JPS605599B2 - Method for producing aminobenzophenone derivatives - Google Patents

Method for producing aminobenzophenone derivatives

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Publication number
JPS605599B2
JPS605599B2 JP49090566A JP9056674A JPS605599B2 JP S605599 B2 JPS605599 B2 JP S605599B2 JP 49090566 A JP49090566 A JP 49090566A JP 9056674 A JP9056674 A JP 9056674A JP S605599 B2 JPS605599 B2 JP S605599B2
Authority
JP
Japan
Prior art keywords
methyl
acid
group
hydrogen
formula
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
Application number
JP49090566A
Other languages
Japanese (ja)
Other versions
JPS5126854A (en
Inventor
健太郎 平井
てる之 石破
和幸 笹倉
裕彦 杉本
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shionogi and Co Ltd
Original Assignee
Shionogi and Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd
Priority to JP49090566A priority Critical patent/JPS605599B2/en
Priority to CA000232782A priority patent/CA1181065A/en
Priority to NLAANVRAGE7509258,A priority patent/NL175789C/en
Priority to SE7508829A priority patent/SE427030B/en
Priority to CH1020275A priority patent/CH617668A5/de
Priority to DK356475A priority patent/DK155088C/en
Priority to ES440032A priority patent/ES440032A1/en
Priority to MX000859U priority patent/MX3332E/en
Priority to HU75SI1485A priority patent/HU176016B/en
Priority to AR259900A priority patent/AR213076A1/en
Priority to AU83734/75A priority patent/AU491928B2/en
Priority to DE2535171A priority patent/DE2535171C3/en
Priority to DD187724A priority patent/DD119213A5/xx
Priority to GB32916/75A priority patent/GB1511669A/en
Priority to FR7524559A priority patent/FR2281131A1/en
Publication of JPS5126854A publication Critical patent/JPS5126854A/ja
Priority to US05/716,265 priority patent/US4076702A/en
Priority to US05/716,267 priority patent/US4076704A/en
Priority to US05/716,268 priority patent/US4076705A/en
Priority to US05/716,266 priority patent/US4076703A/en
Priority to ES455504A priority patent/ES455504A1/en
Priority to ES455506A priority patent/ES455506A1/en
Priority to ES455505A priority patent/ES455505A1/en
Priority to ES455507A priority patent/ES455507A1/en
Priority to US05/775,646 priority patent/US4240957A/en
Priority to AR270154A priority patent/AR219307A1/en
Priority to AR270151A priority patent/AR213453A1/en
Priority to AR270152A priority patent/AR215035A1/en
Priority to AR270153A priority patent/AR220325A1/en
Priority to US05/867,605 priority patent/US4154727A/en
Priority to CH461879A priority patent/CH627439A5/en
Priority to CH461779A priority patent/CH627438A5/en
Priority to CH827079A priority patent/CH627440A5/en
Priority to CA339,232A priority patent/CA1091652A/en
Publication of JPS605599B2 publication Critical patent/JPS605599B2/en
Expired legal-status Critical Current

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

【発明の詳細な説明】 本発明は一般式 ［式中、 Ｒは水素またはアルキル基（例えば、メチル、エチル、
プロピル、ブチル、ベンチル）、ＲＩは水素またはペン
ジル、 Ｒ２は水素、 Ｒ３は水素またはハロゲン（例えば、フッ素、塩素、臭
素）、Ｒ４はハロゲン（例えば、フッ素、塩素、臭素、
）、Ｚはアミノ保護塞く例えば、カルボベンゾキシ、ト
リチル、メトキシカルポニル、ｔーブトキシカルボニル
、ｐーメトキシベンジルオキシカルボニル、ｏーニトロ
フエニルオキシカルボニル、クロロベンジルオキシカル
ボニル）を表わすか、まけば−☆−批フタルィミド基を
形成してもよい］，！。DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula [wherein R is hydrogen or an alkyl group (e.g., methyl, ethyl,
RI is hydrogen or pendyl, R2 is hydrogen, R3 is hydrogen or halogen (e.g., fluorine, chlorine, bromine), R4 is halogen (e.g., fluorine, chlorine, bromine,
), Z represents an amino-protected group such as carbobenzoxy, trityl, methoxycarbonyl, t-butoxycarbonyl, p-methoxybenzyloxycarbonyl, o-nitrophenyloxycarbonyl, chlorobenzyloxycarbonyl), or −☆− may form a phthalimide group],! .

