CN105085517A - Crystal-type palbociclib free-alkali hydrate and preparation method thereof - Google Patents
Crystal-type palbociclib free-alkali hydrate and preparation method thereof Download PDFInfo
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract
The invention provides a crystal-type palbociclib free-alkali hydrate. An X-ray diffraction pattern of the crystal-type palbociclib free-alkali hydrate comprises characteristic peaks shown in 2 theta of 5.7 degrees, 7.8 degrees, 8.3 degrees, 8.9 degrees, 11.4 degrees, 13.1 degrees and 16.7 degrees, wherein the accuracy of the 2 theta is -0.2 degree to +0.2 degree. Compared with a crystal form A and a crystal form B, the crystal-type palbociclib free-alkali hydrate Form I has good storage stability, and meanwhile the solubility of the crystal-type palbociclib free-alkali hydrate Form I in water and polar solvent is significantly improved compared with the crystal form A and the crystal form B.
Description
Technical field
The present invention relates to a kind of preparation method of Pa Boxini free alkali, particularly relate to a kind of preparation method of crystal type Pa Boxini free alkali hydrate.
Background technology
At present, Pa Boxini (Palbociclib) is a selectivity, daily cell cycle protein dependent kinase (CDK) 4/6 inhibitor once developed by Pfizer, in the advanced breast cancer of the postmenopausal women ER positive, HER2 negative form, demonstrate powerful curative effect, obtain the breakthrough medicine certification of FDA.On February 3rd, 2015, Pa Boxini obtains approval listing in the U.S..The chemical name of Pa Boxini free alkali is: 6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2,3-D] pyrimidin-7-ones, shown in I
Patent WO2014128588A1 discloses free alkali crystal form A and the crystal form B of Pa Boxini.The X powder diffraction figure of crystal form A about 8.0 °, 10.1 °, 10.3 ° and 11.5 ° ± 0.2 °
ο2 θ places of deviation have characteristic peak; The X powder diffraction figure of crystal form B about 6.0 °, 10.9 °, 12.8 °, 16.4 ° and 19.8 ° ± 0.2
ο2 θ places of deviation have characteristic peak.
Pa Boxini free alkali FormI provided by the invention has good shelf-stability relative to crystal form A and crystal form B, and the solubleness simultaneously in water and in polar solvent is significantly improved than crystal form A and crystal form B.The preparation technology of this free alkali is amplified to feather weight, process stabilizing at present, is applicable to large-scale industrial production.
Summary of the invention
The object of the invention is to solve the subproblem existed in existing Pa Boxini free alkali technology of preparing, a kind of crystal type Pa Boxini free alkali hydrate and preparation method thereof is provided.
Crystal type Pa Boxini free alkali hydrate provided by the invention is named as FormI, and molecular formula is such as formula shown in I, and this crystallization is pharmaceutically acceptable form.
The object of the invention is to be achieved through the following technical solutions:
A kind of crystal type Pa Boxini free alkali hydrate; its chemical name is 6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] pyrimidin-7-ones; comprise the characteristic peaks shown in following 2 θ angles at its X-ray diffraction spectrogram: 5.7 °, 7.8 °, 8.3 °, 8.9 °, 11.4 °, 13.1 ° and 16.7 °, 2 θ value tolerance range are ± 0.2 °.
Preferably, the infrared wave spectrogram of described crystal type Pa Boxini free alkali hydrate comprises following main crest: 2947cm
-1, 1650cm
-1, 1260cm
-1, 1142cm
-1and 825cm
-1.
Preferably, described crystal type Pa Boxini free alkali hydrate has the thermo-gravimetric loss of 4.0-4.4% at 100 DEG C-150 DEG C.
Preferably, the water content of described crystal type Pa Boxini free alkali hydrate is 3.69-4.07%.
Preferably, in differential scanning calorimetry spectrogram, there is endothermic event 152 DEG C and 277 DEG C in described crystal type Pa Boxini free alkali hydrate; Exothermal event is there is at 198 DEG C.
Prepare the method for above-mentioned crystal type Pa Boxini free alkali hydrate, stir suction filtration after the salt compounds of Pa Boxini is free in the aqueous solution of mineral alkali and obtain.
Preferably, described mineral alkali be sodium bicarbonate, sodium carbonate, lithium hydroxide, saleratus one or more.
Preferably, the salt compounds of described Pa Boxini be Pa Boxini isethionate, Pa Boxini hydroxyethylsulfonic acid disalt, Pa Boxini mono-hydrochloride, Pa Boxini dihydrochloride, the mono-mesylate of Pa Boxini, Pa Boxini dimethanesulfonate one or more.
