JPH051035A - Production of quinolinone derivative - Google Patents
Production of quinolinone derivativeInfo
- Publication number
- JPH051035A JPH051035A JP3181924A JP18192491A JPH051035A JP H051035 A JPH051035 A JP H051035A JP 3181924 A JP3181924 A JP 3181924A JP 18192491 A JP18192491 A JP 18192491A JP H051035 A JPH051035 A JP H051035A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- mol
- reaction
- formula
- group
- 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.)
- Granted
Links
Landscapes
- Quinoline Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、環化反応によりアセト
アミド誘導体からキノリノン誘導体を製造する方法に関
する。TECHNICAL FIELD The present invention relates to a method for producing a quinolinone derivative from an acetamide derivative by a cyclization reaction.
【０００２】[0002]
【従来の技術と発明が解決しようとする課題】キノリノ
ン誘導体は、抗潰瘍剤などの医薬品を製造するための中
間原料として使用されている。このキノリノン誘導体を
製造する方法として、アセトアミド誘導体を、酸の存在
下、環化反応に付す方法が知られている。この環化反応
に使用される酸として、硫酸、ポリリン酸、塩化アルミ
ニウムが使用されている。例えば、４−フェニル−２−
キノリノンは、３−オキソ−３−フェニル−Ｎ−フェニ
ルプロパンアミドをポリリン酸中で環化反応に付すこと
により得られる(Practical Heterocyclic Chemistry 19
68, p88)。しかし、ポリリン酸および塩化アルミニウム
を使用すると、目的化合物の収率が低い。BACKGROUND OF THE INVENTION Quinolinone derivatives are used as an intermediate raw material for the production of pharmaceuticals such as anti-ulcer agents. As a method of producing this quinolinone derivative, a method of subjecting an acetamide derivative to a cyclization reaction in the presence of an acid is known. As the acid used for this cyclization reaction, sulfuric acid, polyphosphoric acid, and aluminum chloride are used. For example, 4-phenyl-2-
Quinolinones are obtained by subjecting 3-oxo-3-phenyl-N-phenylpropanamide to a cyclization reaction in polyphosphoric acid (Practical Heterocyclic Chemistry 19
68, p88). However, when polyphosphoric acid and aluminum chloride are used, the yield of the target compound is low.
【０００３】そこで、酸として一般に硫酸が使用されて
いる。硫酸を用いたキノリノン誘導体の製造方法とし
て、例えば、３−オキソ−Ｎ−フェニルブタンアミドを
濃硫酸中で環化反応に付し、４−メチル−２（１Ｈ）−
キノリノンを製造する方法（Org. Synth. 1955年, III,
p580 ）、３−オキソ−Ｎ−フェニルブタンアミドの４
位をブロム化した後、濃硫酸中で環化反応に付し、４−
ブロモメチル−２（１Ｈ）−キノリノンを製造する方法
（特公昭６３−３５６２３号公報）、４−クロロ−３−
オキソ−Ｎ−フェニルブタンアミドを濃硫酸中で環化反
応に付し、４−クロロメチル−２（１Ｈ）−キノリノン
を製造する方法（特公昭４７−９５９２号公報）が知ら
れている。また、３−オキソ−Ｎ−（２′−フェニル）
ブタンアミドを濃硫酸中で環化反応に供し、４−メチル
−８−メチルキノリノンを製造する方法（薬学雑誌 196
9年, p759）も知られている。Therefore, sulfuric acid is generally used as the acid. As a method for producing a quinolinone derivative using sulfuric acid, for example, 3-oxo-N-phenylbutanamide is subjected to a cyclization reaction in concentrated sulfuric acid to give 4-methyl-2 (1H)-
Method for producing quinolinone (Org. Synth. 1955, III,
p580), 4-oxo-N-phenylbutanamide 4
After brominating the position, it was subjected to a cyclization reaction in concentrated sulfuric acid to give 4-
Method for producing bromomethyl-2 (1H) -quinolinone (JP-B-63-35623), 4-chloro-3-
A method (Japanese Patent Publication No. 47-9592) for producing 4-chloromethyl-2 (1H) -quinolinone by subjecting oxo-N-phenylbutanamide to a cyclization reaction in concentrated sulfuric acid is known. Also, 3-oxo-N- (2'-phenyl)
A method for producing 4-methyl-8-methylquinolinone by subjecting butanamide to a cyclization reaction in concentrated sulfuric acid (Pharmaceutical Journal 196
9 years, p759) is also known.
