CN1057092C - Preparation of Anranofin - Google Patents
Preparation of Anranofin Download PDFInfo
- Publication number
- CN1057092C CN1057092C CN97119444A CN97119444A CN1057092C CN 1057092 C CN1057092 C CN 1057092C CN 97119444 A CN97119444 A CN 97119444A CN 97119444 A CN97119444 A CN 97119444A CN 1057092 C CN1057092 C CN 1057092C
- Authority
- CN
- China
- Prior art keywords
- liquid
- auranofin
- water
- methanol
- room temperature
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 60
- 229960005207 auranofin Drugs 0.000 claims abstract description 32
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000000243 solution Substances 0.000 claims abstract description 14
- 238000001953 recrystallisation Methods 0.000 claims abstract description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000000956 alloy Substances 0.000 claims abstract description 8
- 229910045601 alloy Inorganic materials 0.000 claims abstract description 8
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000013078 crystal Substances 0.000 claims abstract description 7
- 239000011259 mixed solution Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 30
- 239000000047 product Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- SCJFMBCXOLDHCO-UHFFFAOYSA-N C(C)P(CC)CC.[Cl] Chemical compound C(C)P(CC)CC.[Cl] SCJFMBCXOLDHCO-UHFFFAOYSA-N 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 235000015320 potassium carbonate Nutrition 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 4
- -1 2-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-thioisourea hydrogen Bromate Chemical compound 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 239000010931 gold Substances 0.000 abstract description 9
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052737 gold Inorganic materials 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- LPWXFIYOTKUODB-UHFFFAOYSA-N 2-chloroethyl(diethyl)phosphane Chemical compound C(C)P(CCCl)CC LPWXFIYOTKUODB-UHFFFAOYSA-N 0.000 abstract 1
- QNVDHERXTIAGPT-SXQUUHMTSA-N [(2r,3r,4s,5r,6s)-3,4,5-triacetyloxy-6-carbamimidoylsulfanyloxan-2-yl]methyl acetate;hydrobromide Chemical compound Br.CC(=O)OC[C@H]1O[C@@H](SC(N)=N)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O QNVDHERXTIAGPT-SXQUUHMTSA-N 0.000 abstract 1
- 230000003356 anti-rheumatic effect Effects 0.000 abstract 1
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000001291 vacuum drying Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001816 cooling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- VXIHRIQNJCRFQX-UHFFFAOYSA-K disodium aurothiomalate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S[Au])C([O-])=O VXIHRIQNJCRFQX-UHFFFAOYSA-K 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002344 gold compounds Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000003132 pyranosyl group Chemical group 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- GOMPLJOPYGQBPL-UHFFFAOYSA-K [F-].[F-].[F-].F.[B+3] Chemical compound [F-].[F-].[F-].F.[B+3] GOMPLJOPYGQBPL-UHFFFAOYSA-K 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229960001799 aurothioglucose Drugs 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000011133 lead Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229960001315 sodium aurothiomalate Drugs 0.000 description 1
- SDKPSXWGRWWLKR-UHFFFAOYSA-M sodium;9,10-dioxoanthracene-1-sulfonate Chemical compound [Na+].O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2S(=O)(=O)[O-] SDKPSXWGRWWLKR-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种金诺芬的制备方法，以2-S-(2，3，4，6-四-O-乙酰基-β-D-吡喃葡萄糖基)-2-硫代异脲氢溴酸盐(I)，一氯(三乙基膦)合金(IV)和碳酸钾(II)为原料，其特征是：先将(I)的甲醇-水溶液与(IV)的甲醇溶液混合，在0～5℃搅拌下向混合溶液中滴加(II)的水溶液，反应60～90分钟，再于室温下反应30～40分钟，所得晶体金诺芬，再经甲醇-水溶液重结晶提纯得金诺芬纯品，本发明方法用于制备抗类风湿口服金药物-金诺芬。A preparation method of auranofin, using 2-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-thioisourea hydrobromide (I), monochloro (triethylphosphine) alloy (IV) and potassium carbonate (II) are raw materials, it is characterized in that: first the methanol-water solution of (I) is mixed with the methanol solution of (IV), at 0～ Add the aqueous solution of (II) dropwise to the mixed solution under stirring at 5°C, react for 60 to 90 minutes, and then react at room temperature for 30 to 40 minutes to obtain crystal auranofin, which is then purified by methanol-water solution recrystallization to obtain auranofin Pure product, the method of the present invention is used to prepare anti-rheumatoid oral gold medicine-auranofin.
