CN103664836B - Crystal form A of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound and preparation method thereof - Google Patents
Crystal form A of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound and preparation method thereof Download PDFInfo
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- CN103664836B CN103664836B CN201210351552.8A CN201210351552A CN103664836B CN 103664836 B CN103664836 B CN 103664836B CN 201210351552 A CN201210351552 A CN 201210351552A CN 103664836 B CN103664836 B CN 103664836B
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
Abstract
The invention belongs to field of medicine and chemical technology, be specifically related to a kind of 7 β, deuterated acetone compound crystal form A of 10 β-dimethoxy docetaxel and preparation method thereof, 7 described β, the crystal form A of 10 β-dimethoxy docetaxel deuterated acetone compound has satisfactory stability, and has good solvability and dissolution rate in ethanol.
Description
Technical field
The invention belongs to field of medicine and chemical technology, be specifically related to crystal form A of a kind of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound and preparation method thereof; The crystal form A of described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound has satisfactory stability, and has good solvability and dissolution rate in ethanol.
Background technology
Prostate cancer is the modal malignant tumour of male reproductive system, occupies the second of male tumor, and the new cases of the annual increase more than 90 ten thousand in the whole world, and nearly 260,000 people are dead.The sickness rate of prostate cancer increased with the age, and at present the medicine for the treatment of carcinoma of prostate mainly contains bicalutamide, docetaxel, rice drags anthraquinone etc.Initial therapy suppresses to start mainly with male sex hormone; But with the development of the state of an illness, castration opposing is inevitable.
7 β, 10 β-dimethoxy docetaxel, its chemical name is 4-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy group(ing)-1-hydroxyl-7 β, 10 β-dimethoxy-9-oxo yew-11-alkene-13 α-Ji (2R, 3S)-3-tertbutyloxycarbonylamino-PLA ester, having the chemical structure shown in formula I, is the new molecular design small molecules taxane anti-tumor medicament of the treatment prostate cancer of Sanofi-Aventis (Sanofi-aventis) company research and development.7 β, the mechanism of anticancer action of 10 β-dimethoxy docetaxel is similar to docetaxel with feature, belong to anti-microtubule class medicine, by with tubulin binding, promote that microtubule dimer is assembled into microtubule, make microtubule stabilization by preventing polymerisation process from suppressing microtubule to decompose, blocks cellular is in G2 and the M phase simultaneously, thus the mitotic division of anticancer and propagation.7 β, 10 β-dimethoxy Taxotere not only also has activity to the strain of docetaxel susceptible neoplasms, and comprises in the insensitive tumor model of docetaxel chemotherapy and still have activity.
U.S. FDA ratifies 7 β in June, 2010,10 β-dimethoxy docetaxel listing, and commodity are called Jevtana, is mainly used in treating with prednisone coupling previously with containing Docetaxel treatment plan hormone refractory metastatic prostate cancer patient.
At present, CN1849311A discloses 7 β, acetone compound of 10 β-dimethoxy docetaxel and preparation method thereof; WO2012088433 discloses 7 β that heavy hydrogen replaces or fluorine replaces, 10 β-dimethoxy docetaxel compound, and WO2012088445 discloses the higly branched chain polymerization prodrug conjugates based on 7 β, 10 β-dimethoxy docetaxel; Although be disclosed more and more based on the various structure compounds that change of 7 β, 10 β-dimethoxy docetaxel, 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound and crystal formation thereof are not yet by bibliographical information.
Summary of the invention
For above-mentioned the deficiencies in the prior art, deuterated acetone compound crystal form A that the invention provides a kind of 7 β, 10 β-dimethoxy docetaxel and preparation method thereof; It should be noted that, deuterated acetone of the present invention to refer in acetone molecules hydrogen atom entirely for deuterium (D or
2h) acetone of atom, has CD
3(CO) CD
3molecular formula and
structural formula.The present inventor surprisingly finds, some form of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound is the crystalline substance with favourable character.
First aspect present invention provides a kind of 7 β, the crystal form A of the deuterated acetone solvate of 10 β-dimethoxy docetaxel, described 7 β, in 10 β-dimethoxy docetaxel deuterated acetone compound, the content of deuterated acetone is massfraction 5.5%-7.5%, preferred 6.0%-7.0%, more preferably 6.5%-6.9%, most preferably 6.7%; Described 7 β, the crystal form A of the deuterated acetone compound of 10 β-dimethoxy docetaxel uses Cu-K α radiation, the X-ray powder diffraction represented with 2 θ angles is at 8.9 ± 0.2 °, 10.3 ± 0.2 °, 12.9 ± 0.2 °, 17.7 ± 0.2 °, 19.9 ± 0.2 °, there is characteristic peak at 21.9 ± 0.2 ° of places.
