CN103012331A - Preparation method of cabazitaxel and intermediate thereof - Google Patents
Preparation method of cabazitaxel and intermediate thereof Download PDFInfo
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- CN103012331A CN103012331A CN2012105874879A CN201210587487A CN103012331A CN 103012331 A CN103012331 A CN 103012331A CN 2012105874879 A CN2012105874879 A CN 2012105874879A CN 201210587487 A CN201210587487 A CN 201210587487A CN 103012331 A CN103012331 A CN 103012331A
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Abstract
The invention discloses a preparation method of a cabazitaxel intermediate 7,10-dimethoxy-10-baccatin III. In the presence of alkali, 10-deacetylbaccatin III and a specific methylation reagent are subjected to selective methylation reaction at low temperature to obtain the cabazitaxel intermediate 7,10-dimethoxy-10-baccatin III. In the preparation method, the methylation reaction has high selectivity for C-7 and C-10 hydroxy sites on the 10-deacetylbaccatin III, so the yield is high. The invention also discloses a preparation method of cabazitaxel, which comprises the following steps: preparing the cabazitaxel intermediate according to the preparation method above; condensing the cabazitaxel intermediate with one side chain of docetaxel; and hydrolyzing the obtained condensation product under acidic conditions to obtain the cabazitaxel. The preparation method of cabazitaxel has the advantage of high total yield and is suitable for commercialized production.
Description
Technical field
The present invention relates to medicine synthetic field, the particularly preparation method of a kind of Cabazitaxel and intermediate thereof.
Background technology
Cabazitaxel is the Second line Drug of the treatment prostate cancer of Sanofi-aventis company research and development, and go on the market in the U.S. in June, 2010.Cabazitaxel is a kind of molecular design taxanes micromolecular compound, and its structural formula is as follows:
Cabazitaxel is a kind of microtubule inhibitors, is applicable to the associating Prednisone Therapy and has previously accepted a kind of transitivity hormone refractoriness patients with prostate cancer that contains the treatment of docetaxel treatment plan.
At present the synthetic method of Cabazitaxel has two kinds, and a kind of is to synthesize first the Docetaxel or derivatives thereof, then at the HM (CN102311410, CN102060815, CN102675256) of C-7 and C-10 position.Another is that elder generation is at C-7 and the C-10 position HM of 10-deacetylation baccatin III (10-DAB); then obtain Cabazitaxel (US5962705 with the condensation of one of various docetaxel side chains, hydrolysis; US20010051736; CN102285947; CN102336726, US20120149925).Because three hydroxyls of C-7, C-10 and C-13 position of 10-deacetylation baccatin III (10-DAB) can methylate, existing method selectivity when methylating is not high, and preparation Cabazitaxel yield is low, and the product purification difficulty is not suitable for commercially producing.
Summary of the invention
For the defective of above-mentioned prior art, the technical problem to be solved in the present invention is the preparation method of Cabazitaxel intermediate that a kind of high yield is provided, and based on the preparation method of this intermediate preparation method's Cabazitaxel.
Particularly, (chemical name is 7 suc as formula compound shown in the I to the invention provides a kind of structure, 10-dimethoxy-10-bar card fourth III) preparation method, under the condition that alkali exists, compound shown in the formula II (chemical name is 10-deacetylation baccatin III) carries out the selective methylation reaction with methylating reagent and gets;
Described methylating reagent is any one in trifluoromethanesulfonic acid methyl esters, methyl fluorosulfonate or the methyl mesylate, and the temperature of described selective methylation reaction is-80 ℃～-20 ℃.
Preferably, the temperature of described selective methylation reaction is-70 ℃～-60 ℃.
Preferably, described alkali is any one in sodium hydride, potassium hydride KH, n-Butyl Lithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide or the LHMDS.
Preferably, compound shown in the described formula II is 1:2～3 with the ratio of the amount of substance of methylating reagent.
Preferably, compound shown in the described formula II is 1:2～4 with the ratio of the amount of substance of alkali.
