CN107200742A - A kind of Ba Ruike is for Buddhist nun's phosphate crystal and preparation method thereof - Google Patents
A kind of Ba Ruike is for Buddhist nun's phosphate crystal and preparation method thereof Download PDFInfo
- Publication number
- CN107200742A CN107200742A CN201610287305.4A CN201610287305A CN107200742A CN 107200742 A CN107200742 A CN 107200742A CN 201610287305 A CN201610287305 A CN 201610287305A CN 107200742 A CN107200742 A CN 107200742A
- Authority
- CN
- China
- Prior art keywords
- buddhist nun
- ruike
- phosphate crystal
- preparation
- replaces
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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 discloses a kind of Ba Ruike for Buddhist nun's phosphate crystal and preparation method thereof.The Ba Ruike has characteristic peak for the powder x-ray diffraction spectrogram that Buddhist nun's phosphate crystal is represented with 2 θ angles at 3.57 ± 0.2 °, 7.28 ± 0.2 °, 8.06 ± 0.2 °, 14.47 ± 0.2 °, 18.19 ± 0.2 °, 19.29 ± 0.2 °, 20.55 ± 0.2 °, 22.27 ± 0.2 °, 25.22 ± 0.2 °, 29.29 ± 0.2 °.The Ba Ruike that the present invention is provided has the advantages that purity height, stability are good, easy to maintain for Buddhist nun's phosphate crystal.In addition, the Ba Ruike that the present invention is provided has the advantages that technique is simple, easily dry, it is with low cost to prepare for the preparation method of Buddhist nun's phosphate crystal, is easy to industrialized production, easily promotes.
Description
Technology neighborhood
Buddhist nun's phosphate crystal and its preparation side are replaced the present invention relates to chemical field, more particularly to a kind of Ba Ruike
Method.
Background technology
Ba Ruike is for a kind of selection that Buddhist nun (Baricitinib) is that Li Lai companies and Incyte companies develop jointly
Property JAK1 and JAK2 inhibitor, IC50 is respectively 5.9nM and 5.7nM, be compared to be used for JAK3
With selectively high 70 and 10 times or so of Tyk2, there is no inhibitory action to c-Met and Chk2.Current gift
To carry out one large-scale III phases project with Incyte, it is included in 4 researchs of U.S.'s development and in
1 research that state carries out, is related to 3000 rheumatoid arthritis (RA) patients, assesses baricitinib
Curative effect and security.Gift come be expected by the end of the year 2015 complete the U.S. 4 III phase clinical researches,
And Baricitinib application for quotation is submitted to FDA according to result.
Original grind patent (CN102026999) etc. report Ba Ruike for Buddhist nun (Baricitinib) it is phosphatic
Preparation process.Acetonitrile is used in preparation process as solvent, and acetonitrile toxicity is big, gas phase remnants limits
It is low, also more difficult removal acetonitrile is washed using normal heptane, therefore the Ba Ruike prepared using the above method is replaced
Buddhist nun's phosphate is difficult in accordance with quality standard.
The content of the invention
For the deficiencies in the prior art, it is an object of the invention to provide a kind of stabilization, high-purity
The Ba Ruike as shown in formula I for Buddhist nun's phosphate crystal and preparation method thereof.
To achieve the above object, the technical solution adopted by the present invention is as follows：
A kind of Ba Ruike replaces Buddhist nun's phosphate crystal, with the chemical constitution shown in formula I, it is characterised in that
The powder x-ray diffraction spectrogram that the Ba Ruike is represented with 2 θ angles for Buddhist nun's phosphate crystal 3.57 ±
0.2°、7.28±0.2°、8.06±0.2°、14.47±0.2°、18.19±0.2°、19.29±0.2°、
There is characteristic peak at 20.55 ± 0.2 °, 22.27 ± 0.2 °, 25.22 ± 0.2 °, 29.29 ± 0.2 °.