Preferably, described preparation temperature is 10 DEG C-60 DEG C.
Beneficial effect of the present invention: Pa Boxini free alkali FormI provided by the invention has good shelf-stability relative to crystal form A and crystal form B, the solubleness simultaneously in water and in polar solvent is significantly improved than crystal form A and crystal form B.The preparation technology of this free alkali is amplified to feather weight, process stabilizing at present, is applicable to large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffractogram of FormI of the present invention;
Fig. 2 is the infrared rays spectrogram of FormI of the present invention;
Fig. 3 is the thermogravimetric analysis spectrogram of FormI of the present invention;
Fig. 4 is differential scanning calorimetry (DSC) spectrogram of FormI of the present invention.
Embodiment
The present inventor has been found that crystallization goes out the compound of formula I from moisture solvent, and the crystal of hydrate type FormI of this compound has the good character of operation and characteristic.In order to better the present invention is described, below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described.
A preparation method of crystal type Pa Boxini free alkali hydrate FormI, after the salt compounds of Pa Boxini is free in the aqueous solution of mineral alkali, constant temperature stirring suction filtration obtains.Described mineral alkali be sodium bicarbonate, sodium carbonate, lithium hydroxide, saleratus one or more.The salt compounds of described Pa Boxini be Pa Boxini isethionate, Pa Boxini hydroxyethylsulfonic acid disalt, Pa Boxini mono-hydrochloride, Pa Boxini dihydrochloride, the mono-mesylate of Pa Boxini, Pa Boxini dimethanesulfonate one or more.Described preparation temperature is 10 DEG C-60 DEG C.The X-ray diffraction spectrogram of the crystal type Pa Boxini free alkali hydrate FormI obtained by aforesaid method comprises the characteristic peaks shown in following 2 θ angles: 5.7 °, 7.8 °, 8.3 °, 8.9 °, 11.4 °, 13.1 ° and 16.7 °, 2 θ value tolerance range are ± 0.2 °, as shown in Figure 1.The infrared wave spectrogram of described crystal type Pa Boxini free alkali hydrate FormI comprises following main crest: 2947cm
-1, 1650cm
-1, 1260cm
-1, 1142cm
-1and 825cm
-1, as shown in Figure 2.The water content of described crystal type Pa Boxini free alkali hydrate FormI is 3.69-4.07%, has the thermo-gravimetric loss of 4.0-4.4%, as shown in Figure 3 at 100 DEG C-150 DEG C.Endothermic event is there is 152 DEG C and 277 DEG C in described crystal type Pa Boxini free alkali hydrate FormI differential scanning calorimetry spectrogram; Exothermal event is there is, as shown in Figure 4 at 198 DEG C.
Testing method is as follows:
X-ray powder diffraction data uses XPertProMPD (Multi-PurposeDiffractometer) to measure, light pipe type: EmpyreanXRDtubeCuLFFHR; Electric current and voltage: 45kV, 40mA; The super detector of detector: X ' Celerator; Scan pattern: continuous sweep; Sweep limit: 3 ° of-40 ° of 2 θ;
Infrared test INSTRUMENT MODEL: intelligent Fourier infrared spectrograph, NicoletI5s.
Differential scanning calorimeter model DSCNETZSCH200F3.Test condition is 80ml/minN
2, heat-up rate 10 DEG C/min.
Specific embodiment:
Pa Boxini free alkali hydrate FormI is prepared by Pa Boxini isethionate
Example one: 8.6g sodium bicarbonate is dissolved in stirring and dissolving in 400ml water, is warming up to 60 DEG C.By 7.0g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] the hydroxyethylsulfonic acid disalt (Pa Boxini hydroxyethylsulfonic acid disalt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 60 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 60 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.5g, records XRPD spectrogram consistent with Fig. 1.
Example two: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 7.0g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] the hydroxyethylsulfonic acid disalt (Pa Boxini hydroxyethylsulfonic acid disalt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.5g, records XRPD spectrogram consistent with Fig. 1.
Example three: 10.3g saleratus is dissolved in 400ml water in 10 DEG C of stirring and dissolving.By 7.0g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] isethionate (Pa Boxini hydroxyethylsulfonic acid disalt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the potassium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.0g, records XRPD spectrogram consistent with Fig. 1.
Example four: 10.6g sodium carbonate is dissolved in 400ml water in 10 DEG C of stirring and dissolving.By 7.0g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] isethionate (Pa Boxini hydroxyethylsulfonic acid disalt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the aqueous sodium carbonate of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.1g, records XRPD spectrogram consistent with Fig. 1.
