JPH047345B2 - - Google Patents
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- Publication number
- JPH047345B2 JPH047345B2 JP2407584A JP2407584A JPH047345B2 JP H047345 B2 JPH047345 B2 JP H047345B2 JP 2407584 A JP2407584 A JP 2407584A JP 2407584 A JP2407584 A JP 2407584A JP H047345 B2 JPH047345 B2 JP H047345B2
- Authority
- JP
- Japan
- Prior art keywords
- methoxyphenyl
- methanol
- acid
- reaction
- aminoethyl
- 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
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は式（）
で示されるフエニルピペラジン誘導体又はその塩
に関する。[Detailed Description of the Invention] The present invention is based on the formula () The present invention relates to a phenylpiperazine derivative or a salt thereof.
本発明の化合物（）は新規化合物であり、例
えば以下式示する方法により製造される。 The compound () of the present invention is a new compound, and is produced, for example, by the method shown in the formula below.
この反応式において化合物（）から本発明の
化合物（）を得る段階で反応は不活性溶媒中、
トリエチルアミン等の塩基の存在下クロル炭酸エ
チルを反応せしめることにより行なわれる。 In this reaction formula, the reaction is carried out in an inert solvent at the stage of obtaining the compound () of the present invention from the compound ().
This is carried out by reacting ethyl chlorocarbonate in the presence of a base such as triethylamine.
反応混合物から本発明の化合物（）の単離は
常法により、例えば反応液を中和後、抽出、カラ
ムクロマトグラフイー等の手段に付すことにより
行なわれる。 The compound () of the present invention is isolated from the reaction mixture by a conventional method, for example, by neutralizing the reaction solution and subjecting it to extraction, column chromatography, or other means.
本発明の化合物（）は有機酸または無機酸と
塩を形成する。酸としては薬学的に許容されるも
のであり、例えば塩酸、硫酸、硝酸、リン酸等の
有機酸およびフマール酸、マレイン酸、酒石酸、
コハク酸等の有機酸である。 The compounds () of the present invention form salts with organic or inorganic acids. Acids are pharmaceutically acceptable, such as organic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, fumaric acid, maleic acid, tartaric acid,
Organic acids such as succinic acid.
このようにして製造した本発明の化合物は循環
器疾患、特に脳における循環器疾患の治療剤とし
て有用である。 The compounds of the present invention produced in this manner are useful as therapeutic agents for cardiovascular diseases, particularly those in the brain.
実施例
ａ） １−（２−メトキシフエニル）−４−（２−
アミノエチル）ピペラジン塩酸塩3.445ｇを重
炭酸ナトリウム4.03ｇを含む水溶液50mlに溶解
し氷冷下撹拌する。次にアセチルサリチル酸ク
ロライド2.38ｇを加え20〜30分間撹拌し、続い
て室温で更に30分間撹拌する。反応後酢酸エチ
ルを加え抽出し、有機層を水、飽和食塩水で洗
浄の後、無水硫酸ナトリウムで乾燥し減圧下濃
縮する。残渣をシリカゲルカラムクロマトグラ
フイー（溶媒クロロホルム：メタノール＝30：
１）に付し1.985ｇの１−（２−メトキシフエニ
ル）−４−〔２−（２−アセトキシベンゾイル）
アミノエチル〕ピペラジンを得る。融点122℃
（ベンゼン−ｎ−ヘキサンより再結晶）。Example a) 1-(2-methoxyphenyl)-4-(2-
3.445 g of (aminoethyl)piperazine hydrochloride is dissolved in 50 ml of an aqueous solution containing 4.03 g of sodium bicarbonate and stirred under ice cooling. Next, 2.38 g of acetylsalicylic acid chloride is added and stirred for 20 to 30 minutes, followed by further stirring for 30 minutes at room temperature. After the reaction, ethyl acetate is added for extraction, and the organic layer is washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (solvent: chloroform: methanol = 30:
1.985g of 1-(2-methoxyphenyl)-4-[2-(2-acetoxybenzoyl)]
Aminoethyl]piperazine is obtained. Melting point 122℃
(Recrystallized from benzene-n-hexane).
ｂ） 前記ａ）で得られた１−（２−メトキシフ
エニル）−４−〔２−（２−アセトキシベンゾイ
ル）アミノエチル〕ピペラジン3.97ｇをメタノ
ール25mlに懸濁し次いで苛性ソーダ0.45ｇを含
む水25mlを加え室温で20〜30分間撹拌する。反
応後メタノールを減圧下濃縮し、1N−塩酸水
で中和しクロロホルム抽出する。クロロホルム
層を無水硫酸ナトリウムで乾燥の後、減圧下溶
媒を留去し得られた残渣をカラムクロマトグラ
フイー（溶媒クロロホルム：メタノール＝30：
１）に付し2.1ｇの１−（２−メトキシフエニ
ル）−４−〔２−（２−ハイドロキシベンゾイル）
アミノエチル〕ピペラジン2.1ｇを油状物とし
て得る。この油状物にメタノールを加え塩化水
素ガスを吹込み溶媒を濃縮すると１−（２−メ
トキシフエニル）−４−〔２−（２−ハイドロキ
シベンゾイル）アミノエチル〕ピペラジン塩酸
塩を得る。融点200〜202℃（メタノール−イソ
プロパノールより再結晶）。b) Suspend 3.97 g of 1-(2-methoxyphenyl)-4-[2-(2-acetoxybenzoyl)aminoethyl]piperazine obtained in step a) in 25 ml of methanol, then add 25 ml of water containing 0.45 g of caustic soda. Add and stir at room temperature for 20 to 30 minutes. After the reaction, methanol is concentrated under reduced pressure, neutralized with 1N hydrochloric acid, and extracted with chloroform. After drying the chloroform layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the resulting residue was subjected to column chromatography (solvent: chloroform: methanol = 30:
2.1 g of 1-(2-methoxyphenyl)-4-[2-(2-hydroxybenzoyl)]
2.1 g of aminoethyl]piperazine are obtained as an oil. Methanol is added to this oil, hydrogen chloride gas is blown in and the solvent is concentrated to obtain 1-(2-methoxyphenyl)-4-[2-(2-hydroxybenzoyl)aminoethyl]piperazine hydrochloride. Melting point: 200-202°C (recrystallized from methanol-isopropanol).