【０００４】しかし、これらの方法では、基質に対して
約５モル倍以上の大過剰の硫酸を使用するため、排水処
理時の負荷が大きくなる。しかも酸に対する目的化合物
の溶解性が大きいためか、収率が小さい。However, in these methods, a large excess of sulfuric acid, which is about 5 mol times or more with respect to the substrate, is used, so that the load at the time of wastewater treatment becomes large. Moreover, the yield is low probably because the target compound has a high solubility in the acid.
【０００５】従って、本発明の目的は、酸の使用量が少
なくても環化反応を円滑に行なうことができると共に、
高い収率で高純度のキノリノン誘導体を得ることができ
る製造方法を提供することにある。Therefore, an object of the present invention is to allow the cyclization reaction to be carried out smoothly even if the amount of acid used is small, and
An object of the present invention is to provide a production method capable of obtaining a high-purity quinolinone derivative with a high yield.
【０００６】[0006]
【発明の構成】本発明者らは、前記目的を達成するた
め、鋭意検討の結果、脱水しながら環化反応を行なう
と、酸の量が少量であっても反応が円滑に進行し、かつ
目的化合物が高い収率で得られることを見いだし、本発
明を完成した。The present inventors have made earnest studies to achieve the above object, and as a result, when the cyclization reaction was carried out while dehydrating, the reaction proceeded smoothly even if the amount of acid was small, and The present invention has been completed by finding that the target compound can be obtained in a high yield.
【０００７】すなわち、本発明は、一般式（Ｉ）That is, the present invention has the general formula (I)
【０００８】[0008]
【化３】
（式中、Ｒ1 は水素原子、ハロゲン原子、アルキル基又
はアルコキシ基を示し、Ｒ2 はアルキル基、ハロゲン化
アルキル基、シクロアルキル基、アリール基又はアラル
キル基を示し、これらは置換基を有していてもよい）で
表されるアセトアミド誘導体から、一般式（ＩＩ）[Chemical 3] (In the formula, R 1 represents a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group, R 2 represents an alkyl group, a halogenated alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, and these have a substituent. From the acetamide derivative represented by the general formula (II)
【０００９】[0009]
【化４】
（式中、Ｒ1 およびＲ2 は前記に同じ）で表されるキノ
リノン誘導体を製造する方法であって、酸の存在下、脱
水しながら環化反応を行なうキノリノン誘導体の製造方
法を提供する。[Chemical 4] A method for producing a quinolinone derivative represented by the formula (wherein R 1 and R 2 are the same as above), which comprises performing a cyclization reaction while dehydrating in the presence of an acid.
【００１０】置換基Ｒ1 のうちハロゲン原子には、フッ
素、塩素、臭素、ヨウ素原子が含まれる。アルキル基と
しては、例えば、メチル、エチル、プロピル、イソプロ
ピル、ブチル、イソブチル、ｔ−ブチル、ペンチル、ヘ
キシル、ヘプチル、オクチル基などが例示される。これ
らのアルキル基のなかで炭素数１〜６、好ましくは１〜
４程度の低級アルキル基が繁用される。The halogen atom in the substituent R1 includes fluorine, chlorine, bromine and iodine atoms. Examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl and octyl groups. Among these alkyl groups, the number of carbon atoms is 1 to 6, preferably 1 to
A lower alkyl group of about 4 is commonly used.
【００１１】アルコキシ基としては、例えば、メトキ
シ、エトキシ、プロポキシ、イソプロポキシ、ブトキ
シ、イソブトキシ、ｔ−ブトキシ、ペンチルオキシ、ヘ
キシルオキシ、ヘプチルオキシ、オクチルオキシ基など
が挙げられる。これらのアルコキシ基のなかで炭素数１
〜６、好ましくは１〜４程度の低級アルコキシ基が繁用
される。Examples of the alkoxy group include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy, hexyloxy, heptyloxy and octyloxy groups. C1 among these alkoxy groups
Lower alkoxy groups of about 6, preferably about 1 to 4, are commonly used.