で示されるインドール誘導体を酸化することを特徴とす
る一般式［式中、Ｒ、Ｒ１、Ｒ２、Ｒ３、Ｒ４およびＺ
は前記と同意義を有する。[wherein R, R1, R2, R3, R4 and Z
has the same meaning as above.

］で示されるアミノベンゾフェノン誘導体の製造法。] A method for producing an aminobenzophenone derivative.

本発明方法は次式によって示される。The method of the present invention is shown by the following equation.

［式中、Ｒ、Ｒ１、Ｒ２、Ｒ３、Ｒ４およびＺは前記と
同意義を有する。[In the formula, R, R1, R2, R3, R4 and Z have the same meanings as above.

］本発明方法に従って、原料物質（ロ）を酸化して目的
物質（１）を生成させ、必要ならさらに保護基（ただし
、ここで保護基とはアミノ保護基のほかフタルィミド基
の場合も含む）を脱離させてアミノベンゾフェノン誘導
体（１′）に導く。] According to the method of the present invention, the raw material (b) is oxidized to produce the target substance (1), and if necessary, a protecting group is added (however, the protecting group here includes not only an amino protecting group but also a phthalimide group). is eliminated to lead to the aminobenzophenone derivative (1').

酸化手段としては、酸素、オゾン、過酸化水素、クロム
酸、過酸（例えば、過酢酸）、過マンガン酸カリウム、
二酸化マンガン、過ヨウ素酸ナトリウムなどが例示され
る。この酸化反応は二重結合を酸化してケトンに導くた
めの一般的な処理手段に従えばよい。またこの酸化反応
による生成物がアミノ保護基またはフタルィミド基を有
するときに、必要ならば、さらにこれを脱離させてもよ
い。そのためにはべプチド類のアミノ保護基を脱離させ
る一般的処理手段を採用すればよい。例えば、アミノ基
がカルボベンゾキシ基によって保護されているときには
、目的物質（１）を臭化水素酸、フツ化水素酸、トリフ
ルオロ酢酸などと処理すればよいし、トリチル基で保護
されているときには希酢酸と加熱処理すればよく、さら
にフタリル基で保護され＊ているときには、例えば、ヒ
ドラジン／ジメチルホルムアミドと室温下に処理すれば
よい。原料物質であるインドール譲導体（０）は、例え
ば、２−メチルインドール類（ｍ）から数工程で得られ
る：［式中、Ｒ、Ｒ１、Ｒ２、Ｒ３、Ｒ４およびＺは前
記と同意義を有する。Oxidation means include oxygen, ozone, hydrogen peroxide, chromic acid, peracids (e.g. peracetic acid), potassium permanganate,
Examples include manganese dioxide and sodium periodate. This oxidation reaction may be carried out in accordance with general treatment methods for oxidizing double bonds to lead to ketones. Furthermore, when the product of this oxidation reaction has an amino protecting group or a phthalimide group, this may be further removed if necessary. For this purpose, a general treatment means for removing the amino protecting group of peptides may be employed. For example, when the amino group is protected by a carbobenzoxy group, the target substance (1) may be treated with hydrobromic acid, hydrofluoric acid, trifluoroacetic acid, etc.; Sometimes, it is sufficient to heat-treat with dilute acetic acid, and when it is further protected with a phthalyl group, it may be treated with, for example, hydrazine/dimethylformamide at room temperature. The indole derivative (0), which is a raw material, can be obtained, for example, from 2-methylindoles (m) in several steps: [wherein R, R1, R2, R3, R4 and Z have the same meaning as above] have

］本発明の目的物質（１）を製剤化、結晶化、安定性の
向上などのために適当な酸付加塩、例えば、塩酸、硫酸
、硝酸、リン酸、チオシアン酸などの無機酸の酸付加塩
あるいは酢酸、コハク酸、修酸、マレィン酸〜リンゴ酸
、フタル酸などの有機酸の酸付加塩に導くこともできる
。] In order to formulate the target substance (1) of the present invention, crystallize it, improve its stability, etc., use an appropriate acid addition salt, for example, acid addition of an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, or thiocyanic acid. It can also be converted into acid addition salts of organic acids such as acetic acid, succinic acid, oxalic acid, maleic acid to malic acid, and phthalic acid.

