JPH115786A - Novel aminohydroxypropylpiperazine derivative - Google Patents
Novel aminohydroxypropylpiperazine derivativeInfo
- Publication number
- JPH115786A JPH115786A JP9173239A JP17323997A JPH115786A JP H115786 A JPH115786 A JP H115786A JP 9173239 A JP9173239 A JP 9173239A JP 17323997 A JP17323997 A JP 17323997A JP H115786 A JPH115786 A JP H115786A
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- aminohydroxypropylpiperazine
- formula
- hydroxy
- 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
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は各種医薬品原薬の原
料として有用な、アミノヒドロキシプロピルピペラジン
誘導体又はそれらの塩に関する。TECHNICAL FIELD The present invention relates to an aminohydroxypropylpiperazine derivative or a salt thereof, which is useful as a raw material for various active pharmaceutical ingredients.
【０００２】[0002]
【従来の技術】アミノヒドロキシプロピルピペラジン構
造は、医薬の分野では薬効を発現させるに有益な部分構
造であり、例えば、ピペラジンのもう一方の窒素原子上
の水素原子が４，４−ビス（４−フルオロフェニル）ブ
チル基やビス（４−フルオロフェニル）メチル基に置換
した化合物は、ドーパミン再取込阻害作用やカルシウム
拮抗作用等を有することが知られているし、ジベンゾス
ベラニル基やジフェニルアセチル基で置換された化合物
は、多剤耐性癌に対して耐性を低下させ、薬剤に対する
感受性を回復せしめる作用を有することが知られてい
る。更に、この様な薬理的に有用なアミノヒドロキシプ
ロピルピペラジン構造に於いては、水酸基の結合した炭
素原子が不斉炭素となり、光学異性体を生じ光学異性体
によってその薬効が大きく異なる場合があることも既に
知られていることである。2. Description of the Related Art The aminohydroxypropylpiperazine structure is a partial structure useful for exhibiting a medicinal effect in the field of medicine. For example, a hydrogen atom on the other nitrogen atom of piperazine is 4,4-bis (4- Compounds substituted with a (fluorophenyl) butyl group or bis (4-fluorophenyl) methyl group are known to have a dopamine reuptake inhibitory action, a calcium antagonizing action, etc., and a dibenzosuberanyl group or a diphenylacetyl group. Compounds substituted with a group are known to have an effect of reducing resistance to multidrug-resistant cancer and restoring sensitivity to a drug. Further, in such a pharmacologically useful aminohydroxypropylpiperazine structure, the carbon atom bonded to the hydroxyl group becomes an asymmetric carbon, and an optical isomer is generated, and the medicinal effect may vary greatly depending on the optical isomer. Is also already known.
【０００３】この様な観点から、アミノヒドロキシプロ
ピルピペラジン構造を有する医薬品の立体構造を保持し
た種々の合成法が考案されてきた。例えば、予め置換ア
ミノヒドロキシプロピル基以外の部分を構築しておき、
これに光学活性な２，３−エポキシプロピルハライド又
はグリシジルトシレートを反応させ続いて置換アミン体
をを反応させる方法や、光学活性な置換アミノプロペン
オキシド類を開環付加させる方法などが開発され、光学
純度の高い化合物が得られるようになった。しかしなが
ら、時としてこの様な反応に於いては一部ラセミ化が起
こる場合があり、その様な場合には精製などを行って光
学純度を向上させなければならないことがあった。即
ち、立体保持に優れた、アミノヒドロキシプロピルピペ
ラジン構造を有する化合物の合成の手段が望まれてい
た。[0003] From such a viewpoint, various synthetic methods have been devised while maintaining the three-dimensional structure of a drug having an aminohydroxypropylpiperazine structure. For example, a part other than the substituted aminohydroxypropyl group is constructed in advance,
A method of reacting this with an optically active 2,3-epoxypropyl halide or glycidyl tosylate and subsequently reacting a substituted amine compound, a method of ring-opening addition of an optically active substituted aminopropene oxide, and the like have been developed. Compounds having high optical purity can be obtained. However, in some cases, racemization may occur in such a reaction, and in such a case, purification and the like must be performed to improve the optical purity. That is, a means for synthesizing a compound having an aminohydroxypropylpiperazine structure which is excellent in steric retention has been desired.