Description
The present invention relates to the preparation method of gold compound, particularly gold compound (2,3,4, the preparation method of (triethyl phosphine) alloy of 6-four-O-ethanoyl-1-sulfo--β-D-glucopyranosyl-S), this compound claims auranofin (Auranofin) again.
Gold salt has the resisting rheumatoid disease activity and is used for the treatment of the rheumatoid arthritis history of existing decades as goldinjection, as sodium aurothiomalate (Myocrisin) and aurothioglucose (Solganol) etc.Use by influence because toxic side effect is big for this type of non-enteron aisle gold medicine
The organophosphite ligand compound auranofin of gold is the oral golden medicine of a kind of novel resisting rheumatoid disease (US3635945), compare with goldinjection, it has safe in utilization, convenient and toxic side effect features of smaller, and be used for clinically, become the oral prescription drug of a new generation treatment rheumatoid arthritis.
In the whole bag of tricks of preparation auranofin, the disclosed method of US 3635945 (1972.1.18) is a kind of by top-priority method.This method is with 2-S-(2; 3; 4; 6-four-O-ethanoyl-β-D-glucopyranosyl)-2-sulfo-isourea halogen acid salt (I) is a raw material, through the solution-treated of alkali metals carbonate (II), generates intermediate (2 earlier; 3; 4,6-four-O-ethanoyl-β-D-Glucopyranose) derivative (III), react with a halogen (triethyl phosphine) alloy (IV) again; obtain auranofin; product productive rate 90% (J.Med.Chem., 1972,15; 1095); in building-up process, make solvent with ethanol, temperature of reaction-20～-10 ℃.It is brief that this method has flow process, the characteristics that the product productive rate is higher, and raw material (I) chemical stability is good, makes easily,
Therefore, has higher Practical significance.But, this method is in (I) and intermediate formation reaction (II), the process of its hydrolysis reaction can't be judged, the intermediate that is generated (III) is extremely unstable again, generate the back if the untimely reaction that generates auranofin, in alkali solution, multiple unmanageable side reaction will take place, cause the productive rate of product to reduce.Product is difficult for purifying; And this method operational condition is harsh, carries out below requiring to be reflected at low temperature-10 ℃, solvent for use ethanol is to raw material (I), (IV) and the solubleness of auranofin less, be difficult to guarantee to be reflected in the liquid phase of homogeneous and carry out, influence the stable of auranofin productive rate, also bring difficulty to operation; Simultaneously, this method does not relate to the purification of auranofin, has reduced its Practical significance to a certain extent.
US 4125710 (1978.11.14) discloses the another kind of method for preparing auranofin.This method with a kind of general formula is:
Compound (in the formula M be a kind of stable positively charged ion from basic metal, ammonium, lead, silver or copper positively charged ion, selected or
(wherein Ac is an acetyl)), with a kind of general formula be:
(Et
3P)
2The compound reaction (X is a kind of stable negatively charged ion of selecting from halogenide, nitrate, thiocyanate-, perchlorate, tetrafluoride boron or trifluoroacetate in the formula) of AuX is reflected in methyl alcohol or the ethanol and carries out, about 0 ℃ of temperature of reaction or room temperature.But, the gold complex [(Et that this method will be formed with two triethyl phosphines in building-up process
3P)
2AuX, cost is higher; And, with the highest ability 42% of auranofin productive rate of this method acquisition.
