JPS62298596A - Production of platinum complex - Google Patents
Production of platinum complexInfo
- Publication number
- JPS62298596A JPS62298596A JP14181086A JP14181086A JPS62298596A JP S62298596 A JPS62298596 A JP S62298596A JP 14181086 A JP14181086 A JP 14181086A JP 14181086 A JP14181086 A JP 14181086A JP S62298596 A JPS62298596 A JP S62298596A
- Authority
- JP
- Japan
- Prior art keywords
- platinum
- aminomethylpyrrolidine
- optically active
- formula
- usually
- 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.)
- Pending
Links
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- AUKXFNABVHIUAC-UHFFFAOYSA-N pyrrolidin-2-ylmethylamine Chemical compound NCC1CCCN1 AUKXFNABVHIUAC-UHFFFAOYSA-N 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims abstract description 10
- CCQPAEQGAVNNIA-UHFFFAOYSA-N cyclobutane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-N 0.000 claims abstract description 7
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000013543 active substance Substances 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 abstract description 6
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 abstract description 5
- 229940116357 potassium thiocyanate Drugs 0.000 abstract description 4
- QPINXQCQOKBINJ-UHFFFAOYSA-K potassium;platinum(2+);trichloride Chemical compound [Cl-].[Cl-].[Cl-].[K+].[Pt+2] QPINXQCQOKBINJ-UHFFFAOYSA-K 0.000 abstract description 2
- 239000012295 chemical reaction liquid Substances 0.000 abstract 2
- VCBOVIRRWXUOOY-UHFFFAOYSA-L C1(CCC1)(C(=O)[O-])C(=O)[O-].[Ag+2] Chemical compound C1(CCC1)(C(=O)[O-])C(=O)[O-].[Ag+2] VCBOVIRRWXUOOY-UHFFFAOYSA-L 0.000 abstract 1
- 229910020427 K2PtCl4 Inorganic materials 0.000 abstract 1
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- VMPYTOIPVPQDNX-UHFFFAOYSA-N pyrrolidin-1-ylmethanamine Chemical compound NCN1CCCC1 VMPYTOIPVPQDNX-UHFFFAOYSA-N 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 238000000034 method Methods 0.000 description 7
- -1 dichloro compound Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 229910021607 Silver chloride Inorganic materials 0.000 description 3
- VYIWZEHRTLSWFL-UHFFFAOYSA-N [Pt+2].NCC1NCCC1 Chemical compound [Pt+2].NCC1NCCC1 VYIWZEHRTLSWFL-UHFFFAOYSA-N 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 150000003057 platinum Chemical class 0.000 description 3
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- AUKXFNABVHIUAC-RXMQYKEDSA-N (R)-pyrrolidin-2-ylmethylamine Chemical compound NC[C@H]1CCCN1 AUKXFNABVHIUAC-RXMQYKEDSA-N 0.000 description 1
- AUKXFNABVHIUAC-YFKPBYRVSA-N (S)-pyrrolidin-2-ylmethylamine Chemical compound NC[C@@H]1CCCN1 AUKXFNABVHIUAC-YFKPBYRVSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- IPOHICDGJPRKMS-UHFFFAOYSA-N platinum pyrrolidin-2-ylmethanamine Chemical compound [Pt].NCC1CCCN1 IPOHICDGJPRKMS-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RHUVFRWZKMEWNS-UHFFFAOYSA-M silver thiocyanate Chemical compound [Ag+].[S-]C#N RHUVFRWZKMEWNS-UHFFFAOYSA-M 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 125000004436 sodium atom Chemical group 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
工業」Ｊ」ｕ帽た１
本発明は、制癌剤として有用である１、１−シクロブタ
ンジ力ルポキシラト（２−アミノメチルピロリジン）プ
ラチナム（ｎ）およびその光学活性体の製造方法に関す
る。さらに詳しくは、プラチナム（ＩＩ）ポタシウムク
ロライドとチオシアン酸カリウムとの反応液に、２−ア
ミノメチルピロリジンまたはその光学活性体を反応させ
式
で表されるシス−ジチオシアナト（２−アミノメチルピ
ロリジン）プラチナム（ｎ）またはその光学活性体を得
て、これを水に懸濁し、さらに１，１−シクロブタンジ
カルボン酸の銀塩を加え、０〜１００°Ｃで反応させる
ことを特徴とする
で表わされる白金錯体またはその光学活性体の製造方法
に関する。Detailed Description of the Invention The present invention relates to the production of 1,1-cyclobutanedihydrupoxylate(2-aminomethylpyrrolidine)platinum (n) and its optically active substance, which are useful as anticancer agents. Regarding the method. More specifically, cis-dithiocyanato(2-aminomethylpyrrolidine)platinum ( n) or an optically active substance thereof is obtained, suspended in water, further added with a silver salt of 1,1-cyclobutanedicarboxylic acid, and reacted at 0 to 100°C. Or relates to a method for producing an optically active substance thereof.
