CN106674157A - Novel cabazitaxel anhydrous compound and preparation method and crystal form thereof - Google Patents
Novel cabazitaxel anhydrous compound and preparation method and crystal form thereof Download PDFInfo
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- 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
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Abstract
The invention specifically relates to a cabazitaxel anhydrous compound and a preparation method and crystal form thereof. The method is fewer in steps, mild in reaction conditions, simple and convenient in purification, high in reaction yield, less in pollution, and available in raw materials, and the obtained novel crystal form is stable and facilitates industrial production.
Description
The invention belongs to pharmaceutical technology field, is particularly related to new Cabazitaxel anhydrous compound and preparation method thereof
And crystal form.
Background technology
Cabazitaxel, English entitled Cabazitaxel, -2 α of the chemical entitled 4- acetoxyl groups-β of benzoyloxy -5,20-
The β of epoxy -1- hydroxyls -7,10 β-dimethoxy -9- oxo Ramulus et folium taxi cuspidatae -11- -13 α of alkene-base (2R, 3S) -3- t-butoxycarbonyl aminos -
PLA ester, IUPAC titles are (2 α, 5 β, 7 β, 10 β, 13 α) -4-acetoxy-13- ({ (2R, 3S) -3
[(tert-butoxy carbonyl)amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydrox y-7,
10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl-benzoate, are by French Sanofi-aventi s
A kind of molecular design taxaneses micromolecular compound of company's research and development, and in June, 2010 before U.S.'s approval listing
The Second line Drug of row adenocarcinoma, structure is shown in formula I：
The mechanism of anticancer action and feature of Cabazitaxel Cabazitaxel is similar to docetaxel, belongs to anti-micro-pipe class medicine
Thing.Cabazitaxel by with tubulin binding, promote it to be assembled into micro-pipe, while prevent the micro-pipe that assembled from disintegrating,
Microtubule stabilization is made, and then suppresses the mitosiss of cell and the performance of Interphase cells function, be first and using conventional late period
Carcinoma of prostate medicine Docetaxel is invalid or even treatment late period, the medicine of hormone antagonist type carcinoma of prostate first-selected during aggravation
Thing.Cabazitaxel provides a kind of novel therapeutic for castration-resistant prostate cancer patient, and this brings to patients with prostate cancer
Wish, although only obtain moderate income, but confirm the effectiveness of carcinoma of prostate immunization therapy.Into controlling of testing of III phases
Strategy is treated, including to the more strong suppression of androgen receptor signal, (this can affect for the regulation of novel signal path in Bone tumour
Late stage prostate patient to more than 90%), and strengthen antineoplastic immune.
Yuan Yan Sanofi-Aventis company discloses the synthesis technique and crystal formation patent of Cabazitaxel, and its patent is as follows：CN
100429207 C and CN101918385 A.In recent years, on the basis of original research, domestic each R＆D institution and pharmaceutical manufacturer
Many different synthesis techniques are also disclosed that in succession, and from 2011 so far, domestic disclosed patent mainly has as follows：CN
102285947 A、CN 102311410 A、CN 102336726 A、CN102417491 A、CN 102532064 A、CN
102532065 A、CN 102659721 A、CN 102675256A、CN 102786502 A、CN102746258 A、
CN103467416A etc.；Make a general survey of existing patent and can be seen that to prepare the Major Difficulties of Cabazitaxel be first step Ramulus et folium taxi cuspidatae alcohol extraction
C-7, C-10 position methylation reaction of thing 10-DAB is taken, it can introduce substantial amounts of by-product, to reaction temperature and reaction reagent
Require more strictly also or using other protection group indirect reactions, but no matter which kind of method adopted, to pharmaceutical producing enterprise
Yan Douhui brings inconvenience.In view of, can be at home at present Formula II institute with the double methyl 10-DAB in legal acquisition C-7, C-10 positions
Show compound, therefore, adopt 7,10- bi-methoxy -10-DAB to be prepared Cabazitaxel as initiation material, can shorten anti-
Answer the cycle, the production difficulty of enterprise is reduced, beneficial to the realization of later stage industrialized production.In the Cabazitaxel of other document reports
Preparation method, though with 7,10- bi-methoxy -10-DAB as initiation material, be all first carry out condensation reaction, by intermediate
After compound IV is isolated and purified, then the reaction that is hydrolyzed.The purge process of compound IV increased operation, extend the cycle,
It is unfavorable for industrial big production.