The reaction solvent of described selective methylation reaction is tetrahydrofuran (THF), dioxane or glycol dimethyl ether.
The preparation method of Cabazitaxel intermediate shown in the above-mentioned formula I because methylation reaction is higher in the selectivity of the C-7 of compound shown in the formula II, C-10 position hydroxyl, therefore makes the yield higher (reaching about 90%) of Cabazitaxel intermediate shown in the formula I.
Another object of the present invention is to provide a kind of preparation method of Cabazitaxel, comprises the steps:
(1) makes compound shown in the formula I according to above-mentioned preparation method;
(2) under the condition that alkali exists, step (1) gained formula I compound and formula III compound carry out condensation reaction and get compound shown in the formula IV;
(3) under acidic conditions, step (2) gained formula IV compound generation hydrolysis reaction obtains Cabazitaxel.
Among the preparation method of above-mentioned Cabazitaxel, the described alkali of step (2) is any one in sodium hydride, potassium hydride KH, n-Butyl Lithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide or the LHMDS.
Preferably, the described formula I compound of step (2) is 1:(1～2 with the ratio of the amount of substance of formula III compound, alkali): (0.1～1.2).
The reaction solvent of the described condensation reaction of step (2) is tetrahydrofuran (THF), dioxane or glycol dimethyl ether, and the temperature of reaction of described condensation reaction is-20 ℃～20 ℃.
Preferably, the described acidic conditions of step (3) is provided by the hydrochloric acid of 0.1～1.2mol/L.
The preparation method of above-mentioned Cabazitaxel also comprises the step of Cabazitaxel being carried out crystallization in organic solvent.
Preferably, described organic solvent is methylene dichloride and sherwood oil; Described crystallisation step is: step (3) gained Cabazitaxel is dissolved in methylene dichloride, adds sherwood oil to it under stirring, stir rear still aging, rear filtration namely gets the Cabazitaxel crystallization.
X-ray powder diffraction (XPRD) analysis is carried out in above-mentioned Cabazitaxel crystallization, its XPRD collection of illustrative plates as shown in Figure 1, Fig. 1 shows: the XPRD collection of illustrative plates characteristic peak of gained Cabazitaxel crystallization represents to be positioned at 5.02 °, 7.40 °, 10.18 °, 10.62 °, 11.20 °, 11.56 °, 12.84 °, 14.00 °, 15.96 °, 20.66 °, 21.16 °, 22.16 ° and 23.88 ° with 2 θ and locates.
The preparation method of Cabazitaxel of the present invention has yield high (total recovery reaches about 75%), low cost and other advantages, is fit to the industrial production of mass-producing.
Description of drawings
Fig. 1 is the X-ray powder diffraction collection of illustrative plates of Cabazitaxel crystallization;
Embodiment
In order to make those skilled in the art understand better technical scheme of the present invention, the present invention is described in further detail below in conjunction with specific embodiment.
Among the embodiment 1-5, the calculation formula of yield is: yield=product (formula I compound) mole number/raw material (formula II compound) mole number * 100%.
The preparation of Cabazitaxel intermediate shown in the embodiment 1 formula I
With compound 16.6g(30.5mmol shown in the formula II) join in the 2000ml there-necked flask, dissolve with the 1000ml anhydrous tetrahydro furan, add trifluoromethanesulfonic acid methyl esters 10.5g(64.1mmol) be cooled to-60 ℃, slowly dropping concentration is that the tetrahydrofuran solution 50.8ml(LiHMDS content of the LiHMDS of 1.2M is 61mmol), after dripping end, close freezing tank, naturally be warming up to-30 ℃ of reaction 40min, after reaction finishes, in reaction system, add the saturated NaHCO of 50ml
3Aqueous solution cancellation reaction.Add the mixed solvent that 200ml methylene dichloride and 800ml isopropyl ether form in the reaction mixture, separate out white solid, filter, with 30ml methylene dichloride and 30ml isopropyl ether washing solid, vacuum-drying gets white powder and is compound shown in the formula I successively, output is 13.1g, and yield is 75.0%; Its spectroscopic data is:
1HNMR（500MHz，DMSO-d
6）：0.924(s,6H);1.453-1.479(m,1H);1.508(s,3H);1.965(s,3H);2.152-2.169(d,2H);2.191(s,3H);2.642-2.676(m,1H);3.210(s,3H);3.288(s,3H);3.734-3.748(d,1H);3.785-3.819(m,1H);4.000-4.045(m,2H);4.377(s,1H);4.622-4.661(m,1H);4.736(s,1H);4.955-4.973(d,1H);5.277-5.286(d,1H);5.355-5.370(d,1H);7.539-7.570(t,2H);7.639-7.669(t,1H);7.996-8.011(d,2H).
