CN107698647B - A kind of improved method recycling the underproof fulvestrant of isomer proportion - Google Patents
A kind of improved method recycling the underproof fulvestrant of isomer proportion Download PDFInfo
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- CN107698647B CN107698647B CN201710859763.5A CN201710859763A CN107698647B CN 107698647 B CN107698647 B CN 107698647B CN 201710859763 A CN201710859763 A CN 201710859763A CN 107698647 B CN107698647 B CN 107698647B
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- Prior art keywords
- fulvestrant
- underproof
- acid
- isomer proportion
- improved method
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- 229960002258 fulvestrant Drugs 0.000 title claims abstract description 29
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 15
- 238000004064 recycling Methods 0.000 title claims abstract description 8
- 150000004820 halides Chemical class 0.000 claims abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 6
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 6
- 238000006722 reduction reaction Methods 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 150000003568 thioethers Chemical class 0.000 claims description 5
- 239000002798 polar solvent Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229910015900 BF3 Inorganic materials 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000007171 acid catalysis Methods 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229940071870 hydroiodic acid Drugs 0.000 claims description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 238000011084 recovery Methods 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract 1
- -1 fulvestrant of isomers Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000011519 second-line treatment Methods 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of improved methods for recycling the underproof fulvestrant of isomers, use halide by reducing catalyst replace in original process there are security risk and pollution environment reducing agent, not only reduce three waste discharge, and substantially increase the rate of recovery of fulvestrant, the unqualified fulvestrant rate of recovery can be made up to 70% or so, be conducive to commercial introduction.
Description
Technical field
The present invention relates to pharmaceutical preparation fields, and in particular to a kind of recycling underproof fulvestrant of isomer proportion changes
Into method.
Background technique
Fulvestrant (Fulvestrant), entitled (7a, 17b) -7- [9- (4,4,5,5,5- five fluorine, penta sulfenyl of chemistry
Base) nonyl]-female steroid -1,3,5- (10)-triolefin -3,17- glycol, structural formula are as follows:
Fulvestrant is to be used to treat by one kind of Astrazeneca AB's research and development still to become to disliking by anti-estrogen therapy disease
The intramuscular injection drug of the metastatic breast cancer for the estrogen receptor positive that the postmenopausal women of change is suffered from, in April, 2002 obtain beauty
State's food and Drug Administration's approval list, be uniquely can be widely used for after tamoxifen effect failure it is clinical resist it is female
Hormonal medicaments, multinomial clinical research discovery, fulvestrant 250mg dosage late have good treatment in the second line treatment of breast cancer
Effect and safety stabilization.
Fulvestrant has following two isomers:
The fulvestrant clinically used at present is the mixture of both the above isomers, European Pharmacopoeia clear stipulaties isomery
Body A: isomers B=42:58~48:52.Existing fulvestrant production technology yield is not high, some is because of isomer proportion
Underproof fulvestrant is present in mother liquor, if do not recycled, not only causes waste of raw materials, leads to high production cost,
And three waste discharge is serious.Chinese patent CN106146599 discloses a kind of underproof fulvestrant of recycling isomer proportion
Preparation method, the method be because the underproof fulvestrant of sulfoxide configuration ratio is raw material, sulfoxide radicals to be reduced into
Thioether, then again by sulfide oxidation at sulfoxide.It is restored in this method using catalytic hydrogenation, the method uses hydrogen and palladium chtalyst
Agent and metallic aluminium or zinc, lithium aluminium hydride reduction, these are all combustible and explosive articles, and metallic boron hydrides reaction is released largely
Hydrogen, borine or dimethyl sulphide borine are toxic articles, and oxalyl chloride has high toxicity and corrosivity.Therefore, there are poles for the prior art
Big security risk is unfavorable for amplification production, and environmental pollution is serious.
Based on disadvantages mentioned above, art methods are not suitable for commercial mass production, it is therefore desirable to a kind of improved commercial
Feasible method, it is related in art methods to solve the problems, such as, it is allowed to be suitable for large-scale production.
