CN103910690A - New iressa crystal form and preparation methods thereof - Google Patents
New iressa crystal form and preparation methods thereof Download PDFInfo
- Publication number
- CN103910690A CN103910690A CN201310003832.4A CN201310003832A CN103910690A CN 103910690 A CN103910690 A CN 103910690A CN 201310003832 A CN201310003832 A CN 201310003832A CN 103910690 A CN103910690 A CN 103910690A
- Authority
- CN
- China
- Prior art keywords
- gefitinib
- crystal form
- solvent
- crystal
- peak
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a new iressa crystal form and preparation methods thereof, wherein the new iressa crystal form is named the crystal form A, and the characteristic peaks are showed at positions of about 6.5 DEG, 8.3 DEG, 11.4 DEG, 13.0 DEG, 14.1 DEG, 15.6 DEG, 16.7 DEG, 18.5 DEG, 19.2 DEG, 20.3 DEG, 21.4 DEG, 22.9 DEG, 24.3 DEG, 24.7 DEG, 25.1 DEG, 25.8 DEG, 26.2 DEG, 28.5 DEG and 30.0 DEG (2[theta]) in the X-ray powder diffraction spectrum obtained by adopting Cu-K[alpha] radiation detection. The present invention further provides two methods for preparing the iressa crystal form A, wherein the methods have characteristics of simpleness and good reproducibility, and are suitable for industrial production, and the obtained iressa crystal form A has characteristics of good stability and high purity.
Description
Technical field
The new crystal that the present invention relates to a kind of Gefitinib (N-(the chloro-4-fluorophenyl of 3-)-7-methoxyl group-6-(3-morpholine propoxy-) quinazoline-4-amine) with and preparation method thereof.
Background technology
Gefitinib chemistry N-(the chloro-4-fluorophenyl of 3-)-7-methoxyl group-6-(3-morpholine propoxy-) quinazoline-4-amine by name, structural formula is as shown in the formula shown in I:
Gefitinib, have another name called Iressa (Iressa), be a kind of selectivity EGF-R ELISA (EGFR) tyrosine kinase inhibitor, be applicable to local late period or Metastatic Nsclc (NSCLC) that treatment was previously accepted chemotherapy or was unsuitable for chemotherapy.
Patent WO96/33980 discloses the preparation method of formula I compound: use the mixture (9:1) of methylene dichloride and methyl alcohol as elutriant, and by column chromatography purifying, then recrystallization in toluene.This patent also discloses the another kind of route of synthesis of formula I compound, uses the mixture of ethyl acetate and methyl alcohol as elutriant, by column chromatography purifying, and then recrystallization in toluene, prepared melting point compound is 119-120 DEG C.But this patent is crystal type or armorphous with no specific disclosure of formula I compound, form that also whether can solvation with no specific disclosure of described compound exists.
Patent CN100404032C discloses Gefitinib Form 1(polymorphic form), Form 2(methanol solvate compound), Form 3(DMSO solvate), Form 5(trihydrate) four kinds of crystal formations and preparation method thereof.
This patent is pointed out with solvent or solvent mixture thing washing Form 3 ZD1839 DMSO solvates, Form 2 ZD1839 MeOH solvates or Form 5 ZD1839 trihydrates, separation obtains Form 1 ZD1839 polymorphic form, and its X-ray diffraction figure is at [2 theta(θ) number of degrees] approximately 7.0,11.2,15.8,19.3,24.0(climax) and 26.3 ° located characteristic peak.Form 1 good stability, is particularly suitable for the solid preparation of Gefitinib as Tablet and Capsula agent, but in actual fabrication process, the poor reproducibility of Form 1.
The X powder diffraction figure of Form 2 ZD1839 MeOH solvates is at [2 theta(θ) number of degrees] about 6.5(climax), 10.0 and 26.3 ° located characteristic peak.The X powder diffraction figure of Form 3 ZD1839 DMSO solvates is at [2 theta(θ) number of degrees] approximately 8.9,17.8,22.6(climax) and 23.2 ° located characteristic peak.These two kinds of solvate stability are all lower than Form 1.