従】じ刈支術−
ローゼンベルグらによるンスプラチン（ＣＯＤＰ）の抗
腫瘍活性の発見［ネイチャーｍ３８５ （１９８９）］
以来、抗腫瘍活性を有する白金錯体の研究が盛んに行わ
れるようになり、各種のリガンドを有する有機白金錯体
が多数合成され、その抗腫瘍活性も検討されている。そ
の中でも（式１）で表わされる１、１−シクロブタンジ
カルボキシラト（２−アミノメチルピロリジン）プラチ
ナム（ＩＩ）およびその光学活性体が特に優れた抗腫瘍
活性を打している。この白金錯体はジャーナルΦオブ・
メディシナル・ケミストリー（Ｊ、Ｍｅｄ、Ｃｈｅｍ、
）。[Follow] Jarijutsu - Discovery of anti-tumor activity of cosplatin (CODP) by Rosenberg et al. [Nature m385 (1989)]
Since then, research on platinum complexes having antitumor activity has been actively conducted, and a large number of organic platinum complexes having various ligands have been synthesized, and their antitumor activity is also being investigated. Among them, 1,1-cyclobutanedicarboxylate(2-aminomethylpyrrolidine)platinum (II) represented by (Formula 1) and its optically active substance exhibit particularly excellent antitumor activity. This platinum complex was published in the journal Φ of
Medicinal Chemistry (J, Med, Chem,
).
ｑ １３１５（１９７８）、特開昭５９−１３９３６
０号、特開昭５４−４８７５２号等に記載されている下
式で示される製造方法により合成されていた（特願昭５
９−１８９６５７号）。q 1315 (1978), JP-A-59-13936
No. 0, JP-A No. 54-48752, etc., it was synthesized by the manufacturing method shown by the following formula (Japanese Patent Application No. 54-48752).
No. 9-189657).
（式中、Ｍは水素原子またはナトリウム原子をわ表わす
。）
ロ 、 よ・ −−Ｆ占
上記の従来の製造方法は以下に示す通りの問題点を有し
ていた。すなわち、
■ （式２）で表わされるジアミンを出発物質として目
的化合物である（式１）で表わされる白金錯体を得るま
でに３行程を要し、合成にかなりの日数を要した。(In the formula, M represents a hydrogen atom or a sodium atom.) B, YO, --F The conventional manufacturing method described above had the following problems. That is, (1) It took three steps to obtain the target compound, the platinum complex represented by Formula 1, using the diamine represented by Formula 2 as a starting material, and the synthesis required a considerable number of days.
■ （式３）で表わされるジクロロ体からジニトラト体
を合成する行程において、溶媒として用いた水を低温で
濃縮しなければならず後処理に非常に時間を要した。(2) In the step of synthesizing the dinitrate compound from the dichloro compound represented by (Formula 3), water used as a solvent had to be concentrated at a low temperature, which required a very long post-treatment.