【０００４】[0004]
【発明が解決しようとする課題】本発明はかかる状況下
為されたものであり、立体保持に優れたアミノヒドロキ
シプロピルピペラジン構造を有する化合物の合成に有用
な中間体を提供することを課題とする。SUMMARY OF THE INVENTION The present invention has been made under such circumstances, and it is an object of the present invention to provide an intermediate useful for synthesizing a compound having an aminohydroxypropylpiperazine structure excellent in steric retention. .
【０００５】[0005]
【課題の解決手段】本発明者等はこの様な状況に鑑み
て、立体保持に優れたアミノヒドロキシプロピルピペラ
ジン構造を有する化合物の合成に有用な中間体を求めて
鋭意研究を重ねた結果、下記一般式（Ｉ）に示される化
合物又はそれらの塩がその様な性質を有していることを
見いだし発明を完成させるに至った。以下、本発明につ
いて発明の実施の形態を中心に詳細に説明する。In view of such circumstances, the present inventors have conducted intensive studies for an intermediate useful for synthesizing a compound having an aminohydroxypropylpiperazine structure excellent in steric retention. The inventors have found that the compound represented by the general formula (I) or a salt thereof has such properties and completed the invention. Hereinafter, the present invention will be described in detail focusing on embodiments of the invention.
【０００６】[0006]
【化２】 一般式（Ｉ） （但し式中Ｒ１は水素原子又は保護基を表し、Ｒ２、Ｒ
３はそれぞれ独立に水素原子、炭素数１〜４のアルキル
基又は置換基を有していても良い芳香族基を表す。）Embedded image Formula (I) (wherein R1 represents a hydrogen atom or a protecting group, and R2, R
3 independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or an aromatic group which may have a substituent. )
【０００７】[0007]
【発明の実施の形態】本発明の化合物は上記一般式
（Ｉ）に表される化合物からなる。ここでＲ１に表され
る基の内、保護基としては、アミノヒドロキシプロピル
基を導入する反応においては安定であって、酸などで容
易に脱離しうるものが好ましく、例えばこの様な基とし
てはトリフェニルメチル基、パラトルエンスルホニル
基、ジベンゾスベラニル基等が例示でき、これらの内で
はトリフェニルメチル基が特に好ましい。これらは対応
するクロリドを過剰のピペラジンに作用させることによ
って容易に得ることが出来る。即ち、片方の窒素原子に
保護基を導入したピペラジンをこの様に作成し、このも
のに置換アミノハロゲン化ヒドロキシプロパンをアルカ
リ存在下縮合させれば、一般式（Ｉ）に表される化合物
の内、Ｒ１が保護基である化合物を得ることが出来る。
ここで置換アミノ基としては置換基を有していても良い
フェニルアミノ基が好適に例示できる。勿論のこりのア
ミノ基の窒素原子上の水素原子を置換基で置換すること
も可能であり、このものも本発明の化合物である。かか
る置換基を有していても良いフェニル基以外のアミノ基
の置換基としてはアルキル基が例示でき、炭素数は１〜
４が好ましい。置換基を有していても良いフェニル基の
置換基としては、例えば炭素数１〜４のアルコキシル
基、炭素数１〜４のアルキル基、水酸基、カルボキシル
基、炭素数１〜４のアルキルオキシカルボニル基、ハロ
ゲン原子等が例示できる。置換基の数は０〜３が好まし
く、０〜２が更に好ましい。ここで導入する置換アミノ
ヒドロキシプロピル基は光学活性体であることが本発明
では好ましい。これはこの様に製造される本発明の一般
式（Ｉ）の化合物において、置換アミノハロゲン化ヒド
ロキシプロパンの立体が良く保持されて導入されるから
である。例えば、ラセミ体を導入すればそのまま立体が
保持されてラセミ体が得られ、光学活性体を導入すれ
ば、この光学活性が極めて良く保持されるためである。
かくして得られた、Ｒ１に保護基を有する一般式（Ｉ）
の化合物は例えば塩酸などの酸を作用させることによ
り、保護基を自由に外すことが出来る。塩としては通常
医薬で用いられているものであれば何れも使用が可能で
あり、例えば、硫酸、塩酸、燐酸、硝酸、炭酸、マレイ
ン酸、フマル酸、シュウ酸、クエン酸、メタンスルホン
酸、パラトルエンスルホン酸、ベンゼンスルホン酸等が
例示できる。これら一般式（Ｉ）に表される化合物及び
これらの塩は何れも文献未記載の新規化合物である。本
発明の化合物としては例えば、（Ｓ）−１−（２−ヒド
ロキシ−３−フェニルアミノプロピル）−４−トリフェ
ニルメチルピペラジン、（Ｒ）−１−（２−ヒドロキシ
−３−フェニルアミノプロピル）−４−トリフェニルメ
チルピペラジン、（Ｓ）−１−（２−ヒドロキシ−３−
フェニルアミノプロピル）ピペラジン、（Ｒ）−１−
（２−ヒドロキシ−３−フェニルアミノプロピル）ピペ