Its method of preparation method that US 4125711 also discloses a kind of auranofin is to make 1-β-D-sulfo--2,3,4, and 6-four-O-ethanoyl Glucopyranose and a kind of general formula are:
(C
2H
5)
3The compound reaction of PAuS-R, R is the alkyl of 1～8 carbon in the formula, phenyl or Et
3PAuS-; Being reflected at a kind of organic solvent for example carries out in the chloroform.Yet, this method finally will under-23 ℃ in 3: 5 methanol aqueous solution recrystallization obtain auranofin, after perhaps purifying earlier, carry out twice recrystallization with methanol-water again and obtain auranofin, its productive rate only 55% with column chromatography.
The objective of the invention is to overcome the deficiency that prior art exists, a kind of improved auranofin preparation method is provided,, improve the purity of product, and make to be reflected under the relatively mild condition and carry out, thereby reduce preparation cost to improve the productive rate of auranofin.
Technical scheme of the present invention is: (1) changes the raw material interpolation order of 2-S-(2,3,4,6-four-O-ethanoyl-β-D-glucopyranosyl)-2-sulfo-isourea hydrobromate (I), a chlorine (triethyl phosphine) alloy (IV) and salt of wormwood (II); (2) methyl alcohol replaces ethanol, does reaction solvent with methanol-water; (3) improve temperature of reaction, make to be reflected under the mild conditions that taps into 0～20 ℃ of room temperature and carry out; (4) auranofin that makes is purified at the room temperature recrystallization.
The inventive method comprises that a chlorine (triethyl phosphine) alloy (IV) and salt of wormwood (II) are raw material, it is characterized in that synthesis procedure is as follows with 2-S-(2,3,4,6-four-O-ethanoyl-β-D-glucopyranosyl)-2-sulfo-isourea hydrobromate (I):
A. (I) is dissolved in methyl alcohol: water=1.5～2: in the solution of 1 (volume ratio), obtain A liquid;
B. (IV) is dissolved in the methyl alcohol, obtains B liquid;
C. (II) is soluble in water, obtain C liquid;
D.A liquid mixes with B liquid, is cooled to 0～5 ℃, under 0～5 ℃ of stirring to mixed solution and dripping C liquid, add C liquid, reacted 90～100 minutes, and continued reaction 30～40 minutes again under room temperature, heating in water bath is to the solid dissolving that generates, filter, adding distil water to precipitation occurs in the filtrate, and cooling is filtered, leach thing methyl alcohol: the solution washing of water=0.4: 1 (volume ratio), room temperature vacuum-drying get white auranofin crystal.
Resulting auranofin crystal is carried out methanol-water solution weight crystallization and purification again under room temperature, vacuum-drying gets pure product.
In aforesaid method, input starting raw material should satisfy the measuring requirement of chemical reaction, under the principle of not wasting, by near waiting mole or suitably excessive (I), (II) for well; Institute's solubilizing agent should guarantee that the starting raw material that drops into dissolves fully, under the principle of not wasting, and can be suitably excessive.
Compare with prior art, the present invention has following advantage:
1, improve the temperature of building-up reactions, reaction can be carried out under near the mild conditions of room temperature, operated the simple and easy little energy that expends, with low cost.
2, the productive rate height of auranofin product, the auranofin product productive rate that obtains with the inventive method is not less than 94.0%, and the product yield that recrystallization is purified is not less than 89.5%.
3, flow process is short, and the time of consumption is few.
4, the reliable easily row of recrystallization method of purification.
Therefore, in known each preparation method, the present invention has very high Practical significance.
Embodiment 1
Get 5.0 gram (10.3mmol) 2-S-(2,3,4,6-four-O-ethanoyl-β-D-glucopyranosyl)-2-sulfo-isourea hydrobromates (I) and be dissolved in 15ml water and the 30ml methanol solution, obtain A liquid; 3.4 gram (9.7mmol) chlorine (triethyl phosphine) alloy (IV) is dissolved in the 50ml methyl alcohol, obtains B liquid; 1.6 gram (11.6mmol) salt of wormwood (II) is dissolved in the 15ml water, obtains C liquid.
