CN102603724A - Method for purifying and refining dimethoxy taxane compound - Google Patents
Method for purifying and refining dimethoxy taxane compound Download PDFInfo
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- CN102603724A CN102603724A CN2012100386313A CN201210038631A CN102603724A CN 102603724 A CN102603724 A CN 102603724A CN 2012100386313 A CN2012100386313 A CN 2012100386313A CN 201210038631 A CN201210038631 A CN 201210038631A CN 102603724 A CN102603724 A CN 102603724A
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- dimethoxy
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- bearing taxanes
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- 238000000034 method Methods 0.000 title claims abstract description 19
- 229940123237 Taxane Drugs 0.000 title claims abstract description 14
- 238000007670 refining Methods 0.000 title claims abstract description 6
- -1 dimethoxy taxane compound Chemical class 0.000 title abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 150000002148 esters Chemical class 0.000 claims abstract description 9
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- 230000006837 decompression Effects 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 12
- 238000000746 purification Methods 0.000 claims description 12
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 229960003328 benzoyl peroxide Drugs 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 229960001866 silicon dioxide Drugs 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 239000012074 organic phase Substances 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 35
- 239000012043 crude product Substances 0.000 abstract description 8
- 239000006227 byproduct Substances 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract description 4
- 238000013329 compounding Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000003208 petroleum Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical class C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
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- Epoxy Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for purifying and refining a dimethoxy taxane compound, in particular to the method for purifying and refining 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidinyl-5-carboxylic acid-4alpha-acetoxyl-2alpha-benzoyloxy-5beta,20-epoxy-1beta-hydroxy-9-oxo-7beta,10beta-dimethoxy-11-taxadiene-13alpha ester. The method comprises the following steps: carrying out silica-gel column chromatography on a crude product; eluting the crude product by using petroleum ether/ethyl acetate; collecting the eluate; concentrating to obtain an initial product; allowing reaction between a compounding reagent with the initial product; washing; and refining to prepare the required product. The method is simple in operation and easy for industrial production; and byproducts cannot be generated in the reaction process, so that the reaction yield is increased and the product purity is improved.
Description
Technical field
The present invention relates to a kind of method of dimethoxy bearing taxanes purification refine; Be specifically related to a kind of 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R; 4S, 5R)-1,3-oxazoles alkane-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β; 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification refine of 10 β-dimethoxy-11-yew alkene-13 α ester.
Background technology
3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R; 4S; 5R)-and 1,3-oxazoles alkane-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β; 10 β-dimethoxy-11-yew alkene-13 α ester is that compound (1) is an important taxane compounds, in multiple antineoplastic taxane hydride compounds of preparation and bulk drug, application is arranged all.A kind of method for preparing this compound is disclosed among the patent CN 1179776A; In this method with the dimethyl sulphide midbody at Raney Ni; After reaction obtains the bullion of compound (1) under hydrogen and the alcoholic acid condition, directly pass through the product that silica gel column chromatography (dichloromethane/ethyl acetate is a moving phase) obtains compound (1).But the applicant finds this preparation method and can produce a large amount of byproducts of reaction, and all is difficult to separating of realization response by product and compound (1) through conventional column chromatography and mesohigh preparative column, thereby causes obtaining the compound (1) of higher degree.
The reaction equation that patent CN 1179776A mentions is as follows:
Summary of the invention
The objective of the invention is to overcome above-mentioned weak point; Provide a kind of simple to operate, be easy to 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, the 4S of suitability for industrialized production; 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification of 10 β-dimethoxy-11-yew alkene-13 α ester.
According to technical scheme provided by the invention, a kind of method of dimethoxy bearing taxanes purification refine, step is following:
(1) preparation of primary product: get 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the 10 β-dimethoxy-thick product of 11-yew alkene-13 α ester; Carry out silica gel column chromatography; Use sherwood oil: 1: 10～10: 1 pairs of thick products of ETHYLE ACETATE carry out wash-out, collect elutriant, concentrate and obtain primary product;
(2) preparation of pending product: any one agent combination below in primary product, adding, in the quality of primary product: 1. diacetyl oxide, Cerous chloride heptahydrate and THF; 2. 2,2,2-trichlorine ethoxy carbonyl chloride, pyridine and methylene dichloride; 3. methyl-sulphoxide, diacetyl oxide and acetate;-80～100 ℃ of stirring reaction 1-96h; In reaction solution impouring 15～20 normal frozen water, add 10～20 normal organic solvents again, fully stir 30～60min; Isolate organic phase; Clean organic phase 1-3 time with the saturated common salt moisture of 3000mL, use anhydrous sodium sulfate drying then, be concentrated under 30～40 ℃ of decompression 2.1～2.7kPa and obtain pending product after doing;
(3) refinement treatment: the pending product of step (2) gained is used silica gel column chromatography; The mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out; Collection contain 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β; 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the elutriant of 10 β-dimethoxy-11-yew alkene-13 α ester, 30～40 ℃ of decompressions are concentrated into the dried product dimethoxy bearing taxanes that obtains after refining under 2.1～2.7kPa.
