JP2918899B2 - Method for producing cyclic imide derivative - Google Patents
Method for producing cyclic imide derivativeInfo
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- JP2918899B2 JP2918899B2 JP1056583A JP5658389A JP2918899B2 JP 2918899 B2 JP2918899 B2 JP 2918899B2 JP 1056583 A JP1056583 A JP 1056583A JP 5658389 A JP5658389 A JP 5658389A JP 2918899 B2 JP2918899 B2 JP 2918899B2
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- group
- general formula
- represented
- cyclic imide
- formula
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- 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
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、環状イミド誘導体またはその酸付加塩の新
規な製造方法に関する。Description: TECHNICAL FIELD The present invention relates to a novel method for producing a cyclic imide derivative or an acid addition salt thereof.
一般式〔Ｉ〕 〔式中、 で示される基を表わし、Ｒは、置換又は無置換のフェニ
ル基、置換又は無置換の２−ピリジル基、置換又は無置
換の２−ピリミジル基、置換又は無置換の1,2−ベンゾ
−３−イソチアゾリル基を表わし、前記の置換基は、ハ
ロゲン原子、炭素数１から４のアルコキシ基またはシア
ノ基を表わす。〕 で表わされる本発明目的化合物は抗精神病作用あるいは
抗不安作用を有し、医薬として有用であることが知られ
ている。General formula [I] (In the formula, Wherein R is a substituted or unsubstituted phenyl group, a substituted or unsubstituted 2-pyridyl group, a substituted or unsubstituted 2-pyrimidyl group, a substituted or unsubstituted 1,2-benzo-3 Represents an isothiazolyl group, and the substituent represents a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. The compound of the present invention has an antipsychotic or anxiolytic effect and is known to be useful as a medicament.
例えば、これら化合物群は特開昭58−126865号、特開
昭58−38277号、特開昭58−110576号、特開昭59−14878
0号、特開昭62−123179号及びJ.Med.Chem.,26,194（198
3）などに記載されており、その製造方法も各種の合成
経路が知られていた。For example, these compounds are described in JP-A-58-126865, JP-A-58-38277, JP-A-58-110576, and JP-A-59-14878.
No. 0, JP-A-62-123179 and J. Med. Chem., 26 , 194 (198
3) and the like, and various synthetic routes have been known for the production method.
特に、一般式〔II〕で表わされる化合物を用いた本発
明目的化合物〔Ｉ〕の製造については、以下に示す反応
経路による製造方法がより簡便なものであるとされてい
た（特開昭60−87262号）。In particular, for the production of the target compound [I] of the present invention using the compound represented by the general formula [II], the production method according to the following reaction route was considered to be simpler (Japanese Patent Application Laid-Open No. -87262).
〔式中、ＡおよびＲは前述と同じ意味を表す。〕 即ち、一般式〔II〕で表わされるイミド化合物と１、
４ジブロムブタン〔III〕とを縮合させ、一般式〔IV〕
で表わされる化合物へ導き、これを単離後、一般式〔I
V〕で表わされるアミン誘導体と縮合させることによ
り、目的とする化合物〔Ｉ〕を得る方法である。 [Wherein A and R represent the same meaning as described above. That is, the imide compound represented by the general formula [II] and 1,
4 Dibromobutane [III] is condensed to give the general formula [IV]
, And after isolating it, the compound represented by the general formula (I
This is a method of obtaining the desired compound [I] by condensation with the amine derivative represented by V].
従来の製法においては、例えば前述の化合物〔II〕と
１、４−ジブロムブタン〔III〕との反応において、化
合物〔II〕に対して化合物〔III〕を等モル使用した場
合は副成物である２量体〔VI〕 〔式中、Ａは前述と同じ意味を表わす。〕 が、大量に副成した（収率30％以上）。In the conventional production method, for example, in the reaction between the compound [II] and 1,4-dibromobutane [III], when the compound [III] is used in an equimolar amount to the compound [II], it is a by-product. Dimer [VI] [Wherein, A represents the same meaning as described above. Was produced in large quantities (yield 30% or more).
この副成物の生成を避ける為に、１、４−ジブロムブ
タン〔III〕を化合物〔II〕に対して大過剰（５倍モル
量以上）用いる必要があった。In order to avoid the formation of this by-product, it was necessary to use 1,4-dibromobutane [III] in a large excess (at least 5 times the molar amount) with respect to compound [II].
