JPS62238297A - Production of platinum complex - Google Patents
Production of platinum complexInfo
- Publication number
- JPS62238297A JPS62238297A JP7986086A JP7986086A JPS62238297A JP S62238297 A JPS62238297 A JP S62238297A JP 7986086 A JP7986086 A JP 7986086A JP 7986086 A JP7986086 A JP 7986086A JP S62238297 A JPS62238297 A JP S62238297A
- Authority
- JP
- Japan
- Prior art keywords
- platinum
- aminomethylpyrrolidine
- optically active
- formula
- water
- 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 40
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- AUKXFNABVHIUAC-UHFFFAOYSA-N pyrrolidin-2-ylmethylamine Chemical compound NCC1CCCN1 AUKXFNABVHIUAC-UHFFFAOYSA-N 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 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 5
- 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 4
- 239000013543 active substance Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 abstract description 5
- VMPYTOIPVPQDNX-UHFFFAOYSA-N pyrrolidin-1-ylmethanamine Chemical compound NCN1CCCC1 VMPYTOIPVPQDNX-UHFFFAOYSA-N 0.000 abstract 2
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 6
- -1 potassium thionanate Chemical compound 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 229910021607 Silver chloride Inorganic materials 0.000 description 3
- 230000000259 anti-tumor effect Effects 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
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000002904 solvent 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
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-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
- VYIWZEHRTLSWFL-UHFFFAOYSA-N [Pt+2].NCC1NCCC1 Chemical compound [Pt+2].NCC1NCCC1 VYIWZEHRTLSWFL-UHFFFAOYSA-N 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 125000004436 sodium atom Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
面又上至上月ユ立
本発明は、制癌剤として有用である１、１−ンクロブタ
ンジカルボキ７ラト（２−アミノメチルピロリ／／）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、／スー／千オンアナ１−（２−ア
ミノメチルピロリジン）プラチナム（ｎ）またはその光
学活性体を水に懸濁し、これに１，１−７クロブタンジ
カルボン酸の銀１−を加え、０〜１００°Ｃで反応させ
ることを特徴とする。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 1,1-chlorobutane dicarboxylat(2-aminomethylpyrroli//)platinum (n) which is useful as an anticancer agent and its optical activity. Concerning a method of manufacturing a body. More specifically, /Su/1,000 Ana1-(2-aminomethylpyrrolidine)platinum (n) or its optically active substance is suspended in water, and silver 1- of 1,1-7 clobutane dicarboxylic acid is added thereto. , characterized in that the reaction is carried out at 0 to 100°C.
弐 〇
て表わされる白金錯体またはその光学話性体の製造方法
に関する。The present invention relates to a method for producing a platinum complex represented by 2 〇 or an optically talkative form thereof.
従」銘λ技ｉ−
ローセンベルブらによる／スフーラ千ン（ＣＩ）Ｄ Ｐ
）の抗腫瘍活性の発見［ネイチャー２−１２３８５
（１９８９）コ以来、抗腫１０活性をイーｒする白金錯
体の研究か盛んに行われるようになり、各種のりカント
を仔する有機白金錯体か多数合成され、その抗腫ヌ！Ｊ
活性も検討されている。その中でも（式１）で表わされ
るｔ、 ｔ−／クロブタン７カルポキ／ラド（２−了
ミツメ千ルビロリ７／／）フーラチナム（ｎ）およびそ
の光学ｌＪ＋性体か特に優れた抗腫場活性を＠−してい
る。``Jou'' signature λ technique i- by Rosenbelb et al./Shurasen (CI) D P
) discovery of antitumor activity [Nature 2-12385
(1989), research on platinum complexes with antitumor activity has been actively conducted, and many organic platinum complexes with various adhesive properties have been synthesized. J
Activity is also being investigated. Among them, t, t-/klobutane7carpoki/rad(2-ryomitsumechiruvirori7//)furatinum(n) expressed by (Formula 1) and its optical lJ+ form have particularly excellent anti-tumor activity. -I am doing it.
