JPS5821625B2 - Aminothican phenyl ketone - Google Patents
Aminothican phenyl ketoneInfo
- Publication number
- JPS5821625B2 JPS5821625B2 JP48018645A JP1864573A JPS5821625B2 JP S5821625 B2 JPS5821625 B2 JP S5821625B2 JP 48018645 A JP48018645 A JP 48018645A JP 1864573 A JP1864573 A JP 1864573A JP S5821625 B2 JPS5821625 B2 JP S5821625B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- substituted
- aminothican
- phenyl ketone
- acid
- 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
Links
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Description
【発明の詳細な説明】
本発明は新規なフェニルケトン誘導体の製法に関するも
のであり、さらに詳しく述べるならば、一般式ＣＩ）
〔式中、Ｒはハロゲン原子を、Ａは低級アルキレン鎖を
、Ｚは一般式
（ただし式中、Ｒ１はハロゲン原子で置換されたフェニ
ル基またはトリフルオロメチル基で置換されたフェニル
基をあられす。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a novel phenylketone derivative, and more specifically, it relates to a method for producing a novel phenylketone derivative, and more specifically, it has the general formula CI) [wherein R represents a halogen atom, A represents a lower alkylene chain, and Z is a general formula (wherein R1 is a phenyl group substituted with a halogen atom or a phenyl group substituted with a trifluoromethyl group).
）で示される基をあられす。) Hail the group shown in ).
〕であられされる新規なアミン置換フェニルケトン誘導
体およびその酸付加塩の新規な製法である。] A novel method for producing a novel amine-substituted phenylketone derivative and its acid addition salt.
前記一般式〔■〕においてハロゲン原子とは、弗素、塩
素、臭素および沃素原子が含まれる。In the general formula [■], the halogen atom includes fluorine, chlorine, bromine and iodine atoms.
また一般式〔Ｉ〕においてＡであられされるアルキレン
鎖としては、メチレン、エチレン、プロピレン、テトラ
メチレン、１−メチルプロピレン、２−メチル−プロピ
レンなどがあげられる。Examples of the alkylene chain represented by A in general formula [I] include methylene, ethylene, propylene, tetramethylene, 1-methylpropylene, and 2-methyl-propylene.
本発明方法によって製造される前記一般式〔０であられ
されるアミン置換フェニルケトン誘導体は、新規化合物
であるばかりでなく種々の薬理学的に有用な作用を有し
ており、医薬として価値あるものである。The amine-substituted phenyl ketone derivative represented by the general formula [0] produced by the method of the present invention is not only a new compound but also has various pharmacologically useful actions and is valuable as a medicine. It is.
すなわち、これらの化合物は中枢神経作用、自律神経作
用、抗炎症作用などを有し、たとえば精神作用剤、神経
弛緩剤、鎮痛剤、消炎剤、鎮痙剤、鎮咳剤、降圧剤、ト
ランキライザーなどとしてきわめて有用に用いられる。In other words, these compounds have central nervous effects, autonomic nervous effects, anti-inflammatory effects, etc., and are extremely useful as psychoactive agents, neuroleptics, analgesics, anti-inflammatory agents, antispasmodics, antitussives, antihypertensive agents, tranquilizers, etc. used.
本発明はかかる有用な化合物を工業的に有利に製造する
方法を提供するものである。The present invention provides an industrially advantageous method for producing such useful compounds.
本発明の製法によれば前記一般式〔Ｉ〕であられされる
アミン置換フェニルケトン誘導体は一般式用〔式中、Ｒ
，ＡおよびＺは前述のとおりであり、ＸおよびＹは両者
が同時に水素原子をあられさないという条件下でそれぞ
れ水素原子、ベンジル基をあられす。According to the production method of the present invention, the amine-substituted phenylketone derivative represented by the general formula [I] can be used for the general formula [wherein R
, A and Z are as described above, and X and Y each produce a hydrogen atom and a benzyl group under the condition that both do not produce a hydrogen atom at the same time.
〕であられされる化合物を水素添加することによって製
造される。] It is produced by hydrogenating a compound prepared by:
なお、前記一般式世においてＸおよびＹがあられすベン
ジル基としては、無置換の、またはたとえばハロゲン原
子、低級アルキル基、低級アルコキシル基、アミン基、
アシルアミノ基、アルキルアミノ基、ジアルキルアミン
基などの中から選ばれる１〜５個の基によってベンゼン
環が任意に置換されたベンジル基を意味し、置換基の有
無は本発明方法には何ら妨げとならない。In addition, in the above general formula, the benzyl group represented by X and Y is an unsubstituted or, for example, a halogen atom, a lower alkyl group, a lower alkoxyl group, an amine group,
It refers to a benzyl group in which the benzene ring is optionally substituted with 1 to 5 groups selected from acylamino groups, alkylamino groups, dialkylamine groups, etc., and the presence or absence of substituents does not interfere with the method of the present invention. No.