The X powder diffraction figure of Form 5 ZD1839 trihydrates is at [2 theta(θ) number of degrees] the exclusive peak of about 6.1(), 7.1,9.3,14.2,18.5,18.8,19.8,22.3,23.3,24.7,25.7 have characteristic peak.Its preparation method is: Gefitinib free alkali is contacted to enough time with water, be translated into Form 5 ZD1839 trihydrates; Or Gefitinib free alkali is dissolved in the solvent systems that contains water and organic solvent, reducing the temperature of solvent systems, there is nucleogenesis in induction, separates and obtains Form 5 ZD1839 trihydrates, this crystal formation is very stable in water, is applicable to the formulation administration with aqueous suspension.
Patent WO2006090413A1 points out formula I compound F 17-hydroxy-corticosterone orm 6 crystal formations and preparation method, and its X-ray diffraction figure is at [2 theta(θ) number of degrees] approximately 7.05,9.36,12.3,14.8,16.8,18.6, and 20.68,24.72 have characteristic peak.Preparation method: anhydrous Gefitinib is mixed with water, stir 18-20h under envrionment temperature, the dry Form 6 that obtains of filtrated air.This crystal formation is monohydrate crystal formation, and stability is lower than Form 1.
In recent years, the polymorphism of drug molecule more and more causes scientist's attention.Because different polycrystalline kenels has a very large difference stability, liberation degree, bioavailability are first-class; therefore be necessary drug molecule to carry out polymorphic research as much as possible; to guarantee to obtain best crystalline form; thereby obtain higher stability, liberation degree, bioavailability etc., thereby produce higher biological activity.
Summary of the invention
The invention discloses that a kind of good stability, purity are high, the Gefitinib crystal form A of favorable reproducibility and preparation method thereof.
Gefitinib crystal form A of the present invention, uses in the X-ray powder diffraction collection of illustrative plates of Cu-K α radiation detection, has following characteristics peak, and its 2 θ angle value and relative intensity are as shown in the table:
Gefitinib crystal form A of the present invention has X powder diffraction collection of illustrative plates as shown in Figure 1.
Gefitinib crystal form A of the present invention, it is characterized in that this crystal formation is without thermal weight loss, dsc analysis collection of illustrative plates is presented at approximately 105 ~ 115 DEG C and has located exothermic peak, shows that it starts recrystallizations at about approximately 105 DEG C and changes, and locate melting at 192 ~ 198 DEG C, there is endotherm(ic)peak.
Thermogravimetric analysis collection of illustrative plates and dsc that Gefitinib crystal form A of the present invention has as shown in accompanying drawing 2, accompanying drawing 3 are analyzed collection of illustrative plates.
Gefitinib crystal form A of the present invention has Raman spectrum as shown in Figure 4, and its Raman shift is at 3077.5,3018.3,2936.3,2877.5,1605.9,1475.5,1341.2,772.6,365.8,228.7,182.4cm
-1there is characteristic peak at place.
Gefitinib crystal form A of the present invention has infrared absorption spectrum as shown in Figure 5, and it is 2925.6,2854.2, and there is absorption peak at 1533.0,1501.9,1377.5,1228.3 places.
The present invention provides a kind of method of preparing Gefitinib crystal form A simultaneously, and the method comprises:
(a) Gefitinib heating is dissolved in a kind of solvent, is configured to saturated solution;
(b) under heating condition, slowly drip by the good Gefitinib saturated solution of another kind of configured in advance, drip and finish, insulated and stirred certain hour;
(c) be slowly down to room temperature, separate out solid, filtration drying obtains Gefitinib new crystal A.
The present invention also provides the another kind of method of preparing Gefitinib crystal form A, and the method comprises:
(a) Gefitinib heating is dissolved in a kind of solvent, is configured to saturated solution;
(b) under heating condition, slowly drip another kind of solvent, drip and finish, insulated and stirred certain hour;
(c) be slowly down to room temperature, separate out solid, filtration drying obtains Gefitinib new crystal A.
Above two kinds of preparation methods of the present invention, the solvent using in step (a) comprises dehydrated alcohol, propyl carbinol, tetrahydrofuran (THF), 4-methyl-2 pentanone, Nitromethane 99Min., Isosorbide-5-Nitrae-dioxane, preferably dehydrated alcohol, tetrahydrofuran (THF), 4-methyl-2 pentanone.
Above two kinds of preparation methods of the present invention, the solvent using in step (b) comprises acetonitrile, n-propyl acetate, n-butyl acetate, isopropyl acetate, isopropyl ether, methyl tertiary butyl ether, Virahol, normal hexane, normal heptane, preferably acetonitrile, n-propyl acetate, n-butyl acetate, methyl tertiary butyl ether, Virahol, normal hexane.