Example five: 2.4g lithium hydroxide is dissolved in 400ml water in 10 DEG C of stirring and dissolving.By 7.0g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] isethionate (Pa Boxini hydroxyethylsulfonic acid disalt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the lithium hydroxide aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.2g, records XRPD spectrogram consistent with Fig. 1.
Example six: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 5.7g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] hydroxyethylsulfonic acid one salt (Pa Boxini hydroxyethylsulfonic acid one salt) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.5g, records XRPD spectrogram consistent with Fig. 1.
Pa Boxini free alkali hydrate FormI is prepared by Pa Boxini hydrochloride
Example seven: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 5.2g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] dihydrochloride (Pa Boxini dihydrochloride) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.7g, records XRPD spectrogram consistent with Fig. 1.
Example eight: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 4.8g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] hydrochloride (Pa Boxini mono-hydrochloride) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.0g, records XRPD spectrogram consistent with Fig. 1.
Example nine: use 5.2g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] dihydrochloride (Pa Boxini dihydrochloride) of pyrimidin-7-ones is raw material; saleratus, sodium carbonate, lithium hydroxide is used to do alkali respectively; acquired results, as described in example seven, displays as shown in table 1 below by concrete operations mode.
Table 1 Pa Boxini dihydrochloride uses dissimilar mineral alkali to prepare Pa Boxini free alkali FormI
Pa Boxini free alkali hydrate FormI is prepared by Pa Boxini mesylate
Example ten: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 6.4g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] two methylsulfonic acids (Pa Boxini dimethanesulfonate) of pyrimidin-7-ones are dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.6g, records XRPD spectrogram consistent with Fig. 1.
Example 11: 8.6g sodium bicarbonate is dissolved in 400ml water in 10 DEG C of-20 DEG C of stirring and dissolving.By 5.4g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] methylsulfonic acid (Pa Boxini mono-mesylate) of pyrimidin-7-ones is dissolved in 80ml water; be made into the aqueous solution; again this aqueous solution is added dropwise in the sodium bicarbonate aqueous solution of 10 DEG C of above-mentioned preparation; drip while stir, separate out yellow solid.Drip and finish, be incubated 10 DEG C and stir 2 hours, suction filtration obtains Pa Boxini free alkali hydrate 3.5g, records XRPD spectrogram consistent with Fig. 1.
Example 12: use 6.4g6-ethanoyl-8-cyclopentyl-5-methyl-2-[[5-(piperazine-1-base) pyridine-2-base] is amino]-8H-pyrido [2; 3-D] dimethanesulfonate (Pa Boxini dimethanesulfonate) of pyrimidin-7-ones is raw material; saleratus, sodium carbonate, lithium hydroxide is used to do alkali respectively; acquired results, as described in example seven, displays as shown in table 2 below by concrete operations mode.
Table 2 Pa Boxini dihydrochloride uses dissimilar mineral alkali to prepare Pa Boxini free alkali FormI
Above-mentioned crystal type Pa Boxini free alkali hydrate FormI provided by the invention contrasts former crystal Form A and FormB that grind and has good solubleness and storage stability.Concrete correlation data is as follows:
1. Pa Boxini free alkali hydrate FormI and free alkali crystal form A and crystal form B solubleness correlation data (mg/ml) in water, as shown in table 3:
Table 3 Pa Boxini free alkali hydrate FormI, crystal form A, crystal form B solubleness correlation data in water
Above data can be found out, the solubleness under the differing temps of Pa Boxini free alkali hydrate FormI crystal formation in water, are all better than formerly grinding free alkali crystal form A and crystal form B.
2. the stability correlation data that stores in room temperature (25 DEG C) of Pa Boxini free alkali hydrate FormI and free alkali crystal form A and crystal form B is as shown in table 4:
Table 4 Pa Boxini free alkali hydrate FormI, crystal form A, crystal form B are in the stability correlation data of room temperature storage
Above correlation data can be found out, Pa Boxini free alkali hydrate FormI storage stability is at room temperature substantially identical with FormB crystal formation with Yuan Yan producer free alkali FormA crystal formation.
The above; be only the present invention's preferably embodiment, but protection scope of the present invention is not limited thereto, is anyly familiar with those skilled in the art in the technical scope that the present invention discloses; the change that can expect easily or replacement, all should be encompassed within protection scope of the present invention.Therefore, protection scope of the present invention should be as the criterion with the protection domain of claims.
Claims (9)
1. a crystal type Pa Boxini free alkali hydrate, it is characterized in that, the X-ray diffraction spectrogram of described crystal type Pa Boxini free alkali hydrate comprises the characteristic peaks shown in following 2 θ angles: 5.7 °, 7.8 °, 8.3 °, 8.9 °, 11.4 °, 13.1 ° and 16.7 °, 2 θ value tolerance range are ± 0.2 °, and molecular structure as shown in Equation 1.