On the other hand, crystal formation is one of key factor of impact drug quality, curative effect and preparation processing performance.Polymorphic shows
As, same compound is referred to, by controlling its different formation condition, two or more molecule space arrangement can be formed
Mode, so as to produce the phenomenon of different solid crystals.Polymorph in pharmaceuticals is the common phenomenon in drug research and development, is to affect medicine
The key factor of quality.The different crystal forms of same compound, its chemical composition is identical, but microcosmic crystal structure is different, thus leads
Them are caused to have differences on mode of appearance, physicochemical property and biological activity.These characteristics directly affect the preparation processing of medicine
Performance, and stability, dissolubility and the bioavailability of medicine can be affected, and then have influence on the quality of medicine, safety, have
Effect property and its application.Therefore, in drug research and development, the polymorphic problem of medicine should comprehensively be considered.
At present, there are various crystal formations known to Cabazitaxel, patent WO2005/028462 determines and characterize Cabazitaxel crystalline substance
The β of type A, i.e. -2 α of 4- acetoxyl groups-β of benzoyloxy -5,20- epoxy -1- hydroxyls -7, -9- oxos -11- is purple for 10 β-dimethoxy
The acetone solvate form of (2R, the 3S) -3- tertbutyloxycarbonylaminos-PLA ester of China fir -13 α of alkene-base alcohol.
Patent WO2009/115655 determines and characterizes anhydride form B, C, D, E, F of Cabazitaxel, ethanolates shape
Formula B, D, E, the different solvate F of ethanol/water, monohydrate form C and dihydrate form C.
Patent CN102746258 determine and characterize Cabazitaxel ester solvate form crystal formation J, hydrate forms crystal formation G and
Crystal formation I.
Patent CN105849093 determines and characterizes anhydrous crystal forms H of Cabazitaxel.
The content of the invention
In view of this, the invention provides a kind of preparation method of Cabazitaxel and a kind of new anhydrous compound,
It is to carry out condensation reaction with compound shown in III shown in Formula II that preparation method uses 7,10- bi-methoxy 10-DAB, obtains formula IV
Shown compound, compound purification without isolation, according to the processing means of " one kettle way ", is directly sloughed by the way of gentle
Protection group obtains Cabazitaxel crude product, and by further purification highly purified Cabazitaxel is prepared, and reduces reactions steps,
Reaction time is shortened, is very beneficial for industrialized production, and the anhydrous compound stable crystal form for preparing, with extensive
Application prospect, concrete reaction equation is as follows：
Formula III and IV, wherein R1Selected from 1- methyl isophthalic acids-methoxy ethyl ether (MIP-OR), 1- ethoxyethyl group ether (EE-
) or the hydroxy-protective group such as methoxyisopfopyl OR；
Concretely comprise the following steps：
Step 1：In ether solvent or DMSO, DMF, THF, DMA, III shownization of compound shown in Formula II and excess
Compound mixes, carries out condensation reaction under the inorganic base or organic base catalytic of catalytic amount, is then hydrolyzed in acid condition,
Obtain crude compound Cabazitaxel shown in Formulas I；
Step 2：By the halogenated alkane that crude product Cabazitaxel carbon number is 1~6 esters and carbon number is 1~5
Mixed solvent is stirred, then sucking filtration, filtration cakes torrefaction obtain final product it is single it is miscellaneous be less than 0.1%, it is total it is miscellaneous be less than 1.0% high-purity kappa he
Match；
Step 3：Cabazitaxel is dissolved in alcohols solvent, and stirring is lower to be instilled in water, and stirring is filtered, and filter cake is washed with water, very
Empty dry the Cabazitaxel anhydrous compound.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
State compound shown in Formula II, the mol ratio of compound and the inorganic base or organic base shown in the formula III is 1：1~5：0.10
~0.75, it is preferably in a proportion of：1.0：2.0：0.5.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
Reaction temperature is stated for -5~5 DEG C, the response time is 1~10h, preferable reaction temperature is 0 DEG C, and preferred reaction time is 4h.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
Solvent is stated including one or more the mixture in tetrahydrofuran, DMSO, DMF, DMA, tetrahydrofuran is preferable over.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
The inorganic base stated or organic base include the mixed of one or more in NaHMDS, LiHMDS, KHMDS, NaH, n-BuLi, KH