かくして得られるアミノベンゾフェノン譲導体（１）お
よびその酸付加塩は優れた向精神作用、とくに静穏作用
、抗けいれん作用、催眠作用、筋弛緩作用などを示し、
抗不安剤、抗けいれん剤、催眠剤などの向精神薬または
これらの合成中間体として有用である。この目的物質（
１）はさらに家禽類や家畜類の生長促進剤としての用途
も期待できる。例えば、２−ｏークロロベンゾイルー４
−クロローＮーメチルーＮＱーグリシルグリシンアニリ
ド・一水和物は抗けいれん作用（ペンチレンテトラゾー
ルに対する）ではＥＤ５ｏｏ．６の９／ｋ９（マウス、
経口投与）または馴化作用ではＥＤ５。３．０奴／ｋ９
（マウス、経口投与）を示した。The aminobenzophenone derivative (1) and its acid addition salt thus obtained exhibit excellent psychoactive effects, particularly sedative, anticonvulsant, hypnotic, and muscle relaxing effects.
It is useful as a psychotropic agent such as an anxiolytic agent, an anticonvulsant, a hypnotic agent, or a synthetic intermediate thereof. This target substance (
1) can also be expected to be used as a growth promoter for poultry and livestock. For example, 2-o-chlorobenzoyl-4
-Chloro-N-methyl-NQ-glycylglycine anilide monohydrate has an anticonvulsant effect (against pentylenetetrazole) with an ED5oo. 6 of 9/k9 (mouse,
Oral administration) or habituation effect: ED5.3.0 n/k9
(mouse, oral administration).

以下に本発明方法の実験例を示す。Experimental examples of the method of the present invention are shown below.

実施例 １ （１）１−メチル−２−（カルボベンゾキシ−ｄｌ−フ
エニルアラニル）アミノメチルー３一ｏ−クロロフヱニ
ルー５ークロロインドール２．８６夕を酢酸１５の‘に
懸濁させ、これに無水クロム酸１．５夕を水１．４机上
；こ溶解した溶液を１３〜２１℃で５分間にて滴下し、
室温下に４時間櫨拝する。Example 1 (1) 2.86 g of 1-methyl-2-(carbobenzoxy-dl-phenylalanyl)aminomethyl-3-o-chlorophenyl-5-chloroindole was suspended in 15% of acetic acid, and chromic anhydride was added to this. 1.5 minutes of water and 1.4 minutes of water were dissolved on the desk; the solution was added dropwise at 13 to 21°C for 5 minutes,
Let it stand at room temperature for 4 hours.

反応液に氷水を加え、クロロホルムで抽出する。有機層
を水洗し、乾燥し、溶媒を留去する。残櫨をシリカゲル
のカラムクロマトグラフイーに付し、エーテルにて溶出
させると、飴状物として２一ｏークロロベンゾイル−４
ークロロ−Ｎ−メチル−ＮＱ一（カルボベンゾキシーｄ
ｌーフエニルアラニル）グリシンアニリド１．７５夕を
得る。ＵＶ：入幕磯２５６（ｓｈ）、２９８（ｓｈ）の
ｒ（ｌｏｇご：４．０１・３．４４）。‘２） ２−ｏ
ークロロベンゾイル−４ークロロ−Ｎーメチル−ＮＱ−
（カルボベンゾキシ−ｄｌーフェニルアラニル）グリシ
ンアニリド１．６５のこ臭化水素酸２１．８％を含む酢
酸を加え、１時間３０分間室温下に鷹拝する。Add ice water to the reaction solution and extract with chloroform. The organic layer is washed with water, dried, and the solvent is distilled off. When the residue was subjected to silica gel column chromatography and eluted with ether, 2-o-chlorobenzoyl-4 was obtained as a candy.
-Chloro-N-methyl-NQ-(carbobenzoxy d
1.75 g of l-phenylalanyl)glycine anilide are obtained. UV: Irimakuiso 256 (sh), 298 (sh) r (log: 4.01, 3.44). '2) 2-o
-chlorobenzoyl-4-chloro-N-methyl-NQ-
Acetic acid containing 1.65% of (carbobenzoxy-dl-phenylalanyl)glycinanilide and 21.8% of hydrobromic acid was added, and the mixture was allowed to stand at room temperature for 1 hour and 30 minutes.