2. crystal type Pa Boxini free alkali hydrate according to claim 1, is characterized in that, the infrared wave spectrogram of described crystal type Pa Boxini free alkali hydrate comprises following main crest: 2947cm
-1, 1650cm
-1, 1260cm
-1, 1142cm
-1and 825cm
-1.
3. crystal type Pa Boxini free alkali hydrate according to claim 1, is characterized in that, described crystal type Pa Boxini free alkali hydrate has the thermo-gravimetric loss of 4.0-4.4% at 100 DEG C-150 DEG C.
4. crystal type Pa Boxini free alkali hydrate according to claim 1, is characterized in that, in differential scanning calorimetry spectrogram, described crystal type Pa Boxini free alkali hydrate occurs endothermic event 152 DEG C and 277 DEG C; Exothermal event is there is at 198 DEG C.
5. crystal type Pa Boxini free alkali hydrate according to claim 1, is characterized in that, the water content of described crystal type Pa Boxini free alkali hydrate is 3.69-4.07%%.
6. prepare the method for above-mentioned crystal type Pa Boxini free alkali hydrate, it is characterized in that, stir suction filtration after the salt compounds of Pa Boxini is free in the aqueous solution of mineral alkali and obtain.
7. preparation method according to claim 6, is characterized in that, described mineral alkali be sodium bicarbonate, sodium carbonate, lithium hydroxide, saleratus one or more.
8. preparation method according to claim 6, it is characterized in that, the salt compounds of described Pa Boxini be Pa Boxini isethionate, Pa Boxini hydroxyethylsulfonic acid disalt, Pa Boxini mono-hydrochloride, Pa Boxini dihydrochloride, the mono-mesylate of Pa Boxini, Pa Boxini dimethanesulfonate one or more.
9. preparation method according to claim 6, is characterized in that, described preparation temperature is 10 DEG C-60 DEG C.
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106336411A (en) * | 2016-04-27 | 2017-01-18 | 上海医药集团股份有限公司 | Preparation method and use of CDK4/6 inhibitor palbociclib highly-pure raw drug |
| WO2017076288A1 (en) * | 2015-11-02 | 2017-05-11 | 浙江华海药业股份有限公司 | Preparation methods for palbociclib free base crystal form a and crystal form b |
| CN106800553A (en) * | 2015-11-26 | 2017-06-06 | 上海科胜药物研发有限公司 | A kind of crystal formation of Pa Boxini dihydroxy ethyls sulfonate |
| CN106800554A (en) * | 2015-11-26 | 2017-06-06 | 上海科胜药物研发有限公司 | A kind of crystal formation of Pa Boxini dihydrochlorides and preparation method thereof |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1835951A (en) * | 2003-07-11 | 2006-09-20 | 沃尼尔·朗伯有限责任公司 | Isethionate salt of a selective CDK4 inhibitor |
| CN101001857A (en) * | 2002-01-22 | 2007-07-18 | 沃尼尔·朗伯有限责任公司 | 2-(pyridin-2-ylamino)-pyrido [2,3-d]pyrimidin-7-ones |
| WO2014128588A1 (en) * | 2013-02-21 | 2014-08-28 | Pfizer Inc. | Solid forms of a selective cdk4/6 inhibitor |
| CN104478874A (en) * | 2014-12-08 | 2015-04-01 | 新发药业有限公司 | Preparation method of palbociclib |
| CN104496983A (en) * | 2014-11-26 | 2015-04-08 | 苏州明锐医药科技有限公司 | Palbociclib preparation method |
| CN104610254A (en) * | 2015-01-26 | 2015-05-13 | 新发药业有限公司 | Low-cost preparation method for palbociclib |
-
2015
- 2015-08-06 CN CN201510477254.7A patent/CN105085517B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101001857A (en) * | 2002-01-22 | 2007-07-18 | 沃尼尔·朗伯有限责任公司 | 2-(pyridin-2-ylamino)-pyrido [2,3-d]pyrimidin-7-ones |
| CN1835951A (en) * | 2003-07-11 | 2006-09-20 | 沃尼尔·朗伯有限责任公司 | Isethionate salt of a selective CDK4 inhibitor |
| WO2014128588A1 (en) * | 2013-02-21 | 2014-08-28 | Pfizer Inc. | Solid forms of a selective cdk4/6 inhibitor |
| CN104496983A (en) * | 2014-11-26 | 2015-04-08 | 苏州明锐医药科技有限公司 | Palbociclib preparation method |