Further, described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, uses Cu-K α radiation, the X-ray powder diffraction represented with 2 θ angles also at 7.6 ± 0.2 °, 8.0 ° ± 0.2 °, 12.7 ± 0.2 °, 13.6 ± 0.2 °, 14.5 ± 0.2 °, 15.1 ± 0.2 °, 15.9 ± 0.2 °, 16.7 ± 0.2 °, 17.1 ± 0.2 °, 18.3 ± 0.2 °, 20.5 ± 0.2 °, 21.2 ± 0.2 °, 22.3 ± 0.2 °, 23.1 ± 0.2 °, there is characteristic peak at 24.0 ± 0.2 ° of places.
Further, described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A has X-ray powder diffraction as shown in Figure 1.
Contriver carries out differential scanning calorimetric analysis (DSC) to 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A and detects, and its detected result is presented within the scope of 131-187 DEG C endotherm(ic)peak, within the scope of 206-248 DEG C, have exothermic peak; Particularly, the differential scanning calorimetric analysis (DSC) of described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A detects has endotherm(ic)peak at 171 ± 2 DEG C of places, has exothermic peak at 227 ± 2 DEG C of places; More specifically, described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A has differential scanning calorimetric thermogram spectrum as shown in Figure 2.
7 β, the thermogravimetric analysis (TGA) of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A detects and occurs weight loss at 116-204 DEG C, this weight loss should be that sample loses caused by crystallization deuterated acetone in this temperature range, its weight loss is massfraction 5.5%-7.5%, preferred 6.0%-7.0%, more preferably 6.5%-6.9%, most preferably 6.7%.
7 β, thermogravimetric analysis (TGA) detection display of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, sample is being warming up to 280 DEG C of process losses 45%-50% of initial sample mass from 205 DEG C, the 25%-35% that have lost initial sample mass in 240 DEG C of processes is being warming up to, preferred 26%-31% from 215 DEG C; The 17%-27% that have lost initial sample mass in the process of 230 DEG C is being warming up to, preferred 18%-23% from 220 DEG C; The weight loss of this temperature range should be caused by sample decomposes within the scope of said temperature.
Particularly, 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A has the differential scanning calorimetric analysis (DSC) shown in Fig. 2 and thermogravimetric analysis collection of illustrative plates (TGA) as shown in Figure 3.
Second aspect present invention provides a kind of 7 β, the preparation method of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, the method comprises the following steps: by 7 β, 10 β-dimethoxy docetaxel is dissolved in the mixed solvent of deuterated acetone and water, separate out after leaving standstill solvent flashing, filtration, washing, drying obtain 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A; Wherein, this preparation method completes under 15-40 DEG C of condition, preferred 20-35 DEG C, more preferably 25-30 DEG C; In described deuterated acetone and the mixing solutions of water, the volume ratio of water and deuterated acetone is 1:0.1-10, preferred 1:0.5-5, more preferably 1:1-5, most preferably 1:5.
More specifically, 7 β described in a second aspect of the present invention, the preparation method of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A comprises the following steps: by 7 β, 10 β-dimethoxy docetaxel is dissolved in the mixing solutions of deuterated acetone and water, leave standstill volatilization 10-20 hour, suction filtration, with the mixing solutions washing leaching cake of deuterated acetone and water, 40 DEG C of vacuum-dryings obtain 7 β, the crystal form A of 10 β-dimethoxy docetaxel deuterated acetone compound; Wherein, this preparation method completes under 15-40 DEG C of condition, preferred 20-35 DEG C, more preferably 25-30 DEG C; In described deuterated acetone and the mixing solutions of water, the volume ratio of water and deuterated acetone is 1:0.1-10, preferred 1:0.5-5, more preferably 1:1-5, most preferably 1:5.
In preparation process of the present invention, 7 β, 10 β-dimethoxy docetaxel does not limit with the mass volume ratio of the mixed solvent that deuterated acetone and water form, as long as 7 β, 10 β-dimethoxy docetaxel can dissolve by mixed solvent.
The present invention adopts water and deuterated acetone to carry out volatilization crystallization as solvent, and pollute little, and can obtain highly purified crystal formation, HPLC purity reaches more than 99%, and technique favorable reproducibility.
The present invention also finds and 7 β, 10 β-dimethoxy docetaxel is compared, 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A has good solubility (5g/100ml ethanol) and dissolution rate at ethanol, 7 β can be improved in preparation process, the property prepared of 10 β-dimethoxy docetaxel injection, is more conducive to suitability for industrialized production.