Further, the Ba Ruike is similar to figure for the powder x-ray diffraction spectrogram of Buddhist nun's phosphate crystal
Shown in 1.
Further, the Ba Ruike is 180.5 DEG C for the fusing point of Buddhist nun's phosphate crystal.
Further, the Ba Ruike is similar to shown in Fig. 2 for the DSC collection of illustrative plates of Buddhist nun's phosphate crystal.
Further, described Ba Ruike is similar to Fig. 3 for the DSC-TGA collection of illustrative plates of Buddhist nun's phosphate crystalline
It is shown.
Further, the Ba Ruike is more than 99.8% for the purity of Buddhist nun's phosphate crystal.
A kind of Ba Ruike replaces the preparation method of Buddhist nun's phosphate crystal, comprises the following steps：
Ba Ruike is dissolved in organic solvent for Buddhist nun's free alkali, Ba Ruike is obtained for Buddhist nun's solution, it is described organic
Solvent is one or both of ethanol and acetone；
After the Ba Ruike is heated up for Buddhist nun's solution, phosphoric acid alcoholic solution is added dropwise；
Stirring；
Cool crystallization, filters, dries.
Further, the Ba Ruike replaces Buddhist nun's free alkali purity more than 95%.
Further, the temperature range after the heating is 30~80 DEG C.
Further, the temperature range after the heating is 55~65 DEG C.
Further, the phosphoric acid alcoholic solution is phosphoric acid ethanol solution.
Further, the temperature conditionss of the stirring are 30~80 DEG C.
Further, the temperature conditionss of the stirring are 55~65 DEG C.
Further, the time of the stirring is 1~5h.
Further, the time of the stirring is 2~3h.
Further, the gas phase residual of crystal prepared by the preparation method is less than 500ppm.
Compared with prior art, bar Rake of the present invention is for Buddhist nun's phosphate crystal stability is good, purity
It is high；And bar Rake of the present invention replaces the preparation method of Buddhist nun's phosphate crystal, with technique is simple, system
It is standby it is with low cost, be easy to industrial amplification production, the advantages of suitable for promoting.
On the other hand, bar Rake of the present invention for Buddhist nun's phosphate crystal preparation method using ethanol and
Acetone is easily dried as solvent, prepared Ba Ruike for Buddhist nun's phosphate crystal, and gas phase residual is less than
500ppm, it is easy to reach quality standards.
Brief description of the drawings
Fig. 1 is the powder x-ray diffraction spectrogram that bar Rake of the present invention replaces Buddhist nun's phosphate crystal；
Fig. 2 is the DSC spectrograms that bar Rake of the present invention replaces Buddhist nun's phosphate crystal；
Fig. 3 is the DSC-TGA spectrograms that bar Rake of the present invention replaces Buddhist nun's phosphate crystal.
Embodiment
The present invention is described in more detail with reference to the accompanying drawings and examples.It is understood, however, that
These embodiments, which are only used for specifically describing in more detail, to be used, and is not to be construed as appointing
What form limits the present invention.
The method of reagent and use used in the embodiment of the present invention be this area conventional reagent and often
Rule method.It will be apparent to those skilled in the art that hereinafter, if not otherwise specified, temperature is with Celsius
Degree (DEG C) represents that operation temperature is carried out under room temperature environment, and shown room temperature refers to 10 DEG C~30 DEG C, preferably