【００１２】置換基Ｒ2 のうちアルキル基としては前記
と同様のアルキル基が例示される。Examples of the alkyl group in the substituent R2 include the same alkyl groups as described above.
【００１３】ハロゲン化アルキル基としては、前記ハロ
ゲン原子を有する炭素数１〜６程度の低級アルキル基、
例えば、フルオロメチル、クロロメチル、ジクロロメチ
ル、ブロモメチル、２−フルオロエチル、２，２，２−
トリフルオロエチル、２−クロロエチル、２，２−ジク
ロロエチル、１−クロロエチル、２−ブロモエチル、３
−フルオロエチル、３−クロロプロピル、２−クロロプ
ロピル、３−ブロモプロピル、４−クロロブチル、５−
クロロペンチル、６−クロロヘキシル基などが例示され
る。ハロゲン化アルキル基としては、通常、前記ハロゲ
ン原子を有する炭素数１〜４、特に炭素数１〜２程度の
低級アルキル基が好ましい。The halogenated alkyl group includes a lower alkyl group having the above halogen atom and having about 1 to 6 carbon atoms,
For example, fluoromethyl, chloromethyl, dichloromethyl, bromomethyl, 2-fluoroethyl, 2,2,2-
Trifluoroethyl, 2-chloroethyl, 2,2-dichloroethyl, 1-chloroethyl, 2-bromoethyl, 3
-Fluoroethyl, 3-chloropropyl, 2-chloropropyl, 3-bromopropyl, 4-chlorobutyl, 5-
Examples include chloropentyl and 6-chlorohexyl groups. As the halogenated alkyl group, a lower alkyl group having 1 to 4 carbon atoms, particularly about 1 to 2 carbon atoms, which has the halogen atom, is usually preferable.
【００１４】シクロアルキル基には、例えば、シクロペ
ンチル、シクロヘキシル、シクロヘプチル、シクロオク
チル基などが含まれる。アリール基としては、例えば、
フェニル、１−ナフチル、２−ナフチル、アントリル、
フェナントリル基などが挙げられる。アラルキル基に
は、例えば、ベンジル、フェネチル、ベンズヒドリル基
などが含まれる。Cycloalkyl groups include, for example, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl groups and the like. As the aryl group, for example,
Phenyl, 1-naphthyl, 2-naphthyl, anthryl,
Examples thereof include a phenanthryl group. Aralkyl groups include, for example, benzyl, phenethyl, benzhydryl groups, and the like.
【００１５】これらの置換基Ｒ1 及びＲ2 は、必要に応
じて、ハロゲン原子、低級アルキル基、ヒドロキシル
基、低級アルコキシ基、カルボキシル基、アルコキシカ
ルボニル基、ジアルキルアミノ基、ニトロ基などの置換
基を有していてもよい。These substituents R 1 and R 2 are, if necessary, a substituent such as a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, a carboxyl group, an alkoxycarbonyl group, a dialkylamino group and a nitro group. May have.
【００１６】前記一般式（Ｉ）で表されるアセトアミド
誘導体を、酸の存在下、脱水しながら環化反応に供する
ことにより、前記一般式（ＩＩ）で表されるキノリノン
誘導体が生成する。By subjecting the acetamide derivative represented by the general formula (I) to a cyclization reaction in the presence of an acid while dehydrating, the quinolinone derivative represented by the general formula (II) is produced.
【００１７】前記酸としては、例えば、硫酸、塩酸、過
塩素酸、硝酸、リン酸、ポリリン酸、五酸化リン、フッ
化水素、塩化アルミニウム、塩化亜鉛などが挙げられ
る。これらの酸のなかで硫酸が繁用される。酸の使用量
は、一般式（Ｉ）で表されるアセトアミド誘導体１モル
に対して、１モル以上、好ましくは１〜３モル、さらに
好ましくは１〜２モル程度である。Examples of the acid include sulfuric acid, hydrochloric acid, perchloric acid, nitric acid, phosphoric acid, polyphosphoric acid, phosphorus pentoxide, hydrogen fluoride, aluminum chloride, zinc chloride and the like. Of these acids, sulfuric acid is frequently used. The amount of the acid used is 1 mol or more, preferably 1 to 3 mol, and more preferably 1 to 2 mol per 1 mol of the acetamide derivative represented by the general formula (I).
【００１８】この反応機構は、一般式（Ｉ）で表される
アセトアミド誘導体のうちカルボニル基の炭素原子がフ
ェニル基の２位に付加した環化物と、脱水した環化物と
の間に平衡反応が存在し、反応系から生成した水を脱水
するため、反応が円滑に進行するものと推測される。This reaction mechanism is based on the equilibrium reaction between the dehydrated cyclized product and the cyclized product of the acetamide derivative represented by the general formula (I) in which the carbon atom of the carbonyl group is added to the 2-position of the phenyl group. It is presumed that the reaction proceeds smoothly because it exists and dehydrates the water generated from the reaction system.
【００１９】反応は、通常、有機溶媒中で行なわれる。
有機溶媒としては、反応に悪影響を及ぼさない種々の溶
媒、例えば、ヘキサン、オクタンなどの脂肪族炭化水
素；シクロヘキサンなどの脂環族炭化水素；ベンゼン、
トルエン、キシレンなどの芳香族炭化水素；塩化メチレ
ン、クロロホルム、四塩化炭素、ジクロロエタン、クロ
ロベンゼンなどのハロゲン化炭化水素；メチルエチルケ
トンなどのケトン類；酢酸エチルなどのエステル類；こ
れら混合溶媒が使用できる。好ましい有機溶媒には、疎
水性溶媒、例えば、脂肪族炭化水素、脂環族炭化水素、
芳香族炭化水素やこれらの混合溶媒が含まれる。The reaction is usually carried out in an organic solvent.
As the organic solvent, various solvents that do not adversely influence the reaction, for example, aliphatic hydrocarbons such as hexane and octane; alicyclic hydrocarbons such as cyclohexane; benzene,
Aromatic hydrocarbons such as toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane and chlorobenzene; ketones such as methyl ethyl ketone; esters such as ethyl acetate; mixed solvents thereof can be used. Preferred organic solvents include hydrophobic solvents such as aliphatic hydrocarbons, alicyclic hydrocarbons,
Aromatic hydrocarbons and mixed solvents thereof are included.
【００２０】脱水反応は、例えば、５０〜２００℃、好
ましくは７０〜１５０℃、さらに好ましくは８０〜１２
０℃程度の温度で行なうことができる。反応は、減圧下
で行なってもよく還流下で行なってもよい。The dehydration reaction is, for example, 50 to 200 ° C, preferably 70 to 150 ° C, more preferably 80 to 12 ° C.
It can be performed at a temperature of about 0 ° C. The reaction may be carried out under reduced pressure or under reflux.
【００２１】さらには、一般式（Ｉ）で表される化合物
を有機溶媒中に懸濁させ、上層を還流させ、生成した下
層の水を反応系から除去してもよい。なお、上層還流
は、留出液を２層に分液し、上層を反応系にリサイクル
し、下層水を系外に除去する方法である。この反応で
は、前記一般式（Ｉ）で表されるアセトアミド誘導体に
対して溶解性の低い溶媒を使用し、不均一系で反応させ
ることにより、生成する水を順次反応系外に除去でき、
環化反応がさらに円滑に進行する。また、反応混合液を
冷却し、析出した沈澱物を回収するだけで、一般式（Ｉ
Ｉ）で表される高純度のキノリノン誘導体を高い収率で
得ることができ、目的化合物の単離精製操作も容易であ
る。アセトアミド誘導体に対して溶解性の低い溶媒とし
ては、前記疎水性溶媒が挙げられる。Further, the compound represented by the general formula (I) may be suspended in an organic solvent, the upper layer may be refluxed, and the produced lower layer water may be removed from the reaction system. The upper layer reflux is a method in which the distillate is separated into two layers, the upper layer is recycled to the reaction system, and the lower layer water is removed to the outside of the system. In this reaction, a solvent having a low solubility for the acetamide derivative represented by the general formula (I) is used, and the produced water can be sequentially removed from the reaction system by reacting in a heterogeneous system,
The cyclization reaction proceeds more smoothly. In addition, the reaction mixture is cooled, and the deposited precipitate is recovered.
The high-purity quinolinone derivative represented by I) can be obtained in high yield, and the isolation and purification operation of the target compound is easy. Examples of the solvent having a low solubility in the acetamide derivative include the above-mentioned hydrophobic solvents.
【００２２】前記反応は、例えば、３０分〜４８時間程
度で終了する。反応終了後、反応生成物を、例えば、濾
過、濃縮、再結晶法、溶媒抽出法、カラムクロマトグラ
フィーなどの慣用の分離精製手段に供することにより、
一般式（ＩＩ）で表されるキノリノン誘導体を容易に単
離精製できる。The above reaction is completed, for example, in about 30 minutes to 48 hours. After completion of the reaction, the reaction product is subjected to conventional separation and purification means such as filtration, concentration, recrystallization method, solvent extraction method, column chromatography, and the like,
The quinolinone derivative represented by the general formula (II) can be easily isolated and purified.
【００２３】[0023]
【発明の効果】本発明の方法によれば、酸の使用量が少
なくても環化反応を円滑に行なうことができるので、排
水処理の負荷を低減できると共に、高純度のキノリノン
誘導体を収率よく得ることができる。According to the method of the present invention, the cyclization reaction can be carried out smoothly even when the amount of acid used is small, so that the load of waste water treatment can be reduced and a high-purity quinolinone derivative can be obtained. You can get well.
【００２４】[0024]
【実施例】以下に、実施例に基づいて本発明をより詳細
に説明するが、本発明は以下の実施例に限定されるもの
ではない。The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited to the following examples.
【００２５】実施例
４−クロロ−３−オキソ−Ｎ−フェニルブタンアミド１
５７．８ｇ（０．７４６モル）をｎ−ヘキサン１９０ｇ
及びベンゼン３７６ｇに懸濁させた。懸濁液に濃硫酸８
７．７ｇ（０．８７７モル）を添加した後、昇温し、上
層還流を行ない、生成した下層水を抜き取りながら、２
時間反応させた。反応終了後、反応混合液を室温に冷却
し、沈澱物を濾取し、水洗、乾燥し、４−クロロメチル
−２（１Ｈ）−キノリノンを得た。Example 4-Chloro-3-oxo-N-phenylbutanamide 1
190 g of 57.8 g (0.746 mol) of n-hexane
And 376 g of benzene. Concentrated sulfuric acid 8 in suspension
After adding 7.7 g (0.877 mol), the temperature was raised and the upper layer was refluxed.
Reacted for hours. After completion of the reaction, the reaction mixture was cooled to room temperature, the precipitate was collected by filtration, washed with water and dried to obtain 4-chloromethyl-2 (1H) -quinolinone.
【００２６】得量：１４０．９ｇ（０．７２７モル）
収率：９７．５％
ｍｐ：２５１−２５２．６℃
比較例１
下層水を抜き取ることなく、実施例と同様に反応させた
ところ、以下の結果を得た。Yield: 140.9 g (0.727 mol) Yield: 97.5% mp: 251-252.6 ° C. Comparative Example 1 A reaction was carried out in the same manner as in Example 1 without extracting the lower layer water. The following results were obtained.
【００２７】得量：１３４ｇ（０．０９７モル、オイル
状物質）
収率：１３．３％
ｍｐ：測定不可
比較例２
４−クロロ−３−オキソ−Ｎ−フェニルブタンアミド１
５７．８ｇ（０．７４６モル）を濃硫酸３９５ｇ（３．
９５モル）に加え、９０〜１００℃で２０分間加熱撹拌
した。反応終了後、反応混合液を冷却し、水７Ｋｇに注
入した。生成した沈澱物を濾取し、水洗、乾燥し、４−
クロロメチル−２（１Ｈ）−キノリノンを得た。Amount: 134 g (0.097 mol, oily substance) Yield: 13.3% mp: not measurable Comparative Example 2 4-chloro-3-oxo-N-phenylbutanamide 1
57.8 g (0.746 mol) of concentrated sulfuric acid 395 g (3.
95 mol) and heated and stirred at 90 to 100 ° C. for 20 minutes. After completion of the reaction, the reaction mixture was cooled and poured into 7 Kg of water. The formed precipitate was collected by filtration, washed with water, dried, and
Chloromethyl-2 (1H) -quinolinone was obtained.
【００２８】得量：１２２ｇ（０．６２６モル）
収率：８４％
ｍｐ：２１８−２２０℃
比較例３
３−オキソ−Ｎ−フェニルブタンアミド３０ｇ（０．１
６９モル）をクロロホルム３０ｍｌに溶解し、溶液を室
温で撹拌しながら、臭素２７ｇとクロロホルム３０ｍｌ
との溶液を滴下した。滴下終了後、混合液を３０分間還
流し、減圧濃縮した。７０〜７５℃に保ちながら、残渣
を、濃硫酸１２８．８ｇ（１．２９モル）に撹拌しなが
ら添加し、９５℃で３０分間撹拌した。反応混合液を氷
水中に注入し、沈澱物を濾取し、メタノール／クロロホ
ルムから再結晶し、４−ブロモメチル−２（１Ｈ）−キ
ノリノンを得た。Amount: 122 g (0.626 mol) Yield: 84% mp: 218-220 ° C. Comparative Example 3 3-oxo-N-phenylbutanamide 30 g (0.1
69 mol) in 30 ml of chloroform and 27 g of bromine and 30 ml of chloroform while stirring the solution at room temperature.
The solution of and was dripped. After the completion of dropping, the mixed solution was refluxed for 30 minutes and concentrated under reduced pressure. While maintaining the temperature at 70 to 75 ° C, the residue was added to 128.8 g (1.29 mol) of concentrated sulfuric acid with stirring, and the mixture was stirred at 95 ° C for 30 minutes. The reaction mixture was poured into ice water, the precipitate was collected by filtration, and recrystallized from methanol / chloroform to obtain 4-bromomethyl-2 (1H) -quinolinone.
【００２９】得量：２０ｇ（０．０８４モル）
収率：４９．７％
ｍｐ：２６５−２６６℃
比較例４
３−オキソ−Ｎ−フェニルブタンアミド１３１．３ｇ
（０．７４６モル）を濃硫酸５４９ｇ（５．４９モル）
に添加し、７０〜７５℃で１．５時間、１００℃で１時
間撹拌した。反応終了後、反応混合液を冷却し、水３Ｋ
ｇに注入し、沈澱物を濾取し、水洗、乾燥し、４−メチ
ル−２（１Ｈ）−キノリノンを得た。Amount: 20 g (0.084 mol) Yield: 49.7% mp: 265-266 ° C. Comparative Example 4 3-oxo-N-phenylbutanamide 131.3 g
(0.746 mol) of concentrated sulfuric acid 549 g (5.49 mol)
And stirred at 70-75 ° C for 1.5 hours and 100 ° C for 1 hour. After the reaction is complete, the reaction mixture is cooled and water 3K
Then, the precipitate was collected by filtration, washed with water and dried to obtain 4-methyl-2 (1H) -quinolinone.
【００３０】得量：９９ｇ（０．６１２モル） 収率：８２％ ｍｐ：２００−２０２℃Yield: 99 g (0.612 mol) Yield: 82% mp: 200-202 ° C
Claims (2)
はアルコキシ基を示し、Ｒ2 はアルキル基、ハロゲン化
アルキル基、シクロアルキル基、アリール基又はアラル
キル基を示し、これらは置換基を有していてもよい）で
表されるアセトアミド誘導体から、一般式（ＩＩ） 【化２】 （式中、Ｒ1 およびＲ2 は前記に同じ）で表されるキノ
リノン誘導体を製造する方法であって、酸の存在下、脱
水しながら環化反応を行なうキノリノン誘導体の製造方
法。1. A compound represented by the general formula (I): (In the formula, R 1 represents a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group, R 2 represents an alkyl group, a halogenated alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, and these have a substituent. From the acetamide derivative represented by the general formula (II) A method for producing a quinolinone derivative represented by the formula (wherein R 1 and R 2 are the same as above), wherein the cyclization reaction is carried out in the presence of an acid while dehydrating.
導体１モルに対して、酸を１〜３モル使用する請求項１
記載のキノリノン誘導体の製造方法。2. The acid is used in an amount of 1 to 3 mol with respect to 1 mol of the acetamide derivative represented by the general formula (I).
