JP2001139554A - Method for producing halogen-substituted quinoline derivative - Google Patents
Method for producing halogen-substituted quinoline derivativeInfo
- Publication number
- JP2001139554A JP2001139554A JP31903599A JP31903599A JP2001139554A JP 2001139554 A JP2001139554 A JP 2001139554A JP 31903599 A JP31903599 A JP 31903599A JP 31903599 A JP31903599 A JP 31903599A JP 2001139554 A JP2001139554 A JP 2001139554A
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- derivative represented
- halogen
- substituted quinoline
- reaction
- 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)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ハロゲン置換キノ
リン誘導体の製造方法に関する。[0001] The present invention relates to a method for producing a halogen-substituted quinoline derivative.
【０００２】[0002]
【従来の技術】一般式[Prior Art] General formula
【０００３】[0003]
【化３】 Embedded image
【０００４】〔式中、Ｘ1、Ｘ2及びＸ3は、各々ハロゲ
ン原子を示す。Ｒ1は水素原子又は低級アルキル基を示
す。〕で表されるハロゲン置換キノリン誘導体は、例え
ば抗菌剤等の医薬品を合成するための中間体として有用
な化合物である。[Wherein X 1 , X 2 and X 3 each represent a halogen atom. R 1 represents a hydrogen atom or a lower alkyl group. Is a compound useful as an intermediate for synthesizing a pharmaceutical such as an antibacterial agent.
【０００５】従来、デーブナー・ミラー（Doebner-Mill
er）反応は、２−アルキルキノリンを合成するための方
法として広く利用されている。ところが、この反応を適
用して、上記一般式（１）のハロゲン置換キノリン誘導
体を製造する場合、反応後の反応混合物がコールタール
状のものとなり、目的とする一般式（１）のハロゲン置
換キノリン誘導体と反応副生物との沸点が近いこと等の
理由から、目的化合物を低収率、低純度でしか製造し得
なかった。Conventionally, Doebner-Mill
er) The reaction is widely used as a method for synthesizing 2-alkylquinoline. However, when this reaction is applied to produce a halogen-substituted quinoline derivative of the above general formula (1), the reaction mixture after the reaction becomes a coal-tar, and the desired halogen-substituted quinoline of the general formula (1) is obtained. Because of the close boiling point between the derivative and the reaction by-product, the target compound could be produced only in low yield and low purity.
【０００６】このような欠点を解消するために、一般式
（２）で表されるアニリン誘導体と一般式（３）で表さ
れるアルデヒド誘導体との反応を、ｍ−ニトロベンゼン
スルホン酸のアルカリ金属塩、硫酸鉄及びホウ酸の存在
下に行う方法が開発されている（特開平２−１８８５７
０号公報）。この方法に従えば、目的とする一般式
（１）のハロゲン置換キノリン誘導体を比較的高い収率
で得られるようになったものの、反応混合物がタール状
となって目的化合物が着色する等の不都合があり、純度
の高い目的化合物を得ようとすれば煩雑な精製工程が必
要となり、その場合には収率が低下するのが避けられな
い。このため、特開平２−１８８５７０号公報に記載の
方法は目的化合物の収率及び純度の点で尚不充分であっ
た。更に特開平２−１８８５７０号公報に記載の方法で
は、一般式（３）で表されるアルデヒド誘導体を反応系
内に徐々に添加する必要があり、しかもその滴下条件に
より目的化合物の収率が左右され、目的化合物を再現性
よく同レベルの収率で製造するのが困難であった。In order to solve such a drawback, a reaction between an aniline derivative represented by the general formula (2) and an aldehyde derivative represented by the general formula (3) is carried out by an alkali metal salt of m-nitrobenzenesulfonic acid. , Iron sulfate and boric acid have been developed (JP-A-2-18857).