In addition, because deuterated acetone is volatile, with 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A is the residual lower than detection limit of deuterated acetone in the injection for preparing of bulk drug, the residual of deuterated acetone do not detected, therefore there is the advantage of low residue, can Drug safety be improved.
7 β, 10 β provided by the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A has the purposes of the medicine for the preparation for the treatment of prostate cancer.
In sum, the invention provides a kind of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A and preparation method thereof, this crystal formation stable in properties, purity are high, solvability is good in ethanol, dissolution rate is fast, be conducive to raising 7 β, the property prepared of 10 β-dimethoxy docetaxel injection, is more conducive to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A;
Fig. 2 is the thermogravimetric analysis collection of illustrative plates of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A;
Fig. 3 is the differential scanning calorimetric thermogram spectrum of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment
Further illustrate the present invention below by specific embodiment, but should be understood to, these embodiments are only used for the use specifically describing the present invention more in detail, and should not be construed as and limit the present invention in any form.The material that the present invention is used in test is well known in the art or can prepares according to prior art; The test method used is well known in the art or conventional; It is important to note that the present invention prepares 7 β, 7 β that 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A uses, 10 β-dimethoxy docetaxel is that method prepares disclosed in the embodiment 1 of WO96030355.
The inspection apparatus that the present invention is used:
(1) nuclear magnetic resonance spectrum
INSTRUMENT MODEL: VarianINOVA-400 nuclear magnetic resonance analyser.
Test condition: solvent carbon deuterium chloride.
(2) X-ray powder diffractometer
Source of radiation: Cu target K α radiation.
Sample preparation: after sample porphyrize, is placed in standard model frame and measures.
(3) TGA/DSC1 synchronous solving
INSTRUMENT MODEL: METTLERTGA/DSC1.
Test condition: initial measuring tempeature: 30 DEG C
Temperature rise rate: 10 DEG C/min
Embodiment 1
Under 15 DEG C of temperature environments, by 100mg7 β, 10 β-dimethoxy docetaxel drops into 50ml reaction flask, adds the water of 1ml and the deuterated acetone of 5ml, stirs clearly molten, uncovered standing crystallization 10h, suction filtration, with mixed solvent (volume ratio the is 45:55) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 2 hours, obtain 45mg needle-like crystal, HPLC purity 99%.
1H-NMR(600MHz,CDCl
3,δppm)：1.20(d,3H),1.25(d,3H),1.36(s,9H),1.71(s,3H),1.79(mt,1H),1.87(s,3H),2.25-2.32(mt,2H),2.36(s,3H),2.69(mt,1H),3.30(s,3H),3.41(mt,1H),3.45(s,3H),3.82(d,1H),3.85(dd,1H),4.17(d,1H),4.30(d,1H),4.63(s,1H),4.79(s,1H),4.97(d,1H),5.27(d,1H),5.41(d,1H),5.63(d,1H),6.20(t,1H),7.31-7.41(mt,5H),7.48(t,2H),7.60(t,1H),8.09(d,2H)。
7 β are analyzed by X-ray powder diffraction (XRPD), 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, measurement result shows, this crystal formation uses Cu-K α radiation, the X-ray powder diffraction represented with 2 θ angles at 8.9 ± 0.2 °, 10.3 ± 0.2 °, 12.9 ± 0.2 °, 17.7 ± 0.2 °, 19.9 ± 0.2 °, there is characteristic peak at 21.9 ± 0.2 ° of places; Also at 7.6 ± 0.2 °, 8.0 ° ± 0.2 °, 12.7 ± 0.2 °, 13.6 ± 0.2 °, 14.5 ± 0.2 °, 15.1 ± 0.2 °, 15.9 ± 0.2 °, 16.7 ± 0.2 °, 17.1 ± 0.2 °, 18.3 ± 0.2 °, 20.5 ± 0.2 °, 21.2 ± 0.2 °, 22.3 ± 0.2 °, 23.1 ± 0.2 °, there is characteristic peak at 24.0 ± 0.2 ° of places.Its representative XRPD figure is shown in accompanying drawing 1.