Above two kinds of preparation methods of the present invention, in the quantity of solvent using in step (b) and step (a), solvent for use amount volume ratio is 1:0.5 ~ 5, preferably 1:0.5 ~ 2.
Above two kinds of preparation methods of the present invention, step (a) Heating temperature is 35 ~ 110 DEG C, step (b) Heating temperature is 35 ~ 100 DEG C.
Two kinds of methods of preparing Gefitinib crystal form A provided by the present invention, simple to operate, favorable reproducibility, obtains that crystal form A purity is high, good stability, can meet large-scale industrial production.
Brief description of the drawings
X-ray powder diffraction (XRPD) collection of illustrative plates of the Gefitinib crystal form A that accompanying drawing 1 obtains according to the embodiment of the present invention 1.
Thermogravimetric analysis (TGA) collection of illustrative plates of the Gefitinib crystal form A that accompanying drawing 2 obtains according to the embodiment of the present invention 1.
The dsc of the Gefitinib crystal form A that accompanying drawing 3 obtains according to the embodiment of the present invention 1 is analyzed collection of illustrative plates (DSC).
The Raman spectrum spectrogram of the Gefitinib crystal form A that accompanying drawing 4 obtains according to the embodiment of the present invention 1.
The infrared spectra of the Gefitinib crystal form A that accompanying drawing 5 obtains according to the embodiment of the present invention 1.
Embodiment
Following embodiment is to describe in detail the present invention, and unrestricted the present invention.
Analyzing and testing condition of the present invention is as follows:
1, DSC-TGA is measured by the SDT Q600 of TA company of the U.S., and test condition is 120ml/min N2,10 DEG C/min of heat-up rate.
2, X-ray powder diffraction data are to use X ' Pert Pro MPD (Multi-Purpose Diffractometer) to measure, light pipe type: Empyrean XRD tube Cu LFF HR; Electric current and voltage: 45 kV, 40 mA; The vertical goniometer of goniometer: PW3050/60, radius 240mm; Slit: DS=2 °, SS=1/2 °, mask=15mm, RS=5.0mm; The super detector of detector: X ' Celerator; Scan pattern: continuous sweep; Sweep limit: 3 ° of-40 ° of 2 θ; Every step gate time: 20s; Scanning total time: 6min.
Embodiment 1
Get Gefitinib anhydride 200mg, add dehydrated alcohol 8ml, be warming up to 70 ~ 75 DEG C, stir 30min, while hot filtering solid.Under 65 ~ 70 DEG C of conditions of filtrate maintenance temperature, the saturated acetonitrile solution 8ml of agitation and dropping Gefitinib, drips and finishes, and 65 ~ 70 DEG C are stirred 30min, are then slowly down to room temperature, filters, is dried to obtain Gefitinib crystal form A 183.5mg.
Solid carries out X-ray powder diffraction (XRPD) and analyzes (seeing accompanying drawing 1), the analysis of TGA heat (seeing accompanying drawing 2), DSC spectrogram (accompanying drawing 3), Raman spectrum (seeing accompanying drawing 4), infrared spectra (seeing accompanying drawing 5).
Embodiment 2
Get Gefitinib anhydride 300mg, add 4-methyl-2 pentanone 15ml, be warming up to 80 ~ 85 DEG C, stir 30min, while hot filtering solid.Under 80 ~ 85 DEG C of conditions of filtrate maintenance temperature, agitation and dropping Gefitinib Virahol saturated solution 7.5ml, drips and finishes, and 80 ~ 85 DEG C are stirred 30min, are then slowly down to room temperature, filters, is dried to obtain Gefitinib crystal form A 280.2mg.
Embodiment 3
Get Gefitinib anhydride 300mg, be warming up under 55 ~ 60 DEG C of conditions, add tetrahydrofuran (THF), add-on is suitable can make Gefitinib be dissolved as completely.Under 45 ~ 50 DEG C of conditions of maintenance temperature, agitation and dropping methyl tertiary butyl ether (volume ratio 1:2), drips and finishes, and 45 ~ 50 DEG C are stirred 30min, are then slowly down to room temperature, filters, is dried to obtain Gefitinib crystal form A 251.2mg.