■ （式３）で表わされるジクロロ体からジニトラト体
を合成する行程において生成する塩化銀は粒子が小さく
その除去には非常に手間がかかった。(2) The silver chloride produced in the process of synthesizing the dinitrate compound from the dichloro compound represented by (Formula 3) has small particles and requires much effort to remove.
などである。そこで本発明者らは、短時間で効率の良い
（式１）で表わされる白金錯体の製造方法を見い出すべ
く鋭意研究を重ね次のような手段により、本発明の製造
方法を見い出し、上記の問題点を解決した。etc. Therefore, the present inventors conducted extensive research to find a short and efficient method for producing the platinum complex represented by formula 1, and by the following means, discovered the production method of the present invention, and solved the above problem. Resolved the point.
口 占ｔ ｔ ための−；
本発明者らは、プラチナム（ＩＩ）ボタシウムクロライ
ドとチオシアン酸カリウムとの反応液に２−アミノメチ
ルピロリジンまたはその光学活性体を反応させ、シス−
ジチオシアナト（２−アミノメチルピロリジン）プラチ
ナム（ＩＩ）またはその光学活性体を得て、これを水に
懸濁し、さらに１，１−シクロブタンジカルボン酸の銀
塩を加え、０〜１００″Ｃで反応させることを特徴とす
る１、１−シクロブタンジ力ルポキシラト（２−アミノ
メチルピロリジン）プラチナム（ｎ）またはその光学活
性体の製造方法を確立し、前記の問題点を解決し、本発
明を完成するに至った。The present inventors reacted 2-aminomethylpyrrolidine or its optically active substance with a reaction solution of platinum (II) botanium chloride and potassium thiocyanate to form a cis-
Obtain dithiocyanato(2-aminomethylpyrrolidine)platinum (II) or its optically active substance, suspend it in water, add silver salt of 1,1-cyclobutanedicarboxylic acid, and react at 0 to 100"C. In order to solve the above-mentioned problems and complete the present invention, we have established a method for producing 1,1-cyclobutanedihydrupoxylate(2-aminomethylpyrrolidine)platinum (n) or its optically active substance, which is characterized by the following: It's arrived.
本発明の製造方法は下式に示す通りである。The manufacturing method of the present invention is as shown in the formula below.
本発明の製造方法をさらに詳しく述べる。プラチナム（
ＩＩ）ボタシウムクロライドと４倍モルのチオシアン酸
カリウムとを水に溶解し、温度Ｏ〜１００°Ｃ好ましく
は２０〜８０’Ｃの範囲で通常０．５〜５時間の範囲で
撹拌上反応させ、これに２−アミノメチルピロリジンま
たはその光学活性体をプラチナム（ｎ）ボタシウムクロ
ライドと等モル加え１．侃度Ｏ〜１００°Ｃの範囲で通
常０．５〜ｌＯ時間の範囲で撹拌した後、生成した固体
をろ取し、水洗して通常温度０〜８０’Ｃの範囲で減圧
上乾燥することにより、（式５）で表わされるシス−ジ
チオシアナト（２−アミノメチルピロリジン）プラチナ
ム（ＩＩ）またはその光学活性体を得る。The manufacturing method of the present invention will be described in more detail. Platinum (
II) Botacium chloride and 4 times the mole of potassium thiocyanate are dissolved in water and reacted with stirring at a temperature of 0 to 100°C, preferably 20 to 80°C, usually for 0.5 to 5 hours. , 2-aminomethylpyrrolidine or its optically active substance was added thereto in an equimolar amount as platinum (n) botanium chloride; 1. After stirring for usually 0.5 to 10 hours at a temperature of 0 to 100°C, the solid produced is filtered, washed with water, and dried under reduced pressure at a temperature of 0 to 80°C. Thus, cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (II) represented by (Formula 5) or an optically active substance thereof is obtained.