By embodiment 1 gained 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A detects through METTLERTGA/DSC1 synchronous solving, synchronously obtains thermogravimetric analysis collection of illustrative plates (TGA) and the Differential Scanning Calorimetry (DSC) of this sample.Measurement result shows:
1, the differential scanning calorimetric analysis of described deuterated acetone compound crystal form A detects and has endotherm(ic)peak at 131-187 DEG C, has exothermic peak at 206-248 DEG C;
2, the differential scanning calorimetric analysis of described deuterated acetone compound crystal form A detects and has endotherm(ic)peak at 171 ± 2 DEG C of places, has exothermic peak at 227 ± 2 DEG C of places;
3, the thermogravimetric analysis of described deuterated acetone compound crystal form A detects and occurs weightless at 116-204 DEG C of place, and weight loss is 5.5% ~ 7.5% of initial sample mass, and preferably 6.0% ~ 7.0%, more preferably 6.5% ~ 6.9%, most preferably 6.7%;
4, the thermogravimetric analysis of described deuterated acetone compound crystal form A detects and continues weightlessness at 205-280 DEG C;
Thermogravimetric analysis collection of illustrative plates (TGA) and the Differential Scanning Calorimetry (DSC) of 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A are specifically shown in accompanying drawing 2 and accompanying drawing 3.
Embodiment 2
Under 40 DEG C of temperature environments, by 50mg7 β, 10 β-dimethoxy docetaxel drops into 25ml reaction flask, adds 0.5ml water and 2.5ml deuterated acetone, stirs clearly molten, uncovered standing crystallization 20h, suction filtration, with mixed solvent (volume ratio the is 45:55) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 4 hours, obtain 25mg needle-like crystal, HPLC purity 99.2%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 3
Under 20 DEG C of temperature environments, by 50mg7 β, 10 β-dimethoxy docetaxel drops into 25ml reaction flask, adds 1.0ml water and 2.5ml deuterated acetone, stirs clearly molten, uncovered standing crystallization 15h, suction filtration, with mixed solvent (volume ratio the is 10:25) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 1 hour, obtain 24mg needle-like crystal, HPLC purity 99.5%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 4
Under 35 DEG C of temperature environments, 100mg7 β, 10 β-dimethoxy docetaxel is dropped into 50ml reaction flask, adds the water of 5ml and the deuterated acetone of 5ml, stir clearly molten, uncovered standing crystallization 12h, suction filtration, with mixed solvent (volume ratio the is 45:55) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 3 hours, obtains 49mg needle-like crystal, HPLC purity 99.4%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 5
Under 25 DEG C of temperature environments, by 100mg7 β, 10 β-dimethoxy docetaxel drops into 50ml reaction flask, adds the water of 0.5ml and the deuterated acetone of 5ml, stirs clearly molten, uncovered standing crystallization 18h, suction filtration, with mixed solvent (volume ratio the is 40:50) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 2 hours, obtain 47mg needle-like crystal, HPLC purity 99.6%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 6
Under 30 DEG C of temperature environments, by 100mg7 β, 10 β-dimethoxy docetaxel drops into 50ml reaction flask, adds the water of 2.5ml and the deuterated acetone of 5ml, stirs clearly molten, uncovered standing crystallization 15h, suction filtration, with mixed solvent (volume ratio the is 45:55) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 4 hours, obtain 51mg needle-like crystal, HPLC purity 99.8%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 7
Under 15 DEG C of temperature environments, by 100mg7 β, 10 β-dimethoxy docetaxel drops into 50ml reaction flask, adds the water of 25ml and the deuterated acetone of 5ml, stirs clearly molten, uncovered standing crystallization 20h, suction filtration, with mixed solvent (volume ratio the is 25:25) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 4 hours, obtain 50mg needle-like crystal, HPLC purity 99.5%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
Embodiment 8
Under 15 DEG C of temperature environments, by 100mg7 β, 10 β-dimethoxy docetaxel drops into 50ml reaction flask, adds the water of 50ml and the deuterated acetone of 5ml, stirs clearly molten, uncovered standing crystallization 20h, suction filtration, with mixed solvent (volume ratio the is 55:45) washing leaching cake of water and deuterated acetone, 40 DEG C of vacuum-drying 4 hours, obtain 47mg needle-like crystal, HPLC purity 99.6%.
According to XRPD and thermogravimetric analysis and differential scanning amount data, the crystal formation obtained is 7 β, 10 β of the present invention-dimethoxy docetaxel deuterated acetone compound crystal form A.
The stability study of embodiment 97 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A
7 β that the present invention is obtained to embodiment 1-8, the stability of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A is studied, vacuum-drying at 40 DEG C (under 40mmHg pressure) 20 hours, crystal formation does not all change, 7 β that the present invention obtains are described, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A is 7 β, 10 β-dimethoxy docetaxel comparatively, there is satisfactory stability, be easy to preserve.