No. 0). According to this method, the desired halogen-substituted quinoline derivative of the general formula (1) can be obtained in a relatively high yield, but the reaction mixture becomes tar-like and the desired compound is colored. In order to obtain a highly pure target compound, a complicated purification step is required, and in that case, a reduction in yield is inevitable. For this reason, the method described in JP-A-2-188570 is still insufficient in yield and purity of the target compound. Further, in the method described in JP-A-2-188570, it is necessary to gradually add the aldehyde derivative represented by the general formula (3) into the reaction system. As a result, it was difficult to produce the target compound with good reproducibility at the same level of yield.
【０００７】[0007]
【発明が解決しようとする課題】本発明は、反応混合物
がタール状となって目的化合物が着色するという不都合
がなく、そのため煩雑な精製工程を経ることなく、簡便
な操作で、目的とする一般式（１）のハロゲン置換キノ
リン誘導体を高収率且つ高純度で製造する方法を提供す
ることを課題とする。DISCLOSURE OF THE INVENTION The present invention has no inconvenience that the reaction mixture becomes tar-like and the target compound is colored, so that the desired general compound can be obtained by a simple operation without a complicated purification step. An object of the present invention is to provide a method for producing a halogen-substituted quinoline derivative of the formula (1) in high yield and high purity.
【０００８】本発明は、目的とする一般式（１）のハロ
ゲン置換キノリン誘導体を再現性よく高収率で製造する
方法を提供することを課題とする。An object of the present invention is to provide a method for producing the desired halogen-substituted quinoline derivative of the general formula (1) with good reproducibility and high yield.
【０００９】本発明は、目的とする一般式（１）のハロ
ゲン置換キノリン誘導体の工業的に有利に製造する方法
を提供することを課題とする。It is an object of the present invention to provide a method for industrially and advantageously producing the desired halogen-substituted quinoline derivative of the general formula (1).
【００１０】[0010]
【課題を解決するための手段】本発明者は、上記課題を
達成するために鋭意研究を重ねた結果、溶媒として水と
非水系溶媒との二相系溶媒を使用した場合に上記課題が
解決できることを見い出した。本発明は、斯かる知見に
基づき完成されたものである。Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, when the two-phase solvent of water and a non-aqueous solvent is used as the solvent, the above object is solved. I found what I could do. The present invention has been completed based on such findings.
【００１１】即ち、本発明は、一般式That is, the present invention provides a compound represented by the general formula
【００１２】[0012]
【化４】 Embedded image
【００１３】〔式中、Ｘ1、Ｘ2及びＸ3は、各々ハロゲ
ン原子を示す。〕で表されるアニリン誘導体に一般式 Ｒ1ＣＨ＝ＣＨＣＨＯ （３） 〔式中、Ｒ1は水素原子又は低級アルキル基を示す。〕
で表されるアルデヒド誘導体を反応させて一般式（１）
で表されるハロゲン置換キノリン誘導体を製造する方法
において、一般式（２）で表されるアニリン誘導体と一
般式（３）で表されるアルデヒド誘導体との反応を、酸
の存在下、水と非水系溶媒と界面で行うことを特徴とす
る一般式（１）で表されるハロゲン置換キノリン誘導体
の製造方法に係る。Wherein X 1 , X 2 and X 3 each represent a halogen atom. ] To the aniline derivative represented by the general formula R 1 CH = CHOCHO (3) wherein R 1 represents a hydrogen atom or a lower alkyl group. ]
Reacting the aldehyde derivative represented by the general formula (1)
In the method for producing a halogen-substituted quinoline derivative represented by the following formula, the reaction between the aniline derivative represented by the general formula (2) and the aldehyde derivative represented by the general formula (3) is carried out in the presence of an acid with water. The present invention relates to a method for producing a halogen-substituted quinoline derivative represented by the general formula (1), which is performed at an interface with an aqueous solvent.
【００１４】本発明の方法によれば、反応混合物がター
ル状となって目的化合物が着色するという不都合がな
く、そのため煩雑な精製工程を経ることなく、簡便な操
作で、目的とする一般式（１）のハロゲン置換キノリン
誘導体を高収率且つ高純度で製造し得る。According to the process of the present invention, there is no inconvenience that the reaction mixture becomes tar-like and the target compound is colored. Therefore, the desired compound of the general formula ( The halogen-substituted quinoline derivative of 1) can be produced in high yield and high purity.