Embodiment 4
Get Gefitinib anhydride 500mg, be warming up under 55 ~ 60 DEG C of conditions, add dehydrated alcohol, add-on is suitable can make Gefitinib be dissolved as completely.Under 45 ~ 50 DEG C of conditions of maintenance temperature, agitation and dropping isopropyl ether (volume ratio 1:1.5), drips and finishes, and 45 ~ 50 DEG C are stirred 30min, are then slowly down to room temperature, filters, is dried to obtain Gefitinib crystal form A 401.5mg.
Claims (11)
1. a crystal form A for Gefitinib compound (I), is characterized in that the X-ray powder diffraction collection of illustrative plates of described crystal form A comprises the characteristic peak shown in following 2 θ angles: 6.5 °, and 8.3 °, 11.4 °, 13.0 °, 14.1 °, 15.6 °, 16.7 °, 18.5 °, 19.2 °, 20.3 °, 21.4 °, 22.9 °, 24.3 °, 24.7 °, 25.1 °, 25.8 °, 26.2 °, 28.5 °, 30.0 °.
。
2. Gefitinib crystal form A as claimed in claim 1, is characterized in that it has X powder diffraction collection of illustrative plates as shown in Figure 1.
3. Gefitinib crystal form A as claimed in claim 1, is characterized in that described crystal form A is presented at crystal form A and has located exothermic peak at approximately 105 ~ 115 DEG C without thermal weight loss, dsc analysis collection of illustrative plates, and has located endotherm(ic)peak at 192 ~ 198 DEG C.
4. Gefitinib crystal form A as claimed in claim 1, is characterized in that described crystal formation has Raman spectrum as shown in Figure 4, and its Raman shift is 3077.5,3018.3,2936.3,2877.5,1605.9,1475.5,1341.2,772.6,365.8,228.7,182.4cm
-1there is characteristic peak at place.
5. Gefitinib crystal form A as claimed in claim 1, is characterized in that described crystal formation has infrared absorption spectrum as shown in Figure 5, and it is 2925.6,2854.2, and there is absorption peak at 1533.0,1501.9,1377.5,1228.3 places.
6. a method of preparing formula (I) compound new crystal A described in claim 1, its feature comprises:
(a) Gefitinib heating is dissolved in a kind of solvent, is configured to saturated solution;
(b) under heating condition, slowly drip by the good Gefitinib saturated solution of another kind of configured in advance, drip and finish, insulated and stirred certain hour;
(c) be slowly down to room temperature, separate out solid, filtration drying obtains Gefitinib new crystal A.
7. a method of preparing formula (I) compound new crystal A described in claim 1, its feature comprises:
(a) Gefitinib heating is dissolved in a kind of solvent, is configured to saturated solution;
(b) under heating condition, slowly drip another kind of solvent, drip and finish, insulated and stirred certain hour;
(c) be slowly down to room temperature, separate out solid, filtration drying obtains Gefitinib new crystal A.
8. as described in one of as any in claim 6 or 7, it is characterized in that the solvent using in described step (a) comprises dehydrated alcohol, propyl carbinol, tetrahydrofuran (THF), 4-methyl-2 pentanone, Nitromethane 99Min., 1,4-dioxane, preferably dehydrated alcohol, tetrahydrofuran (THF), 4-methyl-2 pentanone.
9. as described in one of as any in claim 6 or 7, it is characterized in that the solvent using in described step (b) comprises acetonitrile, n-propyl acetate, n-butyl acetate, isopropyl acetate, isopropyl ether, methyl tertiary butyl ether, Virahol, normal hexane, normal heptane, preferably acetonitrile, n-propyl acetate, n-butyl acetate, methyl tertiary butyl ether, Virahol, normal hexane.
10., as described in one of as any in claim 6 or 7, it is characterized in that in the quantity of solvent that uses in described step (b) and step (a), solvent for use amount volume ratio is 1:0.5 ~ 5, preferred 1:0.5 ~ 2.