Claims (10)
1. a β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, described crystal form A, use Cu-K α radiation, the X-ray powder diffraction represented with 2 θ angles is at 7.6 ± 0.2 °, 8.0 ± 0.2 °, 8.9 ± 0.2 °, 10.3 ± 0.2 °, 12.7 ± 0.2 °, 12.9 ± 0.2 °, 13.6 ± 0.2 °, 14.5 ± 0.2 °, 15.1 ± 0.2 °, 15.9 ± 0.2 °, 16.7 ± 0.2 °, 17.1 ± 0.2 °, 17.7 ± 0.2 °, 18.3 ± 0.2 °, 19.9 ± 0.2 °, 20.5 ± 0.2 °, 21.2 ± 0.2 °, 21.9 ± 0.2 °, 22.3 ± 0.2 °, 23.1 ± 0.2 °, there is characteristic peak at 24.0 ± 0.2 ° of places, wherein, in described 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound, the content of deuterated acetone is massfraction 5.5-7.5%.
2. 7 β according to claim 1,10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, the differential scanning calorimetric analysis of described deuterated acetone compound crystal form A detects has endotherm(ic)peak at 131-187 DEG C, has exothermic peak at 206-248 DEG C.
3. 7 β according to claim 1,10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, the differential scanning calorimetric analysis of described deuterated acetone compound crystal form A detects has endotherm(ic)peak at 171 ± 2 DEG C of places, has exothermic peak at 227 ± 2 DEG C of places.
4. 7 β according to claim 1,10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, the thermogravimetric analysis of described deuterated acetone compound crystal form A detects and occurs weightless at 116-204 DEG C of place, and weight loss is the 5.5%-7.5% of initial sample mass.
5. 7 β, 10 β according to claim 1-dimethoxy docetaxel deuterated acetone compound crystal form A, is characterized in that, the thermogravimetric analysis of described deuterated acetone compound crystal form A detects and continues weightlessness at 205-280 DEG C.
6. prepare 7 β according to claim 1 for one kind, the method of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, the method comprises the following steps: be dissolved in by 7 β, 10 β-dimethoxy docetaxel in the mixed solvent of deuterated acetone and water, leave standstill solvent flashing, suction filtration, washing, dry, obtain 7 β, 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A.
7. preparation 7 β according to claim 6, the method of 10 β-dimethoxy docetaxel deuterated acetone compound crystal form A, it is characterized in that, the method comprises the steps: 7 β, 10 β-dimethoxy docetaxel to be dissolved in the mixing solutions of deuterated acetone and water, leaves standstill volatilization 10-20 hour, the solid that suction filtration is separated out, washing, 40 DEG C of vacuum-dryings obtain 7 β, the crystal form A of 10 β-dimethoxy docetaxel deuterated acetone compound.
8. the method according to any one of claim 6-7, is characterized in that, described preparation method completes under 15-40 DEG C of temperature environment.
9. the method according to any one of claim 6-7, is characterized in that, in described deuterated acetone and the mixing solutions of water, the volume ratio of water and deuterated acetone is 1:0.1-10.
10. the method according to any one of claim 6-7, is characterized in that, in described deuterated acetone and the mixing solutions of water, the volume ratio of water and deuterated acetone is 1:1-5.
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| WO2005115454A2 (en) * | 2004-05-07 | 2005-12-08 | Massachusetts Institute Of Technology | Methods and compositions for cancer treatment relating to brca1 brct domain recognition of phosphorylated bach1 |
| CN1849311A (en) * | 2003-09-19 | 2006-10-18 | 安万特医药股份有限公司 | Acetone solvate of dimethoxy docetaxel and its process of preparation |
| CN101918385A (en) * | 2008-01-17 | 2010-12-15 | 安万特医药股份有限公司 | Crystalline forms of dimethoxy docetaxel and methods for preparing same |
| CN102675257A (en) * | 2012-05-10 | 2012-09-19 | 上海金和生物技术有限公司 | Cabazitaxel crystal and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1849311A (en) * | 2003-09-19 | 2006-10-18 | 安万特医药股份有限公司 | Acetone solvate of dimethoxy docetaxel and its process of preparation |
| WO2005115454A2 (en) * | 2004-05-07 | 2005-12-08 | Massachusetts Institute Of Technology | Methods and compositions for cancer treatment relating to brca1 brct domain recognition of phosphorylated bach1 |
| CN101918385A (en) * | 2008-01-17 | 2010-12-15 | 安万特医药股份有限公司 | Crystalline forms of dimethoxy docetaxel and methods for preparing same |
| CN102675257A (en) * | 2012-05-10 | 2012-09-19 | 上海金和生物技术有限公司 | Cabazitaxel crystal and preparation method thereof |
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