ラジンが挙げられる。BEST MODE FOR CARRYING OUT THE INVENTION The compound of the present invention comprises the compound represented by the above general formula (I). Here, among the groups represented by R1, the protecting group is preferably a group which is stable in a reaction for introducing an aminohydroxypropyl group and can be easily removed with an acid or the like. Examples thereof include a triphenylmethyl group, a paratoluenesulfonyl group, and a dibenzosuberanyl group. Of these, a triphenylmethyl group is particularly preferred. These can easily be obtained by reacting the corresponding chloride with excess piperazine. That is, piperazine having a protecting group introduced into one of the nitrogen atoms is prepared in this manner, and the resulting product is condensed with a substituted aminohalogenated hydroxypropane in the presence of an alkali to obtain a compound represented by the general formula (I). , R1 is a protecting group.
Here, as the substituted amino group, a phenylamino group which may have a substituent can be preferably exemplified. Of course, it is also possible to substitute a hydrogen atom on the nitrogen atom of the amino group with a substituent, which is also a compound of the present invention. Examples of the substituent of the amino group other than the phenyl group which may have such a substituent include an alkyl group, and have 1 to 1 carbon atoms.
4 is preferred. Examples of the substituent of the phenyl group which may have a substituent include an alkoxyl group having 1 to 4 carbon atoms, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a carboxyl group, and an alkyloxycarbonyl having 1 to 4 carbon atoms. And a halogen atom. The number of substituents is preferably from 0 to 3, and more preferably from 0 to 2. In the present invention, the substituted aminohydroxypropyl group introduced here is preferably an optically active substance. This is because in the thus-prepared compound of the general formula (I) of the present invention, the substituted aminohalogenated hydroxypropane is introduced with the steric configuration being kept well. For example, when a racemate is introduced, a three-dimensional structure is maintained as it is to obtain a racemate, and when an optically active form is introduced, this optical activity is extremely well maintained.
Formula (I) thus obtained having a protecting group at R1
The compound of formula (1) can be free of a protecting group by the action of an acid such as hydrochloric acid. Any salt can be used as long as it is commonly used in medicine, for example, sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid, carbonic acid, maleic acid, fumaric acid, oxalic acid, citric acid, methanesulfonic acid, Examples thereof include p-toluenesulfonic acid and benzenesulfonic acid. All of the compounds represented by the general formula (I) and salts thereof are novel compounds not described in any literature. Examples of the compound of the present invention include (S) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine, (R) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine, (S) -1- (2-hydroxy-3-
Phenylaminopropyl) piperazine, (R) -1-
(2-hydroxy-3-phenylaminopropyl) piperazine.