本発明方法の水素添加反応は一般に適当な金属触媒の存
在下に溶媒を用いて行なうことが望ましく、触媒として
はたとえば種々の担体を用いて白金、パラジウム、ロジ
ウムなどの貴金属触媒やニッケル、亜クロム酸銅などが
、また溶媒としてはアルコール系溶媒（たとえばメタノ
ール、エタノール、ｎ−プロパツールなどがあげられる
。The hydrogenation reaction in the method of the present invention is generally preferably carried out in a solvent in the presence of a suitable metal catalyst, such as a noble metal catalyst such as platinum, palladium or rhodium, nickel or chromium submerged using a variety of carriers. Examples of the solvent include acidic copper, and alcoholic solvents (for example, methanol, ethanol, n-propanol, etc.).
）酢酸、プロピオン酸、水、酢酸エチル、無極性溶媒（
たとえばベンゼン、トルエン、キシレンなどがあげられ
る。) Acetic acid, propionic acid, water, ethyl acetate, nonpolar solvent (
Examples include benzene, toluene, and xylene.
）、あるいはこれらの混合溶媒系（たとえば水−アルコ
ール類、水−酢酸、トルエン−メタノールなどがあげら
れる。), or mixed solvent systems thereof (for example, water-alcohols, water-acetic acid, toluene-methanol, etc.).
）などが好適に用いられる。) etc. are preferably used.
この水素添加反応は通常、原料物質に対して数％ないし
数１０％（重量）までの触媒の存在下、比較的低温で一
般的には室温付近の温度、また低水素圧一般的には常圧
水素で容易に進行するが、必要に応じて加温あるいは水
素圧を上げることにより反応を促進することができる。This hydrogenation reaction is usually carried out in the presence of a catalyst ranging from several percent to several tens of percent (by weight) of the raw material, at relatively low temperatures, generally around room temperature, and at low hydrogen pressures. Although the reaction proceeds easily with hydrogen pressure, the reaction can be accelerated by heating or increasing the hydrogen pressure, if necessary.
また必要ならば適量の酸（たとえば塩酸、過塩素酸、硫
酸などの鉱酸、酢酸などの有機酸があげられる。If necessary, an appropriate amount of acid (for example, mineral acids such as hydrochloric acid, perchloric acid, and sulfuric acid, and organic acids such as acetic acid) may be used.
）を反応系に添加することにより反応を促進することも
できる。) can also be added to the reaction system to promote the reaction.
本発明方法は反応操作および後処理がきわめて簡便容易
である。In the method of the present invention, reaction operations and post-treatments are extremely simple and easy.
すなわち通常理論量もしくは少過剰の水素を吸収させた
後、反応混合物中より沢過により触媒を除去し、沢液を
縮合乾固するだけで目的生成物を得ることが可能である
。That is, the desired product can be obtained by simply absorbing a theoretical amount or a slight excess of hydrogen, removing the catalyst from the reaction mixture by filtration, and condensing the sap to dryness.
このようにして得られた生成物は、通常高純度でかつ高
収率である。The products thus obtained are usually of high purity and high yield.
このようにして得られた目的化合物は必要に応じて遊離
塩基形から酸付加塩に化学的常法を用いて変換すること
ができる。The target compound thus obtained can be converted from a free base form into an acid addition salt using conventional chemical methods, if necessary.
酸付加塩をつくる酸としては、薬理学的に許容される無
機あるいは有機の酸を用いることができる。As the acid for forming acid addition salts, pharmacologically acceptable inorganic or organic acids can be used.
本発明方法において出発原料として用いられる一般式用
であられされる化合物もまた新規物質であり、これらは
たとえば以下の一般反応式で示すような種々の方法で製
造することができる。The compounds of the general formula used as starting materials in the process of the invention are also new substances and can be prepared by various methods, for example as shown in the following general reaction scheme.
（ただし、 は−Ｃ〇−のオルトまたは バラ位を示す） （ただし、Ａはエチレンを示す。(however, is -C〇- ortho or (indicates rose position) (However, A represents ethylene.
）次に実施例をあげて本発明法をさらに詳しく説明する
が、本発明は何らこれらに限定されるものではない。) Next, the method of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.
実施例 １
１−（γ−（２−ベンジルアミノ−４−フルオロベンゾ
イル）フロビル〕−４−ｐ−クロロフェニル−４−ヒド
ロキシピペリジン３２、濃塩酸３ｍｌおよび１０％パラ
ジウム−炭素１．８７をエタノール７０ｗＬｌに混ぜ、
室温下水素添加した。Example 1 32 1-(γ-(2-benzylamino-4-fluorobenzoyl)furovir]-4-p-chlorophenyl-4-hydroxypiperidine, 3 ml of concentrated hydrochloric acid and 1.87 ml of 10% palladium-carbon were added to 70 wLl of ethanol. Mix,
Hydrogenation was carried out at room temperature.