| CN104478874A (en) * | 2014-12-08 | 2015-04-01 | 新发药业有限公司 | Preparation method of palbociclib |
| CN104610254A (en) * | 2015-01-26 | 2015-05-13 | 新发药业有限公司 | Low-cost preparation method for palbociclib |
Non-Patent Citations (1)
| Title |
|---|
| PETER L. TOOGOOD ET AL.: "Discover of a potent and selective inhibitor of cyclin-dependent kinase 4/6", 《J. MED. CHEM.》 * |
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| US10329290B2 (en) | 2015-11-02 | 2019-06-25 | Zhejiang Huahai Pharmaceutical Co., Ltd | Preparation methods for palbociclib free base crystal form A and crystal form B |
| WO2017076288A1 (en) * | 2015-11-02 | 2017-05-11 | 浙江华海药业股份有限公司 | Preparation methods for palbociclib free base crystal form a and crystal form b |
| CN108137577B (en) * | 2015-11-02 | 2021-04-06 | 浙江华海药业股份有限公司 | Preparation method of crystal form A and crystal form B of palbociclib free base |
| CN108137577A (en) * | 2015-11-02 | 2018-06-08 | 浙江华海药业股份有限公司 | A kind of preparation method of Pa Boxini free alkalis crystal form A and crystal form B |
| US10766895B2 (en) | 2015-11-02 | 2020-09-08 | Zhejiang Huahai Pharmaceutical Co., Ltd. | Preparation methods for palbociclib free base crystal form A and crystal form B |
| CN106800553A (en) * | 2015-11-26 | 2017-06-06 | 上海科胜药物研发有限公司 | A kind of crystal formation of Pa Boxini dihydroxy ethyls sulfonate |
| CN106800554A (en) * | 2015-11-26 | 2017-06-06 | 上海科胜药物研发有限公司 | A kind of crystal formation of Pa Boxini dihydrochlorides and preparation method thereof |
| WO2017130219A1 (en) * | 2016-01-25 | 2017-08-03 | Mylan Laboratories Limited | Amorphous solid dispersion of palbociclib |
| US11464779B2 (en) | 2016-03-29 | 2022-10-11 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| CN106336411B (en) * | 2016-04-27 | 2018-03-06 | 上海医药集团股份有限公司 | The preparation technology and purposes of CDK4/6 inhibitor Pa Boxini high-purity raw medicines |
| CN106336411A (en) * | 2016-04-27 | 2017-01-18 | 上海医药集团股份有限公司 | Preparation method and use of CDK4/6 inhibitor palbociclib highly-pure raw drug |
| CN109661393A (en) * | 2016-05-08 | 2019-04-19 | 上海诚妙医药科技有限公司 | Novel crystal forms of Pabuk former times benefit cloth and preparation method thereof and application thereof |
| JP2019521190A (en) * | 2016-07-07 | 2019-07-25 | プランテックス・リミテッド | Solid form of parvosiclib nimesylate |
| US10597393B2 (en) * | 2016-07-07 | 2020-03-24 | Plantex Ltd. | Solid state forms of Palbociclib dimesylate |
| JP2021063111A (en) * | 2016-07-07 | 2021-04-22 | プランテックス・リミテッド | Solid state forms of palbociclib dimesylate |
| US11332467B2 (en) | 2016-07-07 | 2022-05-17 | Plantex Ltd. | Solid state forms of palbociclib dimesylate |
| WO2018009735A1 (en) * | 2016-07-07 | 2018-01-11 | Plantex Ltd. | Solid state forms of palbociclib dimesylate |
| CN108017629A (en) * | 2016-11-04 | 2018-05-11 | 上海奥博生物医药技术有限公司 | A kind of Pa Boxini amorphous states |
| CN108864078A (en) * | 2017-05-10 | 2018-11-23 | 江苏豪森药业集团有限公司 | The preparation method of Pa Boxini crystal form B |
| CN108864078B (en) * | 2017-05-10 | 2021-10-15 | 江苏豪森药业集团有限公司 | Preparation method of palbociclib crystal form B |
| WO2022068877A1 (en) * | 2020-09-29 | 2022-04-07 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical compositions of amorphous solid dispersions and methods of preperation thereof |
| US11471418B2 (en) | 2020-09-29 | 2022-10-18 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical compositions of amorphous solid dispersions and methods of preparation thereof |
| CN114149426A (en) * | 2021-12-13 | 2022-03-08 | 江苏海洋大学 | Pabociclib pharmaceutical co-crystal and preparation method thereof |
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