【０００８】[0008]
【実施例】以下に実施例を示して本発明について更に詳
細に説明を加えるが、本発明がこれら実施例にのみ限定
を受けないことは言うまでもない。The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited to these examples.
【０００９】実施例１ 下記反応式１に示す方法に従って（Ｓ）−１−（２−ヒ
ドロキシ−３−フェニルアミノプロピル）−４−トリフ
ェニルメチルピペラジンを合成した。即ち、（Ｓ）−Ｎ
−（３−クロロ−２−ヒドロキシプロピル）アニリン
２．４ｇ（１２．９３ｍｍｏｌ）、１−トリフェニルメ
チルピペラジン４．４６ｇ（１３．５８ｍｍｏｌ）炭酸
カリウム２．１６ｇ（１５．６３ｍｍｏｌ）、粉砕した
ヨウ化カリウム１．０８ｇ（６．５１ｍｍｏｌ）に乾燥
エタノール５０ｍｌを加え、窒素雰囲気下、室温で１９
１時間攪拌し、更に３時間攪拌しながら還流した。その
後、室温まで冷却し、０．５Ｎ−水酸化ナトリウム水溶
液１５０ｍｌ、ベンゼン６０ｍｌの系に注ぎ、分液し、
有機層を分離し、水層は更にベンゼンで抽出した（３０
ｍｌ×２）。全有機層は合わせて飽和食塩水５０ｍｌで
洗い、硫酸ナトリウム乾燥後、減圧下濃縮した。残渣を
シリカゲルカラムクロマトグラフィーに付し、目的フラ
クションを濃縮後、ベンゼン４０ｍｌに溶解し、０．５
Ｎ−水酸化ナトリウム水溶液８０ｍｌと共に振とうし有
機層を分離、水層は更にベンゼンで抽出した（２０ｍｌ
×２）。全有機層は合わせて飽和食塩水４０ｍｌで洗浄
後硫酸ナトリウムで乾燥させ、減圧濃縮した。残渣にエ
タノールを加え、結晶化させこれを濾取し、乾燥し
（Ｓ）−１−（２−ヒドロキシ−３−フェニルアミノプ
ロピル）−４−トリフェニルメチルピペラジン（化合物
１）を４．０４ｇ（収率６５．５％）得た。 ｍｐ．：１９８〜２００℃ ＩＲ（ＫＢｒ錠剤、ｃｍ-1）：３４０２、１６０２、１
５０４、１４４８、１００４、７４９、７１４、６９４1 Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：２．３５〜２．７０（８
Ｈ，ｍ）、２．７０〜２．９０（２Ｈ，ｍ）、２．９０
〜３．１０（１Ｈ，ｍ），３．１３〜３．２８（１Ｈ，
ｍ）、３．３５（１Ｈ，ｂｒｓ）、３．８２〜３．９６
（１Ｈ，ｍ）、４．０８（１Ｈ，ｂｒｓ）、６．６０
（２Ｈ，ｄ，Ｊ＝７．６Ｈｚ）、６．７０（１Ｈ，ｔ，
Ｊ＝７．４Ｈｚ）、７．１６（５Ｈ，ｔ，Ｊ＝８．０Ｈ
ｚ），７．２１〜７．３２（７Ｈ，ｍ）、７．３２〜
７．６０（５Ｈ，ｍ）Example 1 (S) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine was synthesized according to the method shown in the following reaction formula 1. That is, (S) -N
2.4 g (12.93 mmol) of-(3-chloro-2-hydroxypropyl) aniline, 4.46 g (13.58 mmol) of 1-triphenylmethylpiperazine 2.16 g (15.63 mmol) of potassium carbonate, pulverized iodide 50 ml of dry ethanol was added to 1.08 g (6.51 mmol) of potassium, and the mixture was added at room temperature under a nitrogen atmosphere at room temperature.