約３時間後、水素の吸収が止んでからセライト？過し、
エタノールで洗浄した後、沢洗液を減圧濃縮し、得られ
た粗結晶をインフロパノールで再結晶すると１−〔γ−
（２−アミノ−４−フルオロベンゾイル）フロビル、ｌ
−４−ｐ−クロロフェニル−４−ヒドロキシピペリジン
塩酸塩の結晶が得られた。After about 3 hours, after hydrogen absorption has stopped, use Celite? passed,
After washing with ethanol, the washing liquid was concentrated under reduced pressure, and the obtained crude crystals were recrystallized with infropanol to give 1-[γ-
(2-amino-4-fluorobenzoyl)furovir, l
Crystals of -4-p-chlorophenyl-4-hydroxypiperidine hydrochloride were obtained.
融点２３６℃（分解）
実施例 ２
１−〔γ−（２−ベンジルアミノ−４−フルオロベンゾ
イル）プロピル〕−４−ｍ−）’）フルオロフェニル−
４−ヒドロキシピペリジン３？、濃塩酸３ｒＩｌｌおよ
び１０％パラジウム−炭素１．８７をエタノール７０ｒ
ｎｌに混ぜ、室温下水素添加した。Melting point 236°C (decomposition) Example 2 1-[γ-(2-benzylamino-4-fluorobenzoyl)propyl]-4-m-)')fluorophenyl-
4-Hydroxypiperidine 3? , 3 ml of concentrated hydrochloric acid and 1.87 ml of 10% palladium-carbon in 70 ml of ethanol.
nl and hydrogenated at room temperature.
実施例１と同様に後処理し、得られた粗塩酸塩をアンモ
ニア水で中和し、酢酸エチルで抽出した。The crude hydrochloride obtained by post-treatment in the same manner as in Example 1 was neutralized with aqueous ammonia and extracted with ethyl acetate.
この酢酸エチル溶液を減圧濃縮し、得られた粗結晶を含
水エタノールで再結晶すると１−（γ−；（２−アミノ
−４−フルオロベンゾイル）フロビル］−４−ｍ−）’
）フルオロメチルフェニル−４−ヒドロキシピペリジン
の結晶が得られた。This ethyl acetate solution was concentrated under reduced pressure, and the obtained crude crystals were recrystallized from aqueous ethanol.
) Crystals of fluoromethylphenyl-4-hydroxypiperidine were obtained.
融点１０５．５℃〜１０７℃Melting point 105.5℃~107℃
Claims (1)
原子をあられさないという条件下にそれぞれ水素原子、
ベンジル基を、Ａは低級アルキレン鎖を、Ｚは一般式 （ただし式中、Ｒ１は〕・ロゲン原子で置換されたフェ
ニル基またはトリフルオロメチル基で置換されたフェニ
ル基をあられす。 ）で示される基をあられす。 〕であられされる化合物あるいはその酸付加塩を水素添
加することを特徴とする一般式 〔式中、Ｒ，ＡおよびＺは前述のとおりである。 〕であられされるアミノ置換フェニルケトン誘導体およ
びその酸付加塩の製法。[Scope of Claims] 1 General formula [wherein, R represents a halogen atom, and X and Y represent a hydrogen atom, respectively, under the condition that no hydrogen atom is formed at the same time,
A benzyl group, A is a lower alkylene chain, and Z is a general formula (wherein, R1 is a phenyl group substituted with a rogen atom or a phenyl group substituted with a trifluoromethyl group). Hail the foundation that will be born. [In the formula, R, A and Z are as described above. ] A method for producing an amino-substituted phenylketone derivative and an acid addition salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP48018645A JPS5821625B2 (en) | 1973-02-14 | 1973-02-14 | Aminothican phenyl ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP48018645A JPS5821625B2 (en) | 1973-02-14 | 1973-02-14 | Aminothican phenyl ketone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS49102680A JPS49102680A (en) | 1974-09-27 |
| JPS5821625B2 true JPS5821625B2 (en) | 1983-05-02 |
Family
ID=11977334
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP48018645A Expired JPS5821625B2 (en) | 1973-02-14 | 1973-02-14 | Aminothican phenyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5821625B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63101638U (en) * | 1986-12-23 | 1988-07-01 |
-
1973
- 1973-02-14 JP JP48018645A patent/JPS5821625B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63101638U (en) * | 1986-12-23 | 1988-07-01 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS49102680A (en) | 1974-09-27 |
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