20 DEG C~25 DEG C；The fusing point can allowable error ± 1%.Described yield is mass percent.
Embodiment 1：
Under nitrogen protection, by 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazoles -1-
Base) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile 10g (26.92mmol), acetone (200ml)
And ethanol (90ml) is added in 500ml there-necked flasks, 55~65 DEG C are then heated to, phosphoric acid methanol is instilled molten
Liquid (3.35g+10ml), after dripping between 55~65 DEG C 2~3h of stirring reaction, add crystal seed simultaneously slowly drop
Warm crystallization is stayed overnight.Solid is collected by filtration, is washed with acetone (20ml), filter cake is placed in 50~55 DEG C
Lower progress baking material obtains (3- (4- (7H- pyrrolo-es [2,3-d] the pyrimidine-4-yl) -1H- of White crystalline solid 2
Pyrazol-1-yl) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile phosphate (10.47g, it is theoretical
Measure and be：12.64g, yield：82.83%), HPLC purity is 99.86%.Phosphate：mp:180.5 DEG C,
It is 20.75% through potential measurement phosphorus acid content；LC-MS(EI)m/e372(M+H)；HNMR (DMSO,
300MHZ)12.18(s,1H),8.94(s,1H),8.71(s,1H),8.47(s,1H),7.62
(dd, 1H, J=3.5,2.3Hz), 7.08 (dd, 1H, J=3.6,1.5Hz), 4.60 (d, 2H, J=9.3,9.2Hz), 4.23
(d, 2H, J=9.3,9.2Hz), 3.68 (s, 2H), 3.25 (q, 2H, J=3.6Hz), 1.25 (t, 3H, J=7.3Hz).
Embodiment 2：
Under nitrogen protection, by 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazoles -1-
Base) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile 10g (26.92mmol), acetone (250ml)
And ethanol (100ml) is added in 500ml there-necked flasks, 20min is stirred between then heating to 30~80 DEG C, is dripped
Enter phosphoric acid ethanol solution (3.35g+50ml), after dripping between 50~65 DEG C 1.5~2h of stirring reaction, plus
Enter crystal seed and slow cooling crystallization is stayed overnight.Solid is collected by filtration, is washed with acetone (20ml),
Filter cake is placed in progress baking material at 50~55 DEG C and obtains (3- (4- (the 7H- pyrrolo-es [2,3-d] of White crystalline solid 2
Pyrimidine-4-yl) -1H- pyrazol-1-yls) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile phosphate
(9.86g, theoretical amount is：12.64g, yield：78.01%), HPLC purity is 99.92%.Phosphate
It is 20.30% through potential measurement phosphorus acid content.
Embodiment 3：
Under nitrogen protection, by 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazoles -1-
Base) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile 10g (26.92mmol), acetone (300ml)
It is added in 500ml there-necked flasks, 15min is stirred between then heating to 55~65 DEG C, instills phosphoric acid ethanol molten
Liquid (3.35g+50ml), after dripping between 30~80 DEG C 1~5h of stirring reaction, add crystal seed simultaneously slowly drop
Warm crystallization is stayed overnight.Solid is collected by filtration, is washed with acetone (30ml), filter cake is placed in 50~55 DEG C
Lower progress baking material obtains (3- (4- (7H- pyrrolo-es [2,3-d] the pyrimidine-4-yl) -1H- of White crystalline solid 2
Pyrazol-1-yl) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile phosphate (10.56g, it is theoretical
Measure and be：12.64, yield：83.54%), HPLC purity is 99.89%.Phosphate is through potential measurement phosphorus
Acid content is 21.10%.
Embodiment 4：
Under nitrogen protection, by 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazoles -1-
Base) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile 10g (26.92mmol) and ethanol (350ml)
It is added in 500ml there-necked flasks, 15min is stirred between then heating to 65~75 DEG C, instills phosphoric acid ethanol molten
Liquid (3.35g+50ml), after dripping between 65~75 DEG C 1.5~2h of stirring reaction, add crystal seed simultaneously it is slow
Cooling crystallization is stayed overnight.Solid is collected by filtration, is washed with acetone (20ml), filter cake is placed in 50~55 DEG C
Lower progress baking material obtains (3- (4- (7H- pyrrolo-es [2,3-d] the pyrimidine-4-yl) -1H- of White crystalline solid 2
Pyrazol-1-yl) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile phosphate (9.80g, theoretical amount
For：12.64g, yield：77.53%), HPLC purity is 99.85%.Phosphate is through potential measurement phosphoric acid
Content is 21.50%.