この白金錯体は／ヤーナル・オブ・メディ／ナル・ゲミ
ストリー（Ｊ、Ｍｅｄ、Ｃｈｅｍ、）。This platinum complex is published in /Yarnal of Medicine/Nal Gemistry (J, Med, Chem, ).
１上 １３１５（１９７８）、特開昭５９−１３９３６
０号、特開昭５４−４８７５２号゛りに記・戒されてい
るＩＪ工（で示される製造方法により合成されていた（
ｉ、’ｉ願１１／ｌ ５９−１８９６５７弓）。1 No. 1315 (1978), JP-A-59-13936
No. 0, JP-A No. 54-48752, it was synthesized by the production method shown in IJ process (
11/l 59-189657 bow).
（式中、Ｍは水素原子−またはナトリウム原子をわ表わ
す。）
、Ｕリート」シと九−声ｅｖ−７ノ監＝Ｌ、＆ ｆｒｙ
−ナー１１、Ｌ記の従来の５ｕ遣方法は以ドに示す通り
の問題Ｉ哉をイ］−シていた。すなわち、
■ （式２）で表わされる／アミンを出発物質として［
１的化合物てあろ（Ｘ：１）て人わされる白金ｌｉ：’
ｉ体を得るまでに３行程を椙し、合成（こかなりの１丁
ｌ数を乃すした。(In the formula, M represents a hydrogen atom or a sodium atom.)
The conventional 5u method described in Section 11 and L had the following problems. That is, ■ Using /amine as a starting material represented by (Formula 2) [
Platinum li:' is a monolithic compound (X:1)
It took three steps to obtain the i-body, and it took a considerable amount of time to synthesize it.
■ （式３）で表わされるンクロロ体からン二トラト体
を合成する行程において、溶媒とし、て用いた水を低温
で濃紺１しなければならす後処理に非常に時間を要した
。(2) In the process of synthesizing the n-nitrato isomer from the n-chloro isomer represented by (Formula 3), the water used as a solvent had to be dark blue at a low temperature, which required a very long post-treatment.
■ （式３）で表わされるノ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１間がかかった。(2) The silver chloride produced in the process of synthesizing the dinitrato compound from the nochloro compound represented by (Formula 3) was small in size and took a very long time to remove.
なとである。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
く鋭意研究を市ね次のような手段により、本発明の製造
方法を見い出し、ｌ−記の問題点を解決した。It is Nato. Therefore, the present inventors conducted extensive research in order to find a method for producing the platinum complex represented by formula 1 in a short time and with high efficiency. The following problems were resolved.
間〕抱−に解決−すｊカー、春−の−１役本発明者らは
、シス−ジチオ／アナ） （２−アミノメチルピロリジ
ン）プラ千ナム（ＩＩ）またはその光学活性体を水に懸
濁し、、これに１゜１−／クロブタ／ジカルボン酸の銀
塩を加え、Ｏ〜ｉｏｏ’ｃで反応させることを特徴とす
る１゜１−／クロブタンジカルボキ／ラド（２−アミノ
メチルピロリジン）ブラ千ナム（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 have solved the problem by adding cis-dithio/ana) (2-aminomethylpyrrolidine) prasennam (II) or its optically active substance to water. 1゜1-/Clobutane dicarboxy/rad (2-aminomethylpyrrolidine) is suspended, and a silver salt of 1゜1-/Clobutane/dicarboxylic acid is added thereto, and the reaction is carried out at O~ioo'c. ) We have established a method for producing brasenum (n) or its optically active substance, solved the above-mentioned problems, and completed the present invention.