しかしながら、１、４−ジブロムブタン〔III〕の大
過剰量の使用は、生成物〔IV〕の単離を難しくしてい
た。即ち、１、４−ジブロムブタン〔III〕は、高沸点
（bp63−65℃/6mmHg）である為、大過剰に使用すると、
化合物〔III〕の留去には高温での減圧蒸留が必要であ
り、生成物〔IV〕の単離精製が問題となっていた。However, the use of a large excess of 1,4-dibromobutane [III] made it difficult to isolate the product [IV]. That is, 1,4-dibromobutane [III] has a high boiling point (bp 63-65 ° C./6 mmHg).
Distillation of the compound [III] requires vacuum distillation at a high temperature, and the isolation and purification of the product [IV] has been a problem.
上記の課題を解決すべく鋭意検討を重ねた結果、相間
移動触媒存在下に水−有機溶媒の二相系で反応を行い、
化合物〔III〕の代わりに、１−ブロモ−４−クロロブ
タンを用いることにより、収率よく、効率的に目的物を
製造する新規な合成法を見出し、本発明を完成するに至
った。As a result of intensive studies to solve the above problems, the reaction was carried out in a water-organic solvent two-phase system in the presence of a phase transfer catalyst
By using 1-bromo-4-chlorobutane instead of the compound [III], a novel synthesis method for efficiently producing the desired product was found in good yield, and the present invention was completed.
さらに詳しく説明すると、本発明は一般式〔II〕 〔式中、Ａは前述と同じ意味を表す。〕で表わされる化
合物を、相関移動触媒として一般式〔VII〕 Q+X- 〔VII〕 〔式中、X-はハロゲンイオン、ヒドロキシイオンまたは
硫酸水素イオンを表わし、Q+は一般式〔VIII〕 R1R2R3R4W+ 〔VIII〕 （式中、R1,R2,R3およびR4はそれぞれ、炭素数が１から
20よりなる直鎖又は分枝状のアルキル基を表わし、Ｗは
窒素原子またはリン原子を表す。）で示される基を表わ
す。〕 で表わされる４級オニウム塩および塩基の存在下に、２
相系の反応溶媒中で１−ブロム−４−クロロブタンと反
応させ、生成物を単離することなし、同じ反応系内に、
一般式〔Ｖ〕 〔式中、Ｒは前述と同じ意味を表わす。〕 で表わされる化合物を加えて、反応させることを特徴と
する 一般式〔Ｉ〕 〔式中、ＡおよびＲは前述と同じ意味を表わす。〕 で表わされる環状イミド誘導体またはそれらの酸付加塩
の製造方法に関するものである。More specifically, the present invention provides a compound represented by the general formula (II): [Wherein, A represents the same meaning as described above. The compound represented by] the general formula as a phase transfer catalyst (VII) Q + X - (VII) wherein, X - represents a halogen ion, hydroxy ion or hydrogen sulfate ion, Q + is the general formula [VIII] R 1 R 2 R 3 R 4 W + [VIII] (wherein R 1 , R 2 , R 3 and R 4 each have 1 to 4 carbon atoms)
Represents a linear or branched alkyl group consisting of 20; W represents a nitrogen atom or a phosphorus atom; ). In the presence of a quaternary onium salt represented by the formula
Reaction with 1-bromo-4-chlorobutane in a phase system reaction solvent, without isolating the product, in the same reaction system,
General formula [V] [Wherein, R represents the same meaning as described above. And reacting the compound represented by the general formula [I] Wherein A and R have the same meanings as described above. And a method for producing the cyclic imide derivative or an acid addition salt thereof.
本発明の方法によれば、化合物〔II〕に対して、等モ
ル量あるいは、やや過剰量の１−ブロム−４−クロロブ
タンを使用するだけで、問題となる二重体〔VI〕の副生
を５％以下に抑制でき、目的物である環状イミド誘導体
〔Ｉ〕を95％以上の高収率で得ることができる。According to the method of the present invention, by using an equimolar amount or a slightly excessive amount of 1-bromo-4-chlorobutane with respect to the compound [II], the by-product of the problematic dimer [VI] can be produced. Thus, the target cyclic imide derivative [I] can be obtained in a high yield of 95% or more.
