparation method according to claim 3, wherein step 1）Middle good solvent addition is every 10 milligrams of formulas（Ⅰ）Compound adds 0.5 ~ 5ml good solvent.
6. preparation method according to claim 3, wherein step 2）Middle poor solvent addition is the 0.4 ~ 4 of good solvent（v/v）Times.
7. preparation method according to claim 3, wherein step 3）In by filtering isolating crystalline solid.
8. preparation method according to claim 3, wherein step 3）In the crystalline solid isolated be dried to constant weight under 30 DEG C ~ 40 DEG C vacuum.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510522362.1A CN106478658A (en) | 2015-08-25 | 2015-08-25 | Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510522362.1A CN106478658A (en) | 2015-08-25 | 2015-08-25 | Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106478658A true CN106478658A (en) | 2017-03-08 |
Family
ID=58233071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510522362.1A Pending CN106478658A (en) | 2015-08-25 | 2015-08-25 | Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106478658A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108395442A (en) * | 2017-02-07 | 2018-08-14 | 浙江普洛得邦制药有限公司 | The crystal form VII and its preparation method and application of Yi Zhong oxazolidinone compounds |
| CN114685529A (en) * | 2020-12-29 | 2022-07-01 | 中国科学院上海药物研究所 | Amorphous substance of oxazolidinone compound and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936763A (en) * | 2013-01-18 | 2014-07-23 | 中国科学院上海药物研究所 | Oxazolidinone compound as well as preparing method and purpose thereof |
| WO2015043364A1 (en) * | 2013-09-29 | 2015-04-02 | 华北制药集团新药研究开发有限责任公司 | Benzoxazoleoxazine ketone compound as blood coagulation factor xa inhibitor |
| CN105085542A (en) * | 2014-05-22 | 2015-11-25 | 广东东阳光药业有限公司 | Crystal forms and amorphism of oxazolidinone compound |
| CN105693746A (en) * | 2014-06-14 | 2016-06-22 | 广东东阳光药业有限公司 | Preparation method and intermediate of oxazolidinone compound |
-
2015
- 2015-08-25 CN CN201510522362.1A patent/CN106478658A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936763A (en) * | 2013-01-18 | 2014-07-23 | 中国科学院上海药物研究所 | Oxazolidinone compound as well as preparing method and purpose thereof |
| WO2015043364A1 (en) * | 2013-09-29 | 2015-04-02 | 华北制药集团新药研究开发有限责任公司 | Benzoxazoleoxazine ketone compound as blood coagulation factor xa inhibitor |
| CN105085542A (en) * | 2014-05-22 | 2015-11-25 | 广东东阳光药业有限公司 | Crystal forms and amorphism of oxazolidinone compound |
| CN105693746A (en) * | 2014-06-14 | 2016-06-22 | 广东东阳光药业有限公司 | Preparation method and intermediate of oxazolidinone compound |
Non-Patent Citations (1)
| Title |
|---|
| TAO XUE，等: "Design, Synthesis, and Structure−Activity and Structure−Pharmacokinetic Relationship Studies of Novel [6,6,5] Tricyclic Fused Oxazolidinones Leading to the Discovery of a Potent, Selective, and Orally Bioavailable FXa Inhibitor", 《J. MED. CHEM.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108395442A (en) * | 2017-02-07 | 2018-08-14 | 浙江普洛得邦制药有限公司 | The crystal form VII and its preparation method and application of Yi Zhong oxazolidinone compounds |
| CN114685529A (en) * | 2020-12-29 | 2022-07-01 | 中国科学院上海药物研究所 | Amorphous substance of oxazolidinone compound and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10689380B1 (en) | Crystalline forms of valbenazine ditosylate | |
| EP3280408B1 (en) | Process for the preparation of dicycloplatin | |
| EP3433233B1 (en) | Novel crystalline form of 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1h-pyrrol-3-yl)-n- methylmethanamine salt | |
| WO2019228485A1 (en) | New crystal form of lenvatinib mesylate and preparation method therefor | |
| WO2022166994A1 (en) | Naphthyl urea compound, preparation method therefor and use thereof | |
| CN106478658A (en) | Crystal formation D of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof | |
| CN106008438A (en) | Racemic dihydromyricetin anhydrous substance crystal | |
| CA2579997A1 (en) | Process for preparing forms of atorvastatin calcium substantially free of impurities | |
| CN105849106B (en) | Key intermediate and impurity in Eliquis synthesis：Eliquis diol ester | |
| CN105085542A (en) | Crystal forms and amorphism of oxazolidinone compound | |
| CN106966944B (en) | Vildagliptin crystal form compound and preparation method thereof | |
| CN106478661A (en) | Crystal formation E of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof | |
| CN104557748A (en) | Novel solid form of sulpho-1,2,4-triazole derivative | |
| CN103596927A (en) | Novel process for the synthesis of 7-chloro-4-(piperazin-1-yl)-quinoline | |
| CN103483334B (en) | Crystal formation of penehyclidine hydrochloride racemic mixture II and preparation method thereof | |
| Muntaner et al. | Synthesis of new bioorganometallic Ir-and Rh-complexes having β-lactam containing ligands | |
| CN107098866A (en) | The method for splitting of medicine Lesinurad axial chirality enantiomers | |
| CN107118153A (en) | A kind of Rui Gefeini monohydrate crystal forms and preparation method thereof | |
| US20150141673A1 (en) | Novel crystalline for w of cabazitaxel and method for preparing it | |
| CN106478660A (en) | Unformed powder of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof | |
| CN105085476B (en) | Crystal formation of 5 [2,6 2 (4 morpholinyl) 4 pyrimidine radicals] 4 (trifluoromethyl) 2 pyridine amine dihydrochlorides and preparation method thereof | |
| CN106478659A (en) | Crystal formation C of benzoxazoles oxazines ketone compounds WA1-089 and preparation method thereof | |
| CN105440083B (en) | A kind of lobaplatin crystal, preparation method and medicinal application | |
| CN112441962A (en) | Tirofiban and purification method thereof | |
| CN114437076A (en) | Ketorolac and isoniazid eutectic crystal and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 052165 North China Pharmaceutical Group new drug research and Development Co., Ltd., No. 98, Hainan Road, Shijiazhuang Economic and Technological Development Zone, Hebei Province Applicant after: NORTH CHINA PHARMACEUTICAL NEW DRUG R&D Co.,Ltd. Address before: 050015 No. 388 Heping East Road, Shijiazhuang, Hebei, Changan District Applicant before: NORTH CHINA PHARMACEUTICAL NEW DRUG R&D Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170308 |
|
| RJ01 | Rejection of invention patent application after publication |