なお、出発物質となる／スーンチオ／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
活性体は新規な白金錯体てあり、プラチナム（ｎ）ボタ
／ラムクロライドとチオンアン酸カリウムとの反応液に
２−アミノメチルピロリ／／′またはその光学活性体を
反応さぜることにより（りることかできる。The starting material /Soonthio/anato(2-aminomethylpyrrolidine)platinum (■) or its optically active substance is a new platinum complex, and is a reaction solution of platinum (n)bota/rum chloride and potassium thionanate. can be reacted with 2-aminomethylpyrroli//' or an optically active substance thereof.
本発明の製造方法をさらに詳しく述ｔ＼る。The manufacturing method of the present invention will be described in more detail.
（式５）で表わされるシス−ジチオシアナト（２−アミ
ノメチルピロリノン）プラチナム（ｎ）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ＳｆＡ １４Ａを等モル加え、温度０〜１０
０°Ｃ，ｌ＋ｉ−士しくは２０〜９０°Ｃの範囲で通常
０．５〜１０時間の範囲で撹拌Ｆ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、威
圧１３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４とに」；す（
式１）で表わされる１、１−／クロブタンジカルボキン
ラト（２−アミツメ千ルビロリジ／）プラチナム（ｎ）
またはその光学活ｔ’ｌＥ体を得る。Cis-dithiocyanato(2-aminomethylpyrrolinon)platinum (n) represented by (Formula 5) or its optically active substance is suspended in water, and an equimolar amount of SfA 14A of 1,1-cyclobutanedicarboxylic acid is added thereto, Temperature 0-10
The reaction is carried out with stirring at 0°C, preferably 20 to 90°C, for usually 0.5 to 10 hours. The reaction solution is filtered to remove the precipitated silver thionanate, and the filtrate is condensed under 13 degrees of pressure.The precipitated product is then washed with water and dried under reduced pressure at a normal temperature range of 0 to 80°C. Toni”；su(
1,1-/Clobutane dicarboquine lato(2-Amitume 1,000 rubirolidi/) platinum (n) represented by formula 1)
Or obtain its optically active t'lE form.
本発明の様にシス−ジチオシアナト（２−アミンメチル
ピロリツノ）プラチナム（ｎ）およびその光学活性体を
用いることにより、制癌剤として優れている１、１−ン
クロブタ／シカルボキンラト（２−アミノメチルピロリ
ジン）フラチナム（ｎ）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）で表わされるノアミンを出発物質として目
的物質である（式１）で表わされろ白金錯体をｒＵるま
てに３行程を要していたものか本発明の製造方法で合成
すると２２１ｉ’程に短縮され、合成にかなりの日数を
認したものが０．５〜１０数時間で行われるようになっ
た。By using cis-dithiocyanato(2-aminemethylpyrrolidine)platinum (n) and its optically active form as in the present invention, 1,1-ncrobuta/cycarboquinelat(2-aminomethylpyrrolidine)platinum is an excellent anticancer agent. (n) and its optically active substance can be efficiently synthesized. That is, (1) It took three steps to prepare the target substance, the platinum complex represented by the formula 1, using the noamine represented by the formula 2 as a starting material, or by the production method of the present invention. As a result, the synthesis time was shortened to about 221i', and what used to take a considerable number of days to synthesize was now completed in 0.5 to 10-odd hours.
■ （弐３）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ｌ
屑綿しなければならす、後処理に非常に時間を装してい
たものが本発明の製造方法では、この行程を経由せずに
反応か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 (23) is
In the production method of the present invention, the reaction is carried out without going through this process, so the work in this process is omitted and the time required is reduced. Very shortened.
■ （弐３）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か小さく
その除去はミリポアフィルタ−などで行わなければなら
す非常に手間のかかる作業であった。しかし、本発明の
製造ノ」法てはｊ−化銀か生成する行程かなく、合成に
要する時間かノＩ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 (23) has small particles, and its removal must be carried out using a Millipore filter, which is a very time-consuming process. However, the production method of the present invention does not require the step of producing silver chloride, thereby significantly shortening the time required for synthesis.