すなわち、前記一般式〔IV〕の単離精製操作は、全く
不要となり、引き続き同一反応系内に、単に一般式
〔Ｖ〕の化合物を加えて加熱するだけで反応が進行し、
目的とする一般式〔Ｉ〕の環状イミド誘導体が高収率で
生成する。このように本発明方法は、実質的に一段階で
一般式〔II〕の化合物から最終目的化合物である〔Ｉ〕
の環状イミド誘導体を合成できる、新規かつ有用な製造
方法である。That is, the isolation and purification operation of the general formula [IV] is completely unnecessary, and the reaction proceeds by simply adding the compound of the general formula [V] and heating in the same reaction system.
The desired cyclic imide derivative of the general formula [I] is produced in high yield. As described above, the method of the present invention substantially converts the compound of the general formula [II] into the final target compound [I] in one step.
Is a novel and useful production method capable of synthesizing a cyclic imide derivative of
本発明方法において、用いられる反応溶媒としては、
水と共に、疎水性有機溶媒が用いられる。疎水性有機溶
媒としては、例えば、ベンゼン、トルエン、キシレン等
の芳香族炭化水素系溶媒、例えば、ｎ−ヘキサン,n−ペ
ンタン等の脂肪族炭化水素系溶媒等が挙げられ、これら
の混合溶媒を用いることもできる。好ましくは、ベンゼ
ン、トルエン、キシレン等の芳香族炭化水素系溶媒を挙
げることができる。In the method of the present invention, the reaction solvent used includes:
Along with water, a hydrophobic organic solvent is used. Examples of the hydrophobic organic solvent include, for example, aromatic hydrocarbon solvents such as benzene, toluene, and xylene, for example, n-hexane, aliphatic hydrocarbon solvents such as n-pentane, and the like. It can also be used. Preferably, aromatic hydrocarbon solvents such as benzene, toluene and xylene can be mentioned.
相関移動触媒としては、例えば、フッ化テトラ−ｎ−
ブチルアンモニウム、塩化テトラ−ｎ−ブチルアンモニ
ウム、臭化テトラ−ｎ−ブチルアンモニウム、ヨウ化テ
トラ−ｎ−ブチルアンモニウム、硫酸水素テトラ−ｎ−
ブチルアンモニウム、水酸化テトラ−ｎ−ブチルアンモ
ニウム等の４級アンモニウム塩、臭化ヘキサデシルトリ
ブチルホスホニウム等の４級ホスホニウム塩が挙げられ
るが、特に好ましいものとしては硫酸水素テトラ−ｎ−
ブチルアンモニウム等が挙げられる。As the phase transfer catalyst, for example, tetra-n-fluoride
Butyl ammonium, tetra-n-butyl ammonium chloride, tetra-n-butyl ammonium bromide, tetra-n-butyl ammonium iodide, tetra-n-hydrogen sulfate
Examples thereof include quaternary ammonium salts such as butylammonium and tetra-n-butylammonium hydroxide, and quaternary phosphonium salts such as hexadecyltributylphosphonium bromide. Particularly preferred are tetra-n-hydrogen sulfate.
Butylammonium and the like.
塩基としては、例えば、水酸化ナトリウム、炭酸ナト
リウム、炭酸カリウム、重炭酸ナトリウム等のアルカリ
金属塩、例えば水酸化カルシウム、等のアルカリ土類金
属塩を挙げることができる。好ましいものとしては、例
えば、炭酸ナトリウム、重炭酸ナトリウム等のアルカリ
金属の炭酸塩、重炭酸塩を挙げることができる。Examples of the base include alkali metal salts such as sodium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate, and alkaline earth metal salts such as calcium hydroxide. Preferred examples include carbonates and bicarbonates of alkali metals such as sodium carbonate and sodium bicarbonate.
反応は、一般的には反応温度を上昇又は降下させるこ
とにより、反応を促進又は抑制させることができるが、
反応温度としては、室温ないしは、溶媒の沸点で実施す
ることが好ましい。In general, the reaction can be promoted or suppressed by increasing or decreasing the reaction temperature.
The reaction is preferably carried out at room temperature or at the boiling point of the solvent.
さらに、本発明方法においては、塩基に加えて、反応
助剤として例えば、ヨウ化カリウム、ヨウ化ナトリウム
等のアルカリ金属のヨウ素酸塩を用いてもよい。Further, in the method of the present invention, for example, an alkali metal iodate such as potassium iodide or sodium iodide may be used as a reaction aid in addition to the base.
反応後、反応液の有機層を分液し、溶媒を留去するこ
とにより、目的とする環状イミド誘導体〔Ｉ〕を通常の
有機化学的手法により、高い収率で単離することができ
る。After the reaction, the organic layer of the reaction solution is separated, and the solvent is distilled off, whereby the target cyclic imide derivative [I] can be isolated in a high yield by a usual organic chemistry technique.