【００１５】また、本発明の方法によれば、一般式
（３）で表されるアルデヒド誘導体の反応系内への滴下
条件により目的化合物の収率が左右されることはなく、
目的とする一般式（１）のハロゲン置換キノリン誘導体
を再現性よく高収率で製造し得る。Further, according to the method of the present invention, the yield of the target compound is not affected by the conditions for dropping the aldehyde derivative represented by the general formula (3) into the reaction system.
The desired halogen-substituted quinoline derivative of the general formula (1) can be produced with high reproducibility and high yield.
【００１６】更に、本発明の方法によれば、ｍ−ニトロ
ベンゼンスルホン酸のアルカリ金属塩や硫酸鉄を反応系
内に添加する必要はなく、経済的な面からも有利な方法
である。Further, according to the method of the present invention, it is not necessary to add an alkali metal salt of m-nitrobenzenesulfonic acid or iron sulfate to the reaction system, which is an economically advantageous method.
【００１７】[0017]
【発明の実施の形態】本明細書において示される各基
は、より具体的には次の通りである。BEST MODE FOR CARRYING OUT THE INVENTION Each group shown in the present specification is more specifically as follows.
【００１８】Ｒ1で示される低級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、tert−ブチル、ペンチル、ヘキシル基等の炭素数１
〜６の直鎖又は分枝鎖状アルキル基を例示できる。Ｒ1
で示される低級アルキル基としては、メチル基が好まし
い。The lower alkyl group represented by R 1 includes
For example, carbon number 1 such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl group, etc.
To 6 linear or branched alkyl groups. R 1
The lower alkyl group represented by is preferably a methyl group.
【００１９】Ｘ1、Ｘ2及びＸ3で示されるハロゲン原子
としては、弗素原子、塩素原子、臭素原子、沃素原子等
を例示できる。Ｘ1及びＸ2で示されるハロゲン原子とし
ては弗素原子が好ましく、Ｘ3で示されるハロゲン原子
としては臭素原子が好ましい。Examples of the halogen atom represented by X 1 , X 2 and X 3 include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The halogen atom represented by X 1 and X 2 is preferably a fluorine atom, and the halogen atom represented by X 3 is preferably a bromine atom.
【００２０】本発明においては、一般式（２）で表され
るアニリン誘導体と一般式（３）で表されるアルデヒド
誘導体との反応は、酸の存在下、水と非水系溶媒との二
相系溶媒中にて行われる。In the present invention, the reaction between the aniline derivative represented by the general formula (2) and the aldehyde derivative represented by the general formula (3) is carried out by a two-phase reaction between water and a non-aqueous solvent in the presence of an acid. This is performed in a system solvent.
【００２１】酸としては、従来公知の鉱酸を広く使用で
き、例えば塩酸、硫酸、臭化水素酸等を挙げることがで
きる。これらの中でも、塩酸が特に好ましい。As the acid, conventionally known mineral acids can be widely used, and examples thereof include hydrochloric acid, sulfuric acid, and hydrobromic acid. Among these, hydrochloric acid is particularly preferred.
【００２２】非水系溶媒としては、反応に悪影響を及ぼ
さず、水と混じり合わずに二相になるものである限り、
従来公知のものを広く使用でき、例えばジエチルエーテ
ル、ジイソプロピルエーテル等のエーテル類、ベンゼ
ン、トルエン、キシレン等の芳香族炭化水素類、ジクロ
ロメタン、ジクロロエタン、クロロホルム、四塩化炭素
等のハロゲン化炭化水素類、酢酸メチル、酢酸エチル、
酢酸ブチル等のエステル類等を挙げることができる。こ
れらの中でも、ベンゼン、トルエン、キシレン等の芳香
族炭化水素類が好ましく、トルエンが特に好ましい。As the non-aqueous solvent, any solvent which does not adversely affect the reaction and forms two phases without being mixed with water may be used.