な占のように１１ｉｉ記の問題点を解決１７て本発明を
−に＝成した。Like a fortune-telling, the problems in Section 11ii were solved 17 and the present invention was made into -=.
以ドに例を挙げて説明する。３
ｉ□−材上
プラチナ１．（ｎ）ボタ／ラムクロライド４．１５ｇ（
０，０１モル）を水１００ｍ１に溶解し、これにチオン
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（０，０１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、ｅｏ’ｃで３時
間減圧ド乾燥し、淡黄色のシスーノチオ／アナト（２−
アミノメチルピロリジン）プラチナム（ＩＩ）３．９１
ｇ （収・令く９５％）を得る。This will be explained below using an example. 3 i□-Platinum on material 1. (n) Bota/Rum chloride 4.15g (
0.01 mol) was dissolved in 100 ml of water, and 3.88 g (0.04 mol) of potassium thionanate was added thereto.
After stirring at room temperature for 30 minutes, 2-aminomethylpyrrolidine 1
Add ゜OOg (0.01 mol). After stirring at room temperature for 1 hour, the generated solid was collected by filtration, washed with water, and dried under reduced pressure for 3 hours on an EO'C to obtain pale yellow cisnotio/anato (2-
Aminomethylpyrrolidine) Platinum(II) 3.91
g (95% yield).
融点 ２０１〜２０４°Ｃ（分解）
元素分析値 分子式Ｃ７ＨｔｚＮ４ Ｐ ｔ Ｓｚとし
て参考例１と同様にして（Ｒ）−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
（Ｒ）−シス−ジチオノアナト（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. Using OOg (0.01 mol), 3.95 g (yield 96%) of pale yellow (R)-cis-dithionoanato(2-aminomethylpyrrolidine)platinum (n) is obtained.
融点 １６６〜１６８°Ｃ
元素分析値 分子式Ｃｒ７ Ｈ７ｚＮ４ Ｐ ｔ ８２
として参考例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ｌ炎
黄色の（Ｓ）−ンスーンチオンアナト（２−アミノメチ
ルピロリジン）プラチナム（ｎ）３゜９４ｇ（収率９６
％）を得る。Melting point 166-168°C Elemental analysis Molecular formula Cr7 H7zN4 P t 82
(S)-2-aminomethylpyrrolidine 1. OOg (0.01 mol) was used to prepare 3.94 g of flame-yellow (S)-soonthioneanato(2-aminomethylpyrrolidine)platinum (n) (yield 96
%).
融点 １６６〜１６９°Ｃ
元素分析値 分子式Ｃ７Ｈ，□Ｎ４ＰｔＳｚとして参４
例１で合成したンスーンチオ／アナト（２−アミノメチ
ルピロリジン）プラチナム（ＩＩ）４゜１２ｇ（０，０
１モル）を水４００ｍ１に懸濁させ、これに常法で合成
した１、 １−／クロブタン／カルボン酸の銀塩３．
５８ｇ （０，０ｆモル）を加え９０ ’Ｃで３時間撹
拌する。析出したチオ７アン酸銀を除去し、得られたろ
液を２０ｍ１まで減圧ｌ屑綿した後、室温で１時間撹拌
すると白色結晶状固体が析出する。生成した固体をろ敗
し、水洗後６０°Ｃで３時間減圧ド乾燥し、１．１−７
クロブタンノカルボキンラト（２−アミノメチルピロリ
ジン）プラチナム（ＩＩ）３．４ｆ３ｇ （収率７９％
）をｉする。Melting point: 166-169°C Elemental analysis: Molecular formula: C7H, □N4PtSz
Soonthio/anato(2-aminomethylpyrrolidine)platinum(II) synthesized in Example 1 4°12g (0,0
1 mole) was suspended in 400 ml of water, and the silver salt of 1, 1-/clobutane/carboxylic acid synthesized by a conventional method was added to the suspension.3.