Summary of the invention
In order to overcome the prior art, there are larger security risks, pollute environment, are unsuitable for realizing industrialized disadvantage, this hair
It is bright that existing preparation process is improved using new technical solution, provide the new recycling isomer proportion of one kind not
The preparation method of qualified fulvestrant, concrete scheme are as follows:
A kind of improved method recycling the underproof fulvestrant of isomer proportion, which comprises the following steps:
(1) reducing agent is made with halide, with acid catalysis, in suitable solvent, by isomer proportion underproof fluorine dimension department
Group is reduced to thioether；
；
(2) thioether Peracetic acid aoxidizes in polar solvent and obtains fulvestrant；
。
Wherein, solvent described in reaction step (1) is acetone, acetonitrile or tetrahydrofuran；The halide be sodium bromide or
Sodium iodide；The acid is hydrobromic acid, hydroiodic acid, boron trifluoride ether or p-methyl benzenesulfonic acid；The temperature of reduction reaction is 20 DEG C -40
℃。
Polar solvent described in reaction step (2) is selected from one of tetrahydrofuran, methanol, acetic acid and ethyl acetate or more
Kind；Oxidant is Peracetic acid.
The method of the present invention has used the reaction reagent of good security, not only reduces three waste discharge, and substantially increase
The rate of recovery of fulvestrant can make the unqualified fulvestrant rate of recovery up to 70% or so, improve raw material availability, reduce life
Cost is produced, commercial introduction is conducive to.
Detailed description of the invention
Fig. 1: the fulvestrant high-efficient liquid phase chromatogram of embodiment 1.
Specific embodiment
Content in order to better understand the present invention combined with specific embodiments below does into one technical solution of the present invention
The explanation of step, but specific embodiment is not the limitation done to the present invention.
Embodiment 1:
(1) reduction reaction
By the underproof fulvestrant of 5g isomer proportion, 2.1g sodium bromide, 3.5g p-methyl benzenesulfonic acid and 25ml acetone add
Enter 100ml three-necked flask, 1.5h is stirred to react at 25 DEG C -35 DEG C, reaction solution is gradually become viscous by clarification, and end of reaction subtracts
Press filtration, filtrate decompression are concentrated to give light yellow oil 4.6g.
(2) oxidation reaction
The 4.6g reduzate that upper step is reacted is added in 50ml three-necked flask, and be added 10.1ml ethyl acetate and
4.66ml Peracetic acid is slowly added dropwise in 2.63ml acetic acid, and temperature control is no more than 25 DEG C, and it is anti-that 20 DEG C of -25 DEG C of stirrings of heat preservation are added dropwise
It answers 2 hours.The aqueous solution of 25% sodium thiosulfate is slowly added dropwise in end of reaction.It is extracted with 100ml ethyl acetate, separates water layer,
Water layer uses 100ml ethyl acetate to extract 2 times again, and organic layer is dry with anhydrous sodium sulfate, and concentration is refined with ethyl acetate, must be closed
Lattice fulvestrant white solid 3.8g, through high performance liquid chromatography detection, the configuration ratio of isomers A/B is 47.2/52.8, sees figure
1.Two-step reaction total recovery 76%.
Embodiment 2:
(1) reduction reaction
By the underproof fulvestrant of 5g isomer proportion, 3g NaI and 25ml acetone is added in 100ml three-necked flask, is delayed
It is slow that 40% boron trifluoride ether solution of 25ml is added dropwise, 1.5h is stirred to react in 25 DEG C -35 DEG C, 30ml toluene is added in end of reaction
With 30ml water, 5min is stirred, it is static to separate water layer, with 30ml water washing toluene layer, it is repeated once.50 DEG C of toluene layer reduced pressures
Obtain light yellow oil 4.4g.