反応液に無水エーテルを加え、析出する結晶を炉取する
と、融点２０６〜２０９００（分解点）の結晶として２
−ｏークロロベンゾイル−４ークロロ−Ｎーメチル−Ｎ
Ｑ−（ｄｌ−フエニルアラニル）グリシンアニリド・臭
化水素酸塩・水和物１．３夕を得る。ＵＶ：＾岳袋日２
５８（ｓｈ）、３００（ｓｈ）の仏（ｌｏｇご＝３．９
７、３．３５）。実施例 ２ １−メチル−２一（トリチルグリシル）アミノメチル−
３−ｏークロロフエニルー５ークロロインドール２．０
２夕を酢酸１０の‘に懸濁し、これに無水クロム酸０．
８１夕を水０．６の‘に溶解した溶液を加え「室温下に
２数時間灘拝する。When anhydrous ether is added to the reaction solution and the precipitated crystals are collected in a furnace, 2
-o-chlorobenzoyl-4-chloro-N-methyl-N
1.3 g of Q-(dl-phenylalanyl)glycinanilide hydrobromide hydrate is obtained. UV: ＾Takebukuro Day 2
58 (sh), 300 (sh) Buddha (log = 3.9
7, 3.35). Example 2 1-Methyl-2-(tritylglycyl)aminomethyl-
3-o-chlorophenyl-5-chloroindole 2.0
2 parts of chromic anhydride was suspended in 10 parts of acetic acid, and 0.0 parts of chromic anhydride was added to this.
Add a solution prepared by dissolving 81g in 0.6 parts of water and let it stand at room temperature for a few hours.

反応液に水２２の‘を加え、析出する結晶を炉去する。
炉液に２８％アンモニア水１２叫を加え、クロロホルム
にて抽出する。有機層を水洗し、乾燥し、溶媒を留去す
る。残鷹をエタノールに溶解し、これに修酸のエタノー
ル溶液を加える。析出する結晶０．５夕をエタノールよ
り再結晶し、融点１６７ｑ０以下の結晶として２一ｏー
クロロベンゾイルー４ークロロ−Ｎ−メチル−ＮＱーグ
リシルグリシンアニリド・修酸塩を得る。ＵＶ：入幕髪
日２５３２９８（ｓｈ）の仏（１■ど＝３．９８３．３
４）。実施例 ３ １ーメチル−２一（カルボベンゾキシグリシル）アミノ
メチルー３一ｏ−クロロフエニル−５ークロロィンドー
ル９．１夕を酢酸５５の‘に熔解し「これに無水クロム
酸５．５夕を水５．１の‘に溶解した溶液を２０ｏｏ以
下にて滴下し、室温下に一夜放置する。Add 22 parts of water to the reaction solution, and remove the precipitated crystals.
Add 12 parts of 28% ammonia water to the furnace solution and extract with chloroform. The organic layer is washed with water, dried, and the solvent is distilled off. Dissolve the residue in ethanol, and add an ethanolic solution of oxalic acid to this. 0.5 days of precipitated crystals are recrystallized from ethanol to obtain 21-chlorobenzoyl-4-chloro-N-methyl-NQ-glycylglycinanilide oxalate as crystals with a melting point of 167q0 or less. UV: Buddha of 253298 (sh) on the opening day (1 ■ = 3.983.3
4). Example 3 1-Methyl-2-(carbobenzoxyglycyl)aminomethyl-3-o-chlorophenyl-5-chloroindole was dissolved in 55 parts of acetic acid, and 5.5 parts of chromic anhydride was added to it. A solution dissolved in 5.1 parts of water was added dropwise at a concentration of 20 ml or less, and the mixture was left overnight at room temperature.