Add 58 g (0.0 fmol) and stir at 90'C for 3 hours. The precipitated silver thio7anate was removed, and the resulting filtrate was filtered under reduced pressure to 20 ml, and then stirred at room temperature for 1 hour to precipitate a white crystalline solid. The generated solid was filtered, washed with water, and dried under reduced pressure at 60°C for 3 hours.
Clobutanenocarboquine lato(2-aminomethylpyrrolidine)platinum(II) 3.4f3g (yield 79%)
) to i.
融・４Ａ２４８〜２５７°Ｃ（分解）
ｎ−桝２゜
万施例１と同様にして参考例２で合成した（Ｒ）−７ス
一７千寸ノアナト（２−アミノメチルピロ□）／７・）
ブ′う壬ナム（ＩＩ）４．１２ｇ （０，０１モル）を
用いて（Ｒ）−１，１−／クロブタフッ勺ルボキンラト
（２−アミツメ千Ｊレビロリノン）プラチナム（ＩＩ）
３．５９ｇ （収・せ８２％）を得る。Melting/4A 248-257°C (decomposition) n-cells 20,000 (R)-7s synthesized in Reference Example 2 in the same manner as Example 1 Noanato (2-aminomethylpyro□)/7・)
Using 4.12 g (0.01 mol) of Butafujinam (II), (R)-1,1-/Kurobutafujirubokinato (2-Amitume 1,000 J Revirorinone) Platinum (II)
Obtain 3.59 g (82% yield).
夫■翌
実施例１と同様にして参考例３で合成した（Ｓ）−／ス
ー／チオ／アナト（２−丁ミツメチルピロリノン）プラ
チナム（Ｉｔ）４．１２ｇ （０，０１ビル）を用いて
（Ｓ）−１，１−／クロブタン／カルホキ／う１ （２
−アミンメチルピロリジン）プラチナム（ＩＩ）３．６
３ｇ （収率８３％）を得も。■Next day, in the same manner as in Example 1, using 4.12 g (0.01 bil) of (S)-/su/thio/anato(2-dimethylpyrrolinon)platinum (It) synthesized in Reference Example 3. (S)-1,1-/Clobutane/Kalhoki/U1 (2
-aminemethylpyrrolidine)platinum(II) 3.6
3 g (83% yield) was obtained.
ｉ！！壇褐祢果
以Ｉ−の様に本完明の製Ｏ方法は、優れた制癌剤の・シ
ソ造方法としてｆｌ−用であり、二〇Ｊ」′法を用いる
こ、とによりＬｌ的、とする制癌剤を短時間て効・ｔへ
良く１１することかできる。。i! ! As in Danganpeikai I-, the O production method of this Kanmei is for fl- as an excellent anticancer drug production method, and by using the 20J'' method, Ll-like and It is possible to improve the effectiveness of anticancer drugs in a short period of time. .
出 願 人 中外〃薬株式会社Applicant: Chugai Pharmaceutical Co., Ltd.
Claims (1)
ン）プラチナム（II）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
加え、０〜１００℃で反応させることを特徴とする。 式 ▲数式、化学式、表等があります▼ 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
。[Scope of Claims] 1) Cis-dithiocyanato(2-aminomethylpyrrolidine)platinum (II) or its optically active substance is suspended in water, and silver salt of 1,1-cyclobutanedicarboxylic acid is added thereto, It is characterized by being reacted at 100°C. A method for producing a platinum complex or its optically active substance represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7986086A JPS62238297A (en) | 1986-04-07 | 1986-04-07 | Production of platinum complex |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7986086A JPS62238297A (en) | 1986-04-07 | 1986-04-07 | Production of platinum complex |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62238297A true JPS62238297A (en) | 1987-10-19 |
Family
ID=13701953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7986086A Pending JPS62238297A (en) | 1986-04-07 | 1986-04-07 | Production of platinum complex |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62238297A (en) |
-
1986
- 1986-04-07 JP JP7986086A patent/JPS62238297A/en active Pending
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