得られたシス−ジチオシアナト（２−アミノメチルピロ
リジン）プラチナム（■）またはその光学活性体を水に
懸濁し、これに１，１−シクロブタンジカルボン酸の銀
塩を等モル加え、温度０〜１００℃、好ましくは２０〜
９０°Ｃの範囲で通常０．５〜１０時間の範囲で撹拌上
反応させる。反応液をろ過して析出したチオンアン酸銀
を除去し、ろ液を減圧濃縮した後、析出した生成物を水
洗して通常温度０〜８０°Ｃの範囲で減圧上乾燥するこ
とにより（式１）で表わされる１、１−シクロブタンジ
力ルポキシラト（２−アミノメチルピロリジン）プラチ
ナム（■）またはその光学活性体を得る。本発明の様に
シス−ジチオシアナト（２−アミノメチルピロリジン）
プラチナム（ｎ）およびその光学活性体を経由する方法
により、制癌剤として優れている１、１−シクロブタン
ジ力ルポキシラト（２−アミノメチルピロリジン）プラ
チナム（■）およびその光学活性体を効率よく合成でき
る。すなわち、
■ （式２）で表わされるジアミンを出発物質として目
的物質である（式１）で表わされる白金錯体を得るまで
に３行程を要していたものが本発明の製造方法で合成す
ると２行程に短縮され、合成にかなりの日数を要したも
のが０．５．〜１０数時間で行われるようになった。The obtained cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (■) or its optically active substance was suspended in water, and an equimolar amount of silver salt of 1,1-cyclobutanedicarboxylic acid was added thereto at a temperature of 0 to 100°C. , preferably 20~
The reaction is carried out with stirring at 90°C for usually 0.5 to 10 hours. The reaction solution was filtered to remove precipitated silver thionanate, the filtrate was concentrated under reduced pressure, and the precipitated product was washed with water and dried under reduced pressure at a normal temperature range of 0 to 80°C (Formula 1 ) 1,1-cyclobutanedilypoxylate(2-aminomethylpyrrolidine)platinum (■) or its optically active substance is obtained. As in the present invention, cis-dithiocyanato (2-aminomethylpyrrolidine)
By a method via platinum (n) and its optically active form, 1,1-cyclobutanedilypoxylate (2-aminomethylpyrrolidine) platinum (■), which is excellent as an anticancer agent, and its optically active form can be efficiently synthesized. That is, (1) it took 3 steps to obtain the target substance, a platinum complex represented by formula 1, using the diamine represented by formula 2 as a starting material, but when synthesized by the production method of the present invention, it takes 2 steps. The process was shortened to 0.5, which took a considerable number of days to synthesize. It started to take place in about 10 hours.
■ （式３）で表わされるジクロロ体からジニトラト体
を合成する行程において溶媒として用いた水を低温で４
縮しなければならず、後処理に非常に時間を要していた
ものが本発明の製造方法では、この行程を経由せずに反
応が行われるのでこの行程の作業が省かれ、要する時間
が非常に短縮された。■ The water used as a solvent in the process of synthesizing the dinitrate compound from the dichloro compound represented by (Formula 3) is heated to 4.
However, in the production method of the present invention, the reaction is performed without going through this step, which eliminates the work in this step and reduces the time required. Very shortened.
■ （式３）で表わされるジクロロ体からジニトラト体
を合成する行程において生成する塩化銀は粒子が小さく
その除去はミリポアフィルタ−などで行わなければなら
ず非常に手間のかかる作業であった。しかし、本発明の
製造方法では塩化銀が生成する行程がなく、合成に要す
る時間が非常に短縮された。(2) The silver chloride produced in the process of synthesizing the dinitrate compound from the dichloro compound represented by (Formula 3) has small particles and must be removed using a Millipore filter, which is a very time-consuming process. However, in the production method of the present invention, there is no step in which silver chloride is produced, and the time required for synthesis is greatly shortened.
なとのように前記の問題点を解決して本発明を完成した
。The present invention was completed by solving the above problems.
以下に例を挙げて説明する。This will be explained below using an example.