反応液を氷水を加え、酢酸エチルで抽出する。有機層を
水洗し、乾燥し、溶媒を蟹去する。残糟をシリカゲルの
カラムクロマトグラフィーに付し、酢酸エチルにて溶出
させると、飴状物として２一ｏ−クロロベンゾイル−４
−クロロ−Ｎ−メチル一ＮＱ−（カルボベンゾキシグリ
シル）グリシンァニリド３．６夕を得る。これに臭化水
素酸２１．８％を含有する酢酸１１．５肌を加え、１時
間３０分室温下に鷹拝する。反応液にエーテルを加え、
結晶を析出させる。この結晶を炉取し、水に溶解し、炭
酸水素ナトリウム水溶液で中和する。析出物を炉取し、
２−ｏークロロベンゾィル−４−クロロ−Ｎーメチル−
ＮＱーグリシルグリシンアニリド・水和物１．８夕を得
る。本品を酢酸エチルより再結晶すれば、融点８〆○以
上のプリズム晶が得られる。実施例 ４〜８ 下記の原料物質（０）を用いて実施例３と同機に反応を
行い、対応する各生成物（ｌａ）（ｌｂ）を得る：表１ 注 表中の各略号は以下の意義を有する：日（水素）、
Ｍｅ（メチル基）、Ｂｚ（ベンジル基）、Ｃｂｚ（カル
ポベンゾキシ基）、Ｃｍ（メトキシカルボニル基）、Ｃ
Ｉ（塩素）。Add ice water to the reaction solution and extract with ethyl acetate. The organic layer is washed with water, dried and the solvent is removed. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate to produce 21o-chlorobenzoyl-4 as a candy.
3.6 hours of -chloro-N-methyl-NQ-(carbobenzoxyglycyl)glycinanilide are obtained. To this was added 11.5% acetic acid containing 21.8% hydrobromic acid, and the mixture was allowed to stand at room temperature for 1 hour and 30 minutes. Add ether to the reaction solution,
Precipitate crystals. The crystals are collected in an oven, dissolved in water, and neutralized with an aqueous sodium bicarbonate solution. The precipitate is removed by furnace,
2-o-chlorobenzoyl-4-chloro-N-methyl-
1.8% of NQ-glycylglycine anilide hydrate is obtained. If this product is recrystallized from ethyl acetate, prismatic crystals with a melting point of 8〆○ or higher can be obtained. Examples 4 to 8 Using the following raw materials (0), the reaction was carried out in the same machine as in Example 3 to obtain the corresponding products (la) and (lb): Table 1 Note Each abbreviation in the table is as follows. Significant: day (hydrogen),
Me (methyl group), Bz (benzyl group), Cbz (carpobenzoxy group), Cm (methoxycarbonyl group), C
I (chlorine).

【ａ｝ １体、【ｂ｝ ｄ体。[a} 1 body, [b} d body.

実施例 ９ １−メチル一２−（カルボベンゾキシグリシル）アミノ
メチル−３一ｏ−フルオロフエニルー５−クロロィンド
ールを使用して、実施例１‘１｝、■と同様に反応を行
いシロップ状物質として２−ｏ−フルオロベンゾイルー
４ークロローＮーメチルーＮＱーグリシルグリシンアニ
リドを得る。Example 9 Using 1-methyl-2-(carbobenzoxyglycyl)aminomethyl-3-o-fluorophenyl-5-chloroindole, the reaction was carried out in the same manner as in Example 1'1}, 2. 2-o-fluorobenzoyl-4-chloro-N-methyl-NQ-glycylglycine anilide is obtained as a syrup-like substance.

本品の塩酸塩は融点８０ｏｏ以上の無定形固形物である
。元素分析 Ｃ，８日，８Ｎ３０３ＣＩ２Ｆとして計算
値 Ｃ、５２．１９；日、４．３８：Ｎ、１０．１４：
ＣＩ、１７．１１：Ｆ、４．５８実験値Ｃ、５１．９７
；日、４．８３：Ｎ、９・８０：ＣＩ、１６．５９；Ｆ
、４．２４実施例 １０ ｍ １−メチル一２一（フタリルグリシル）アミノメチ
ルー３−ｏ−クロロフエニルー５−クロロインドール１
．００夕および酢酸２５のとからなる溶液に、無水クロ
ム酸４０６雌および水２の【からなる溶液を鷹洋下徐々
に加え、２２〜２５ｑｏにて４時間燈拝し、減圧濃縮し
て約半量とする。The hydrochloride of this product is an amorphous solid with a melting point of 80 oo or higher. Elemental analysis C, 8th, calculated value as 8N303CI2F C, 52.19; day, 4.38:N, 10.14:
CI, 17.11: F, 4.58 Experimental value C, 51.97
;Sun, 4.83:N, 9.80:CI, 16.59;F
, 4.24 Example 10 m 1-Methyl-2-(phthalylglycyl)aminomethyl-3-o-chlorophenyl-5-chloroindole 1
．． A solution consisting of 406 parts of chromic anhydride and 2 parts of water was gradually added to a solution of 25 parts of chromic anhydride and 25 parts of acetic acid under an eagle, heated for 4 hours at 22 to 25 qo, and concentrated under reduced pressure to give about half the volume. shall be.