Compound, is preferable over LiHMDS.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
State the mixed solution that acid condition is specially tetrahydrofuran and 0.2~1.0N dilute hydrochloric acid, preferably 0.2N dilute hydrochloric acid；With g/mL
Meter, compound shown in the formula IV is 1 with the mass volume ratio of the tetrahydrofuran and 0.2~1.0N dilute hydrochloric acid：1~10, it is excellent
Elect 1 as：10；The volume ratio of the tetrahydrofuran and 0.2~1.0N dilute hydrochloric acid is 1~10：1~10, preferably 1:10.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 1
Hydrolysising reacting temperature is stated for 25~50 DEG C, preferably 25 DEG C.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 2
It is ethyl acetate, Ethyl formate, diethyl malonate that carbon number is stated for 1~6 ester type compound, is preferable over ethyl acetate.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 2
It is dichloromethane, chloroform, dichloroethanes, trichloroethane, chloro-propane or chloro to state the halogenated hydrocarbons that carbon number is 1~5
Butane, is preferable over dichloromethane.
In some embodiments that the present invention is provided, in the preparation method of compound Cabazitaxel shown in Formulas I, institute in step 2
The ratio for stating the esters that carbon number is 1~6 and the halogenated alkane mixed solvent that carbon number is 1~5 is 10~30：1, preferably
In 30：1；In terms of g/mL, compound shown in the formula IV is 1 with the esters that the carbon number is 1~6 and carbon number
~5 halogenated alkane mixed solvent mass volume ratio is 1：10~30, preferably 1：15.
In some true cases that the present invention is provided, the ratio of alcohols described in step 3 and water is 1:5-20, preferably 1:5；
Alcohols solvent includes the alcohols solvents such as methanol, ethanol, and vacuum drying temperature is 40-120 DEG C.
The present invention is directly sloughed protection group by the way of gentle and obtains Cabazitaxel according to the processing means of " one kettle way "
Crude product, by further purification highly purified Cabazitaxel is prepared, and reduces reactions steps, shortens reaction time, non-
Often be conducive to industrialized production, and the anhydrous compound stable crystal form for preparing, be with a wide range of applications.
Cabazitaxel prepared by the present invention has following advantage without hydrate crystal forms：Noresidue solvent, excellent chemistry
Purity and drug solubility；Preparation process is simple, does not isolate and purify process, is especially suitable for industrialized production.
Such as the new Cabazitaxel anhydrous compound of the present invention can be used as medicine, non-little in particular for treating cancer
Cell lung cancer, transitional cell carcinoma, liposarcoma, hormone-refractory prostate cancer, metastatic breast cancer, metastatic prostate cancer
Disease, cerebral tumor etc., are preferred for carcinoma of prostate.
Description of the drawings
Fig. 1 shows that the present invention implements the 1 Cabazitaxel HPLC collection of illustrative plates for providing；
Fig. 2 shows that the present invention implements the 2 Cabazitaxel HPLC collection of illustrative plates for providing；
Fig. 3 shows that the present invention implements the 3 Cabazitaxel HPLC collection of illustrative plates for providing；
Fig. 4-6 shows that the present invention implements the 4 Cabazitaxel anhydrous crystal single crystal X-ray diffraction collection of illustrative plates for providing；
Fig. 7 shows the anhydrous crystal X-ray powder diffraction pattern of the Cabazitaxel that the embodiment of the present invention 4 is provided；
Fig. 8 shows that the present invention implements 4 Cabazitaxel anhydrous crystal differential scanning calorimetry (DSC) collection of illustrative plates for providing；
Specific embodiment
The invention discloses a kind of preparation method of Cabazitaxel and anhydrous crystal forms Cabazitaxel, those skilled in the art
Present disclosure can be used for reference, technological parameter realization is suitably modified.Specifically, all similar replacements and change are right
It is it will be apparent that they are considered as being included in the present invention for those skilled in the art.The method of the present invention and application are
Jing is described by preferred embodiment, and related personnel substantially can be in without departing from present invention, spirit and scope to this
Methods and applications described in text are modified or suitably the technology of the present invention is realized and applied to change with combining.
With reference to embodiment, the present invention is expanded on further：
The 5g of embodiment 1
Under nitrogen protection, compound shown in 5.0g (8.75mmol) Formula II and 6.0g (17.8mmol) are dissolved in into 50ml anhydrous
Tetrahydrofuran, ice bath is cooled to 0 DEG C, and Deca 8.7mL (8.75mmol) LiHMDS, control temperature is reacted less than 10 DEG C of reaction 4h
After end, add 50mL water quenchings to go out reaction, add 60ml tetrahydrofurans, add 0.2N hydrochloric acid 11mL, 25 DEG C of temperature of control is instead
After answering 6h, reaction to terminate, 200mL ethyl acetate and saturated nacl aqueous solution 100mL, extracting and demixing, collected organic layer is added to satisfy
Wash three times with sodium chloride solution 100mL, purified water 100mL washed once, and anhydrous magnesium sulfate is dried 2h, the crude product of vacuum distillation
Cabazitaxel, HPLC detection purity is more than 90.0%.
8h is stirred during 10g crude product Cabazitaxels are dissolved in into 150mL ethyl acetate and 10mL dichloromethane, sucking filtration obtains white
Solid Cabazitaxel fine work, HPLC detection purity is more than 99.0%, sees Fig. 1.
The 30g of embodiment 2
Under nitrogen protection, compound shown in 30g (52.3mmol) Formula II and 37g (110.3mmol) are dissolved in into 50ml anhydrous
Tetrahydrofuran, ice bath is cooled to 0 DEG C, and Deca 52.3mL (52.3mmol) LiHMDS, control temperature is reacted less than 10 DEG C of reaction 6h
After end, add 100ml water quenchings to go out reaction, sequentially add 100ml tetrahydrofurans and 0.2N hydrochloric acid 20ml, 25 DEG C of temperature of control
Reaction 6h, after reaction terminates, adds 200mL ethyl acetate and saturated nacl aqueous solution 100mL, extracting and demixing, collected organic layer,
Saturated nacl aqueous solution 100mL is washed three times, and purified water 100mL washed once, anhydrous magnesium sulfate is dried 2h, and vacuum distillation is arrived
11g crude product Cabazitaxels, HPLC detection purity is more than 90.0%.
8h is stirred during 45g crude product Cabazitaxels are dissolved in into 350mL ethyl acetate and 20mL dichloromethane, sucking filtration obtains white
Solid Cabazitaxel fine work, HPLC detection purity is more than 99.0%, sees Fig. 2.
The 100g of embodiment 3
Nitrogen protection under, by compound shown in 100g (174.6mmol) Formula II and 120g (357mmol) be dissolved in 100ml without
Water tetrahydrofuran, ice bath is cooled to 0 DEG C, and Deca 174mL (174mmol) LiHMDS, control temperature is reacted less than 10 DEG C of reaction 6h
After end, add 200mL water quenchings to go out reaction, sequentially add 200ml tetrahydrofurans and 0.2N hydrochloric acid 50mL, 25 DEG C of temperature of control is instead
After answering 6h, reaction to terminate, 600mL ethyl acetate and saturated nacl aqueous solution 300mL, extracting and demixing, collected organic layer is added to satisfy
Wash three times with sodium chloride solution 300mL, purified water 300mL washed once, anhydrous magnesium sulfate is dried 2h, vacuum distillation to thick
Product Cabazitaxel, HPLC detection purity is more than 90.0%.
8h is stirred during 110g crude product Cabazitaxels are dissolved in into 1500mL ethyl acetate and 100mL dichloromethane, sucking filtration is obtained
White solid Cabazitaxel fine work, HPLC detection purity is more than 99.0%, and magnetic resonance detection result shows,1H composes (400MHz；
CDCl3；δ is in units of ppm；Coupling constant J, in units of Hz)：1.14(s,3H,CH3)；1.28(s,3H,CH3)；1.38(s,
9H,C(CH3)；1.74(s,1H,OH)；1.94(s,3H,CH3)；1.98(s,3H,CH3)；2.20~2.27 (2dd, J=16Hz,
2H, 14 * CCH2)；2.25~2.84 (m, 2H, 6 * CCH2)；2.55(s,3H,COCH3)；4.02 (s, 1H, 10 OH)；
4.04 (d, J=7Hz, 1H, 3 CH)；4.24~4.38 (m, 2H, 20 CH2)；4.54 (s, 1H, 2 H)；4.96(m,1H,5
Position H)；5.28 (m, 1H, 3 H)；5.38 (s, 1H, 10 H)；5.44 (dd, J=10 and 7.5Hz, 1H, 7 H)；5.52(d,J
=10Hz, 1H, CONH)；5.74 (dd, J=7Hz, 1H, 2 H)；6.34 (t, J=9Hz, 1H, 13 H)；7.24~7.40 (m,
5H, 3 ' position aromatic compounds)；7.50 (t, J=7.5Hz, 2H, metas OCOC6H5H)；7.63 (t, J=7.5Hz, 1H, para-positions
OCOC6H5H))；8.12 (d, J=7.5Hz, 2H, ortho position OCOC6H5H), HPLC detections purity is 99.75%, sees Fig. 3.
Embodiment 4
100g Cabazitaxels are dissolved in into 500ml ethanol, in being slowly dropped to 2.5L water, 1h, sucking filtration, 105 degree of lower bakings is stirred
Material 30h, obtains anhydrous Cabazitaxel crystal formation.
Cabazitaxel prepared by embodiment 4 carries out single crystal X-ray diffraction experiment without crystal of hydrate.Its single crystal X-ray
Diffracting spectrum is shown in Fig. 4-6.
Cabazitaxel prepared by embodiment 4 carries out X-ray powder diffraction experiment without crystal of hydrate.Through testing table
Levy, the 2-theta of its X-ray powder diffraction figure is at 7.3099 ± 0.2 °, 7.7968 ± 0.2 °, 8.1665 ± 0.2 °, 9.8706
±0.2°,10.3414±0.2°,11.1464±0.2°,12.6816±0.2°,13.0260±0.2°,14.2842±0.2°,
15.3433±0.2°,15.8223±0.2°,16.3962±0.2°,17.1633±0.2°,17.6038±0.2°,17.9544
± 0.2 °, 18.4899 ± 0.2 °, 18.8239 ± 0.2 °, 19.6630 ± 0.2 °, 20.4986 ± 0.2 °, 21.9593 ± 0.2 °,
There is diffraction maximum at 22.6240 ± 0.2 ° and 23.9552 ± 0.2 °, see Fig. 7.
The Cabazitaxel of embodiment 4 is carried out into differential scanning calorimetric analysis (DSC) experiment without crystal of hydrate.The experiment is adopted
It is analyzed with Netzsch DSC 204F1Phoenix detecting instruments, heat flow is recorded in 20-190 DEG C, linear heating rate
(10 DEG C/min) its collection of illustrative plates is shown in accompanying drawing 8, and its DSC collection of illustrative plates has obvious crystalline exotherm peak at 150.2 ± 2 DEG C and 160.0 ± 2 DEG C,
See Fig. 8.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of simple and convenient process for preparing of Cabazitaxel, it is characterised in that comprise the steps：
Step 1：In ether solvent or DMSO, DMF, THF, DMA, compound shown in the III of compound shown in Formula II and excess
Mix, carry out condensation reaction under the inorganic base or organic base catalytic of catalytic amount, be then hydrolyzed in acid condition, obtain
The crude product of compound Cabazitaxel shown in Formulas I；
Step 2：Esters and the alkane or halogenated alkane that carbon number is 1 ~ 5 by Cabazitaxel crude product carbon number for 1 ~ 6
Mixed solvent is stirred, then sucking filtration, filtration cakes torrefaction obtain final product it is single it is miscellaneous be less than 0.1%, total miscellaneous high-purity Cabazitaxel for being less than 1.0%；
Formulas I Formula II
Formula III formula IV
Formula III and IV, wherein R1Selected from ethoxyethyl group（EE）, methoxy（MOP）, the hydroxyl protection such as methoxyisopfopyl
Base.