The mixture was stirred for 1 hour, and further refluxed with stirring for 3 hours. Thereafter, the mixture was cooled to room temperature, poured into a system of 150 ml of a 0.5N aqueous solution of sodium hydroxide and 60 ml of benzene, and separated.
The organic layer was separated and the aqueous layer was further extracted with benzene (30
ml × 2). All organic layers were combined, washed with 50 ml of saturated saline, dried over sodium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fraction was concentrated and then dissolved in 40 ml of benzene.
The organic layer was separated by shaking with 80 ml of an aqueous solution of N-sodium hydroxide, and the aqueous layer was further extracted with benzene (20 ml).
× 2). All organic layers were combined, washed with 40 ml of saturated saline, dried over sodium sulfate, and concentrated under reduced pressure. Ethanol was added to the residue to crystallize it, which was collected by filtration and dried, and 4.04 g of (S) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine (compound 1) ( Yield 65.5%). mp. : 198 to 200 ° C IR (KBr tablet, cm -1 ): 3402, 1602, 1
504, 1448, 1004, 749, 714, 694 1 H-NMR (CDCl 3 ) δ: 2.35 to 2.70 (8
H, m), 2.70 to 2.90 (2H, m), 2.90
To 3.10 (1H, m), 3.13 to 3.28 (1H,
m), 3.35 (1H, brs), 3.82 to 3.96
(1H, m), 4.08 (1H, brs), 6.60
(2H, d, J = 7.6 Hz), 6.70 (1H, t,
J = 7.4 Hz), 7.16 (5H, t, J = 8.0H)
z), 7.21-7.32 (7H, m), 7.32-
7.60 (5H, m)
【００１０】[0010]
【化３】 反応式１Embedded image Reaction formula 1
【００１１】実施例２ 下記反応式２に示す方法に従って（Ｓ）−１−（２−ヒ
ドロキシ−３−フェニルアミノプリピル）ピペラジン・
３塩酸塩を合成した。即ち、（Ｓ）−１−（２−ヒドロ
キシ−３−フェニルアミノプロピル）−４−トリフェニ
ルメチルピペラジン（化合物１）７ｇ（１４．６６ｍｍ
ｏｌ）をテトラヒドロフラン１４６ｍｌに溶解し、これ
を室温で攪拌しながら濃塩酸５．８ｍｌを加え、更に４
５分間攪拌した。その後反応液を減圧濃縮し、残渣にベ
ンゼン１００ｍｌを加え再び減圧濃縮した。残渣をジエ
チルエーテルで洗い、エタノール５０ｍｌ、メタノール
２５ｍｌを加え、更にジエチルエーテル２５０ｍｌを加
えて粉末とし、濾取しジエチルエーテルで洗い、乾燥さ
せて、（Ｓ）−１−（２−ヒドロキシ−３−フェニルア
ミノプロピル）ピペラジン・３塩酸塩（化合物２）を
５．００ｇ（収率９９％）得た。Example 2 According to the method shown in the following reaction scheme 2, (S) -1- (2-hydroxy-3-phenylaminopropyl) piperazine.
Trihydrochloride was synthesized. That is, 7 g of (S) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine (compound 1) (14.66 mm
ol) was dissolved in 146 ml of tetrahydrofuran, and 5.8 ml of concentrated hydrochloric acid was added thereto while stirring at room temperature.
Stir for 5 minutes. Thereafter, the reaction solution was concentrated under reduced pressure, 100 ml of benzene was added to the residue, and the mixture was again concentrated under reduced pressure. The residue was washed with diethyl ether, 50 ml of ethanol and 25 ml of methanol were added, and 250 ml of diethyl ether was further added to make a powder. The powder was collected by filtration, washed with diethyl ether, and dried to give (S) -1- (2-hydroxy-3- 5.00 g (99% yield) of phenylaminopropyl) piperazine trihydrochloride (compound 2) was obtained.