残笹に氷水を加え、沈澱物を炉取する。炉液を酢酸エチ
ルで抽出し、上記沈澱物を酢酸エチル層に溶解する。酢
酸エチル溶液をシリカゲルによるカラムクロマトグラフ
ィーに付し、溶出液を濃縮する。孫笹を塩化メチレン／
メタノールから再結晶すると融点２１６〜２１８ｑ０の
結晶として２−ｏ−クロロベンゾイル−４−クロローＮ
−メチル一ＮＱ一（フタリルグリシル）グリシンアニリ
ド５８０の９を得る。（２’ ２−ｏークロロベンゾイ
ルー４−クロローＮーメチル−Ｎ一（フタリルグリシル
）グリシンアニリド１．０５６夕をジメチルホルムアミ
ド２０Ｍに溶解し、これにヒドラジンヒドラート１８０
の９およびジメチルホルムアミド４の【からなる溶液を
−８〜一６℃にて櫨梓下に加え、一８℃〜室温にて１時
間鷹拝する。Add ice water to the remaining bamboo and filter out the precipitate. The furnace liquor is extracted with ethyl acetate, and the precipitate is dissolved in the ethyl acetate layer. The ethyl acetate solution is subjected to column chromatography on silica gel, and the eluate is concentrated. Magozasa with methylene chloride/
Recrystallization from methanol gives 2-o-chlorobenzoyl-4-chloroN as crystals with a melting point of 216-218q0.
-Methyl-NQ-(phthalylglycyl)glycine anilide 580 9 is obtained. (2' 1.056 ml of 2-o-chlorobenzoyl-4-chloro-N-methyl-N-(phthalylglycyl)glycinanilide was dissolved in 20 M dimethylformamide, and 180 ml of hydrazine hydrate was dissolved in this.
A solution consisting of (9) and dimethylformamide (4) was added to the lily pad at -8 to -6°C, and incubated at -8°C to room temperature for 1 hour.

０℃に冷却したのち、反応液にＮ塩酸４の‘を２０分間
で加え、０℃に１７時間放置する。After cooling to 0°C, 4 parts of N-hydrochloric acid was added to the reaction solution over 20 minutes, and the mixture was left at 0°C for 17 hours.

反応液を氷水２００舷および酢酸エチル１００の‘の混
合液に注ぎ、２８％アンモニア水溶液でアルカリ性（ｐ
Ｈ８）とする。酢酸エチル層を分離し、水洗し、無水洋
硝にて乾燥し、減圧濃縮すると残澄５００の９を得る。
水層はクロロホルム抽出を繰り返し同一物質４１０の９
を得る。両物質を合し、エタノール１０の‘に溶解し、
０℃以下に冷却下水２５地と混合する。沈澱した結晶を
炉過して融点９５〜１００ｏｏの結晶として２一ｏ−ク
ロロベンゾイルー４ークロロ−Ｎ−メチル−ＮＱ−グリ
シルグリシンアニリド・一水和物７２２の９を得る。収
率８７％。本品のへミシトレートは融点１１４〜１１６
ｏｏを示す。実施例 １１ 前記実施例１０と同機に反応を行い、２ーベンゾイル−
４ークロローＮーメチルーＮＱーグリシルグリシンアニ
リドを得る。The reaction solution was poured into a mixture of 200 g of ice water and 100 g of ethyl acetate, and made alkaline (p
H8). The ethyl acetate layer was separated, washed with water, dried over anhydrous nitrogen, and concentrated under reduced pressure to obtain a residue of 9 of 500.
The aqueous layer was extracted with chloroform repeatedly and the same substance 410-9
get. Both substances were combined and dissolved in 10 parts of ethanol,
Mix with 25 sewage cooled to below 0℃. The precipitated crystals are filtered to obtain 21o-chlorobenzoyl-4-chloro-N-methyl-NQ-glycylglycinanilide monohydrate 722-9 as crystals with a melting point of 95-100 oo. Yield 87%. This product's hemicitrate has a melting point of 114-116.
Indicates oo. Example 11 A reaction was carried out in the same machine as in Example 10, and 2-benzoyl-
4-chloro N-methyl-NQ-glycylglycine anilide is obtained.

融点約６０００附近の無定形物。実施例 １２ ｛１｝ １−メチル−２−（フタリルグリシル）アミノ
メチル−３−ｏークロロフエニルー５ークロロィンドー
ルを使用して、実施例１ｍと同様に反応を行い、２−ｏ
ークロロフェニル−４ークロロ−Ｎ−メチル一ＮＱ−（
フタリルグリシル）グリシンアニリドを得る。Amorphous substance with melting point around 6000. Example 12 {1} A reaction was carried out in the same manner as in Example 1m using 1-methyl-2-(phthalylglycyl)aminomethyl-3-o-chlorophenyl-5-chloroindole, and 2-o
-chlorophenyl-4-chloro-N-methyl-NQ-(
phthalylglycyl)glycine anilide is obtained.