The preparation of compound shown in the embodiment 2 formula I
With compound 16.6g(30.5mmol shown in the formula II) join in the 2000ml there-necked flask, dissolve with the 1000ml anhydrous tetrahydro furan, add methyl fluorosulfonate 7.3g(64.1mmol) be cooled to-60 ℃, slowly dropping concentration is that the tetrahydrofuran solution 50.8ml(LiHMDS content of the LiHMDS of 1.2M is 61mmol), after dripping end, close freezing tank, naturally be warming up to-30 ℃ of reaction 40min, after reaction finishes, in reaction system, add the saturated NaHCO of 50ml
3Aqueous solution cancellation reaction.In reaction mixture, add in the mixed solvent of 200ml methylene dichloride and 800ml isopropyl ether composition, separate out white solid, filter, successively with 30ml methylene dichloride and 30ml isopropyl ether washing solid, vacuum-drying, get white powder and be compound shown in the formula I, output is 12.2g, and yield is 70.0%; Its spectroscopic data is with embodiment 1.
The preparation of compound shown in the embodiment 3 formula I
With compound 16.6g(30.5mmol shown in the formula II) join in the 2000ml there-necked flask, dissolve with the 1000ml tetrahydrofuran (THF), add methyl mesylate 7.1g(64.1mmol) be cooled to-60 ℃, slowly dropping concentration is that the tetrahydrofuran solution 61.0ml(NaHMDS content of the NaHMDS of 1.0M is 61.0mmol), after dripping end, close freezing tank, naturally be warming up to-30 ℃ of reaction 40min, after reaction finishes, add the saturated NaHCO of 50ml
3Aqueous solution cancellation reaction.Add the mixed solvent that 200ml methylene dichloride and 800ml isopropyl ether form in the reaction mixture, separate out white solid, filter, with 30ml methylene dichloride and 30ml isopropyl ether washing solid, vacuum-drying gets white powder and is compound shown in the formula I successively, output is 14.3g, and yield is 81.9%; Its spectroscopic data is with embodiment 1.
The preparation of compound shown in the embodiment 4 formula I
With compound 16.6g(30.5mmol shown in the formula II) join in the 2000ml there-necked flask, dissolve with the 1000ml tetrahydrofuran (THF), add methyl mesylate 7.1g(64.1mmol) be cooled to-40 ℃, slowly dropping concentration is that the tetrahydrofuran solution 50.8ml(LiHMDS content of the LiHMDS of 1.2M is 61.0mmol), after dripping end, stirring reaction 1h, TLC monitoring reaction finishes.Add the saturated NaHCO of 50ml
3Aqueous solution cancellation reaction.Add the mixed solvent that 200ml methylene dichloride and 800ml isopropyl ether form in the reaction mixture, separate out white solid, filter, with 30ml methylene dichloride and 30ml isopropyl ether washing solid, vacuum-drying gets white powder and is compound shown in the formula I successively, output is 15.5g, and yield is 88.8%; Its spectroscopic data is with embodiment 1.