A liquid mixes with B liquid, is cooled to 0～5 ℃, in this temperature range, in mixed liquid, drip C liquid, add C liquid, continue reaction 60 minutes, continue reaction 30 minutes again under room temperature, heating in water bath filters to the solid dissolving that generates, adding distil water to precipitation occurs in the filtrate, cooling is filtered, and leach thing methyl alcohol: the solution washing of water=0.4: 1 (volume ratio) leaches thing, room temperature vacuum-drying gets white crystal product 6.2 grams, productive rate 94.0%.Through the methanol-water recrystallization, room temperature vacuum-drying gets pure product 5.5 grams of auranofin, recrystallization product yield 89.5% to products therefrom under room temperature.
After tested, 113～114.5 ℃ of the fusing points of the pure product of gained auranofin, [α]
D 20=-59.01 (1% methyl alcohol); Ultimate analysis (weight %) measured value (calculated value): C35.33 (35.40), H5.06 (5.06), S5.01 (4.73), Au 28.95 (29.02); UV: λ
Shoulder=220, ε
220=2900 (95% methyl alcohol); IR:(cm
-1); KBr pressed disc method: ν
CH3(2956,2884), ν
CH2(2922,2855), ν
C=O(1746), δ
CH2(1450), δ
CH3(1370), ν
C-O-C(1230), ν
C-O-C(1090,1052,1032), pyranose ring vibration (910), ρ
CH2(770), ν
P-C(738,604); Valelinum Liquidum pressed disc method: ν
P-Au(380), ν
S-Au(270).
Embodiment 2
Get 44.0 gram (0.090mol) 2-S-(2,3,4,6-four-O-ethanoyl-β-D-glucopyranosyl)-2-sulfo-isourea hydrobromates (I) and be dissolved in 120ml water and the 234ml methanol solution, obtain A liquid; 30.0 gram (0.086mol) chlorine (triethyl phosphine) alloy (IV) is dissolved in the 400ml methyl alcohol, obtains B liquid; 14.0 gram (0.101mol) salt of wormwood (II) is dissolved in the 115ml water, obtains C liquid.
A liquid mixes with B liquid, is cooled in 0～5 ℃ of scope, drips C liquid in mixed liquid, add C liquid, continue reaction 90 minutes, under room temperature, continue reaction 40 minutes again, heating in water bath is to the solid dissolving that generates, filter, adding distil water to precipitation occurs in the filtrate, cooling, filter, leach thing methyl alcohol: the solution washing of water=0.4: 1 (volume ratio) leaches thing, and room temperature vacuum-drying gets white crystal product 55.2 grams, productive rate 95.0%.Through the methanol-water recrystallization, room temperature vacuum-drying gets pure product 49.6 grams of auranofin, recrystallization product yield 90.0% to products therefrom under room temperature.
After tested, 112～114 ℃ of the fusing points of the pure product of gained auranofin, [α]
D 20=-54.40 (1% methyl alcohol); Ultimate analysis (weight %) measured value (calculated value): C 35.32 (35.40), H 5.09 (5.06), S4.68 (4.73), Au29.25 (29.02); UV: λ
Shoulder=220, ε
220=5900 (95% methyl alcohol); IR:(cm
-1), KBr pressed disc method: ν
CH3(2954,2878), ν
CH2(2930,2854), ν
C=O(1748), δ
CH2(1450), δ
CH3(1372), ν
C-O-C(1233), ν
C-O-C(1092,1052,1033), pyranose ring vibration (910), ρ
CH2(771), ν
P-C(738,604); Valelinum Liquidum pressed disc method: ν
P-Au(380), ν
S-Au(270).