１巨匠上
プラチナム（ＩＩ）ポタシウムクロライド４．１５ｇ（
０，０１モル）を水１００ｍ１に溶解し、これにチオシ
アン酸カリウム３．８８ｇ （０，０４モル）を加え、
室温で３０分間撹拌後、２−アミノメチルピロリジン１
．ＯＯｇ （０，０ｆモル）を加える。室温で１時間撹
拌後生成した固体をろ取し、水洗した後、６０°Ｃで３
時間減圧上乾燥し、淡黄色のシス−ジチオシアナト（２
−アミノメチルピロリジン）プラチナム（ＩＩ） ３．
９１ｇ （収率９５％）を得る。1 Master Platinum (II) Potassium Chloride 4.15g (
0.01 mol) was dissolved in 100 ml of water, and 3.88 g (0.04 mol) of potassium thiocyanate was added thereto.
After stirring at room temperature for 30 minutes, 2-aminomethylpyrrolidine 1
．． Add OOg (0,0 fmol). After stirring for 1 hour at room temperature, the solid produced was collected by filtration, washed with water, and then stirred at 60°C for 3 hours.
Dry under reduced pressure for hours, pale yellow cis-dithiocyanato (2
-aminomethylpyrrolidine) platinum(II) 3.
91 g (95% yield) are obtained.
融点 ２０１〜２０４°Ｃ（分解）
元素分析値 分子式Ｃ７ＨＨｌ Ｎ４ Ｐ ｔ Ｓｚと
して実施例１と同様にして（Ｒ）−２−アミノメチルピ
ロリジン１．ＯＯｇ （０，０ｆモル）を用いて淡黄色
の（Ｒ）−シス−ジチオシアナト（２−アミノメチルピ
ロリジン）プラチナム（ｎ）３゜９５ｇ（収率９６％）
を得る。Melting point: 201-204°C (decomposed) Elemental analysis value: (R)-2-aminomethylpyrrolidine 1. 3°95 g of pale yellow (R)-cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (n) using OOg (0,0 f mol) (yield 96%)
get.
融点 １６６〜１６８°Ｃ
元素分析値 分子式Ｃｒ７ Ｈ，ｚＮ４ Ｐ ｔ Ｓ、
として実施例１と同様にして（Ｓ）−２−アミノメチル
ピロリジン１．ＯＯｇ （０，０１モル）を用いて淡黄
色の（Ｓ）−シス−ジチオシアナト（２−７ミノメチル
ピロリジン）プラチナム（ＩＩ）３゜９４ｇ（収率９６
％）を得る。Melting point 166-168°C Elemental analysis Molecular formula Cr7H,zN4PtS,
(S)-2-aminomethylpyrrolidine 1. OOg (0.01 mol) was used to prepare 3.94 g of pale yellow (S)-cis-dithiocyanato(2-7minomethylpyrrolidine)platinum(II) (yield 96
%).
融点 １６６〜１６９°Ｃ
元素分析値 分子式Ｃ，Ｈ，Ｎ４ＰｔＳｚとして実温」
ト１
実施例１で合成したシス−ジチオシアナト（２−アミノ
メチルピロリジン）プラチナム（ｎ）４゜１２ｇ（０，
０１モル）を水４００ｍ１に！！！！濁させ、これに常
法で合成した１、１−シクロブタンジカルボン酸の銀塩
３．５８ｇ （０，０ｆモル）を加え９０℃で３時間撹
拌する。析出したチオシアン酸銀を除去し、得られたろ
液を２０ｍ１まで減圧濃縮した後、室温で１時間撹拌す
ると白色結晶状固体が析出する。生成した固体をろ取し
、水洗後６０°Ｃで３時間域圧下乾燥し、１，１−シク
ロブタンジカルボンラト（２−アミツメ千ルビロリジン
）プラチナム（ＩＩ） ３．４６ｇ （収率７９％）を
得る。Melting point 166-169°C Elemental analysis value Molecular formula C, H, N4PtSz (actual temperature)
1 cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (n) synthesized in Example 1 4°12g (0,
01 mol) to 400ml of water! ! ! ! The mixture was made cloudy, and 3.58 g (0.0 fmol) of silver salt of 1,1-cyclobutanedicarboxylic acid synthesized by a conventional method was added thereto and stirred at 90°C for 3 hours. After removing the precipitated silver thiocyanate and concentrating the obtained filtrate under reduced pressure to 20 ml, the mixture was stirred at room temperature for 1 hour to precipitate a white crystalline solid. The generated solid was collected by filtration, washed with water, and then dried under pressure at 60°C for 3 hours to obtain 3.46 g (yield: 79%) of 1,1-cyclobutane dicarbonate (2-amythylvirolidine) platinum (II). .