The amount that adds reagent in the step (2) is following, in the quality of step (1) gained primary product: 1. diacetyl oxide 0.1～10 equivalent, Cerous chloride heptahydrate 0.1～10 equivalent and THF 5～15 equivalents; 2. 2,2,2-trichlorine ethoxy carbonyl chloride 0.1～10 equivalent, pyridine 0.2～20 equivalent and methylene dichloride 5～15 equivalents; Or 3. methyl-sulphoxide 0.1～100 equivalent, diacetyl oxide 0.1～100 equivalent and acetate 0.1～100 equivalent.
Said silicagel column is 400～800 orders.
Temperature of reaction is a room temperature in the step (2), and the reaction times is 22～26h.
Organic solvent is ETHYLE ACETATE or methylene dichloride in the step (2).
The elutriant that adopts during said silica gel column chromatography is formed and ratio is a sherwood oil: ETHYLE ACETATE is 100: 1～1: 100.
The present invention has following advantage: the invention provides a kind of 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification refine of 10 β-dimethoxy-11-yew alkene-13 α ester; It is simple to operate; Be easy to suitability for industrialized production, in reaction process, can not produce by product, improved reaction yield and product purity.
Description of drawings
The product nuclear magnetic resonance map of Fig. 1 the present invention preparation.
Embodiment
Embodiment 1
To restrain at the chromatography column that 1.2 kilograms of 400-800 order silica gel are housed (20 centimetres of internal diameters according to the thick product of the resulting product of preparation method (purity is 73.8%) 30.0 of the compound (1) that proposes among the patent CN 1179776A; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 12.0 gram crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in the THF (120mL), add diacetyl oxide (1.2mL), Cerous chloride heptahydrate (0.94g), room temperature reaction in the impouring frozen water (500mL), added ETHYLE ACETATE (200mL) after 24 hours, fully stirred 30 minutes.Isolate organic phase, saturated common salt washing (1000mL * 3), anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dried slightly product.
Concentrate thick product at the chromatography column that 0.8 kilogram of 400-800 order silica gel is housed (20 centimetres of internal diameters with above-mentioned; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form 1: 10 carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 11.2 gram refined products that obtain, and purity is 94.5%.
Embodiment 2
To restrain at the chromatography column that 1.2 kilograms of 400-800 order silica gel are housed (20 centimetres of internal diameters according to the thick product of the resulting product of preparation method (purity is 73.8%) 30.0 of the compound (1) that proposes among the patent CN 1179776A; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 12.0 gram crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in the methylene dichloride (60mL), add pyridine (1.0mL), 0 ℃ drips 2,2 down; 2-trichlorine ethoxy carbonyl chloride (0.87mL) drips and finishes, and room temperature reaction is after 24 hours; In the impouring frozen water (500mL), add methylene dichloride (400mL), fully stirred 30 minutes.Isolate organic phase, saturated common salt washing (1000mL * 3), anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dried slightly product.
Concentrate thick product at the chromatography column that 0.8 kilogram of 400-800 order silica gel is housed (20 centimetres of internal diameters with above-mentioned; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form at 1: 100 carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 11.2 gram refined products that obtain, and purity is 93.6%.
Embodiment 3
To restrain at the chromatography column that 1.2 kilograms of 400-800 order silica gel are housed (20 centimetres of internal diameters according to the thick product of the resulting product of preparation method (purity is 73.8%) 30.0 of the compound (1) that proposes among the patent CN 1179776A; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 12.0 gram crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in the methyl-sulphoxide (24.0mL), add diacetyl oxide (16.0mL), acetate (1.0mL), room temperature reaction in the impouring frozen water (1000mL), added ETHYLE ACETATE (800mL) after 96 hours, fully stirred 30 minutes.Isolate organic phase, saturated sodium bicarbonate aqueous solution is washed (1000mL * 3), saturated common salt washing (1000mL * 3), and anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dried slightly product.
Concentrate thick product at the chromatography column that 0.8 kilogram of 400-800 order silica gel is housed (20 centimetres of internal diameters with above-mentioned; High 80 centimetres) in separate; The mixed solvent that uses petrol ether/ethyl acetate to form at 100: 1 carries out wash-out; Collection contains the elutriant of compound (1), and 40 ℃ of decompressions (2.7KPa) are concentrated into the dried 11.2 gram refined products that obtain, and purity is 92.8%.
Get embodiment 3 products and carry out nucleus magnetic resonance.