The preparation of compound shown in the embodiment 5 formula I
With compound 16.6g(30.5mmol shown in the formula II) join in the 2000ml there-necked flask, dissolve with the 1000ml tetrahydrofuran (THF), add methyl mesylate 7.1g(64.1mmol) be cooled to-80 ℃, the content of the tetrahydrofuran solution 61.0ml(KHMDS of the KHMDS that slow dropping concentration is 1.0M is 61.0mmol), after dripping end, close freezing tank, naturally be warming up to-60 ℃ of reaction 1h, after reaction finishes, add the saturated NaHCO of 50ml
3Aqueous solution cancellation reaction.Add the mixed solvent that 200ml methylene dichloride and 800ml isopropyl ether form in the reaction mixture, separate out white solid, filter, with 30ml methylene dichloride and 30ml isopropyl ether washing solid, vacuum-drying gets white powder and is compound shown in the formula I successively, output is 11.9g, and yield is 68.1%; Its spectroscopic data is with embodiment 1.
The preparation of embodiment 6 Cabazitaxels
(1) selective methylation:
Press embodiment 4 described method preparation I compounds.
(2) condensation reaction:
Modus ponens I compound 7.0g(12.23mmol), formula III compound 12.3g(36.7mmol) join in the 1000ml there-necked flask, add the dissolving of 500ml tetrahydrofuran (THF), ice-water bath is cooled to 0 ℃, be that the tetrahydrofuran solution 12.3ml(NaHMDS content of the NaHMDS of 1.0M is 12.3mmol to wherein adding concentration), stirring reaction 6h.The TLC(sherwood oil: ethyl acetate=1:1) the monitoring raw material reaction is complete, adds the saturated NaHCO of 20ml in reaction system
3Aqueous solution cancellation reaction, the mixed liquid of reaction extracts with ethyl acetate (100ml * 3); Organic phase saturated common salt water washing, anhydrous Na
2SO
4Drying is filtered, and evaporated under reduced pressure obtains crude product.Crude product is carried out column chromatography purification (leacheate sherwood oil: ethyl acetate=2:1), get white solid and be compound shown in the formula IV, its output is 10.0g, and yield is that the calculation formula of 90.1%[condensation reaction yield is: yield=product (formula IV compound) mole number/raw material (formula I compound) mole number * 100%].
(3) hydrolysis reaction:
With step (2) gained formula IV compound 6.8g(7.5mmol) join in the 100ml there-necked flask, add the dissolving of 70ml tetrahydrofuran (THF), under the room temperature, add the aqueous hydrochloric acid of 10ml, 0.2N, stirring reaction 3h under the room temperature; The TLC(sherwood oil: ethyl acetate=1:1) the monitoring raw material reaction is complete, adds the saturated NaHCO of 15ml in reaction system
3The aqueous solution, the mixed liquid of reaction extracts with ethyl acetate (60ml * 3); Organic phase saturated common salt water washing, anhydrous Na
2SO
4Dry, filter, evaporated under reduced pressure, obtaining product is white solid, and the solid that obtains is dissolved in the 5ml methylene dichloride, stir lower, add the 100ml sherwood oil to it, after stirring, still aging 1h, filter to get Cabazitaxel white crystalline solid 5.8g, yield is that the yield calculation formula of 92.6%[hydrolysis reaction is: yield=product (Cabazitaxel) mole number/raw material (formula IV compound) mole number * 100%].
As calculated, the present embodiment total recovery of preparing Cabazitaxel is about 74%.
The fusing point of gained Cabazitaxel crystallization is: 154.1-157.2 ℃; HPLC analyzes demonstration, its purity approximately 99.9%; Its spectroscopic data is:
1HNMR（500MHz，CDCl
3）：
1.205（s,3H）;1.214(s,3H);1.359(s,9H);1.615(s,1H);1.716(s,3H);
1.767-1.821(m,1H);1.874(s,3H);2.248-2.326(m,2H);2.359(s,3H);
2.665-2.725(m,1H);3.301(s,3H);3.440(brs,1H);3.452(s,3H);
3.802-3.815(d,1H);3.851-3.872(m,1H);4.162-4.304(2d,J=8.5Hz,2H);
4.623(s,1H);4.794(s,1H);4.961-4.978(d,1H);5.260-5.275(broad?d,1H);
5.405-5.423(d,1H);5.622-5.636(d,1H);6.190-6.225(broad?t,1H);
7.318-7.400(m,5H);7.469-7.500(t,2H);7.588-7.617(t,1H);
8.083-8.099(d,2H).