Conventionally known ones can be widely used, for example, diethyl ether, ethers such as diisopropyl ether, benzene, toluene, aromatic hydrocarbons such as xylene, dichloromethane, dichloroethane, chloroform, halogenated hydrocarbons such as carbon tetrachloride, Methyl acetate, ethyl acetate,
Esters such as butyl acetate can be exemplified. Among these, aromatic hydrocarbons such as benzene, toluene, and xylene are preferable, and toluene is particularly preferable.
【００２３】非水系溶媒の使用量としては、特に制限さ
れるものではないが、通常一般式（２）で表されるアニ
リン誘導体に対して少なくとも３倍体積量（Ｖ／Ｖ）、
好ましくは３〜５倍体積量（Ｖ／Ｖ）とするのがよい。
また、水の使用量としても、特に制限されるものではな
いが、通常一般式（２）で表されるアニリン誘導体に対
して少なくとも１３倍体積量（Ｖ／Ｖ）、好ましくは１
３〜２０倍体積量（Ｖ／Ｖ）とするのがよい。The amount of the non-aqueous solvent used is not particularly limited, but is usually at least three times the volume (V / V) of the aniline derivative represented by the general formula (2).
Preferably, the volume is 3 to 5 times the volume (V / V).
Although the amount of water used is not particularly limited, it is usually at least 13 times the volume (V / V) of the aniline derivative represented by the general formula (2), preferably 1%.
The volume is preferably 3 to 20 times the volume (V / V).
【００２４】また、本発明においては、一般式（３）で
表されるアルデヒド誘導体は、非水系溶媒に溶解させる
のがよい。In the present invention, the aldehyde derivative represented by the general formula (3) is preferably dissolved in a non-aqueous solvent.
【００２５】本発明では、水と非水系溶媒との界面で、
一般式（２）で表されるアニリン誘導体と一般式（３）
で表されるアルデヒド誘導体との反応が進行する。In the present invention, at the interface between water and the non-aqueous solvent,
The aniline derivative represented by the general formula (2) and the general formula (3)
The reaction with the aldehyde derivative represented by
【００２６】本発明の方法においては、反応系内にホウ
酸を存在させてもよい。反応系内にホウ酸を存在させる
ことにより、一般式（２）で表されるアニリン誘導体と
一般式（３）で表されるアルデヒド誘導体との反応がよ
り一層有利に進行し、収率が一段と向上する場合があ
る。ホウ酸の使用量としては、通常一般式（２）で表さ
れるアニリン誘導体に対して少なくとも等モル量、好ま
しくは等モル〜２倍モル量とするのがよい。ホウ酸は、
水及び非水系溶媒のどちらの系に存在させておいてもよ
い。In the method of the present invention, boric acid may be present in the reaction system. By the presence of boric acid in the reaction system, the reaction between the aniline derivative represented by the general formula (2) and the aldehyde derivative represented by the general formula (3) proceeds more advantageously, and the yield is further increased. May improve. The amount of boric acid to be used is usually at least equimolar, preferably equimolar to 2 times the molar amount of the aniline derivative represented by the general formula (2). Boric acid
It may be present in either the aqueous or non-aqueous solvent system.
【００２７】一般式（２）で表されるアニリン誘導体と
一般式（３）で表されるアルデヒド誘導体との反応にお
いて、両者の使用割合としては、特に制限されるもので
はなく、広い範囲内から適宜選択され得るが、通常前者
に対して後者を少なくとも等モル量、好ましくは等モル
〜３倍モル量とするのがよい。In the reaction between the aniline derivative represented by the general formula (2) and the aldehyde derivative represented by the general formula (3), the ratio of the two used is not particularly limited, and may be within a wide range. Although it can be appropriately selected, the latter is usually at least equimolar, preferably equimolar to 3 times the molar amount of the former.