Be illustrated in figure 1 as the product nuclear magnetic resonance spectrum
1H-NMR (400MHz:CDCl
3Chemical shift δ ppm; Coupling constant J Hz)
1.03(s，9H)；1.07(s，3H)；1.19(s，3H)；1.51(s，3H)；1.68(s，3H)；1.82(dd，J＝15.9，1H)；1.89(s，3H)；2.09(m，2H)；2.65(dd，J＝15.9，1H)；3.25(s，3H)；3.39(s，3H)；3.83(d，J＝7，1H)；3.83(s，3H)；4.12(d，J＝8，1H)；4.26(d，J＝8，1H)；4.55(d，J＝8，1H)；4.70(s，1H)；4.88(d，J＝12，1H)；5.40(bs，1H)；5.60(d，J＝12，1H)；6.12(t，J＝10，1H)；6.39(bs，1H)；6.91(d，J＝10，2H)；7.38-7.64(mt，10H)；8.03(d，J＝10，2H)
Claims (6)
1. the method for a dimethoxy bearing taxanes purification refine is characterized in that step is following:
(1) preparation of primary product: get 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the 10 β-dimethoxy-thick product of 11-yew alkene-13 α ester; Carry out silica gel column chromatography; Use sherwood oil and eluent ethyl acetate liquid that thick product is carried out wash-out, collect elutriant, concentrate and obtain primary product;
(2) preparation of pending product: any one agent combination below in primary product, adding, in the quality of primary product: 1. diacetyl oxide, Cerous chloride heptahydrate and THF; 2. 2,2,2-trichlorine ethoxy carbonyl chloride, pyridine and methylene dichloride; 3. methyl-sulphoxide, diacetyl oxide and acetate;-80～100 ℃ of stirring reaction 1-96h; In reaction solution impouring 15～20 normal frozen water, add 10～20 normal organic solvents again, fully stir 30～60min; Isolate organic phase; Clean organic phase 1-3 time with the saturated common salt moisture of 3000mL, use anhydrous sodium sulfate drying then, be concentrated under 30～40 ℃ of decompression 2.1～2.7kPa and obtain pending product after doing;
(3) refinement treatment: the pending product of step (2) gained is used silica gel column chromatography; The mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out; Collection contain 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1; 3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β; 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the elutriant of 10 β-dimethoxy-11-yew alkene-13 α ester, 30～40 ℃ of decompressions are concentrated into the dried product dimethoxy bearing taxanes that obtains after refining under 2.1～2.7kPa.
2. according to the method for the said dimethoxy bearing taxanes of claim 1 purification refine; It is characterized in that: the amount that adds reagent in the step (2) is following, in the quality of step (1) gained primary product: 1. diacetyl oxide 0.1～10 equivalent, Cerous chloride heptahydrate 0.1～10 equivalent and THF 5～15 equivalents; 2. 2,2,2-trichlorine ethoxy carbonyl chloride 0.1～10 equivalent, pyridine 0.2～20 equivalent and methylene dichloride 5～15 equivalents; 3. methyl-sulphoxide 0.1～100 equivalent, diacetyl oxide 0.1～100 equivalent and acetate 0.1～100 equivalent.
3. according to the method for the said dimethoxy bearing taxanes of claim 1 purification refine, it is characterized in that: said silicagel column is 400～800 orders.
4. according to the method for the said dimethoxy bearing taxanes of claim 1 purification refine, it is characterized in that: temperature of reaction is a room temperature in the step (2), and the reaction times is 22～26h.
5. according to the method for the said dimethoxy bearing taxanes of claim 1 purification refine, it is characterized in that: organic solvent is ETHYLE ACETATE or methylene dichloride in the step (2).
6. according to the method for the said dimethoxy bearing taxanes of claim 1 purification refine, it is characterized in that: the elutriant that adopts during said silica gel column chromatography is formed and ratio is a sherwood oil: ETHYLE ACETATE is 100: 1～1: 100.
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| CN201210038631.3A CN102603724B (en) | 2011-10-20 | 2012-02-20 | Method for purifying and refining dimethoxy taxane compound |
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| CN201110322882 | 2011-10-20 | ||
| CN201110322882.X | 2011-10-20 | ||
| CN201210038631.3A CN102603724B (en) | 2011-10-20 | 2012-02-20 | Method for purifying and refining dimethoxy taxane compound |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
| CN1944435A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | New 4-substituent-1-dehydroxy baccatin VI derivative and its preparing method |
| CN102093315A (en) * | 2010-12-23 | 2011-06-15 | 上海大学 | C7 and C10 modified 1-dehydroxyl taxol analogue and preparation method thereof |
-
2012
- 2012-02-20 CN CN201210038631.3A patent/CN102603724B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
| CN1944435A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | New 4-substituent-1-dehydroxy baccatin VI derivative and its preparing method |
| CN102093315A (en) * | 2010-12-23 | 2011-06-15 | 上海大学 | C7 and C10 modified 1-dehydroxyl taxol analogue and preparation method thereof |
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| CN102603724B (en) | 2014-02-26 |
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