Embodiment 5：
Under nitrogen protection, by 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazoles -1-
Base) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile 30g (26.92mmol), acetone (600ml)
And ethanol (500ml) is added in 2000ml there-necked flasks, stirred between then heating to 55~65 DEG C
20~30min, instills phosphoric acid ethanol solution (10.15g+150ml), is stirred after dripping between 55~65 DEG C
3~5h is reacted, crystal seed is added and slow cooling crystallization is stayed overnight.Solid is collected by filtration, with acetone (80ml)
Washed, filter cake is placed in progress baking material at 50~55 DEG C and obtains (3- (4- (the 7H- of White crystalline solid 2
Pyrrolo- [2,3-d] pyrimidine-4-yl) -1H- pyrazol-1-yls) -1- (ethylsulfonyl) azetidines -3-
Base) (31.10g, theoretical amount is acetonitrile phosphate：37.92g, yield：82%), HPLC purity is 99.89%.
Phosphate is 20.12% through potential measurement phosphorus acid content.
Embodiment 6：
By 2 (3- (4- (7H- pyrrolo-es [2,3-d] pyrimidine-4-yl) -1H- pyrazol-1-yls) -1- (ethyl sulphurs
Acyl group) azetidine -3- bases) acetonitrile 5.0g (13.50mmol), acetone (100ml) and ethanol (80ml)
It is added in 250ml there-necked flasks, 15min is stirred between then heating to 55~65 DEG C, instills phosphoric acid ethanol molten
Liquid (1.67g+25ml), after dripping between 55~65 DEG C 1.5~2h of stirring reaction, add crystal seed simultaneously it is slow
Cooling crystallization is stayed overnight.Solid is collected by filtration, is washed with acetone (20ml), filter cake is placed in 50~55 DEG C
Lower progress baking material obtains (3- (4- (7H- pyrrolo-es [2,3-d] the pyrimidine-4-yl) -1H- of White crystalline solid 2
Pyrazol-1-yl) -1- (ethylsulfonyl) azetidine -3- bases) acetonitrile phosphate (4.90g theoretical amounts
For：6.32g, yield：77.53%), HPLC purity is 99.80%.Phosphate is through potential measurement phosphoric acid
Content is 19.96%.
Bar Rake of the present invention for Buddhist nun's crystal powder x-ray diffraction spectrogram 3.57 ± 0.2 °, 7.28
±0.2°、8.06±0.2°、14.47±0.2°、18.19±0.2°、19.29±0.2°、20.55±
There is characteristic peak at 0.2 °, 22.27 ± 0.2 °, 25.22 ± 0.2 °, 29.29 ± 0.2 °, with similar to figure
X-ray diffractogram of powder spectrum shown in 1.
Bar Rake of the present invention has for Buddhist nun's crystal is similar to DSC collection of illustrative plates as shown in Figure 2, and fusing point is
180.5℃。
Bar Rake of the present invention has for Buddhist nun's phosphate crystal is similar to DSC-TGA as shown in Figure 3
Collection of illustrative plates, there is certain weightlessness between 30~60 DEG C, and its moisture for containing 1.2~1.8% is determined as through Moisture Meter；
Without obvious weightless step between 60~150 DEG C, it is not solvated compoundses to illustrate the crystal.
Finally it should be noted that：Above example is served only for that the present invention is further described, it is impossible to
Limiting the scope of the invention is interpreted as, those skilled in the art is according to the above of the invention
Some the nonessential modifications and adaptations made belong to protection scope of the present invention.