The Cabazitaxel crystallized product is carried out the X-ray powder diffraction analysis, its X-ray powder diffraction collection of illustrative plates as shown in Figure 1, Fig. 1 shows: XPRD collection of illustrative plates characteristic peak represents to be positioned at 5.02 °, 7.40 °, 10.18 °, 10.62 °, 11.20 °, 11.56 °, 12.84 °, 14.00 °, 15.96 °, 20.66 °, 21.16 °, 22.16 ° and 23.88 ° with 2 θ and locates.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (15)
1. a structure is characterized in that suc as formula the preparation method of compound shown in the I, and under the condition that alkali exists, compound shown in the formula II and methylating reagent carry out selective methylation and react and get;
Described methylating reagent is any one in trifluoromethanesulfonic acid methyl esters, methyl fluorosulfonate or the methyl mesylate, and the temperature of described selective methylation reaction is-80 ℃～-20 ℃.
2. preparation method as claimed in claim 1 is characterized in that, the temperature of described selective methylation reaction is-70 ℃～-60 ℃.
3. preparation method as claimed in claim 1 is characterized in that, described alkali is any one in sodium hydride, potassium hydride KH, n-Butyl Lithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide or the LHMDS.
4. preparation method as claimed in claim 1 is characterized in that, compound shown in the described formula II is 1:2～3 with the ratio of the amount of substance of methylating reagent.
5. preparation method as claimed in claim 1 is characterized in that, compound shown in the described formula II is 1:2～4 with the ratio of the amount of substance of alkali.
6. preparation method as claimed in claim 1 is characterized in that, the reaction solvent of described selective methylation reaction is tetrahydrofuran (THF), dioxane or glycol dimethyl ether.
7. the preparation method of a Cabazitaxel is characterized in that, comprises the steps:
(1) according to claim 1 each described preparation method makes compound shown in the formula I-6;
(2) under the condition that alkali exists, step (1) gained formula I compound and formula III compound carry out condensation reaction and get compound shown in the formula IV;
(3) under acidic conditions, step (2) gained formula IV compound generation hydrolysis reaction obtains Cabazitaxel.
8. preparation method as claimed in claim 7 is characterized in that, the described alkali of step (2) is any one in sodium hydride, potassium hydride KH, n-Butyl Lithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide or the LHMDS.
9. preparation method as claimed in claim 7 is characterized in that, the described formula I compound of step (2) is 1:(1～2 with the ratio of the amount of substance of formula III compound, alkali): (0.1～1.2).
10. preparation method as claimed in claim 7 is characterized in that, the reaction solvent of the described condensation reaction of step (2) is tetrahydrofuran (THF), dioxane or glycol dimethyl ether.
11. preparation method as claimed in claim 7 is characterized in that, the temperature of reaction of the described condensation reaction of step (2) is-20 ℃～20 ℃.
12. preparation method as claimed in claim 7 is characterized in that, the described acidic conditions of step (3) is provided by the hydrochloric acid of 0.1～1.2mol/L.
13. preparation method as claimed in claim 7 is characterized in that, also comprises the step of Cabazitaxel being carried out crystallization in organic solvent.
14. preparation method as claimed in claim 13 is characterized in that, described organic solvent is methylene dichloride and sherwood oil.