（２） ２一ｏークロロベンゾイル−４ークロロ−Ｎ−
メチル−ＮＱ一（フタリルグリシル）グリシンアニリド
８１．０夕をエタノール５０の‘に懸濁した溶液にヒド
ラジンヒドラート２０柵を加えたのち「約３０分間還流
する。(2) 21o-chlorobenzoyl-4-chloro-N-
To a solution of 81.0 g of methyl-NQ-(phthalylglycyl)glycine anilide suspended in 50 g of ethanol, 20 g of hydrazine hydrate was added and refluxed for about 30 minutes.

冷後、反応液を炉遇して析出したフェニルヒドラジッド
を除く。炉液を濃縮したのち、エーテルで洗浄すると２
−ｏ−クロロベンゾイル−４−クロロ−Ｎーメチル−Ｎ
Ｑ−グリシルグリシンアニｌｊド・一水和物５５．雛を
得る。本品を希エタノールより再結晶すると融点９５〜
１００℃の結晶となる。塩酸塩・１′が２０ 融点２１
４〜２１５ｑｏ（分解）Ｃ瓜Ｓ０３別塩 融点２２１〜
２２３ｑｏへミシトレート 融点１１４〜１１がｏ オキザレート 融点１６７ｑ０以下After cooling, the reaction solution was heated in a furnace to remove precipitated phenyl hydrazide. After concentrating the furnace liquid and washing with ether, 2
-o-chlorobenzoyl-4-chloro-N-methyl-N
Q-glycylglycine aniljde monohydrate 55. get chicks. When this product is recrystallized from dilute ethanol, the melting point is 95~
It becomes a crystal at 100°C. Hydrochloride, 1' is 20, melting point 21
4~215qo (decomposition) C melon S03 different salt Melting point 221~
223qo Hemisitrate Melting point 114-11 is o Oxalate Melting point 167q0 or less

Claims (1)

【特許請求の範囲】 １ 一般式 ▲数式、化学式、表等があります▼ ［式中、 Ｒは水素またはアルキル基、 Ｒ＾１は水素またはベンジル基、 Ｒ＾２は水素、 Ｒ＾３は水素またはハロゲン、 Ｒ＾４はハロゲン、 Ｚはアミノ保護基を表わすか、または ▲数式、化学式、表等があります▼ はフタルイミド基を形成してもよい。 ］で示されるインドール誘導体を酸化することを特徴と
する一般式▲数式、化学式、表等があります▼ ［式中、Ｒ、Ｒ＾１、Ｒ＾２、Ｒ＾３、Ｒ＾４およびＺ
は前記と同意義を有する。 ］で示されるアミノベンゾフエノン誘導体の製造法。[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R is hydrogen or an alkyl group, R^1 is hydrogen or a benzyl group, R^2 is hydrogen, R^3 is hydrogen or halogen, R^4 is halogen, Z represents an amino protecting group, or ▲a numerical formula, chemical formula, table, etc.▼ may form a phthalimide group. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by the oxidation of indole derivatives represented by ▼ [In the formula, R, R^1, R^2, R^3, R^4 and Z
has the same meaning as above. ] A method for producing an aminobenzophenone derivative.
JP49090566A 1974-08-06 1974-08-06 Method for producing aminobenzophenone derivatives Expired JPS605599B2 (en)

Priority Applications (33)