A method for producing the quinolinone derivative described.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3181924A JP2989689B2 (en) | 1991-06-25 | 1991-06-25 | Method for producing quinolinone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3181924A JP2989689B2 (en) | 1991-06-25 | 1991-06-25 | Method for producing quinolinone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH051035A true JPH051035A (en) | 1993-01-08 |
| JP2989689B2 JP2989689B2 (en) | 1999-12-13 |
Family
ID=16109287
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3181924A Expired - Fee Related JP2989689B2 (en) | 1991-06-25 | 1991-06-25 | Method for producing quinolinone derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2989689B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4956670A (en) * | 1988-08-04 | 1990-09-11 | Fuji Xerox Co., Ltd. | Electrostatic latent image forming apparatus controlling the direction of derivation of ions |
| KR100669823B1 (en) * | 2001-02-20 | 2007-01-17 | 경동제약 주식회사 | Process for Preparing 2-4-Chlorobenzoylamino-3-[21?- quinolinon-4-yl]propionic acid and intermediate thereof |
-
1991
- 1991-06-25 JP JP3181924A patent/JP2989689B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4956670A (en) * | 1988-08-04 | 1990-09-11 | Fuji Xerox Co., Ltd. | Electrostatic latent image forming apparatus controlling the direction of derivation of ions |
| KR100669823B1 (en) * | 2001-02-20 | 2007-01-17 | 경동제약 주식회사 | Process for Preparing 2-4-Chlorobenzoylamino-3-[21?- quinolinon-4-yl]propionic acid and intermediate thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2989689B2 (en) | 1999-12-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0916675B1 (en) | Process for preparing sildenafil | |
| JPH04507085A (en) | Improved method for producing substituted isoflavone derivatives | |
| JP2846042B2 (en) | Method for producing indolecarboxylic acid derivative | |
| DK146720B (en) | METHOD OF ANALOGY FOR THE PREPARATION OF 5-SUBSTITUTED-1,2-DIHYDRO-3H-PYRROLO (1,2-A) -PYRROL-1-CARBOXYLIC ACIDS OF THEIR SIMILAR NITRILS | |
| JP3491506B2 (en) | Method for producing dihydropyridine derivative | |
| JP2989689B2 (en) | Method for producing quinolinone derivative | |
| US20050245750A1 (en) | Process for preparing 1,3-benzodioxole-2-spirocycloalkane derivative | |
| JP4408578B2 (en) | 3- (1-Hydroxy-pentylidene) -5-nitro-3H-benzofuran-2-one, production method thereof and use thereof | |
| US10640465B2 (en) | Method for preparing phenylalanine compound | |
| JP2002531440A (en) | Method for preparing 4-hydroxyquinoline and / or tautomers | |
| JPH0524158B2 (en) | ||
| JP3629052B2 (en) | Process for the production of substituted quinazoline-2,4-diones | |
| EP0260724B1 (en) | Intermediates for the production of 2-substituted phenyl-4,5,6,7-tetrahydro-2h-isoindole-1,3-diones | |
| KR100641825B1 (en) | Preparation method of 4-biphenylacetic acid | |
| JPH09268186A (en) | Production of 4-chromanones | |
| US6465653B2 (en) | Noncatalyzed synthesis of 4-hydroxyquinolines and/or tautomers thereof | |
| JP3084577B2 (en) | Method for producing optically active atrolactic acid and intermediate for production | |
| JP3561148B2 (en) | Method for separating quinaldine isomers | |
| JP3538631B2 (en) | Quinoline derivative and method for producing the same | |
| JP3288847B2 (en) | Method for producing 7-azaphthalide derivative | |
| JPH0881456A (en) | Production of 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran derivative | |
| KR900008171B1 (en) | Process for preparing benzodiazepine acetate | |
| JP3855514B2 (en) | Purification method of pyridazin-3-one derivatives | |
| JPS5916878A (en) | Production of 2,4-dihydroxy-3-acetylquinoline | |
| KR950008528B1 (en) | A process for the preparation of halogenated quinolone carboxylic acids |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313532 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081008 Year of fee payment: 9 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081008 Year of fee payment: 9 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081008 Year of fee payment: 9 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091008 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091008 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101008 Year of fee payment: 11 |
|
| LAPS | Cancellation because of no payment of annual fees |