さらに環状イミド誘導体〔Ｉ〕は、所望に応じて、各
種の無機酸又は有機酸、例えば、塩酸，蓚酸，クエン
酸，リンゴ酸，酒石酸，フマール酸，マレイン酸等と酸
付加塩を形成することができる。Further, the cyclic imide derivative [I] may form an acid addition salt with various inorganic or organic acids, for example, hydrochloric acid, oxalic acid, citric acid, malic acid, tartaric acid, fumaric acid, maleic acid and the like, if desired. Can be.
次に実施例をあげて、本発明を詳細に説明するが、本
発明はこの実施例に限定されものではない。Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
実施例１ 水117kg,トルエン29.3kgにビシクロ〔2,2,1〕ヘプタ
ン−2,3−ジ−エキソ−カルボキシイミド19.5kg,無水炭
酸カリウム24.48kg,硫酸水素テトラ−ｎ−ブチルアンモ
ニウム4.01kg,1−ブロモ−４−クロロブタン26.31kgを
加え、60〜70℃を保ちながら、２時間撹拌した。反応液
を冷却し、１−（２−ピリミジル）ピペラジン27.14kg,
ヨウ化カリウム19.6kg,無水炭酸カリウム8.16kgを加
え、加熱還流下、５時間撹拌した。反応液にトルエン13
6.5kgを注入し、70℃で分液し、有機相をpH6.75のリン
酸緩衝液117kgで３回、水117kgで１回洗浄した。無水硫
酸マグネシウム9.75kg,活性炭0.8kgを加え、30分間撹拌
後、濾過し、トルエン32.5kgで洗浄した。得られたトル
エン溶液を、クエン酸−水和物25.04kg,イソプロピルア
ルコール163.13kgよりなる溶液に滴下し、生成した結晶
を濾取、乾燥したところ61.4kgのヘキサヒドロ−２−
〔４−｛４−（２−ピリミジニル）−１−ピペラジニ
ル｝ブチル〕−4,7−メタノ−1H−イソインドール−1,3
（2H）−ジオン（クエン酸塩）を得た。収率90.5％融点
174−175℃ 実施例２ 水110kg,トルエン27.2kgにシクロヘキサン−1,2−ジ
−カルボキシイミド16.9kg無水炭酸カリウム22.9kg,硫
酸水素テトラ−ｎ−ブチルアンモニウム3.8kg,1−ブロ
モ−４−クロロブタン20.9kgを加え、60−65℃に保ちな
がら、２時間撹拌した。反応液を冷却し、３−（１−ピ
ペラジニル）−1,2−ベンズイソチアゾール25.4kgヨウ
化カリウム18.3kg、無水炭酸カリウム7.6kgを加え加熱
還流下５時間撹拌した。反応液にトルエン102kgを注入
し、70−80℃で分液し、水110kgで２回洗浄を行った。
トルエン層へ無水硫酸マグネシウム3.2kgを加え、40分
間撹拌後、濾過し、トルエン25kgで洗浄した。得られた
トルエン溶液を減圧下、濃縮を行い、残渣へイソプロピ
ルアルコール283kgを加え60℃まで加熱し、冷却後、生
成した結晶を濾取した。イソプロピルアルコール47kgで
洗浄後、得られた結晶を乾燥し、シス−２−〔４−〔４
−（1,2−ベンズイソチアゾール−３−イル）−１−ピ
ペラジニル〕ブチル〕ヘキサヒドロ−1H−イソインドー
ル−1,3（2H）ジオン35.4kgを得た。収率75.3％、融点5
3−56℃Example 1 Bicyclo [2,2,1] heptane-2,3-di-exo-carboximide 19.5 kg in water 117 kg, toluene 29.3 kg, anhydrous potassium carbonate 24.48 kg, tetra-n-butylammonium hydrogen sulfate 4.01 kg, 26.31 kg of 1-bromo-4-chlorobutane was added, and the mixture was stirred for 2 hours while maintaining the temperature at 60 to 70 ° C. The reaction solution was cooled and 1- (2-pyrimidyl) piperazine 27.14 kg,
19.6 kg of potassium iodide and 8.16 kg of anhydrous potassium carbonate were added, and the mixture was stirred with heating under reflux for 5 hours. Toluene 13 in the reaction solution
6.5 kg was injected, the mixture was separated at 70 ° C., and the organic phase was washed three times with 117 kg of a pH 6.75 phosphate buffer and once with 117 kg of water. After adding 9.75 kg of anhydrous magnesium sulfate and 0.8 kg of activated carbon, the mixture was stirred for 30 minutes, filtered, and washed with 32.5 kg of toluene. The resulting toluene solution was added dropwise to a solution consisting of 25.04 kg of citric acid-hydrate and 163.13 kg of isopropyl alcohol, and the resulting crystals were collected by filtration and dried to give 61.4 kg of hexahydro-2-.
[4- {4- (2-pyrimidinyl) -1-piperazinyl} butyl] -4,7-methano-1H-isoindole-1,3
(2H) -dione (citrate) was obtained. 90.5% melting point
174-175 ° C Example 2 110 kg of water, 27.2 kg of toluene, 16.9 kg of cyclohexane-1,2-di-carboximide 22.9 kg of anhydrous potassium carbonate, 3.8 kg of tetra-n-butylammonium hydrogen sulfate, 1 kg of 1-bromo-4-chlorobutane 20.9 kg was added, and the mixture was stirred for 2 hours while maintaining at 60-65 ° C. The reaction solution was cooled, 3- (1-piperazinyl) -1,2-benzisothiazole (25.4 kg), potassium iodide (18.3 kg) and anhydrous potassium carbonate (7.6 kg) were added, and the mixture was stirred under reflux with heating for 5 hours. 102 kg of toluene was poured into the reaction solution, liquid separation was performed at 70 to 80 ° C., and washing was performed twice with 110 kg of water.
3.2 kg of anhydrous magnesium sulfate was added to the toluene layer, stirred for 40 minutes, filtered, and washed with 25 kg of toluene. The obtained toluene solution was concentrated under reduced pressure, 283 kg of isopropyl alcohol was added to the residue, and the mixture was heated to 60 ° C. After cooling, the generated crystals were collected by filtration. After washing with 47 kg of isopropyl alcohol, the obtained crystals were dried and cis-2- [4- [4
-(1,2-Benzisothiazol-3-yl) -1-piperazinyl] butyl] hexahydro-1H-isoindole-1,3 (2H) dione (35.4 kg) was obtained. 75.3% yield, melting point 5
3-56 ° C
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ Ｃ０７Ｄ 277/60 Ｃ０７Ｄ 277/60 // Ｃ０７Ｂ 61/00 ３００ Ｃ０７Ｂ 61/00 ３００ (72)発明者 石墨 紀久夫 大阪府大阪市此花区春日出中３丁目１番 98号 住友製薬株式会社内 (56)参考文献 特開 昭63−10760（ＪＰ，Ａ) 特開 昭55−154973（ＪＰ，Ａ) 特開 昭58−170753（ＪＰ，Ａ) 特開 昭57−95964（ＪＰ，Ａ) 米国特許4675403（ＵＳ，Ａ) 欧州公開296048（ＥＰ，Ａ１) (58)調査した分野(Int.Cl.6，ＤＢ名) C07D 209/48 C07D 209/76 C07D 211/40 C07D 277/60 C07D 221/20 ＣＡ，ＲＥＧＩＳＴＲＹ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 6 Identification symbol FI C07D 277/60 C07D 277/60 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Kikuo Ishigumi Konohana, Osaka City, Osaka No. 3-98, Kasuganaka-ku, Sumitomo Pharmaceutical Co., Ltd. (56) References JP-A-63-10760 (JP, A) JP-A-55-154973 (JP, A) JP-A-58-170753 (JP) JP-A-57-95964 (JP, A) U.S. Pat. No. 4,674,003 (US, A) European publication 296048 (EP, A1) (58) Fields investigated (Int. Cl. 6 , DB name) C07D 209/48 C07D 209/76 C07D 211/40 C07D 277/60 C07D 221/20 CA, REGISTRY (STN)
Claims (4)
中で、一般式 Q+X- ［式中、X-はハロゲンイオン、ヒドロキシイオンまたは
硫酸水素イオンを表わし、Q+は一般式 R1R2R3R4W+ （式中、R1、R2、R3およびR4はそれぞれ炭素数１から20
よりなる直鎖又は分枝状のアルキル基を表わし、Ｗは窒
素原子またはリン原子を表わす。）で表される基を表わ
す。］ で示される４級オニウム塩および塩基の存在下に１−ブ
ロモ−４−クロロブタンと反応させることを特徴とする
一般式 ［式中、 は前述と同じ意味を表わす。Ｙは塩素原子または臭素原
子を表す。］ で表わされる環状イミド化合物の製造方法。(1) General formula [Where, Represents a group represented by A compound represented by, water and a mixed solvent of a hydrophobic organic solvent, the general formula Q + X - in the Formula, X - represents a halogen ion, hydroxy ion or hydrogen sulfate ion, Q + has the general formula R 1 R 2 R 3 R 4 W + (wherein R 1 , R 2 , R 3 and R 4 each have 1 to 20 carbon atoms
Represents a linear or branched alkyl group, and W represents a nitrogen atom or a phosphorus atom. ) Represents a group represented by Wherein the compound is reacted with 1-bromo-4-chlorobutane in the presence of a quaternary onium salt and a base represented by the formula: [Where, Has the same meaning as described above. Y represents a chlorine atom or a bromine atom. ] The manufacturing method of the cyclic imide compound represented by these.