元素分析値 C20H25N3O3・2HClとして
Ｃ Ｈ Ｎ
計算値(%) 56.08 6.35 9.81
実測値(%) 56.33 6.45 9.54
ｃ） 前記ｂ）で得られた１−（２−メトキシフ
エニル）−４−〔２−（２−ハイドロキシベンゾ
イル）アミノエチル〕ピペラジンの油状物3.55
ｇにトリエチルアミン1.1ｇとトルエン100mlを
加え撹拌下クロル炭酸エチル1.194ｇを少しづ
つ加え続いて３時間還流する。反応後重炭酸ナ
トリウム水溶液で中和し、水洗した後、有機層
を無水硫酸ナトリウムで乾燥後減圧下濃縮す
る。得られた残渣をシリカゲルカラムクロマト
グラフイー（溶媒クロロホルム：メタノール＝
30：１）に付し得られた溶出液を濃縮し、少量
のイソプロパノールを加えると３−〔２−〔４−
（２−メトキシフエニル）−１−ピペラジニル〕
エチル〕−１，３（3H）ベンズオキサジン−２，
４−ジオンを1.9ｇを得る。融点124.5℃（イソ
プロパノールより再結晶）。Elemental analysis value C 20 H 25 N 3 O 3・2HCl C H N Calculated value (%) 56.08 6.35 9.81 Actual value (%) 56.33 6.45 9.54 c) 1-(2-methoxyphenyl obtained in b) above )-4-[2-(2-hydroxybenzoyl)aminoethyl]piperazine oil 3.55
1.1 g of triethylamine and 100 ml of toluene were added to the mixture, and while stirring, 1.194 g of ethyl chlorocarbonate was added little by little, followed by refluxing for 3 hours. After the reaction, the mixture was neutralized with an aqueous sodium bicarbonate solution and washed with water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (solvent chloroform: methanol =
30:1), the eluate obtained was concentrated, and a small amount of isopropanol was added to give 3-[2-[4-
(2-methoxyphenyl)-1-piperazinyl]
ethyl]-1,3(3H)benzoxazine-2,
Obtain 1.9 g of 4-dione. Melting point: 124.5℃ (recrystallized from isopropanol).
元素分析値 C21H23N3O4として
Ｃ Ｈ Ｎ
計算値(%) 66.13 6.08 11.02
実測値(%) 65.82 6.04 10.90
ｄ） 前記ｃ）で得られた３−〔２−〔４−（２−
メトキシフエニル）−１−ピペラジニルエチル〕
−１，３（3H）ベンズオキサジン−２，４−ジ
オンをメタノールに溶解し冷却下塩化水素ガス
を吹込み減圧下濃縮すると３−〔２−〔４−（２
−メトキシフエニル）−１−ピペラジニル〕エ
チル〕−１，３（3H）ベンズオキサジン−２，
４−ジオンの塩酸塩を得る。融点220.1℃（分
解）。Elemental analysis value C 21 H 23 N 3 O 4 C H N Calculated value (%) 66.13 6.08 11.02 Actual value (%) 65.82 6.04 10.90 d) 3-[2-[4-(2) obtained in c) above −
methoxyphenyl)-1-piperazinylethyl]
3-[2-[4-(2
-methoxyphenyl)-1-piperazinyl]ethyl]-1,3(3H)benzoxazine-2,
4-dione hydrochloride is obtained. Melting point: 220.1℃ (decomposition).
Claims (1)
塩。[Claims] 1 formula A phenylpiperazine derivative or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2407584A JPS60169470A (en) | 1984-02-10 | 1984-02-10 | Novel phenylpiperazine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2407584A JPS60169470A (en) | 1984-02-10 | 1984-02-10 | Novel phenylpiperazine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60169470A JPS60169470A (en) | 1985-09-02 |
| JPH047345B2 true JPH047345B2 (en) | 1992-02-10 |
Family
ID=12128299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2407584A Granted JPS60169470A (en) | 1984-02-10 | 1984-02-10 | Novel phenylpiperazine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60169470A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2807577B2 (en) * | 1990-06-15 | 1998-10-08 | エーザイ株式会社 | Cyclic amide derivative |
-
1984
- 1984-02-10 JP JP2407584A patent/JPS60169470A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60169470A (en) | 1985-09-02 |
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