Claims (16)
1. a kind of Ba Ruike replaces Buddhist nun's phosphate crystal, its chemical structural formula is as follows：
Characterized in that, the Ba Ruike replaces the powder x-ray diffraction that Buddhist nun's phosphate crystal is represented with 2 θ angles
Spectrogram 3.57 ± 0.2 °, 7.28 ± 0.2 °, 8.06 ± 0.2 °, 14.47 ± 0.2 °, 18.19 ± 0.2 °,
Have at 19.29 ± 0.2 °, 20.55 ± 0.2 °, 22.27 ± 0.2 °, 25.22 ± 0.2 °, 29.29 ± 0.2 °
Characteristic peak.
2. bar Rake according to claim 1 replaces Buddhist nun's phosphate crystal, it is characterised in that the Ba Ruike
It is similar to for the powder x-ray diffraction spectrogram of Buddhist nun's phosphate crystal shown in Fig. 1.
3. bar Rake according to claim 1 replaces Buddhist nun's phosphate crystal, it is characterised in that the Ba Ruike
It it is 180.5 DEG C for the fusing point of Buddhist nun's phosphate crystal.
4. bar Rake according to claim 1 replaces Buddhist nun's phosphate crystal, it is characterised in that the Ba Ruike
It is similar to for the DSC collection of illustrative plates of Buddhist nun's phosphate crystal shown in Fig. 2.
5. bar Rake according to claim 1 replaces Buddhist nun's phosphate crystal, it is characterised in that the Ba Ruike
It is similar to for the DSC-TGA collection of illustrative plates of Buddhist nun's phosphate crystal shown in Fig. 3.
6. bar Rake according to claim 1 replaces Buddhist nun's phosphate crystal, it is characterised in that the Ba Ruike
It is more than 99.8% for the purity of Buddhist nun's phosphate crystal.
7. bar Rake according to claim 1 replaces the preparation method of Buddhist nun's phosphate crystal, it is characterised in that
Comprise the following steps：
Ba Ruike is dissolved in organic solvent for Buddhist nun's free alkali, Ba Ruike is obtained for Buddhist nun's solution, it is described organic
Solvent is one or both of ethanol and acetone；
After the Ba Ruike is heated up for Buddhist nun's solution, phosphoric acid alcoholic solution is added dropwise；
Stirring；
Cool crystallization, filters, dries.
8. preparation method according to claim 7, it is characterised in that the Ba Ruike is pure for Buddhist nun's free alkali
Degree is more than 95%.
9. preparation method according to claim 7, it is characterised in that the temperature range after the heating is
30~80 DEG C.
10. preparation method according to claim 9, it is characterised in that the temperature range after the heating
For 55~65 DEG C.
11. preparation method according to claim 7, it is characterised in that the phosphoric acid alcoholic solution is phosphoric acid
Ethanol solution.
12. preparation method according to claim 7, it is characterised in that the temperature conditionss of the stirring are
30~80 DEG C.
13. preparation method according to claim 12, it is characterised in that the temperature conditionss of the stirring are
55~65 DEG C.
14. preparation method according to claim 7, it is characterised in that the time of the stirring is 1~5h.
15. preparation method according to claim 14, it is characterised in that the time of the stirring is 2~3h.