【００２８】本発明の反応は、室温下及び加温下のいず
れでも進行するが、通常室温〜１５０℃程度、好ましく
は８０〜１２０℃程度で反応を行うのがよく、一般に１
〜３時間程度で該反応は完結する。Although the reaction of the present invention proceeds at room temperature or under heating, it is usually carried out at room temperature to about 150 ° C., preferably at about 80 to 120 ° C.
The reaction is completed in about 3 hours.
【００２９】斯くして得られる本発明の一般式（１）で
表されるハロゲン置換キノリン誘導体は、通常の分離手
段により反応混合物から容易に単離精製される。該分離
手段としては、例えば溶媒抽出法、希釈法、再結晶法、
カラムクロマトグラフィー、プレパラティブ薄層クロマ
トグラフィー等を挙げることができる。The thus obtained halogen-substituted quinoline derivative represented by the general formula (1) of the present invention can be easily isolated and purified from the reaction mixture by ordinary separation means. Examples of the separation means include a solvent extraction method, a dilution method, a recrystallization method,
Column chromatography, preparative thin layer chromatography and the like can be mentioned.
【００３０】本発明において出発原料として用いられる
一般式（２）で表されるアニリン誘導体は、従来公知の
各種の方法により製造される。例えば一般式（２）で表
されるアニリン誘導体は、一般式（４）The aniline derivative represented by the general formula (2) used as a starting material in the present invention is produced by various conventionally known methods. For example, the aniline derivative represented by the general formula (2)
【００３１】[0031]
【化５】 Embedded image
【００３２】〔式中、Ｘ1、Ｘ2及びＸ3は、前記に同
じ。Ｒ2は低級アルカノイル基を示す。〕で表されるア
ニリド誘導体を酸により加水分解することにより製造さ
れる。Wherein X 1 , X 2 and X 3 are as defined above. R 2 represents a lower alkanoyl group. ] Is produced by hydrolyzing an anilide derivative represented by the above formula with an acid.
【００３３】一般式（４）において、Ｒ2で示される低
級アルカノイル基としては、例えばアセチル、プロピオ
ニル、ブチリル、イソブチリル、ペンタノイル、tert−
ブチルカルボニル、へキサノイル基等の炭素数２〜６の
直鎖又は分枝鎖状アルカノイル基を例示できる。In the general formula (4), examples of the lower alkanoyl group represented by R 2 include acetyl, propionyl, butyryl, isobutyryl, pentanoyl and tert-yl.
Examples thereof include a linear or branched alkanoyl group having 2 to 6 carbon atoms such as butylcarbonyl and hexanoyl.
【００３４】[0034]
【実施例】以下に実施例を掲げて、本発明をより一層明
らかにする。The present invention will be further clarified with reference to the following examples.
【００３５】実施例１ ５，６−ジフルオロ−８−ブロモキナルジンの製造 ２−ブロモ−４，５−ジフルオロアセトアニリド４．０
２ｇを懸濁させた６Ｎ塩酸水溶液６４．３ｍｌを３０分
間還流し、２−ブロモ−４，５−ジフルオロアニリンを
得た後、トルエン１６．１ｍｌを反応液に加え、クロト
ンアルデヒド２．６６ｍｌを約１０分かけて滴下した。
滴下後、更に２時間還流下に攪拌し、次いで反応混合物
を室温まで冷却し、水層を２５％水酸化ナトリウム水溶
液及び５０％酢酸ナトリウム水溶液にて中和した後、結
晶を濾取し、５，６−ジフルオロ−８−ブロモキナルジ
ンを３．２４ｇ（収率：７８．２％）得た。 融点：１０７〜１０８℃、白色結晶。Example 1 Preparation of 5,6-difluoro-8-bromoquinaldine 2-bromo-4,5-difluoroacetanilide 4.0
After refluxing 64.3 ml of 6N hydrochloric acid aqueous solution in which 2 g was suspended for 30 minutes to obtain 2-bromo-4,5-difluoroaniline, 16.1 ml of toluene was added to the reaction solution, and 2.66 ml of crotonaldehyde was added thereto. It was added dropwise over 10 minutes.