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97119444A CN1057092C (en) | 1997-10-31 | 1997-10-31 | Preparation of Anranofin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97119444A CN1057092C (en) | 1997-10-31 | 1997-10-31 | Preparation of Anranofin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1216305A CN1216305A (en) | 1999-05-12 |
| CN1057092C true CN1057092C (en) | 2000-10-04 |
Family
ID=5175377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97119444A Expired - Fee Related CN1057092C (en) | 1997-10-31 | 1997-10-31 | Preparation of Anranofin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1057092C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105418696B (en) * | 2014-09-10 | 2018-09-21 | 华中科技大学 | A kind of synthetic method of glycosyl mercaptan and Anranofin |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3635945A (en) * | 1969-10-28 | 1972-01-18 | Smith Kline French Lab | Trialkylphosphinegold complexes of 1-beta-d-glucopyranosides |
| US4115642A (en) * | 1977-06-30 | 1978-09-19 | Smithkline Corporation | Method for preparing auranofin |
| US4125711A (en) * | 1977-06-30 | 1978-11-14 | Smithkline Corporation | Process for preparing auranofin |
| US4131732A (en) * | 1977-04-21 | 1978-12-26 | Smithkline Corporation | Method for preparing auranofin |
| US4200738A (en) * | 1977-04-21 | 1980-04-29 | Smithkline Corporation | Method for preparing auranofin |
-
1997
- 1997-10-31 CN CN97119444A patent/CN1057092C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3635945A (en) * | 1969-10-28 | 1972-01-18 | Smith Kline French Lab | Trialkylphosphinegold complexes of 1-beta-d-glucopyranosides |
| US4131732A (en) * | 1977-04-21 | 1978-12-26 | Smithkline Corporation | Method for preparing auranofin |
| US4200738A (en) * | 1977-04-21 | 1980-04-29 | Smithkline Corporation | Method for preparing auranofin |
| US4115642A (en) * | 1977-06-30 | 1978-09-19 | Smithkline Corporation | Method for preparing auranofin |
| US4125711A (en) * | 1977-06-30 | 1978-11-14 | Smithkline Corporation | Process for preparing auranofin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1216305A (en) | 1999-05-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103467528B (en) | A kind of preparation method of lobaplatin | |
| CN101402655B (en) | Process for producing platinum | |
| CN101830933B (en) | Novel method for synthesizing antitumor medicament platinum | |
| US7888390B2 (en) | Preparation of platinum(II) complexes | |
| CN1057092C (en) | Preparation of Anranofin | |
| WO2005035544A1 (en) | Oxaliplatin with a low content of accompanying impurities and a method for preparation thereof | |
| TW201741326A (en) | Method for synthesizing and purifying platinum phosphate (PHOSPHAPLATIN) compound and use thereof | |
| CN114314701B (en) | Preparation method of potassium ammonium platinum trichloride and application of potassium ammonium platinum trichloride in preparation of cis-ammonium-water-platinum complex | |
| CN111039767B (en) | A kind of method for preparing deuterated aldehyde catalyzed by triazole carbene | |
| CN1022410C (en) | Pyrimidine derivatives and process for preparation thereof | |
| CN114195830A (en) | Preparation method of cis-ammonia-water-platinum complex | |
| CN103739635B (en) | A kind of purification process of mannose triflate intermediate | |
| EP0258655B1 (en) | Complexes of platinum (ii) 2,3-dinitrilo-2-butene-2,3-dithiolate, a process for preparing them and pharmaceutical compositions containing them | |
| JPWO2009090903A1 (en) | Platinum complex compounds and uses thereof | |
| CN100582115C (en) | Novel method for synthesizing antineoplastic medicine carboplatin | |
| CN1269829C (en) | Process for purifying satraplatin | |
| JP3022264B2 (en) | Synthesis method of platinum complex | |
| CN101514182B (en) | Method for preparing beta, beta'-binary (4-pyridyl) divinylbenzene | |
| EP0261044B1 (en) | Novel platinum-riboflavin-complexes | |
| CN1837223A (en) | Novel process for synthesis of oxaliplatin as anticancer medicine | |
| CN102140124A (en) | Novel synthesis process of capecitabine | |
| CN1318392C (en) | Improved preparation method of Nagelinei | |
| KR950000982B1 (en) | Manufacturing method of platinum complex | |
| CN112500281A (en) | Preparation method of syringic acid | |
| CN102675236A (en) | Synthesis method of ethyl formate 5-chloro-3-(methylthio)-1,2,4-triazinyl-6-carboxylic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |