WO2001022915A2 - Process for production of cis-dichloro-(trans-1-1,2-cyclohexanediamine)platinum(ii) - Google Patents
Process for production of cis-dichloro-(trans-1-1,2-cyclohexanediamine)platinum(ii) Download PDFInfo
- Publication number
- WO2001022915A2 WO2001022915A2 PCT/CZ2000/000070 CZ0000070W WO0122915A2 WO 2001022915 A2 WO2001022915 A2 WO 2001022915A2 CZ 0000070 W CZ0000070 W CZ 0000070W WO 0122915 A2 WO0122915 A2 WO 0122915A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkali metal
- tetrachloroplatinate
- aqueous solution
- trans
- platinum
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 15
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 14
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 13
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 13
- 229940095064 tartrate Drugs 0.000 claims abstract description 13
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 11
- 239000011541 reaction mixture Substances 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 7
- 239000012431 aqueous reaction media Substances 0.000 claims abstract description 3
- 239000012265 solid product Substances 0.000 claims abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 14
- 229910052700 potassium Inorganic materials 0.000 claims description 14
- 239000011591 potassium Substances 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 10
- 238000007792 addition Methods 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000007900 aqueous suspension Substances 0.000 claims description 3
- LIAWOTKNAVAKCX-UHFFFAOYSA-N hydrazine;dihydrochloride Chemical compound Cl.Cl.NN LIAWOTKNAVAKCX-UHFFFAOYSA-N 0.000 claims description 3
- 238000006386 neutralization reaction Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 230000021962 pH elevation Effects 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- -1 alkali metal salt Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 description 1
- 239000001358 L(+)-tartaric acid Substances 0.000 description 1
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 229910019032 PtCl2 Inorganic materials 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
Definitions
- the invention deals with a new process for production of an antitumor effective compound c/5-dichloro-(tr ⁇ «5-/-l,2-cyclohexanediamine)platinum(II) complex of the formula
- the goal of the present invention is to find a new process for preparation of the cis- dichloro-(tra «5-/-l,2-cyclohexanediamine)platinum(II) which would not suffer from the above disadvantages.
- 1 molar equivalent of an alkali metal salt of tetrachloroplatinate(II) is treated with 1.1 to 1.3 molar equivalents of tr «5-/-l,2-cyclohexanediammonium tartrate.
- the alkalinity of the reaction mixture is maintained during the reaction by additions of an alkali metal hydroxide within the pH range from 8 to 11.
- the aqueous suspension of tr ⁇ «s-/-l,2-cyclohexanediammonium tartrate is first alkalinized by an alkali metal hydroxide to a pH value higher than 8 and , prior to mixing with the aqueous solution of alkali metal tetrachloroplatinate(II), the obtained solution is separated from insoluble impurities present.
- a raw aqueous solution of potassium tetrachloroplatinate(II) obtained by reduction of potassium hexachloroplatinate(IV) by hydrazinium dichloride, separation of insoluble parts and neutralisation of the free hydrochloric acid present in the obtained aqueous solution by an alkali metal hydroxide may advantageously be used .
- Reaction temperature is not a critical parameter within the process of the invention.
- the obtained c/s-dicMoro-(tr ⁇ «s-/-l,2-cyclohexanediamine)platinum(II) may be separated from the reaction mixture by standard separation techniques, washed with a diluted hydrochloric acid and/or by water and/or by a water miscible organic solvent, advantageously by a low boiling alcohol, and optionally also by ether, and subsequently dried.
- the optically active tr ⁇ «5-/-l,2-cyclohexanediammonium tartrate may be prepared in advance by reaction of tr ⁇ ws- 1,2-cyclohexanediamine with L(+)-tartaric acid, wherein it is not necessary to convert the said product to traws-/-l,2-cyclohexanediamine by an otherwise difficult process which is very sensitive to the presence of even trace amounts of the air (decomposition of the tartrate, extraction of the liberated free diamine by an organic solvent, removal thereof by distillation and distillation of trans-l-l,2-cyclo- hexanediamine in vacuo ).
- the trans-/- 1,2-cyclohexanediarnmonium tartrate may, prior to the reaction with alkali metal tetrachloroplatinate(II) , be made free from present insoluble impurities by such a way that its aqueous suspension is made alkaline by an alkali metal hydroxide to pH value of at least 8 and the obtained solution is brought into the reaction after separation of impurities.
- Another advantage of the process for production of c/s-dichloro-(traws-/-l,2-cyclo- hexanediamine)platinum(II) according to the invention is based on the possibility to use a raw solution of potassium tetrachloroplatinate(II) obtained by reduction of potassium hexachloroplatinate(IV) with hydrazinium dichloride, removing insoluble matter and neutralisation of free hydrochloric acid by an alkali metal hydroxide, in the place of the solution of an alkali metal tetrachloroplatinate(II).
- pH value of the reaction mixture was maintained at 9.5-10.0 by addition of approx. 2M solution of potassium hydroxide via a peristaltic pump.
- the yield was 58.1 g of c s-dichloro-(tr ns-/-l,2-cyclohexanediamine)platinum(II), i.e. 97.6% of theoretical yield, based on the starting potassium tetrachloroplatinate(II).
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
A process for production of cis-dichloro-(trans-1-1,2-cyclohexanediamine)platinum(II) complex, based on treatment of 1 mol of alkali metal tetrachloroplatinate(II) in an aqueous solution with 0.9 to 1.7 mol of trans-1-1,2-cyclohexanediammonium tartrate at pH of the reaction mixture between 7 and 12 obtained by alkalinisation by an alkali metal hydroxide, followed by separation of the solid product from the aqueous reaction medium.
Description
Process for production of ris-dichloro-(trans-I-l,2-cyclohexanediamine)plati- num(H)
Field of the Invention
The invention deals with a new process for production of an antitumor effective compound c/5-dichloro-(trα«5-/-l,2-cyclohexanediamine)platinum(II) complex of the formula
which is an intermediate in the synthesis of metal-containing antitumor agent oxaliplatin, i. e. (trans-l- 1 ,2-cyclohexanediamine)-(oxalato)platinum(LT).
Background of the Invention
The c/5-dichloro-(trα«5-/-l,2-cyclohexanediamine)platinum(II) was prepared until now according to US patent No. 4,169,846, by a long-termed reaction of potassium tetrachloroplatinate(II) with tra«s-/-l,2-cyclohexanediarnine followed by recrystallization of the obtained raw product from boiling 0.1 M hydrochloric acid. This known procedure has however several basic disadvantages. One of these disadvantages is in that the starting optically active traws-/-isomer of 1,2-cyclohexanediamine is relatively expensive starting material. Other disadvantage is in that the recrystallization of the obtained raw product requires large amounts of diluted hydrochloric acid due to a low solubility of the cis-dicMoro-(trarø-/-l,2-cydohexanediarrune)platinum(II) complex and the obtained yields of this final product are relatively low. Finally, the second starting material, i.e. crystalline potassium tetrachloroplatinate(II), is rather expensive as well.
The goal of the present invention is to find a new process for preparation of the cis- dichloro-(tra«5-/-l,2-cyclohexanediamine)platinum(II) which would not suffer from the above disadvantages.
Summary of the Invention
The above discussed disadvantages are not exhibited in a novel method for production of the cw-dichloro-(trαw5-/-l,2-cyclohexanediamine)platinum(II) characterised in reacting 1 molar equivalent of alkali metal salt of tetrachloroplatinate(II) in an aqueous solution with 0.9 to 1.7 molar equivalents of trans-l-l,2-cyclo- hexanediammonium tartrate at a pH value of the reaction medium between 7 and 12 that has been obtained by alkalinization thereof by an alkali metal hydroxide, followed by separation of the solid product from the aqueous reaction medium. In a particularly advantageous embodiment of the process of the invention, 1 molar equivalent of an alkali metal salt of tetrachloroplatinate(II) is treated with 1.1 to 1.3 molar equivalents of tr «5-/-l,2-cyclohexanediammonium tartrate. Advantageously, the alkalinity of the reaction mixture is maintained during the reaction by additions of an alkali metal hydroxide within the pH range from 8 to 11. In a preferred embodiment, the aqueous suspension of trø«s-/-l,2-cyclohexanediammonium tartrate is first alkalinized by an alkali metal hydroxide to a pH value higher than 8 and , prior to mixing with the aqueous solution of alkali metal tetrachloroplatinate(II), the obtained solution is separated from insoluble impurities present. As the aqueous solution of an alkali metal tetrachloroplatinate(II), a raw aqueous solution of potassium tetrachloroplatinate(II) obtained by reduction of potassium hexachloroplatinate(IV) by hydrazinium dichloride, separation of insoluble parts and neutralisation of the free hydrochloric acid present in the obtained aqueous solution by an alkali metal hydroxide, may advantageously be used . The process of the invention proceeds according the following reaction scheme : M2PtCU + C6H10( H3)2C4H4O6 + 2 MOH --> [PtCl2[C6H10(NH2)2]] +
+ 2 MCI + 2 H2O wherein M means an alkali metal.
Reaction temperature is not a critical parameter within the process of the invention. The obtained c/s-dicMoro-(trα«s-/-l,2-cyclohexanediamine)platinum(II) may be separated from the reaction mixture by standard separation techniques, washed with a diluted hydrochloric acid and/or by water and/or by a water miscible organic solvent,
advantageously by a low boiling alcohol, and optionally also by ether, and subsequently dried.
The optically active trα«5-/-l,2-cyclohexanediammonium tartrate may be prepared in advance by reaction of trαws- 1,2-cyclohexanediamine with L(+)-tartaric acid, wherein it is not necessary to convert the said product to traws-/-l,2-cyclohexanediamine by an otherwise difficult process which is very sensitive to the presence of even trace amounts of the air (decomposition of the tartrate, extraction of the liberated free diamine by an organic solvent, removal thereof by distillation and distillation of trans-l-l,2-cyclo- hexanediamine in vacuo ). By using a slight excess of trans-/- 1,2-cyclohexanediammonium tartrate, one may obtain almost theoretical consumption of alkali metal tetrachloroplatinate(H) which is the most expensive part of the whole system, whereby eventual losses are mainly the losses during manipulation. Furthermore, one of the advantages of the process for preparation of c/s-dichloro-(tra«s- /-l,2-cyclohexanediamine)platinum(II) according to the invention is a possibility of continual maintaining of the proper alkalinity of the reaction medium by addition of an alkali metal hydroxide at approximately constant value of pH, advantageously in a pH range between 8 and 11. Thereby, formation of both reaction by-products and impurities is minimised. The termination of the reaction is indicated by the fact that the pH of the reaction system does not drop and maintains steady in the absence of addition of the alkali metal hydroxide.
The trans-/- 1,2-cyclohexanediarnmonium tartrate may, prior to the reaction with alkali metal tetrachloroplatinate(II) , be made free from present insoluble impurities by such a way that its aqueous suspension is made alkaline by an alkali metal hydroxide to pH value of at least 8 and the obtained solution is brought into the reaction after separation of impurities.
Another advantage of the process for production of c/s-dichloro-(traws-/-l,2-cyclo- hexanediamine)platinum(II) according to the invention is based on the possibility to use a raw solution of potassium tetrachloroplatinate(II) obtained by reduction of potassium hexachloroplatinate(IV) with hydrazinium dichloride, removing insoluble matter and neutralisation of free hydrochloric acid by an alkali metal hydroxide, in the place of the solution of an alkali metal tetrachloroplatinate(II). This way, one may avoid a necessity
of preparation of a crystalline potassium tetrachloroplatinate(II) requiring concentration of large volumes of a solution of potassium tetrachloroplatinate(π) containing considerably high amounts of free hydrochloric acid and precipitation of the product by concentrated hydrochloric acid, which is difficult and risky as far as exhalations are concerned.
In the next part of the disclosure, the invention will be further illustrated by means of more concrete examples of its embodiment, whereby these examples are of illustrative character only and they by no way limit the scope of the invention which is unambiguously defined by patent claims. Within the examples, the unit operations were performed, whenever necessary or possible, under limited access of air and the used water was purged with nitrogen prior its use.
Examples of the Invention
Example 1
1084.6 g of an intermediate from production of c/'s-diammin-dichloroplatinum(π) represented by an aqueous solution containing lOO.Og of potassium tetrachloroplatinate(II) , was allowed to stand for three days at 5°C. The precipitated part of unreacted potassium hexachloroplatinate(IV) was filtered off. Strongly acidic filtrate was charged into a 2 liter vessel equipped by a stirrer, combined pH-electrode, nitrogen inlet and inlet for reactants, and was neutralised by an aqueous solution (approx. 2 M) of potassium hydroxide to pH = 5.7. The adjusted solution was mixed with a second solution prepared by suspending of 73.5 g of pre-made trans-l-l,2-cyclo- hexanediammonium tartrate in 600 ml water, alkalinisation to pH = 8.3 by potassium hydroxide solution of the above concentration, and filtration. In further, pH value of the reaction mixture was maintained at 9.5-10.0 by addition of approx. 2M solution of potassium hydroxide via a peristaltic pump. After 10 hours of stirring , when the pH value was constant, the formed c/s-dichloro-(traws-/-l,2-cyclohexane- diamine)platinum(II) was filtered off, washed with demineralised water, ethanol and ether and dried in vacuum oven to constant weight.
The yield was 89.0g of c/s-dichloro-(tra«s-/-l,2-cyclohexanediamine)platinum(II) i.e. 97.3% of theory, based on the content of potassium tetrachloroplatinate(II) in the starting material.
Example 2
47.6 g of pre-made trans-l- 1,2-cyclohexanediammonium tartrate was suspended in 400 ml of water and the pH value was adjusted to 8.15 by the aid of an aqueous solution of potassium hydroxide ( approx. 2M) . The obtained solution was filtered and charged together with 65.0 g of crystalline potassium tetrachloroplatinate(II) into 1 liter vessel equipped by a stirrer, combined pH-electrode, nitrogen inlet and inlet of potassium hydroxide. The pH value of the reaction mixture was kept at a value of approx. 10 by additions of potassium hydroxide solution of the above concentration. The formed cis- dichloro-(trαns-/-l,2-cyclohexanediamine)platinum(π) was filtered off, washed with water, diluted hydrochloric acid ( 0.3 M HC1), ethanol and ether and dried in vacuum oven to constant weight.
The yield was 58.1 g of c s-dichloro-(tr ns-/-l,2-cyclohexanediamine)platinum(II), i.e. 97.6% of theoretical yield, based on the starting potassium tetrachloroplatinate(II).
Claims
1. A process for preparation of a cts-dichloro-(trcms-/-l,2-cyclo- hexanediamino)platinum(II) characterised by treating 1 mol of an alkali metal tetrachloroplatinate(II) with 0.9 to 1.7 mol of trans-l- 1,2-cyclohexanediammonium tartrate in an aqueous solution at a pH value of the reaction mixture between 7-12 obtained by alkalinization thereof by an alkali metal hydroxide , followed by separation of the solid product from the aqueous reaction medium.
2. The process according to claim 1 characterised by treating 1 mol of alkali metal tetrachloroplatinate(II) with 1.1 to 1.3 mol of trans-l- 1,2-cyclohexanediammonium tartrate.
3. The process according to claim 1 characterised in that the alkaline value of the reaction mixture is maintained within the course of the reaction by additions of an alkali metal hydroxide at a pH value of from 8 to 11.
4. The process according to claim 1 characterised in that an aqueous suspension of trans-l- 1,2-cyclohexanediammonium tartrate is first made alkaline by an alkali metal hydroxide to a pH value of at least 8 and the obtained solution is separated from present insoluble impurities prior to mixing with the aqueous solution of alkali metal tetrachloroplatinate(II) .
5. The process according to claim 1 characterised by using, as the aqueous solution of alkali metal tetrachloroplatinate (LT), a raw aqueous solution of potassium tetrachloroplatinate(II) obtained by reduction of an aqueous solution of hexachloroplatinate(rV) with hydrazinium dichloride , separation of insoluble matter and neutralisation of the free hydrochloric acid in the obtained aqueous solution by an alkali metal hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU72673/00A AU7267300A (en) | 1999-09-29 | 2000-09-22 | Process for production of cis-dichloro-(trans-1-1,2-cyclohexanediamine)platinum(ii) |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZPV1999-3458 | 1999-09-29 | ||
| CZ19993458A CZ294382B6 (en) | 1999-09-29 | 1999-09-29 | Process for preparing cis-dichloro-(trans-l-1,2-cyclohexanediamine)platinum complex |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2001022915A2 true WO2001022915A2 (en) | 2001-04-05 |
| WO2001022915A3 WO2001022915A3 (en) | 2001-10-25 |
Family
ID=5466775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CZ2000/000070 WO2001022915A2 (en) | 1999-09-29 | 2000-09-22 | Process for production of cis-dichloro-(trans-1-1,2-cyclohexanediamine)platinum(ii) |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU7267300A (en) |
| CZ (1) | CZ294382B6 (en) |
| WO (1) | WO2001022915A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104940151A (en) * | 2015-07-23 | 2015-09-30 | 青岛蓝盛洋医药生物科技有限责任公司 | Oxaliplatin freeze-dried powder injection composition as anti-cancer drug |
| CN104945443A (en) * | 2015-07-23 | 2015-09-30 | 青岛蓝盛洋医药生物科技有限责任公司 | Drug, namely oxaliplatin compound, for treating cancer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2558469B1 (en) * | 1984-01-25 | 1986-06-27 | Bellon Labor Sa Roger | NOVEL PLATINUM COORDINATION COMPOUNDS, METHODS OF MAKING SAME AND THEIR USE AS MEDICAMENTS |
| IL74449A (en) * | 1984-03-01 | 1988-07-31 | Us Commerce | Tetrahalo-1,2-cyclohexane-diamino platinum complexes and anti-neoplastic compositions comprising them |
| US4658047A (en) * | 1985-09-27 | 1987-04-14 | The United States Of America As Represented By The Department Of Health And Human Services | Method of preparing 1,2-diaminocyclohexane tetrachloro platinum (IV) isomers |
| JP2820289B2 (en) * | 1989-10-13 | 1998-11-05 | 田中貴金属工業株式会社 | Method for producing potassium tetrachloroplatinate |
-
1999
- 1999-09-29 CZ CZ19993458A patent/CZ294382B6/en not_active IP Right Cessation
-
2000
- 2000-09-22 AU AU72673/00A patent/AU7267300A/en not_active Abandoned
- 2000-09-22 WO PCT/CZ2000/000070 patent/WO2001022915A2/en active Application Filing
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104940151A (en) * | 2015-07-23 | 2015-09-30 | 青岛蓝盛洋医药生物科技有限责任公司 | Oxaliplatin freeze-dried powder injection composition as anti-cancer drug |
| CN104945443A (en) * | 2015-07-23 | 2015-09-30 | 青岛蓝盛洋医药生物科技有限责任公司 | Drug, namely oxaliplatin compound, for treating cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001022915A3 (en) | 2001-10-25 |
| AU7267300A (en) | 2001-04-30 |
| CZ9903458A3 (en) | 2001-05-16 |
| CZ294382B6 (en) | 2004-12-15 |
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