融点 ２４８〜２５７°Ｃ（分解）
実ＪＬＩ舛ｊ−
実施例４と同様にして実施例２で合成した（Ｒ）−シス
ージチオシアナ＋（２−アミノメチルピロリジン）プラ
チナム（ＩＩ）４．１２ｇ （０，０１モル）を用いて
（Ｒ）−１，１−シクロブタンジカルボンラト（２−ア
ミノメチルピロリジン）プラチナム（ＩＦ） ３．５９
ｇ （収率８２％）を得る。Melting point: 248-257°C (decomposition) 4.12 g of (R)-cis-dithiocyana + (2-aminomethylpyrrolidine) platinum (II) synthesized in Example 2 in the same manner as in Example 4 ( (R)-1,1-cyclobutanedicarbonate(2-aminomethylpyrrolidine)platinum (IF) using 0.01 mol) 3.59
g (82% yield) is obtained.
実ｌ」Ｌ巳
実施例十と同様にして実施例３で合成した（Ｓ）−シス
−ジチオシアナト（２−アミノメチルピロリジン）プラ
チナム（ＩＩ）４．１２ｇ （０，０１モル）を用いて
（Ｓ）−１，１−シクロブタンジ力ルポキシラト（２−
アミノメチルピロリジン）プラチナム（ＩＩ） ３．８
３ｇ （収率８３％）を得る。Using 4.12 g (0.01 mol) of (S)-cis-dithiocyanato(2-aminomethylpyrrolidine)platinum(II) synthesized in Example 3 in the same manner as in Example 10, (S )-1,1-cyclobutanediylupoxylate (2-
Aminomethylpyrrolidine) Platinum(II) 3.8
3 g (83% yield) are obtained.
光可！μ机牝Light possible! μ machine female
Claims (1)
にあたり、プラチナム（II）ポタシウムクロライドとチ
オシアン酸カリウムとの反応液に、２−アミノメチルピ
ロリジンまたはその光学活性体を反応させ、 式 ▲数式、化学式、表等があります▼ で表されるシス−ジチオシアナト（２−アミノメチルピ
ロリジン）プラチナム（II）またはその光学活性体を得
て、これを水に懸濁し、さらに１，１−シクロブタンジ
カルボン酸の銀塩を加え、０〜１００℃で反応させるこ
とを特徴とする製造方法。[Claims] In producing the platinum complex represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or its optically active substance, 2- Aminomethylpyrrolidine or its optically active form is reacted to obtain cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (II) or its optically active form expressed by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, A manufacturing method characterized by suspending this in water, further adding a silver salt of 1,1-cyclobutanedicarboxylic acid, and reacting at 0 to 100°C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14181086A JPS62298596A (en) | 1986-06-18 | 1986-06-18 | Production of platinum complex |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14181086A JPS62298596A (en) | 1986-06-18 | 1986-06-18 | Production of platinum complex |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62298596A true JPS62298596A (en) | 1987-12-25 |
Family
ID=15300656
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14181086A Pending JPS62298596A (en) | 1986-06-18 | 1986-06-18 | Production of platinum complex |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62298596A (en) |
-
1986
- 1986-06-18 JP JP14181086A patent/JPS62298596A/en active Pending
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