11. one of as any in claim 6 or 7 as described in, it is characterized in that described step (a) Heating temperature is 35 ~ 110 DEG C, step (b) Heating temperature is 35 ~ 100 DEG C.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310003832.4A CN103910690A (en) | 2013-01-06 | 2013-01-06 | New iressa crystal form and preparation methods thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310003832.4A CN103910690A (en) | 2013-01-06 | 2013-01-06 | New iressa crystal form and preparation methods thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN103910690A true CN103910690A (en) | 2014-07-09 |
Family
ID=51036741
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310003832.4A Pending CN103910690A (en) | 2013-01-06 | 2013-01-06 | New iressa crystal form and preparation methods thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103910690A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016523899A (en) * | 2013-06-28 | 2016-08-12 | ジェ イル ファーマシューティカル カンパニー リミテッド | Novel crystalline form of gefitinib and process for its production |
CN106083739A (en) * | 2016-05-31 | 2016-11-09 | 华南理工大学 | New gefitinib crystal form and preparation method based on super-critical anti-solvent technology thereof |
US10259805B2 (en) * | 2015-12-30 | 2019-04-16 | Synthon B.V. | Process for making crystalline form a of gefitinib |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1182421A (en) * | 1995-04-27 | 1998-05-20 | 曾尼卡有限公司 | Quinazoline derivatives |
WO2005070909A1 (en) * | 2004-01-22 | 2005-08-04 | Natco Pharma Limited | An improved process for the preparation of gefitinib |
CN1652790A (en) * | 2002-02-26 | 2005-08-10 | 阿斯特拉曾尼卡有限公司 | Novel crystalline forms of the anti-cancer compound ZD1839 |
CN1681796A (en) * | 2002-09-13 | 2005-10-12 | 阿斯利康(瑞典)有限公司 | Process for the preparation of 4- (3'-chloro-4'-fluoroanilino) -7-methoxy-6- (3-morpholinopropoxy) quinazoline |
CN1733738A (en) * | 2005-08-25 | 2006-02-15 | 江苏吴中苏药医药开发有限责任公司 | Preparation method of 4-(3-chlor-4-fluorobenzeneamidocyanogen)-7-methoxy-6-(3-morpholine oxypropyl)quinazoline |
WO2006090413A1 (en) * | 2005-02-23 | 2006-08-31 | Natco Pharma Limited | Novel crystalline form of gefitinib and a process for its preparation |
CN101148439A (en) * | 2007-09-14 | 2008-03-26 | 东南大学 | Preparing method for gefitinib |
CN101402610A (en) * | 2008-11-13 | 2009-04-08 | 浙江精进药业有限公司 | Synthesis method of 4-(3-chlorine-4-fluorobenzene amino)-7-methoxy-6-[3-(4-morpholinyl)-propoxy] quinoline |
CN101973944A (en) * | 2010-10-14 | 2011-02-16 | 江苏先声药物研究有限公司 | New preparation method for crystal form Gefitinib Form 1 |
CN102153519A (en) * | 2011-02-18 | 2011-08-17 | 上海长林化学科技有限公司 | Preparation method of quinazoline derivative |
CN103896863A (en) * | 2012-12-26 | 2014-07-02 | 亚宝药业集团股份有限公司 | Novel crystal form of anticancer compound ZA1839 and preparation method thereof |
-
2013
- 2013-01-06 CN CN201310003832.4A patent/CN103910690A/en active Pending
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1182421A (en) * | 1995-04-27 | 1998-05-20 | 曾尼卡有限公司 | Quinazoline derivatives |
CN1652790A (en) * | 2002-02-26 | 2005-08-10 | 阿斯特拉曾尼卡有限公司 | Novel crystalline forms of the anti-cancer compound ZD1839 |
CN1681796A (en) * | 2002-09-13 | 2005-10-12 | 阿斯利康(瑞典)有限公司 | Process for the preparation of 4- (3'-chloro-4'-fluoroanilino) -7-methoxy-6- (3-morpholinopropoxy) quinazoline |
WO2005070909A1 (en) * | 2004-01-22 | 2005-08-04 | Natco Pharma Limited | An improved process for the preparation of gefitinib |
WO2006090413A1 (en) * | 2005-02-23 | 2006-08-31 | Natco Pharma Limited | Novel crystalline form of gefitinib and a process for its preparation |
CN1733738A (en) * | 2005-08-25 | 2006-02-15 | 江苏吴中苏药医药开发有限责任公司 | Preparation method of 4-(3-chlor-4-fluorobenzeneamidocyanogen)-7-methoxy-6-(3-morpholine oxypropyl)quinazoline |
CN101148439A (en) * | 2007-09-14 | 2008-03-26 | 东南大学 | Preparing method for gefitinib |
CN101402610A (en) * | 2008-11-13 | 2009-04-08 | 浙江精进药业有限公司 | Synthesis method of 4-(3-chlorine-4-fluorobenzene amino)-7-methoxy-6-[3-(4-morpholinyl)-propoxy] quinoline |