2. preparation method according to claim 1, it is characterised in that compound shown in Formula II described in step 1, the formula
The mol ratio of compound shown in III, the inorganic base or organic base is 1：1~5：0.10~0.75；Reaction temperature described in step 1
For -5 ~ 5oC, the response time is 1 ~ 10h；Solvent described in step 1 includes the one kind in tetrahydrofuran, DMSO, DMF, DMA
Or two or more mixture；Inorganic base or organic base described in step 1 includes NaHMDS, LiHMDS, KHMDS, NaH, n-
One or more mixture in BuLi, KH.
3. preparation method according to claim 1, it is characterised in that acid condition described in step 1 is specially tetrahydrochysene furan
The mixed solution muttered with 0.2 ~ 1.0N dilute hydrochloric acid；In terms of g/mL, compound shown in the formula IV and the tetrahydrofuran and 0.2 ~
1.0N the mass volume ratio of dilute hydrochloric acid is 1：1~10；The volume ratio of the tetrahydrofuran and 0.2 ~ 1.0N dilute hydrochloric acid is 1 ~ 10：1~
10；Hydrolysising reacting temperature described in step 1 is 25 ~ 50oC。
4. preparation method according to claim 1, it is characterised in that carbon number described in step 2 is 1 ~ 6 esters chemical combination
Thing is ethyl acetate, Ethyl formate, propyl acetate, diethyl malonate；Carbon number described in step 2 is 1 ~ 5 halogenated hydrocarbons
For dichloromethane, chloroform, dichloroethanes, trichloroethane, chloro-propane or chloro-butane.
5. preparation method according to claim 1, it is characterised in that carbon number described in step 2 for 1 ~ 6 esters with
Carbon number is 10 ~ 30 for the ratio of 1 ~ 5 halogenated alkane mixed solvent：1；In terms of g/mL, compound shown in the formula IV with
The carbon number is 1 for 1 ~ 5 halogenated alkane mixed solvent mass volume ratio with carbon number for 1 ~ 6 esters：10~
30。
6. a kind of anhydrous compound of new Cabazitaxel, it is characterised in that the 2-theta of its X-ray powder diffraction figure exists
7.3099±0.2°,7.7968±0.2°,8.1665±0.2°,9.8706±0.2°,10.3414±0.2°,11.1464±
0.2°,12.6816±0.2°,13.0260±0.2°,14.2842±0.2°,15.3433±0.2°,15.8223±0.2°,
16.3962±0.2°,17.1633±0.2°,17.6038±0.2°,17.9544±0.2°,18.4899±0.2°,18.8239
± 0.2 °, 19.6630 ± 0.2 °, 20.4986 ± 0.2 °, 21.9593 ± 0.2 °, 22.6240 ± 0.2 ° and 23.9552 ± 0.2 °
There is diffraction maximum at place.
7. Cabazitaxel anhydrous compound according to claim 6, it is characterised in that its dsc analysis collection of illustrative plates 150.2 ±
2 °C and 160.0 ± 2 °C have obvious crystalline exotherm peak.
8., according to the arbitrary described Cabazitaxel anhydrous compound of claim 6 or 7, its preparation method includes：Cabazitaxel is molten
In alcohols solvent, stirring is lower to be instilled in water, and stirring is filtered, and filter cake is washed with water, be vacuum dried the Cabazitaxel is anhydrous
Compound.
9. the Cabazitaxel anhydrous compound according to claim 6 or 7 in carcinoma of prostate, the cerebral tumor or pulmonary carcinoma should
With.
10. according to claim 8, alcohols solvent includes the alcohols solvents such as methanol, ethanol, and vacuum drying temperature is 40-
120°C。
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| CN110577507A (en) * | 2019-07-19 | 2019-12-17 | 西安新通药物研究有限公司 | Stable cabazitaxel crystal form and preparation method thereof |
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