(2) oxidation reaction
250ml three-necked flask is added in the 4.4g reduzate that upper step is reacted, and be added 44.5ml tetrahydrofuran and
11.1ml methanol；Ice salt bath is cooled to 0 DEG C, and 4.3ml Peracetic acid is added, and temperature is no more than 5 DEG C；Reaction solution muddiness is added,
20 DEG C -30 DEG C of heat preservation are reacted 20 hours；14.1ml methylene chloride is added, washes dichloromethane layer 4 times, uses water 46.9ml every time；
Dichloromethane layer is dry with 3.5g anhydrous sodium sulfate, and 40 DEG C of water-baths, which are concentrated under reduced pressure into, solid occurs, and solid is refined with ethyl acetate,
Obtain qualified white solid fulvestrant 3.5g.Two step total recoverys 70%.
Claims (1)
1. a kind of improved method for recycling the underproof fulvestrant of isomer proportion, which comprises the following steps:
(1) reducing agent is made with halide, with acid catalysis, in suitable solvent, also by the underproof fulvestrant of isomer proportion
Originally be thioether, wherein halide be sodium bromide or sodium iodide, acid be hydrobromic acid, hydroiodic acid, boron trifluoride ether or toluenesulfonic acid,
Solvent is acetone or tetrahydrofuran, and reduction reaction temperature is 20 DEG C -40 DEG C；
；
(2) thioether Peracetic acid aoxidizes in polar solvent and obtains fulvestrant, and wherein polar solvent is selected from tetrahydrofuran, first
One of alcohol, acetic acid and ethyl acetate are a variety of；
。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710859763.5A CN107698647B (en) | 2017-09-21 | 2017-09-21 | A kind of improved method recycling the underproof fulvestrant of isomer proportion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710859763.5A CN107698647B (en) | 2017-09-21 | 2017-09-21 | A kind of improved method recycling the underproof fulvestrant of isomer proportion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107698647A CN107698647A (en) | 2018-02-16 |
| CN107698647B true CN107698647B (en) | 2019-09-13 |
Family
ID=61173042
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710859763.5A Active CN107698647B (en) | 2017-09-21 | 2017-09-21 | A kind of improved method recycling the underproof fulvestrant of isomer proportion |
Country Status (1)
| Country | Link |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT202100003176A1 (en) | 2021-02-12 | 2022-08-12 | Farmabios Spa | PROCESS FOR THE PREPARATION OF FULVESTRANT |
| CN115974953B (en) * | 2022-12-30 | 2023-11-10 | 江苏诺泰澳赛诺生物制药股份有限公司 | Recovery method of fulvestrant |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102827048A (en) * | 2011-06-17 | 2012-12-19 | 石药集团中奇制药技术（石家庄）有限公司 | Intermediate of fulvestrant and preparation method and application thereof |
| CN106146599A (en) * | 2015-04-07 | 2016-11-23 | 江苏希迪制药有限公司 | A kind of recovery is because of the method for sulfoxide configuration ratio underproof fulvestrant or derivatives thereof |
-
2017
- 2017-09-21 CN CN201710859763.5A patent/CN107698647B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102827048A (en) * | 2011-06-17 | 2012-12-19 | 石药集团中奇制药技术（石家庄）有限公司 | Intermediate of fulvestrant and preparation method and application thereof |
| CN106146599A (en) * | 2015-04-07 | 2016-11-23 | 江苏希迪制药有限公司 | A kind of recovery is because of the method for sulfoxide configuration ratio underproof fulvestrant or derivatives thereof |
Non-Patent Citations (1)
| Title |
|---|
| Sulfonic acid-Sodium Iodide Syetem as an efficient Reagent for the reduction of sulfoxides;J.Drabowicz et al.;《SYNLETT》;19920331(第3期);第252-254页 * |
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Effective date of registration: 20230407 Address after: No. 18, Fenghe Road, Xiaya Town, Jiande City, Hangzhou City, Zhejiang Province, 310000 Patentee after: HANGZHOU AOSAINUO BIOTECHNOLOGY CO.,LTD. Address before: No. 8 Xiyuan 1st Road, Xihu Science and Technology Park, Sandun Town, Xihu District, Hangzhou City, Zhejiang Province, 310030 Patentee before: HANGZHOU SIMBOS PHARM CO.,LTD. |
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