16. preparation method according to claim 7, it is characterised in that crystalline substance prepared by the preparation method
The gas phase residual of body is less than 500ppm.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2016101567530 | 2016-03-18 | ||
| CN201610156753 | 2016-03-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107200742A true CN107200742A (en) | 2017-09-26 |
Family
ID=59904564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610287305.4A Pending CN107200742A (en) | 2016-03-18 | 2016-05-03 | A kind of Ba Ruike is for Buddhist nun's phosphate crystal and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107200742A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019137325A1 (en) * | 2018-01-09 | 2019-07-18 | 广东东阳光药业有限公司 | Novel crystalline form of baricitinib phosphate and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010039939A1 (en) * | 2008-10-02 | 2010-04-08 | Incyte Corporation | Janus kinase inhibitors for treatment of dry eye and other eye related diseases |
| CN102026999A (en) * | 2008-03-11 | 2011-04-20 | 因塞特公司 | Azetidine and cyclobutane derivatives as JAK inhibitors |
| WO2015145286A1 (en) * | 2014-03-28 | 2015-10-01 | Sun Pharmaceutical Industries Limited | Amorphous form of baricitinib |
-
2016
- 2016-05-03 CN CN201610287305.4A patent/CN107200742A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102026999A (en) * | 2008-03-11 | 2011-04-20 | 因塞特公司 | Azetidine and cyclobutane derivatives as JAK inhibitors |
| WO2010039939A1 (en) * | 2008-10-02 | 2010-04-08 | Incyte Corporation | Janus kinase inhibitors for treatment of dry eye and other eye related diseases |
| WO2015145286A1 (en) * | 2014-03-28 | 2015-10-01 | Sun Pharmaceutical Industries Limited | Amorphous form of baricitinib |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019137325A1 (en) * | 2018-01-09 | 2019-07-18 | 广东东阳光药业有限公司 | Novel crystalline form of baricitinib phosphate and preparation method thereof |
| CN111278828A (en) * | 2018-01-09 | 2020-06-12 | 广东东阳光药业有限公司 | Novel crystal form of Baratinib phosphate and preparation method thereof |
| CN111278828B (en) * | 2018-01-09 | 2021-08-31 | 广东东阳光药业有限公司 | Novel crystal form of Baratinib phosphate and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3205653B1 (en) | Crystal form of bisulfate of jak inhibitor and preparation method therefor | |
| CN103360391B (en) | Novel apixaban crystal form and preparation method thereof | |
| CN105367552A (en) | Novel crystal form of neratinib maleate and preparation method thereof | |
| JP2012236841A (en) | Crystal modification b of 8-cyano-1-cyclopropyl-7-(1s,6s-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid | |
| CN105693695A (en) | Delafloxacin meglumine salt crystal form, and preparation method thereof | |
| CN104327051A (en) | Crystal form of fumarate of pyrrole derivative | |
| CN105418483A (en) | Preparation method of crystalline nintedanib esylate | |
| CN107200742A (en) | A kind of Ba Ruike is for Buddhist nun's phosphate crystal and preparation method thereof | |
| CN104910067A (en) | Regorafenib synthesis method by one kettle way | |
| CN103864690B (en) | S crystal formation, its preparation method and the pharmaceutical composition of Ivabradine hydrochloride | |
| CN107129467A (en) | Aripiprazole crystals B | |
| CN104496886A (en) | Preparation method of high-purity apremilast B crystal form | |
| CN101353325B (en) | Stable Ivabradine crystal and preparation thereof | |
| CN103980166B (en) | A kind of novel crystal forms of florfenicol and preparation method thereof | |
| CN105315278A (en) | PQQ (pyrroloquinoline quinone) A crystal form and preparation method thereof | |
| CN102617332B (en) | α-one α-amino-isovaleric acid calcium dihydrate crystal and preparation method thereof | |
| CN104130245A (en) | Pazopanib hydrochloride N crystal form and preparation thereof | |
| CN104557881A (en) | Preparation method of pazopanib hydrochloride crystal form | |
| CN104558034A (en) | Novel crystal form of tedizolid phosphate disodium salt and preparation method of novel crystal form | |
| CN105960393A (en) | lithium styrene sulfonate | |
| CN110964017A (en) | Polymorph of Ribociclib monosuccinate and preparation method and application thereof | |
| CN103274948A (en) | Preparation method of cinacalcet | |
| CN102603516A (en) | D,L-alpha-ketoisovaline calcium dihydrate crystals and preparation method thereof | |
| CN103435559A (en) | New erlotinib hydrochloride crystal form and preparation method thereof | |
| CN102633775B (en) | Method for preparing alpha-crystal-form imatinib mesylate |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170926 |
|
| WD01 | Invention patent application deemed withdrawn after publication |