CN101973944A (en) * | 2010-10-14 | 2011-02-16 | 江苏先声药物研究有限公司 | New preparation method for crystal form Gefitinib Form 1 |
CN102153519A (en) * | 2011-02-18 | 2011-08-17 | 上海长林化学科技有限公司 | Preparation method of quinazoline derivative |
CN103896863A (en) * | 2012-12-26 | 2014-07-02 | 亚宝药业集团股份有限公司 | Novel crystal form of anticancer compound ZA1839 and preparation method thereof |
Non-Patent Citations (3)
Title |
---|
吕同杰,等: "吉非替尼的合成", 《广州化工》 * |
徐国权,等: "吉非替尼的合成研究", 《化学与生物工程》 * |
金波,等: "吉非替尼的合成", 《中国药科大学学报》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016523899A (en) * | 2013-06-28 | 2016-08-12 | ジェ イル ファーマシューティカル カンパニー リミテッド | Novel crystalline form of gefitinib and process for its production |
US10259805B2 (en) * | 2015-12-30 | 2019-04-16 | Synthon B.V. | Process for making crystalline form a of gefitinib |
CN106083739A (en) * | 2016-05-31 | 2016-11-09 | 华南理工大学 | New gefitinib crystal form and preparation method based on super-critical anti-solvent technology thereof |
CN106083739B (en) * | 2016-05-31 | 2019-05-14 | 华南理工大学 | New gefitinib crystal form and its preparation method based on super-critical anti-solvent technology |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2908879C (en) | Crystal of pyrrole derivative and method for producing the same | |
TWI693214B (en) | Coformer salts of (2s,3s)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1h-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxy late and methods of preparing them | |
JP2020521003A (en) | Deuterated AZD9291 crystal form, process and use | |
CN103360391A (en) | Novel apixaban crystal form and preparation method thereof | |
CN103910690A (en) | New iressa crystal form and preparation methods thereof | |
CN104926775A (en) | Preparation method of fluorine-containing pyran derivative | |
CN102869650A (en) | Novel crystal of erlotinib base and the preparation method thereof | |
CN110950847B (en) | Novel crystal form of deuterated AZD9291 compound and application thereof | |
CN107043376A (en) | A kind of Li Gelieting novel crystal forms and preparation method thereof | |
CN103896866A (en) | Method for preparing linezolid crystal form I | |
CN104130207A (en) | Acotiamide hydrobromide hydrate and preparation method of crystal form 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 | |
AU2016304852B2 (en) | Processes for preparing an FGFR inhibitor | |
CN104961676B (en) | Mesylate A crystal formation of nicotinamide derivative and its preparation method and application | |
CN104341410A (en) | New Dasatinib crystal form and preparation method thereof | |
CN111032627B (en) | Crystal form of estrogen receptor inhibitor and preparation method thereof | |
TWI480281B (en) | Novel crystal form of tricyclic benzopyran compound and production method thereof | |
CN110981771A (en) | Preparation method and application of impurity E of suplatast tosilate process | |
CN103664780B (en) | (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline 99.9-2-phenyl formate new crystal and preparation method thereof | |
CN103896925B (en) | A kind of Lapatinib salt and preparation method thereof | |
JP6165335B2 (en) | Novel crystalline form of gefitinib and process for its production | |
CN110818676A (en) | Crystal form of cyclohexane derivative | |
CN103819461B (en) | N-[the chloro-4-of 3-(3-fluorine benzyloxy) phenyl]-6-[5-[[2-(methanesulfinyl) ethyl] amino] methyl]-2-furyl]-4-quinazoline amine polymorph and preparation method thereof | |
CN108218872A (en) | A kind of Ai Dailalisi crystal forms C and preparation method thereof | |
CN104370934A (en) | Prasugrel salt and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB03 | Change of inventor or designer information |
Inventor after: Xu Wei Inventor after: Gu Hong Inventor before: Fang Gan Inventor before: Wang Jubo Inventor before: Si Yongxing Inventor before: Wu Wenju Inventor before: Zhang Xini |
|
COR | Change of bibliographic data | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140709 |
|
RJ01 | Rejection of invention patent application after publication |