15. preparation method as claimed in claim 14 is characterized in that, described crystallisation step is: step (3) gained Cabazitaxel is dissolved in methylene dichloride, adds sherwood oil to it under stirring, stir rear still aging, rear filtration namely gets the Cabazitaxel crystallization.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044364A (en) * | 2013-01-07 | 2013-04-17 | 重庆泰濠制药有限公司 | Cabazitaxel amorphous crystal and preparation method thereof |
| CN103664837A (en) * | 2013-08-30 | 2014-03-26 | 北京阳光诺和药物研究有限公司 | Preparation method of high-purity cabazitaxel intermediate |
| CN104109142A (en) * | 2014-06-22 | 2014-10-22 | 南京工业大学 | Method for preparation of cabazitaxel by using baccatin III as raw material |
| CN104557798A (en) * | 2013-10-29 | 2015-04-29 | 神威药业集团有限公司 | Preparation method for dimethoxy docetaxel |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1270586A (en) * | 1997-11-18 | 2000-10-18 | 阿文蒂斯药物股份有限公司 | Method for preparing derivatives of the taxoid class |
| CN102311410A (en) * | 2011-09-29 | 2012-01-11 | 上海恒和医药科技有限公司 | Preparation method for cabazitaxel |
| CN102336726A (en) * | 2011-09-30 | 2012-02-01 | 重庆泰濠制药有限公司 | Method for preparing cabazitaxel |
| CN102417491A (en) * | 2011-10-31 | 2012-04-18 | 江苏红豆杉生物科技有限公司 | Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material |
| US20120149925A1 (en) * | 2010-12-13 | 2012-06-14 | Liang-Rern Kung | Process for preparing taxoids from baccatin derivatives using lewis acid catalyst |
| CN102516281A (en) * | 2011-10-20 | 2012-06-27 | 江苏红豆杉生物科技有限公司 | 10-deacetylbaccatin III and method for methoxylation of its derivative |
| WO2012142117A1 (en) * | 2011-04-12 | 2012-10-18 | Plus Chemicals Sa | Solid state forms of cabazitaxel and processes for preparation thereof |
-
2012
- 2012-12-28 CN CN2012105874879A patent/CN103012331A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1270586A (en) * | 1997-11-18 | 2000-10-18 | 阿文蒂斯药物股份有限公司 | Method for preparing derivatives of the taxoid class |
| US20120149925A1 (en) * | 2010-12-13 | 2012-06-14 | Liang-Rern Kung | Process for preparing taxoids from baccatin derivatives using lewis acid catalyst |
| WO2012142117A1 (en) * | 2011-04-12 | 2012-10-18 | Plus Chemicals Sa | Solid state forms of cabazitaxel and processes for preparation thereof |
| CN102311410A (en) * | 2011-09-29 | 2012-01-11 | 上海恒和医药科技有限公司 | Preparation method for cabazitaxel |
| CN102336726A (en) * | 2011-09-30 | 2012-02-01 | 重庆泰濠制药有限公司 | Method for preparing cabazitaxel |
| CN102516281A (en) * | 2011-10-20 | 2012-06-27 | 江苏红豆杉生物科技有限公司 | 10-deacetylbaccatin III and method for methoxylation of its derivative |
| CN102417491A (en) * | 2011-10-31 | 2012-04-18 | 江苏红豆杉生物科技有限公司 | Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material |
Non-Patent Citations (1)
| Title |
|---|
| 陆国元: "《有机反应与有机合成》", 30 June 2009 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044364A (en) * | 2013-01-07 | 2013-04-17 | 重庆泰濠制药有限公司 | Cabazitaxel amorphous crystal and preparation method thereof |
| CN103044364B (en) * | 2013-01-07 | 2016-01-20 | 重庆泰濠制药有限公司 | Amorphous crystalline substance of a kind of Cabazitaxel and preparation method thereof |
| CN103664837A (en) * | 2013-08-30 | 2014-03-26 | 北京阳光诺和药物研究有限公司 | Preparation method of high-purity cabazitaxel intermediate |
| CN103664837B (en) * | 2013-08-30 | 2016-01-20 | 北京阳光诺和药物研究有限公司 | A kind of preparation method of high purity Cabazitaxel intermediate |
| CN104557798A (en) * | 2013-10-29 | 2015-04-29 | 神威药业集团有限公司 | Preparation method for dimethoxy docetaxel |
| CN104109142A (en) * | 2014-06-22 | 2014-10-22 | 南京工业大学 | Method for preparation of cabazitaxel by using baccatin III as raw material |
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Application publication date: 20130403 |