Application Number Priority Date Filing Date Title
JP49090566A JPS605599B2 (en) 1974-08-06 1974-08-06 Method for producing aminobenzophenone derivatives
CA000232782A CA1181065A (en) 1974-08-06 1975-07-31 Dipeptide derivatives and their production
NLAANVRAGE7509258,A NL175789C (en) 1974-08-06 1975-08-04 PROCESS FOR PREPARING A PHARMACEUTICAL PREPARATION WITH CALMING ACTION AND PROCESS FOR PREPARING MEDICINAL AMINOIC ACID ANILIDES.
SE7508829A SE427030B (en) 1974-08-06 1975-08-05 PROCEDURE FOR PREPARING BENZOPHENON DERIVATIVES WITH ANTICONVULVIC EFFECT
CH1020275A CH617668A5 (en) 1974-08-06 1975-08-05
DK356475A DK155088C (en) 1974-08-06 1975-08-05 METHOD OF ANALOGUE FOR PREPARING BENZOPHENON-SUBSTITUTED DIPEPTIDE DERIVATIVES OR ACID ADDITION SALTS.
ES440032A ES440032A1 (en) 1974-08-06 1975-08-05 Dipeptide derivatives and their production
MX000859U MX3332E (en) 1974-08-06 1975-08-05 PROCEDURE FOR THE PREPARATION OF DIPEPTIDE DERIVATIVES
HU75SI1485A HU176016B (en) 1974-08-06 1975-08-05 Process for producing dipeptide derivatives
AR259900A AR213076A1 (en) 1974-08-06 1975-08-05 PROCEDURE FOR THE PRODUCTION OF DERIVATIVES OF THE SUBSTITUTED GLICILGLICILANILIDE
AU83734/75A AU491928B2 (en) 1974-08-06 1975-08-06 Dipeptide derivatives and their production
DE2535171A DE2535171C3 (en) 1974-08-06 1975-08-06 Benzophenone derivatives and drugs containing these compounds
DD187724A DD119213A5 (en) 1974-08-06 1975-08-06
GB32916/75A GB1511669A (en) 1974-08-06 1975-08-06 Dipeptide derivatives and their production
FR7524559A FR2281131A1 (en) 1974-08-06 1975-08-06 DIPEPTIDE DERIVATIVES AND THEIR PREPARATION
US05/716,266 US4076703A (en) 1974-08-06 1976-08-20 Dipeptide derivatives and their production
US05/716,267 US4076704A (en) 1974-08-06 1976-08-20 Dipeptide derivatives and their production
US05/716,265 US4076702A (en) 1974-08-06 1976-08-20 Dipeptide derivatives and their production
US05/716,268 US4076705A (en) 1974-08-06 1976-08-20 Dipeptide derivatives and their production
ES455504A ES455504A1 (en) 1974-08-06 1977-01-31 Dipeptide derivatives and their production
ES455506A ES455506A1 (en) 1974-08-06 1977-01-31 Dipeptide derivatives and their production
ES455505A ES455505A1 (en) 1974-08-06 1977-01-31 Dipeptide derivatives and their production
ES455507A ES455507A1 (en) 1974-08-06 1977-01-31 Dipeptide derivatives and their production
US05/775,646 US4240957A (en) 1974-08-06 1977-03-07 Dipeptide derivatives and their production
AR270153A AR220325A1 (en) 1974-08-06 1977-11-28 PROCEDURE FOR THE PREPARATION OF DERIVATIVES OF GLICIL-GLICIL-2-BENZOIL-5-HALOANILIDE AND ITS SALTS
AR270154A AR219307A1 (en) 1974-08-06 1977-11-28 PROCEDURE FOR THE PREPARATION OF DERIVATIVES OF 2-BENXOIL-N ALPHA-GLICIL-GLICIL OR N ALPHA-A-FENILALANILGLICILANILIDA
AR270151A AR213453A1 (en) 1974-08-06 1977-11-28 PROCEDURE FOR THE PREPARATION OF DERIVATIVES OF THE SUBSTITUTED GLICILGLICILANILIDE
AR270152A AR215035A1 (en) 1974-08-06 1977-11-28 PROCEDURE FOR THE PREPARATION OF DERIVATIVES OF 2-BENZOIL-N-ALKYL (C1-C6) -N-A- (GLICIL) GLYCINANILIDE
US05/867,605 US4154727A (en) 1974-08-06 1978-01-06 Dipeptide derivatives and their production
CH461879A CH627439A5 (en) 1974-08-06 1979-05-17 METHOD FOR PRODUCING DIPEPTIDE DERIVATIVES.
CH461779A CH627438A5 (en) 1974-08-06 1979-05-17 METHOD FOR PRODUCING DIPEPTIDE DERIVATIVES.
CH827079A CH627440A5 (en) 1974-08-06 1979-09-12 METHOD FOR PRODUCING DIPEPTIDE DERIVATIVES.
CA339,232A CA1091652A (en) 1974-08-06 1979-11-06 Dipeptide derivatives and their production

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP49090566A JPS605599B2 (en) 1974-08-06 1974-08-06 Method for producing aminobenzophenone derivatives

Publications (2)

Publication Number Publication Date
JPS5126854A JPS5126854A (en) 1976-03-05
JPS605599B2 true JPS605599B2 (en) 1985-02-12

Family

ID=14001969

Family Applications (1)

Application Number Title Priority Date Filing Date
JP49090566A Expired JPS605599B2 (en) 1974-08-06 1974-08-06 Method for producing aminobenzophenone derivatives

Country Status (1)

Country Link
JP (1) JPS605599B2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63148387U (en) * 1987-03-20 1988-09-29
JPS63148389U (en) * 1987-03-20 1988-09-29

Also Published As

Publication number Publication date
JPS5126854A (en) 1976-03-05

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