After the dropwise addition, the mixture was further stirred under reflux for 2 hours, then the reaction mixture was cooled to room temperature, the aqueous layer was neutralized with a 25% aqueous sodium hydroxide solution and a 50% aqueous sodium acetate solution, and the crystals were collected by filtration. 3.24 g (yield: 78.2%) of 2,6-difluoro-8-bromoquinaldine was obtained. Melting point: 107-108 ° C, white crystals.
【００３６】実施例２ ５，６−ジフルオロ−８−ブロモキナルジンの製造 ２−ブロモ−４，５−ジフルオロアセトアニリド５．６
０ｇ及び無水ホウ酸１．３８ｇを懸濁させた６Ｎ塩酸水
溶液１１２ｍｌを３０分間還流し、２−ブロモ−４，５
−ジフルオロアニリンを得た後、トルエン２８ｍｌを反
応液に加え、クロトンアルデヒド３．７１ｍｌを約１０
分かけて滴下した。滴下後、更に２時間還流下に攪拌
し、次いで反応混合物を室温まで冷却し、水層を２５％
水酸化ナトリウム水溶液にて中和した後、結晶を濾取
し、５，６−ジフルオロ−８−ブロモキナルジンを４．
６７ｇ（収率：８１．４％）得た。 融点：１０７〜１０８℃、白色結晶。Example 2 Preparation of 5,6-difluoro-8-bromoquinaldine 2-bromo-4,5-difluoroacetanilide 5.6
0 g and 1.38 g of boric anhydride were suspended in 112 ml of a 6N aqueous hydrochloric acid solution for 30 minutes.
-After obtaining difluoroaniline, 28 ml of toluene was added to the reaction solution, and 3.71 ml of crotonaldehyde was added to about 10 parts.
Dropped over minutes. After the dropwise addition, the mixture was further stirred under reflux for 2 hours, then the reaction mixture was cooled to room temperature, and the aqueous layer was separated by 25%.
After neutralization with an aqueous sodium hydroxide solution, the crystals were collected by filtration, and 5,6-difluoro-8-bromoquinaldine was added.
67 g (yield: 81.4%) was obtained. Melting point: 107-108 ° C, white crystals.
Claims (2)
す。〕で表されるアニリン誘導体に一般式 Ｒ1ＣＨ＝ＣＨＣＨＯ （３） 〔式中、Ｒ1は水素原子又は低級アルキル基を示す。〕
で表されるアルデヒド誘導体を反応させて一般式 【化２】 〔式中、Ｘ1、Ｘ2、Ｘ3及びＲ1は前記に同じ。〕で表さ
れるハロゲン置換キノリン誘導体を製造する方法におい
て、一般式（２）で表されるアニリン誘導体と一般式
（３）で表されるアルデヒド誘導体との反応を、酸の存
在下、水と非水系溶媒との界面で行うことを特徴とする
一般式（１）で表されるハロゲン置換キノリン誘導体の
製造方法。1. A compound of the general formula [Wherein X 1 , X 2 and X 3 each represent a halogen atom. ] To the aniline derivative represented by the general formula R 1 CH = CHOCHO (3) wherein R 1 represents a hydrogen atom or a lower alkyl group. ]
Is reacted with an aldehyde derivative represented by the general formula: [Wherein X 1 , X 2 , X 3 and R 1 are the same as above. In the method for producing a halogen-substituted quinoline derivative represented by the general formula (2), the reaction between the aniline derivative represented by the general formula (2) and the aldehyde derivative represented by the general formula (3) is carried out in the presence of an acid with water. A method for producing a halogen-substituted quinoline derivative represented by the general formula (1), which is performed at an interface with a non-aqueous solvent.