する一般式 で表わされる環状イミド誘導体またはそれらの酸付加塩
の製造方法。 第１工程： 一般式 で表わされる化合物を、水と疎水性有機溶媒の混合溶媒
中で、一般式 Q+X- で示される４級オニウム塩および塩基の存在下に１−ブ
ロモ−４−クロロブタンと反応させる 第２工程： 同一反応系中に、さらに一般式 で表わされるピペラジン誘導体を加えて反応させる ［式中、 X-およびQ+は、請求項１における意義と同義である。Ｒ
は、置換又は無置換のフェニル基、置換又は無置換の２
−ピリジル基、置換又は無置換のピリミジル基、置換又
は無置換の1,2−ベンゾ−３−イソチアゾリル基を表わ
し、前記の置換基は、ハロゲン原子、炭素数１から４の
アルコキシ基またはシアノ基を表わす。］2. A general formula comprising continuously performing the following two steps: A method for producing a cyclic imide derivative represented by the formula: or an acid addition salt thereof. First step: General formula Is reacted with a compound of the water and a mixed solvent of a hydrophobic organic solvent, the general formula Q + X - in a second step of reacting the quaternary onium salt and in the presence of a base 1-bromo-4-chlorobutane shown : In the same reaction system, the general formula A piperazine derivative represented by the formula is added and reacted. X - and Q + have the same meanings as in claim 1. R
Is a substituted or unsubstituted phenyl group, a substituted or unsubstituted 2
Represents a pyridyl group, a substituted or unsubstituted pyrimidyl group, a substituted or unsubstituted 1,2-benzo-3-isothiazolyl group, wherein the substituent is a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Represents ]
求項（２）記載の環状イミド誘導体またはそれらの酸付
加塩の製造方法。(3) The method for producing a cyclic imide derivative or an acid addition salt thereof according to claim 2, wherein R is a 2-pyrimidyl group.
アゾリル基である請求項（２）記載の環状イミド誘導体
またはそれらの酸付加塩の製造方法。(4) The method for producing a cyclic imide derivative or an acid addition salt thereof according to claim 2, wherein R is a 1,2-benzo-3-isothiazolyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1056583A JP2918899B2 (en) | 1989-03-09 | 1989-03-09 | Method for producing cyclic imide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1056583A JP2918899B2 (en) | 1989-03-09 | 1989-03-09 | Method for producing cyclic imide derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02235865A JPH02235865A (en) | 1990-09-18 |
| JP2918899B2 true JP2918899B2 (en) | 1999-07-12 |
Family
ID=13031193
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1056583A Expired - Lifetime JP2918899B2 (en) | 1989-03-09 | 1989-03-09 | Method for producing cyclic imide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2918899B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1117964A (en) * | 1994-08-27 | 1996-03-06 | 中国林业科学研究院林产化学工业研究所 | N-alkylimide and its preparation method |
| CN1073990C (en) * | 1997-06-17 | 2001-10-31 | 中国林业科学研究院林产化学工业研究所 | Process for preparing (inner) N-alkyl imide |
| AU2231502A (en) | 2000-11-30 | 2002-06-11 | Ranbaxy Lab Ltd | 1,4-disubstituted piperazine derivatives useful as uro-selective alpha1-adrenoceptor blockers |
-
1989
- 1989-03-09 JP JP1056583A patent/JP2918899B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02235865A (en) | 1990-09-18 |
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