【００１２】[0012]
【化４】 反応式２Embedded image Reaction formula 2
【００１３】実施例３ 実施例１と同様に（Ｒ）−Ｎ−（３−クロロ−２−ヒド
ロキシプロピル）アニリン５．６７ｇ（３０．５４ｍｍ
ｏｌ）、１−トリフェニルメチルピペラジン１０．５３
ｇ（３２．０６ｍｍｏｌ）、炭酸カリウム５．１０ｇ
（３６．９０ｍｍｏｌ）、粉砕したヨウ化カリウム２．
５５ｇ（１５．３６ｍｍｏｌ）を処理し、（Ｒ）−１−
（２−ヒドロキシ−３−フェニルアミノプロピル）−４
−トリフェニルメチルピペラジン（化合物３）を１０．
６４ｇ（収率７２．９％）得た。旋光度より本発明の化
合物が立体保持性に優れていることが判る。 ｍｐ．：１９６〜１９７．５℃ ＩＲ（ＫＢｒ錠剤、ｃｍ-1）：３４０２、１６０１、１
５０４、１４４８、１００４、７４１、７１５、６９４1 Ｈ−ＮＭＲ（ＣＤＣｌ3）δ：２．３５〜２．７０（８
Ｈ，ｍ）、２．７０〜２．９０（２Ｈ，ｍ）、２．９０
〜３．１０（１Ｈ，ｍ），３．１３〜３．２８（１Ｈ，
ｍ）、３．３５（１Ｈ，ｂｒｓ）、３．８２〜３．９６
（１Ｈ，ｍ）、４．０８（１Ｈ，ｂｒｓ）、６．６０
（２Ｈ，ｄ，Ｊ＝７．６Ｈｚ）、６．７０（１Ｈ，ｔ，
Ｊ＝７．４Ｈｚ）、７．１６（５Ｈ，ｔ，Ｊ＝８．０Ｈ
ｚ），７．２１〜７．３２（７Ｈ，ｍ）、７．３２〜
７．６０（５Ｈ，ｍ） ［α］20 D：−９．７゜（Ｃ＝１．０、ＣＨＣｌ3）Example 3 As in Example 1, 5.67 g (30.54 mm) of (R) -N- (3-chloro-2-hydroxypropyl) aniline
ol), 1-triphenylmethylpiperazine 10.53
g (32.06 mmol), potassium carbonate 5.10 g
(36.90 mmol), ground potassium iodide.
55 g (15.36 mmol) were treated and (R) -1-
(2-hydroxy-3-phenylaminopropyl) -4
10. Triphenylmethylpiperazine (Compound 3).
64 g (72.9% yield) was obtained. The optical rotation shows that the compound of the present invention is excellent in steric retention. mp. : 196 to 197.5 ° C IR (KBr tablet, cm -1 ): 3402, 1601, 1
504, 1448, 1004, 741, 715, 694 1 H-NMR (CDCl 3 ) δ: 2.35 to 2.70 (8
H, m), 2.70 to 2.90 (2H, m), 2.90
To 3.10 (1H, m), 3.13 to 3.28 (1H,
m), 3.35 (1H, brs), 3.82 to 3.96
(1H, m), 4.08 (1H, brs), 6.60
(2H, d, J = 7.6 Hz), 6.70 (1H, t,
J = 7.4 Hz), 7.16 (5H, t, J = 8.0H)
z), 7.21-7.32 (7H, m), 7.32-
7.60 (5H, m) [α] 20 D : -9.7 ° (C = 1.0, CHCl 3 )
【００１４】実施例４ 実施例２と同様に、化合物３の７ｇ（１４．６６ｍｍｏ
ｌ）を処理して、（Ｒ）−１−（２−ヒドロキシ−３−
フェニルアミノプロピル）ピペラジン・３塩酸塩（化合
物４）を５．００ｇ（収率９９％）得た。Example 4 As in Example 2, 7 g of compound 3 (14.66 mmol)
1) to give (R) -1- (2-hydroxy-3-
5.00 g (99% yield) of (phenylaminopropyl) piperazine trihydrochloride (compound 4) was obtained.
【００１５】[0015]
【発明の効果】本発明によれば、立体保持に優れたアミ
ノヒドロキシプロピルピペラジン構造を有する化合物の
合成に有用な中間体を提供することができる。According to the present invention, an intermediate useful for synthesizing a compound having an aminohydroxypropylpiperazine structure excellent in steric retention can be provided.
フロントページの続き (72)発明者 柳 正行 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内 (72)発明者 山田 浩次 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内Continued on the front page (72) Inventor Masayuki Yanagi 560 Pola Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Prefecture Inside the Totsuka Laboratory Co., Ltd. In the laboratory
Claims (4)
ヒドロキシプロピルピペラジン誘導体又はそれらの塩。 【化１】 一般式（Ｉ） （但し式中Ｒ１は水素原子又は保護基を表し、Ｒ２、Ｒ
３はそれぞれ独立に水素原子、炭素数１〜４のアルキル
基又は置換基を有していても良い芳香族基を表す。）1. An aminohydroxypropylpiperazine derivative represented by the following general formula (I) or a salt thereof. Embedded image Formula (I) (wherein R1 represents a hydrogen atom or a protecting group, and R2, R
3 independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or an aromatic group which may have a substituent. )
芳香族基がフェニル基である、請求項１に記載のアミノ
ヒドロキシプロピルピペラジン誘導体又はそれらの塩。2. The protecting group is a triphenylmethyl group,
The aminohydroxypropyl piperazine derivative or a salt thereof according to claim 1, wherein the aromatic group is a phenyl group.
る、請求項１又は２に記載のアミノヒドロキシプロピル
ピペラジン誘導体又はそれらの塩。3. The aminohydroxypropyl piperazine derivative or a salt thereof according to claim 1, which is an optically active compound.
（Ｓ）−１−（２−ヒドロキシ−３−フェニルアミノプ
ロピル）−４−トリフェニルメチルピペラジン、（Ｒ）
−１−（２−ヒドロキシ−３−フェニルアミノプロピ
ル）−４−トリフェニルメチルピペラジン、（Ｓ）−１
−（２−ヒドロキシ−３−フェニルアミノプロピル）ピ
ペラジン、（Ｒ）−１−（２−ヒドロキシ−３−フェニ
ルアミノプロピル）ピペラジンの何れかである、請求項
１〜３何れか一項に記載のアミノヒドロキシプロピルピ
ペラジン誘導体又はそれらの塩。4. A compound represented by the general formula (I):
(S) -1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine, (R)
-1- (2-hydroxy-3-phenylaminopropyl) -4-triphenylmethylpiperazine, (S) -1
The method according to any one of claims 1 to 3, wherein the compound is any one of-(2-hydroxy-3-phenylaminopropyl) piperazine and (R) -1- (2-hydroxy-3-phenylaminopropyl) piperazine. Aminohydroxypropylpiperazine derivatives or salts thereof.
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|---|---|---|---|
| JP9173239A JPH115786A (en) | 1997-06-13 | 1997-06-13 | Novel aminohydroxypropylpiperazine derivative |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9173239A JPH115786A (en) | 1997-06-13 | 1997-06-13 | Novel aminohydroxypropylpiperazine derivative |
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| JPH115786A true JPH115786A (en) | 1999-01-12 |
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ID=15956744
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| JP9173239A Pending JPH115786A (en) | 1997-06-13 | 1997-06-13 | Novel aminohydroxypropylpiperazine derivative |
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