誘導体を溶解乃至分散させた水と一般式（３）で表され
るアルデヒド誘導体を溶解させた非水系溶媒との界面で
アニリン誘導体とアルデヒド誘導体との反応を行う請求
項１に記載のハロゲン置換キノリン誘導体の製造方法。2. An aniline derivative at an interface between water in which an acid and an aniline derivative represented by the general formula (2) are dissolved or dispersed and a non-aqueous solvent in which an aldehyde derivative represented by the general formula (3) is dissolved. 2. The method for producing a halogen-substituted quinoline derivative according to claim 1, wherein the reaction is carried out with an aldehyde derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31903599A JP4258590B2 (en) | 1999-11-10 | 1999-11-10 | Method for producing halogen-substituted quinoline derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31903599A JP4258590B2 (en) | 1999-11-10 | 1999-11-10 | Method for producing halogen-substituted quinoline derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001139554A true JP2001139554A (en) | 2001-05-22 |
| JP4258590B2 JP4258590B2 (en) | 2009-04-30 |
Family
ID=18105796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP31903599A Expired - Lifetime JP4258590B2 (en) | 1999-11-10 | 1999-11-10 | Method for producing halogen-substituted quinoline derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4258590B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114890945A (en) * | 2022-04-06 | 2022-08-12 | 大连万福制药有限公司 | Method for synthesizing nadifloxacin intermediate |
-
1999
- 1999-11-10 JP JP31903599A patent/JP4258590B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114890945A (en) * | 2022-04-06 | 2022-08-12 | 大连万福制药有限公司 | Method for synthesizing nadifloxacin intermediate |
| CN114890945B (en) * | 2022-04-06 | 2023-09-05 | 大连万福制药有限公司 | Method for synthesizing nadifloxacin intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4258590B2 (en) | 2009-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2462098B1 (en) | Process for the preparation of derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid | |
| US6649796B2 (en) | Process for the preparation of acetamide derivatives | |
| TW202000643A (en) | Process for the preparation of a nitric oxide donating prostaglandin analogue | |
| JP2688712B2 (en) | Method for producing halogen-substituted quinoline derivative | |
| JP2005526049A (en) | Preparation of benzisoxazole methanesulfonyl chloride and its method of amidation to form zonisamide | |
| JP2001139554A (en) | Method for producing halogen-substituted quinoline derivative | |
| HU205915B (en) | Process for producing herbicide ortho-carboxy-aryl-imidazolinone derivatives | |
| EP1114812B1 (en) | Processes for the preparation of fluorinated benzoic acids | |
| KR100634721B1 (en) | A process for the preparation of 4,4'-dihalogen-o-hydroxydiphenyl compounds | |
| HU196582B (en) | Process for separating racem mixtures of optically active alpha-naphthyl-propionic acids | |
| JP2009508851A (en) | Process for producing β-ketoester compound | |
| JP2000229930A (en) | Production of cyanoacetate ester | |
| JP2688712C (en) | ||
| JP5087059B2 (en) | Process for producing 4- (2-methyl-1-imidazolyl) -2,2-diphenylbutanamide | |
| JP3573249B2 (en) | 2,3,4-trifluoro-5-iodobenzoic acid, esters thereof and process for producing the same | |
| JP3823385B2 (en) | Process for producing 2,4,5-trifluoro-3-iodobenzoic acid and esters thereof | |
| JPH0623168B2 (en) | Process for producing benzenesulfonyl chloride derivative | |
| EP1082290A1 (en) | Process for the preparation of aceclofenac | |
| US6355836B1 (en) | Process for the preparation of cis 5-fluoro-2-methyl-1[p-(methylthio)benzyliden]-inden-3-acetic acid | |
| JP2520298B2 (en) | Method for producing thiophene dicarboxylic acid diester | |
| JP2003335758A (en) | Pyridine derivative, method for producing the same and use as herbicide intermediate | |
| KR0119280B1 (en) | Substituted n-pyridylme thyl and preparation thereof | |
| JP3443584B2 (en) | Method for producing N-tert-butylpyrazinecarboxamides | |
| KR910003635B1 (en) | Process for the preparation of 2-(2-naphthyloxy)propion anilide derivatives | |
| JPH06135937A (en) | Production of 5,5-disubstituted hydantoin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050113 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080917 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081023 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090107 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090127 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120220 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4258590 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120220 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130220 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160220 Year of fee payment: 7 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |