JPS58222076A - 2-aminothiazole derivative - Google Patents

2-aminothiazole derivative

Info

Publication number
JPS58222076A
JPS58222076A JP57103109A JP10310982A JPS58222076A JP S58222076 A JPS58222076 A JP S58222076A JP 57103109 A JP57103109 A JP 57103109A JP 10310982 A JP10310982 A JP 10310982A JP S58222076 A JPS58222076 A JP S58222076A
Authority
JP
Japan
Prior art keywords
formula
compound
acid
dione
general 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.)
Granted
Application number
JP57103109A
Other languages
Japanese (ja)
Other versions
JPH0375545B2 (en
Inventor
Hiroshi Sadaki
貞木　浩
Hiroyuki Imaizumi
今泉　弘之
Kenji Takeda
竹田　憲治
Takihiro Inaba
太喜広 稲場
Takatsune Takeno
竹野　隆恒
Seiji Morita
清司 森田
Tetsuya Kajita
哲也 梶田
Isamu Saikawa
才川　勇
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.)
Toyama Chemical Co Ltd
Original Assignee
Toyama Chemical 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 Toyama Chemical Co Ltd filed Critical Toyama Chemical Co Ltd
Priority to JP57103109A priority Critical patent/JPS58222076A/en
Priority to AU15500/83A priority patent/AU542287B2/en
Priority to GB08315700A priority patent/GB2122988B/en
Priority to CA000430079A priority patent/CA1191512A/en
Priority to IL68931A priority patent/IL68931A0/en
Priority to DE3348173A priority patent/DE3348173C2/de
Priority to DE19833321127 priority patent/DE3321127A1/en
Priority to US06/504,317 priority patent/US4563534A/en
Priority to AT0219783A priority patent/AT380877B/en
Priority to CH325683A priority patent/CH659470A5/en
Priority to FI832152A priority patent/FI85470C/en
Priority to CH544185A priority patent/CH657613A5/en
Priority to FR8309863A priority patent/FR2528839B1/en
Priority to IT48504/83A priority patent/IT1171839B/en
Priority to PT76880A priority patent/PT76880B/en
Priority to DK278883A priority patent/DK161073C/en
Priority to NZ21230483A priority patent/NZ212304A/en
Priority to SE8303465A priority patent/SE452981B/en
Priority to MX83197676A priority patent/MX156981A/en
Priority to PH29065A priority patent/PH18261A/en
Priority to NO832178A priority patent/NO161114C/en
Priority to KR1019830002682A priority patent/KR860001027B1/en
Priority to NZ204609A priority patent/NZ204609A/en
Priority to ES523348A priority patent/ES8502697A1/en
Priority to NL8302151A priority patent/NL8302151A/en
Priority to BE0/211013A priority patent/BE897063A/en
Publication of JPS58222076A publication Critical patent/JPS58222076A/en
Priority to FR848400472A priority patent/FR2540860B1/en
Priority to FR8400471A priority patent/FR2540873B1/en
Priority to ES530213A priority patent/ES530213A0/en
Priority to ES530212A priority patent/ES530212A0/en
Priority to PH31191A priority patent/PH19985A/en
Priority to PH31192A priority patent/PH20516A/en
Priority to AU36370/84A priority patent/AU567990B2/en
Priority to CA000475355A priority patent/CA1197251A/en
Priority to CA000475356A priority patent/CA1216310A/en
Priority to AT176885A priority patent/AT391469B/en
Priority to AT176785A priority patent/AT391686B/en
Priority to US06/753,068 priority patent/US4667040A/en
Priority to GB08518464A priority patent/GB2167410B/en
Priority to NO85854279A priority patent/NO163366C/en
Priority to NO85854280A priority patent/NO163616C/en
Priority to IL77921A priority patent/IL77921A0/en
Priority to SE8701193A priority patent/SE8701193D0/en
Priority to SE8701192A priority patent/SE8701192D0/en
Priority to FI893076A priority patent/FI85852C/en
Priority to DK229090A priority patent/DK163582C/en
Priority to DK229190A priority patent/DK163816C/en
Publication of JPH0375545B2 publication Critical patent/JPH0375545B2/ja
Granted legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
    • C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/40—Unsubstituted amino or imino radicals

Abstract

NEW MATERIAL:The 2-aminothiazole derivative of formula I (R<1> is amino which may be protected; R<2> is monohalogenomethyl, alkylthiocarbonyl or aralkylthiocarbonyl) and its salt. EXAMPLE:2-Amino-4-chloroacetylthiazole. USE:Useful as a synthetic intermediate for a compound useful as a raw material for the preparation of cephalosporin compound. PROCESS:The compound of formula IV which is one of the compounds of formula I can be prepared by dihalogenating butane-2,3-dione of formula II to obtain 1,4-dihalogenobutane-2,3-dione of formula III (X<1> and X<2> is halogen such as F, Cl, etc.), and reacting the product with e.g. thiourea in an inert solvent such as methanol, at -50-+10 deg.C. The obtained compound of formula IV can be converted to the compound of formula V which is another type of the compound of formula I , by reacting a diaralkylsulfoxide in an inert solvent.

Description

【発明の詳細な説明】 本発明は、 一般式 ｒ　式中、Ｒ１は保鰻されていてもよいアミ）で表わさ
れる２−アミノチアゾール誘導体およびその塩に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a 2-aminothiazole derivative represented by the general formula r (wherein R1 is optionally protected) and a salt thereof.

而して、本発明の目的とするところは、セファロスポリ
ン系化合物を製造する際、有用な原料として知られて（
・る 一般式 で表わされる化合物の新規な中間体を提供することにあ
る。Therefore, the object of the present invention is to use materials known as useful raw materials for producing cephalosporin compounds (
The object of the present invention is to provide a novel intermediate for a compound represented by the general formula.

上述の目的を達成するため、本発明者らは鋭意研究を行
った結果、セファロスポリン系化合物の原料である一般
式（ｎ）で表わされる化合物の新規な中間体およびそれ
らの塩を見出し、本発明を完成したものである。In order to achieve the above object, the present inventors conducted extensive research and discovered novel intermediates of compounds represented by general formula (n), which are raw materials for cephalosporin compounds, and their salts, This completes the present invention.

チオ尿素による ［ＶＩ）　　　　　　　　　　　　　　　　　　（Ｖ）
またはその塩　　　　　　　　　　　またはその塩次に
一般式〔Ｉ〕で表わされる本発明化合物について詳述す
る。[VI] (V) by thiourea
or a salt thereof Next, the compound of the present invention represented by the general formula [I] will be described in detail.

ＲＩにおけるアミン基の保護基としては、通常アミノ保
護基として使用し得るすべての基を含み、たとえば、ト
リブロモエトキシカルボニル、トリブロモエトキシカル
ボニル、ベンジルオキシカルボニル、ｐ−）ルエンスル
ホニル、ｐ−ニトロペンジルオギシ力ルボニル、ｏ−７
”ロモベンジルオキシカルポニル、０−ニトロフェニル
スルフェニル、（モノ−、シー、　　トｖ−）ｐロロア
セチル、トリフルオロアセチル、ホルミル、　　ｔｅｒ
ｔ、−アミルオキシカルボニル、ｔａｒｔ、−ブトキシ
カルボニル、ｐ−メトキシベンジルオキシカルボニル、
３．４−ジメトキシベンジルオキシカルボニル、４−（
）４ニルアソ）ベンジルオキシカルボニル、４−（４−
メトキシフェニルアゾ）ベンジルオキシカルボニル、ピ
リジン−１−オキサイド−２−イルーメトギシカルボニ
ル、２−フリルオキシカルボニル、ジフェニルメトキシ
カルボニル、１．１−ジメチルプロポキシカルボニル、
インプロポキシカルボニル、１−シクロプロピルエトキ
シカルボニル、フタロイル、スクシニル、１−アダマン
チルオキシカルボニル、８−キノリルオキシカルボ−□
ルなどの脱離しやす（・アシル基が挙げられ、更に、ト
リチル、２−ニトロフェニルチオ、２，４−ジニトロフ
ェニルチオ、２−ヒドロキシベンジリデン、２−ヒドロ
キシ−５−クロロベンジリチン、２−ヒドロキシ−１−
ナフチルメチレン、３−ヒドロキシ−°４−ピリジルメ
チレン、１−メトキシカルボニル−２−プロピリデン、
１−エトキシカルボニル−２−プロピリデン、３−エト
キシカルボニル−２−ブチリデン、１−アセチル−２−
プロピリデン、１−ベンゾイル−２−プロピリデン、１
−（Ｎ−（２−−メトキシフェニル）カルバモイル〕−
２−プロピリデン、１−（Ｎ−（４−メトキシフェニル
）カルバモイル〕−２−プロピリテン、２−エトキシカ
ルボニルシクロへキシリデン、２−エトキシカルボニル
シクロペンチリデン、２−アセチルシクロへキシリデン
、３，３−ジメチル−５−オキソシクロヘキシリデンな
どの脱離しやず（・基またはジーもしくはトリーアルキ
ルシリルなどのつ′ミノ基の保論基がφげられる。Protecting groups for amine groups in RI include all groups that can normally be used as amino protecting groups, such as tribromoethoxycarbonyl, tribromoethoxycarbonyl, benzyloxycarbonyl, p-)luenesulfonyl, p-nitropenzyl. Ogishiki Rubonyl, o-7
"Lomobenzyloxycarponyl, 0-nitrophenylsulfenyl, (mono-, c-, tv-)p-roloacetyl, trifluoroacetyl, formyl, ter
t, -amyloxycarbonyl, tart, -butoxycarbonyl, p-methoxybenzyloxycarbonyl,
3.4-dimethoxybenzyloxycarbonyl, 4-(
)4nylaso)benzyloxycarbonyl, 4-(4-
methoxyphenylazo)benzyloxycarbonyl, pyridin-1-oxide-2-ylmethoxycarbonyl, 2-furyloxycarbonyl, diphenylmethoxycarbonyl, 1,1-dimethylpropoxycarbonyl,
Impropoxycarbonyl, 1-cyclopropylethoxycarbonyl, phthaloyl, succinyl, 1-adamantyloxycarbonyl, 8-quinolyloxycarbo-□
(-Acyl groups are included, and trityl, 2-nitrophenylthio, 2,4-dinitrophenylthio, 2-hydroxybenzylidene, 2-hydroxy-5-chlorobenzylitine, 2-hydroxy -1-
Naphthylmethylene, 3-hydroxy-4-pyridylmethylene, 1-methoxycarbonyl-2-propylidene,
1-ethoxycarbonyl-2-propylidene, 3-ethoxycarbonyl-2-butylidene, 1-acetyl-2-
Propylidene, 1-benzoyl-2-propylidene, 1
-(N-(2-methoxyphenyl)carbamoyl]-
2-propylidene, 1-(N-(4-methoxyphenyl)carbamoyl]-2-propyritene, 2-ethoxycarbonylcyclohexylidene, 2-ethoxycarbonylcyclopentylidene, 2-acetylcyclohexylidene, 3,3-dimethyl A leaving group such as -5-oxocyclohexylidene or a group such as a di- or tri-alkylsilyl group can be removed.

Ｒ２におけるモノハロゲノメチル基としては、たとえば
、クロロメチル、ブロモメチル、ヨードメチルなど、ア
ルキルチオカルボニル基としては、たとえば、メチルチ
オカルボニル、エチルチオカルボニルなト、アルアルキ
ルチオカルボニル基トしては、たとえば、ベンジルチオ
カルボニルなどが皐げられる。これらＲ１およびＲ”　
ＩＩＣお（・て　１ｌｊｌがアミ７基またはホルミルア
ミノ基でＲ２がクロロメチル基またはメチルチオカルボ
ニル基である組み合せが特に好ましく・。Examples of the monohalogenomethyl group in R2 include chloromethyl, bromomethyl, and iodomethyl; examples of the alkylthiocarbonyl group include methylthiocarbonyl and ethylthiocarbonyl; and examples of the aralkylthiocarbonyl group include benzylthiocarbonyl. etc. are revealed. These R1 and R”
Particularly preferred is a combination in which R2 is an ami7 group or a formylamino group and R2 is a chloromethyl group or a methylthiocarbonyl group.

また、一般式ＣＩ）で表わされる化合物の塩とは、具体
的には、アミン基における塩を示し、たとえば、地酸、
臭化水素酸、フッ化水素酸、硫酸などの鉱酸との塩、シ
ュウ酸、ギ酸、トリクロロ酢ｙ、トリフルオロ酢酸など
の有機カルボン酸との塩、メタンスルホン酸、ｐ−）ル
エンスルボン酸、ナフタレンスルホン酸なとのスルボン
酸との塩が挙げら７する。さらに、一般式ＣＩ）で表わ
される化合物は、柚々の溶媒と付加物を形成するが、こ
れらは（・ずれも２ＴＩ：発明に包含される。Further, the salt of the compound represented by the general formula CI) specifically refers to a salt at an amine group, such as a base acid,
Salts with mineral acids such as hydrobromic acid, hydrofluoric acid, sulfuric acid, salts with organic carboxylic acids such as oxalic acid, formic acid, trichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, p-)luenesulfonic acid, Examples include salts of naphthalene sulfonic acid and sulfonic acid. Furthermore, the compound represented by the general formula CI) forms an adduct with a yuzu solvent, and these are also included in the invention (2TI).

次に、本発明化合物の製造法について詳述する。Next, the method for producing the compound of the present invention will be described in detail.

式（ｎＤで表わされるブタン−２，３−ジオンをジハロ
ゲン化して一般式（ＩＶ）で表わされる１、４−ジハロ
ゲノブタン−２，３−ジオンを得るには、通常のハロゲ
ン化反応を行えばよく、たとえば、１−ブロモ−４−ク
ロロブタン−２，３−ジオンを製造するには、次のよう
に行うのが望ましい。まず、式（Ｉｌｌ）で表わされる
ブタン−２，３−ジオンを塩素化して１−クロロブタン
−２，３〜ジオンに変換する。In order to dihalogenate butane-2,3-dione represented by the formula (nD) to obtain 1,4-dihalogenobutane-2,3-dione represented by the general formula (IV), a normal halogenation reaction may be carried out. For example, to produce 1-bromo-4-chlorobutane-2,3-dione, it is desirable to proceed as follows. First, butane-2,3-dione represented by formula (Ill) is chlorinated. to convert to 1-chlorobutane-2,3-dione.

この反応は無溶媒下または反応に不活性な溶媒、ｆ、−
１え、１．６．イア１，２．７、ヤ７，７ケ□。　　゛
２芳香族炭化水素類、ジエチルエーテル、ジイソプロピ
ルエーテル、テトラヒドロフラン、ジオキザンナどのエ
ーテル類、塩化メチレン、クロロホルム、四塩化炭素、
ジクロロエタンなどのハロゲン化炭化水素類または酢酸
などのカルボン酸類もしく）　　　はそれらの混合溶媒
の存在下で行われる。また、塩素化剤としては、たとえ
ば、塩素、塩化スルフリル、Ｎ−クロロスクシンイミド
、Ｎ−クロロフタルイミドなどが挙げられ、式〔■〕で
表わされるブタン−２，３−ジオンに対して等モルで十
分である。また、反応条件は、用（・る塩素化剤などの
種類によって異なるが、通常、室温〜溶媒還流温度で３
０分〜１０時間で十分である。This reaction is carried out without a solvent or with an inert solvent, f, -
1, 1.6. Ia 1, 2.7, Ya 7, 7ke□. (2) Aromatic hydrocarbons, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxanna, methylene chloride, chloroform, carbon tetrachloride,
The reaction is carried out in the presence of a mixed solvent of halogenated hydrocarbons such as dichloroethane or carboxylic acids such as acetic acid. Examples of the chlorinating agent include chlorine, sulfuryl chloride, N-chlorosuccinimide, N-chlorophthalimide, etc., and an equimolar amount is sufficient for the butane-2,3-dione represented by the formula [■]. It is. The reaction conditions vary depending on the type of chlorinating agent used, but are usually at room temperature to solvent reflux temperature for 3 to 3 hours.
0 minutes to 10 hours is sufficient.

このようにして得られたｌ−クロロブタン−２，３−ジ
オンを、臭素化して１−ブロモ−４−クロロブタン−２
，３−ジオンに変換する。The l-chlorobutane-2,3-dione thus obtained was brominated to give 1-bromo-4-chlorobutane-2.
,3-dione.

この反応は無溶媒下または反応に不活性な溶媒、たとえ
ば、ベンゼン、トルエン、キシレンなどの芳香族炭化水
素類、ジエチルエーテル、ジイソプロピルエーテル、テ
トラヒドロフラン、ジオキサンなどのエーテル類、塩化
メチレン、クロロホルム、四塩化炭素、ジクロロエタン
などのハロケン化炭化水素類または酢酸などのカルボン
酸もしくはそれらの混合溶媒の存在下で行われる。また
、臭素化剤としては、たとえば、臭素、臭化スルフリル
、Ｎ−ブロモスクシンイミド、Ｎ−ブロモフタルイミド
などが挙げられ、１−クロロブタン−２，３−ジオンに
対して等モルで十分である。This reaction is carried out without a solvent or with an inert solvent, such as aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane, methylene chloride, chloroform, and tetrachloride. It is carried out in the presence of carbon, a halocarbonated hydrocarbon such as dichloroethane, a carboxylic acid such as acetic acid, or a mixed solvent thereof. Further, examples of the brominating agent include bromine, sulfuryl bromide, N-bromosuccinimide, N-bromophthalimide, etc., and an equimolar amount relative to 1-chlorobutane-2,3-dione is sufficient.

また、反応条件は用（・る臭素化剤などの種類によって
異なるが、通常、室温〜溶媒還流温度で、３０分〜１０
時間で十分である。The reaction conditions vary depending on the type of brominating agent used, but are usually room temperature to solvent reflux temperature for 30 minutes to 10 minutes.
Time is enough.

次いで、一般式（ＩＶ）で表わされる１、４−ジハロゲ
ノブタン−２，３−ジオン、たとえば、１−ブロモ−４
−クロロブタン−２，３−ジオンをチオ尿素と反応させ
て一般式〔ｖ〕で表わされる化合物を得るには、反応に
不活性な溶媒、たとえば、メタノール、エタノール、イ
ソプロピルアルコールなどのアルコール類、テトラヒド
ロフラン、ジオキサンなどのエーテル類、Ｎ、Ｎ−ジメ
チルホルムアミド、Ｎ、Ｎ−ジメチルアセトアミド、ヘ
キサメチルホスホルアミドなどのアミド類またはそれら
の混合溶媒もしくはそれらと水との混合溶媒の存在下で
行われる。チオ尿素の使用量は、一般式〔ｌ■〕の化付
物に対して０．９０倍モル以上でよく、とりわけ０．９
５〜１．００倍モル使用すれば好ましく・。この閉場反
応は通常−５０〜１０℃の反応温度で、５分〜２０　時
間で完結する。Next, 1,4-dihalogenobutane-2,3-dione represented by general formula (IV), for example, 1-bromo-4
- To obtain the compound represented by the general formula [v] by reacting -chlorobutane-2,3-dione with thiourea, use a solvent inert to the reaction, such as alcohols such as methanol, ethanol, isopropyl alcohol, tetrahydrofuran, etc. , ethers such as dioxane, amides such as N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoramide, or a mixed solvent thereof or a mixed solvent of these and water. The amount of thiourea to be used may be at least 0.90 times the mole of the compound of general formula [l■], particularly 0.9
It is preferable to use 5 to 1.00 times the mole amount. This closed-field reaction is usually completed at a reaction temperature of -50 to 10°C in 5 minutes to 20 hours.

一般式〔■〕で表わされる化合物から一般式［ＶＩ）で
表わされる化合物を得る反応は、反応に不活性な溶媒、
たとえば、メタノール、エタノール、イングロビルアル
コールなどのアルコール類、テトラヒドロフラン、ジオ
キサンなどのエーテル類、Ｎ、Ｎ−ジメチルホルムアミ
ド、Ｎ、Ｎ−ジメチルアセトアミド、ヘキサメチルホス
ホルアミドなどのアミド類またはそれらの混合溶媒中で
、一般式〔■〕で表わされる化合物と、ジメチルスルホ
キシド、ジエチルスルホキシドなどのジアルキルスルホ
キシドまたはジベンジルスルホキシドなどのシアルアル
キルスルホキシドとを反応させることに１、 より実施する。ジアルキルスルホキシドまたはシアルア
ルキルスルホキシドは一般式〔ｖ〕で表ワサれる化合物
に対して２．０倍モル以上、特に３．０〜４．０倍モル
使甲することが好ましく、所望により、これを溶媒とし
て使用してもよい。一般式〔■〕でＸＩがクロロの場合
には、臭化水素、臭化カリウムなどの臭化物の存在下に
反応を行うのが好ましく、その使用域は、一般式〔Ｖ〕
で表わされる化合物に対して０．５倍モル以上、特に０
．５〜１．０倍モルが好ましく・。この反応は通常１０
〜８０℃の反応温度で、１９分〜２０時間で完結する。The reaction to obtain the compound represented by the general formula [VI] from the compound represented by the general formula [■] is carried out using a solvent inert to the reaction,
For example, alcohols such as methanol, ethanol, and inglovir alcohol, ethers such as tetrahydrofuran and dioxane, amides such as N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoramide, or mixed solvents thereof. In the method, step 1 is carried out by reacting a compound represented by the general formula [■] with a dialkyl sulfoxide such as dimethyl sulfoxide or diethyl sulfoxide or a sialkyl sulfoxide such as dibenzyl sulfoxide. The dialkyl sulfoxide or sialalkyl sulfoxide is preferably used in an amount of 2.0 times or more, particularly 3.0 to 4.0 times in mole, relative to the compound represented by the general formula [v], and if desired, it can be used in a solvent. May be used as When XI is chloro in the general formula [■], it is preferable to carry out the reaction in the presence of a bromide such as hydrogen bromide or potassium bromide.
0.5 times the mole or more, especially 0
．． Preferably 5 to 1.0 times the mole. This reaction is usually 10
At a reaction temperature of ~80°C, it is completed in 19 minutes to 20 hours.

また、ジメチルスルフィド、ジエチルスルフィドなどの
ジアルキルスルフィド、ジメチルジスルフィド、ジエチ
ルジスルフィドなどのジアルキルジスルフィド、ジベン
ジルスルフィドなどのシアルアルキルスルフィド、ジベ
ンジルジスルフィドなどのシアルアルキルジスルフィド
、メチルメルカプタン、エチルメルカプタンなどのアル
キルメルカプタンもしくはベンジルメルカプタンなどの
アルアルキルメルカプタンを一般式〔■〕で表わされる
化合物に対し　　　□て１．０倍モル以上添加すると反
応は促進される。　　　′・・１このような反応で得ら
れる一般式［ＶＩ）で表わされる化合物のアミノ基を所
望により、通常の手段によって保藤してもよい。In addition, dialkyl sulfides such as dimethyl sulfide and diethyl sulfide, dialkyl disulfides such as dimethyl disulfide and diethyl disulfide, sialalkyl sulfides such as dibenzyl sulfide, sialalkyl disulfides such as dibenzyl disulfide, alkyl mercaptans such as methyl mercaptan and ethyl mercaptan, The reaction is accelerated when an aralkyl mercaptan such as benzyl mercaptan is added in an amount of 1.0 times or more mole or more relative to the compound represented by the general formula [■]. '...1 If desired, the amino group of the compound represented by the general formula [VI] obtained by such a reaction may be modified by conventional means.

次に、得られた一般式［ＶＩ）または〔■〕で表わされ
る化合物を通常の加水分ＭＫ付すことによりセファロス
ポリン系化合物の製造に有用な原料である一般式〔■〕
で表わされる化合物に変換する。Next, the obtained compound represented by the general formula [VI) or [■] is subjected to ordinary hydrolysis MK to form a compound represented by the general formula [■], which is a useful raw material for the production of cephalosporin compounds.
Convert to the compound represented by

ここでの加水分解は塩基の存在下での加水分解が好まし
く、水またはメタノール、エタノールナトのアルコール
中で行われる。使用できる塩基としては、たとえば、水
酸化ナトリウム、水酸化カリウム、水酸化バリウム、水
酸化カルシウム、炭酸ナトリウム、炭酸カリウムなどの
無機塩基またはトリエチルアミン、ピリジンなどの有機
塩基などが挙げもｈ、これは一般式［ＶＩ）または［Ｖ
Ｉｌ］で表わされる化合物に対して２．０倍モル以上使
用すればよし・。The hydrolysis here is preferably carried out in the presence of a base, and is carried out in water or an alcohol such as methanol or ethanol. Examples of bases that can be used include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, and potassium carbonate, and organic bases such as triethylamine and pyridine. Formula [VI) or [V
It is sufficient to use 2.0 times the mole or more of the compound represented by Il].

次に本発明を実施例および診考例を挙げて説明するが、
本発明はこれに限定されるものではな（・０実施例１゜ （１）ブタン−２，３−ジオン１７２２およびベンゼン
１７２−の混合溶液中に、塩化スルフリル１６３ｍｔを
６０℃で３時間を要して滴下攪拌する。滴下終了後、同
温度で１時間、次いで還流下で１時間攪拌した後、減圧
精留すれば、節点５３．５〜５５．０℃／　１４　ｗ　
Ｈｇを示す１−り００ブタン−２，３−ジオン１２４　
ｔ　（収率５１．５％）を得る。Next, the present invention will be explained by giving examples and diagnostic examples.
The present invention is not limited to this example (1) 163 mt of sulfuryl chloride was added to a mixed solution of 1722 butane-2,3-dione and 172 benzene at 60°C for 3 hours. After dropping, stir at the same temperature for 1 hour, then under reflux for 1 hour, and then rectify under reduced pressure.
1-ri00butane-2,3-dione 124 showing Hg
t (yield 51.5%).

ＩＲ（＝−ト）　ｃｍ　　’　　：　　’（ヨＱ　　１
７２ＯＮＭＲ（ＣＤＣＩ、　）　　δ値： す （２）１−クロロブタン−２，３−ジオン１２０，５ｆ
およびジクロロエタン１２０−の混合俗液中に還流下、
臭素１６０ｖを２時間を要して滴下攪拌する。IR(=-t) cm':'(YoQ 1
72ONMR (CDCI, ) δ value: Su(2) 1-chlorobutane-2,3-dione 120,5f
and dichloroethane under reflux in a mixed solution of 120-
160 V of bromine was added dropwise and stirred for 2 hours.

滴下終了後、更に３０分間還流した後、反応液を２０℃
に冷却する。析出する結晶を濾取しジクロロエタンで洗
浄した後、乾燥すれば、融点１２０〜１２１．５℃を示
すｌ−プロモー４−クロロブタン−２，３−ジオン１０
９　ｔ　（収率５４．６％）を得る。After the dropwise addition was completed, the reaction solution was heated to 20℃ after refluxing for another 30 minutes.
Cool to The precipitated crystals are collected by filtration, washed with dichloroethane, and dried to give l-promo-4-chlorobutane-2,3-dione 10, which has a melting point of 120 to 121.5°C.
9t (yield 54.6%) is obtained.

ＩＲ（ＫＢｒ）ｚ　　’　−：　　Ｗ。＝。１７６０．
１７３５ＮＭＲ（ＣＤｓＯＤ）　　δ値： ３．７０　（ＩＩＩ、　Ｓ　）、　　３．８３　（ＩＨ
，Ｓ　）。IR(KBr)z'-: W. =. 1760.
1735NMR (CDsOD) δ value: 3.70 (III, S), 3.83 (IH
,S).

４．６３　（ＩＨ，Ｓ　）　、　　４．８１　（ＩＨ，
Ｓ　）（３ｊ　１−ブロモ−４−クロロブタン−２３−
ジオン２０．Ｏｒおよびエタノール１４０−の懸濁液を
一３５℃に冷却し、攪拌下にチオ尿素７．３ｖを添加す
る。反応液を一３５℃で４時間攪拌した後、３０分を要
して一２０℃に昇温し、同温度で更に２時間攪拌する。4.63 (IH,S), 4.81 (IH,
S ) (3j 1-bromo-4-chlorobutane-23-
Zeon 20. The suspension of Or and ethanol 140° C. is cooled to -35° C. and 7.3 v of thiourea are added while stirring. After stirring the reaction solution at -35°C for 4 hours, the temperature was raised to -20°C over 30 minutes, and the mixture was further stirred at the same temperature for 2 hours.

その後、１時間３０分を要して１０℃まで昇温すれば、
白色結晶が析出する。この結晶を濾取し、エタノールで
洗浄した後、乾燥すれば、融点１９１℃（分解）を示す
２−アミノ−４−クロロアセチルチアゾール臭化水素酸
塩・１エタノール付加物２４．９　ｔ′　　　　（収率
８５．４％）を得る。After that, if it takes 1 hour and 30 minutes to raise the temperature to 10℃,
White crystals precipitate. If the crystals are collected by filtration, washed with ethanol, and dried, 24.9 t' of 2-amino-4-chloroacetylthiazole hydrobromide/1 ethanol adduct with a melting point of 191°C (decomposition) is obtained ( Yield: 85.4%).

Ｉｎ（ＫＢｒ）Ｏｎ’　：　　νｃ＝ｏ　１６９５ＮＭ
Ｒ（ａ、−ＤＭＳ　Ｏ）　　δ値：　′１．０９　（３
Ｈ，ｔ　、　Ｊ＝７，５Ｈｚ、　ＣＨ，Ｃ１２０Ｈ）　
。In(KBr)On': νc=o 1695NM
R(a,-DMSO) δ value: '1.09 (3
H, t, J=7,5Hz, CH, C120H)
.

３．５４　（２Ｈ，ｑ　、　Ｊ＝７．５Ｈｚ　、　ＣＨ
，ＣＨＬＯＨ）　。3.54 (2H,q, J=7.5Hz, CH
, CHLOH).

５．１７　（２Ｈ＋　８１　　ＣＣＨＩＣ’　）１Ｔ 実施例２ ２−アミノ−４−クロロアセチルチアゾール・美化水素
酸塩・１エタノール付加物３０．４ｒ。5.17 (2H+ 81 CCHIC') 1T Example 2 2-amino-4-chloroacetylthiazole/hydroboric acid salt/1 ethanol adduct 30.4r.

ジメチルスルホキシド９１−および臭化カリウム１１．
９　ｔの混合溶液を３０℃に加温し、ジメチルジスルフ
ィド８．９ｍｌを添加する。この反応液を３０〜３５℃
で２時間攪拌した後、氷水３００　ｄ中に投入する。Dimethyl sulfoxide 91- and potassium bromide 11.
The mixed solution of 9 t is heated to 30°C, and 8.9 ml of dimethyl disulfide is added. This reaction solution was heated at 30-35°C.
After stirring for 2 hours, the mixture was poured into 300 d of ice water.

次いで炭酸水素ナトリウムでｐＨ５，５に調整する。析
出する固形物を濾取し、この固形物をＩＮ−塩酸８０−
に溶解させ、少量の不溶物を薊去した後、炭酸水素ナト
リウムでｐＨ５，５に調整する。析出する結晶を濾取し
、水洗した後乾燥すれば、融点１３０℃（分解）を示す
（２−アミノチアゾール−４−イル）チオグリオキシル
酸−８−メチルエステル１１．７　ｙ　（収率６１．４
％）を得る。The pH was then adjusted to 5.5 with sodium hydrogen carbonate. The precipitated solid matter was collected by filtration, and this solid matter was dissolved in IN-hydrochloric acid 80-
After removing a small amount of insoluble matter, the pH was adjusted to 5.5 with sodium hydrogen carbonate. If the precipitated crystals are collected by filtration, washed with water, and then dried, 11.7 y of (2-aminothiazol-4-yl)thioglyoxylic acid-8-methyl ester having a melting point of 130°C (decomposed) (yield 61. 4
%).

ＩＲ（ＫＢｒ）ｍ　’　：　　シ、＝ｏ１６７５　１６
５ＯＮＭＲ（ｄ、−ＤＭＳ　Ｏ）　　δ値ニア、６０　
（２Ｈ，ｂｓ、　ＨＮ−）。IR(KBr)m': shi,=o1675 16
5ONMR (d, -DMSO) δ value near, 60
(2H, bs, HN-).

実施例３ （２−アミノチアゾール−４−イル）チオグリオキシル
酸−８−メチルエステル１０．１　？および水８０ｒｄ
中に水冷下、炭酸ナトリウム１０．６？を添加し、同温
度で１時間攪拌する。次−・で、反応液を水冷下にて６
Ｎ−塩酸でｐＨ２，５に調整する。析出した結晶をＭ１
取し、水洗した後乾燥すれば、融点２００℃以上を示す
（２−アミノチアゾール−４−イル）グリオキシル酸６
．２９’（収率６７．８％）を得る。Example 3 (2-aminothiazol-4-yl)thioglyoxylic acid-8-methyl ester 10.1? and water 80rd
Under water cooling inside, sodium carbonate 10.6? and stirred at the same temperature for 1 hour. Next, the reaction solution was cooled with water for 6
Adjust the pH to 2.5 with N-hydrochloric acid. The precipitated crystals are M1
When taken, washed with water and dried, (2-aminothiazol-4-yl)glyoxylic acid 6 having a melting point of 200°C or higher is obtained.
．． 29' (yield 67.8%) is obtained.

Ｉ　Ｒ（Ｋ　Ｂ　ｒ　）　ｃｍ　’　：　　ν（＝Ｑ　
１６６ＯＮＭＲ、（ｄ６−ＤＭＳ　Ｏ）　　δ値：実施
例４ 無水酢酸４０．８　ｔおよび蟻酸１８．４　Ｆの混合物
を４０〜４５℃で１時間攪拌する。この溶液に、水冷下
（２−アミノチアゾール−４−イル）チオグリオキシル
酸−８−メチルエステル２０．２１を加えた後、２５℃
で１時間攪拌する。次いで、この反応液に氷冷下で水１
６０−を滴下した後、水冷下で３０分間攪拌し、析出す
る結晶を濾取する。この結晶を水およびアセトンで順次
洗浄した後乾燥すれば、融点２３０℃以上を示す（２−
ホルミルアミノチアゾール−４−イル）チオグリオキシ
ル酸−８−メチルエステル２１．９９（収率９４．４％
）を得る。I R(K B r ) cm': ν(=Q
166ONMR, (d6-DMSO) δ value: Example 4 A mixture of 40.8 t of acetic anhydride and 18.4 F of formic acid is stirred at 40-45° C. for 1 hour. To this solution was added 20.21% of (2-aminothiazol-4-yl)thioglyoxylic acid-8-methyl ester under water cooling, and the mixture was heated at 25°C.
Stir for 1 hour. Next, 1 part of water was added to this reaction solution under ice cooling.
60- was added dropwise, the mixture was stirred for 30 minutes under water cooling, and the precipitated crystals were collected by filtration. If these crystals are washed successively with water and acetone and then dried, they exhibit a melting point of 230°C or higher (2-
Formylaminothiazol-4-yl) thioglyoxylic acid-8-methyl ester 21.99 (yield 94.4%)
).

ＩＲ（ＫＢｒ）ｃｒｎ’　：　　ν（＝Ｑ　１６１．１
６７０．１６５０実施例５ ２−アミノ−４−クロロアセチルチアゾール、臭化水素
酸塩・ｌエタノール付加物７．８ｆを水５０−に＠濁さ
せ、２０℃で攪拌下に炭酸水素ナトリウム２．３２を１
５分間で徐々に添加した。IR(KBr)crn': ν(=Q 161.1
670.1650 Example 5 7.8f of 2-amino-4-chloroacetylthiazole, hydrobromide/l ethanol adduct was suspended in 50°C of water, and 2.32ml of sodium bicarbonate was added under stirring at 20°C. 1
It was added gradually over 5 minutes.

析出してくる結晶を濾取し、水１ＯｒＲ１で洗浄した後
、真空乾燥すれば、融点１４７℃（分解）を示す２−ア
ミノ−４−クロロアセチルチアゾール４．５　ｙ　（収
率９８．８％）を得る。The precipitated crystals are collected by filtration, washed with 1OrR1 of water, and then vacuum dried to give 4.5 y of 2-amino-4-chloroacetylthiazole (yield 98.8%) with a melting point of 147°C (decomposition). ).

ＩＲ（ＫＢｒ）ｏｎ　’　：　　シ、＝ｏ１６７５．１
６０ＯＮＭＲ（ｄ６−ＤＭＳ　Ｏ）　　δ値：５．００
　（２Ｈ，Ｓ　、　−ＣＣＩ（、、ＣＩ　）。IR(KBr)on': shi,=o1675.1
60ONMR (d6-DMSO) δ value: 5.00
(2H,S, -CCI(,,CI).

７．４７　（２Ｈ，ｂｓ　、　Ｈ２Ｎ−）　。7.47 (2H, bs, H2N-).

径考例 （２−ホルミルアミノチアゾール−４−イル）チ７グけ
“″′酸−８．メチ″”７テ″２３　ｆを水２００　ｍ
ｅ　Ｋ　Ｍ濁させ、これに水冷下で２Ｎ−水酸化ナトリ
ウム水溶液１２５−を３０分を要して滴下し、次（・で
室温で１時間攪拌する。Diameter example (2-formylaminothiazol-4-yl) acid-8. 23 f water 200 m
e KM was made cloudy, and a 2N aqueous solution of sodium hydroxide (125) was added dropwise thereto over 30 minutes under water cooling, and then stirred at room temperature for 1 hour.

反応終了後、反応液を水冷下、６Ｎ−塩酸で、ｐＨ２，
５に調整する。析出した結晶を濾取し、水およびアセト
ンで順次洗浄した後乾燥すれば、融点２１０℃以上を示
す（２−ホルミルアミノチアゾール−４−イル）グリオ
キシル酸１６．２　ｔ（収率８１．６％）を得る。After the reaction was completed, the reaction solution was diluted with 6N hydrochloric acid to pH 2, while cooling with water.
Adjust to 5. If the precipitated crystals are collected by filtration, washed successively with water and acetone, and then dried, 16.2 t (2-formylaminothiazol-4-yl)glyoxylic acid having a melting point of 210°C or higher (yield 81.6%) is obtained. ).

ＩＲ（ＫＢｒ）ｃｒｎ’　：　　ν。−８１６６０特杵
出願人 富山化学工業株式会社 フ）゛IR(KBr)crn': ν. -81660 Special pestle applicant Toyama Chemical Industry Co., Ltd.

Claims (1)

【特許請求の範囲】 （１）一般式 で表わされる２−アミノチアゾール誘導体およびその塩
。 （２１Ｒ”がモノハロゲノメチル基である特許請求）　
　　　　の範囲第（１１項記載の２−アミノチアゾール
誘導体およびその塩。 （３１Ｒ”がクロロメチル基である特許請求の範囲第（
１）項または（２）項記載の２−アミノチアゾール誘導
体およびその塩。 （４１Ｒ’がアミン基である特許請求の範囲第（１）項
〜（３）項いずわかの項記載の２−アミノチアゾール誘
導体およびその塩。 （５１Ｒ２がアルキルチオカルボニル基である特許請求
の範囲第（１）項記載の２−アミノチアゾール誘導体お
よびその塩。 （６１Ｒ”がメチルチオカルボニル基である特許請求の
範囲第（１１または（５）項記載の２−アミノチアゾー
ル誘導体およびその塩。 （７１Ｒ１がアミ７基である％許請求の範囲第（１）。 （５）または（６）項記載の２−アミノチアゾール誘導
体およびその塩。 （８）　　Ｒ１がホルミルアミノ基である特許請求の範
囲第（１）、（５）または（６）項記載の２−アミノチ
アゾール誘導体およびその塩。[Claims] (1) A 2-aminothiazole derivative represented by the general formula and a salt thereof. (Patent claim in which 21R" is a monohalogenomethyl group)
Claim No. (2-aminothiazole derivatives and salts thereof according to claim 11).
The 2-aminothiazole derivative and its salt as described in item 1) or item (2). (2-aminothiazole derivatives and salts thereof according to claims (1) to (3) Izuka, wherein 41R' is an amine group. (Claims, where 51R2 is an alkylthiocarbonyl group) 2-aminothiazole derivatives and salts thereof according to claim (1). (71R1 Claim No. (1) in which is an amine 7 group. 2-aminothiazole derivative and salt thereof according to paragraph (5) or (6). (8) Claim No. 1 in which R1 is a formylamino group. The 2-aminothiazole derivative and its salt as described in (1), (5) or (6).
JP57103109A 1982-06-17 1982-06-17 2-aminothiazole derivative Granted JPS58222076A (en)

Priority Applications (47)

Application Number Priority Date Filing Date Title
JP57103109A JPS58222076A (en) 1982-06-17 1982-06-17 2-aminothiazole derivative
AU15500/83A AU542287B2 (en) 1982-06-17 1983-06-08 Process for producing 2-(2-aminothiazol-4-yl) glyoxylic acid derivative, it:s salt and intermediates therefor
GB08315700A GB2122988B (en) 1982-06-17 1983-06-08 Process for producing 2-(2-aminothiazol-4-yl) glyoxylic acid derivative; intermediates
CA000430079A CA1191512A (en) 1982-06-17 1983-06-09 Process for producing 2-(2-aminothiazol-4- yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
IL68931A IL68931A0 (en) 1982-06-17 1983-06-09 Novel process for producing 2-(2-aminothiazol-4-yl)glyoxylic acid derivative or a salt thereof,and intermediates therefor and process for producing the intermediates
DE3348173A DE3348173C2 (en) 1982-06-17 1983-06-10
DE19833321127 DE3321127A1 (en) 1982-06-17 1983-06-10 NEW METHOD FOR PRODUCING 2- (2-AMINOTHIAZOL-4-YL) GLYOXYL ACID DERIVATIVES OR A SALT OF THE SAME AND INTERMEDIATE PRODUCTS THEREOF AND METHOD FOR PRODUCING THE INTERMEDIATE PRODUCTS
US06/504,317 US4563534A (en) 1982-06-17 1983-06-14 Process for producing 2-(2-aminothiazol-4-yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
AT0219783A AT380877B (en) 1982-06-17 1983-06-14 METHOD FOR PRODUCING TAUTOMERIC 2- (2 AMINOTHIAZOL-4-YL) GLYOXYL ACID DERIVATIVES OR SALTS OR SOLVENT ADDUCTS THEREOF
CH325683A CH659470A5 (en) 1982-06-17 1983-06-14 Process for preparing 2-(2-aminothiazol-4-yl)glyoxylic acid or a derivative or a salt thereof
FI832152A FI85470C (en) 1982-06-17 1983-06-14 Process for the preparation of 2- (2-aminothiazol-4-yl) glyoxylic acid derivative or its salts
CH544185A CH657613A5 (en) 1982-06-17 1983-06-14 Novel intermediates for preparing 2-(2-aminothiazol-4-yl)glyoxylic acid derivatives or a salt thereof, and a process for preparing the intermediates
FR8309863A FR2528839B1 (en) 1982-06-17 1983-06-15 NOVEL PROCESS FOR PRODUCING 2- (2-AMINOTHIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR A SALT THEREOF, THE INTERMEDIATES NECESSARY FOR THE SYNTHESIS OF THE SAME, AND THE PROCESS FOR THE PRODUCTION OF SUCH INTERMEDIATES
IT48504/83A IT1171839B (en) 1982-06-17 1983-06-15 PROCEDURE FOR PRODUCING ACID DERIVATIVES 2- (2-AMINOTHIAZOL-4-IL) -GLYXOLIC OR ITS SALTS, INTERMEDIATE FOR IT AND PROCEDURE FOR PRODUCING INTERMEDIATES
PT76880A PT76880B (en) 1982-06-17 1983-06-16 Process for preparing 2-(2-aminothiazol-4-yl)-glyoxylic acid derivatives or salts thereof and of intermediates therefor
DK278883A DK161073C (en) 1982-06-17 1983-06-16 METHOD FOR PREPARING 2- (2-AMINO-THIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR SALTS THEREOF
NZ21230483A NZ212304A (en) 1982-06-17 1983-06-16 1,4-dihalogenobutane-2,3-diones
SE8303465A SE452981B (en) 1982-06-17 1983-06-16 NEW PROCEDURE FOR THE PREPARATION OF 2- (2-AMINOTIAZOL-4-YL) -GYOXYLIC ACID DERIVATIVE OR A SALT THEREOF
MX83197676A MX156981A (en) 1982-06-17 1983-06-16 PROCEDURE FOR PREPARING A 2- (2-AMINOTIAZOLE 4-IL) GLIOXYL ACID DERIVATIVE
PH29065A PH18261A (en) 1982-06-17 1983-06-16 Novel process for producing 2-(2-aminothiazol-4-yl)glyoxylic acid derivative
NO832178A NO161114C (en) 1982-06-17 1983-06-16 PROCEDURE TE FOR PREPARING GLYOXYLIC ACID DRIVE
KR1019830002682A KR860001027B1 (en) 1982-06-17 1983-06-16 Process for preparing 2-(2-aminothiazol-4-yl) glyoxylic acid derivatives and intermediates therefor
NZ204609A NZ204609A (en) 1982-06-17 1983-06-16 2-aminothiazole derivatives used as intermediates in production of glyoxylic acid derivatives and precursor compounds therefor
ES523348A ES8502697A1 (en) 1982-06-17 1983-06-16 Process for producing 2-(2-aminothiazol-4-yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
NL8302151A NL8302151A (en) 1982-06-17 1983-06-16 METHOD FOR PREPARING 2- (2-AMINOTHIAZOLO-4-YL) -GLYOXYLIC ACID OR A SALT THEREOF, INTERMEDIATES THEREFOR, AND METHOD FOR PREPARING THE INTERMEDIATES
BE0/211013A BE897063A (en) 1982-06-17 1983-06-16 NOVEL PROCESS FOR THE PRODUCTION OF GLYOXYLIC 2- (AMINOTHIA-ZOL-4-YL) ACID DERIVATIVES OR A SALT THEREOF, THE INTERMEDIATES NECESSARY FOR THE SYNTHESIS OF THE SAME, AND THE PROCESS FOR THE PRODUCTION OF SUCH INTERMEDIATES
FR848400472A FR2540860B1 (en) 1982-06-17 1984-01-13 NOVEL INTERMEDIATES FOR THE PRODUCTION OF 2- (2-AMINOTHIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR A SALT OF THE SAME AND THE PROCESS FOR PRODUCING THE INTERMEDIATES
FR8400471A FR2540873B1 (en) 1982-06-17 1984-01-13 NOVEL INTERMEDIATES FOR THE PRODUCTION OF 2- (2-AMINOTHIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR A SALT OF THE SAME AND THE PROCESS FOR PRODUCING THE INTERMEDIATES
ES530213A ES530213A0 (en) 1982-06-17 1984-03-01 A PROCEDURE FOR THE PRODUCTION OF A 1, 4-DIHALOGENOBUTANE-2, 3-DIONA
ES530212A ES530212A0 (en) 1982-06-17 1984-03-01 A PROCEDURE FOR THE PRODUCTION OF A 2-AMINO-THIAZOL DERIVATIVE.
PH31191A PH19985A (en) 1982-06-17 1984-09-07 2-aminothiazole derivatives and process for producing said compounds
PH31192A PH20516A (en) 1982-06-17 1984-09-07 Process for producing a 1,4-dihalogenobutane-3-dione
AU36370/84A AU567990B2 (en) 1982-06-17 1984-12-06 Halogenated vicinal diketones
CA000475355A CA1197251A (en) 1982-06-17 1985-02-27 Process for producing 2-(2-aminothiazol-4- yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
CA000475356A CA1216310A (en) 1982-06-17 1985-02-27 Process for producing 2-(2-aminothiazol-4- yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
AT176885A AT391469B (en) 1982-06-17 1985-06-13 Process for the preparation of a novel 2-aminothiazole derivative
AT176785A AT391686B (en) 1982-06-17 1985-06-13 Process for the preparation of novel 1,4-dihalobutane-2,3- diones
US06/753,068 US4667040A (en) 1982-06-17 1985-07-09 Novel process for producing 2-(2-aminothiazol-4-yl)glyoxylic acid derivative or a salt thereof, and intermediates therefor and process for producing the intermediates
GB08518464A GB2167410B (en) 1982-06-17 1985-07-22 Dihalobutanones
NO85854279A NO163366C (en) 1982-06-17 1985-10-25 NEW 2-AMINOTIAZOLD DERIVATIVES AND PROCEDURES FOR PREPARING THEREOF.
NO85854280A NO163616C (en) 1982-06-17 1985-10-25 NEW 1,4-DIHALOGENBUTAN-2,3-DION.
IL77921A IL77921A0 (en) 1982-06-17 1986-02-19 2-aminothiazol derivatives and process for producing them
SE8701193A SE8701193D0 (en) 1982-06-17 1987-03-23 NEW INTERMEDIATES FOR THE PREPARATION OF 2- (2-AMINOTIAZOL-4-YL) -GYOXYLIC ACID DERIVATIVES OR A SALT THEREOF AND PROCEDURE FOR PREPARING THE INTERMEDIATES
SE8701192A SE8701192D0 (en) 1982-06-17 1987-03-23 NEW 2-AMINOTIAZOLE DERIVATIVES OR SALTS THEREOF FOR PREPARATION OF 2- (2-AMINOTIAZOL-4-YL) -GYOXYLIC ACID DERIVATIVES OR ANY SALT THEREOF AND PROCEDURE FOR PREPARING THESE
FI893076A FI85852C (en) 1982-06-17 1989-06-22 1-bromo-4-chlorobutane-2,3-dione and a process for preparing the t
DK229090A DK163582C (en) 1982-06-17 1990-09-21 INTERMEDIATES FOR USE IN THE PREPARATION OF 2- (2-AMINO-THIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR SALTS THEREOF AND PROCEDURES FOR THE PRODUCTION OF THE INTERMEDIATES
DK229190A DK163816C (en) 1982-06-17 1990-09-21 1,4-DIHALOGENBUTAN-2,3-DIONES FOR USING INTERMEDIATES IN THE PREPARATION OF 2- (2-AMINOTHIAZOL-4-YL) GLYOXYLIC ACID DERIVATIVES OR SALTS THEREOF AND PROCEDURES FOR THE INTERMEDIATE PRODUCTION

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP57103109A JPS58222076A (en) 1982-06-17 1982-06-17 2-aminothiazole derivative

Publications (2)

Publication Number Publication Date
JPS58222076A true JPS58222076A (en) 1983-12-23
JPH0375545B2 JPH0375545B2 (en) 1991-12-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
JP57103109A Granted JPS58222076A (en) 1982-06-17 1982-06-17 2-aminothiazole derivative

Country Status (2)

Country Link
JP (1) JPS58222076A (en)
CH (1) CH657613A5 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4977264A (en) * 1988-11-21 1990-12-11 Lonza Ltd. Process for the production of 4,5-dichloro-6-ethylpyrimidine
US7507750B2 (en) 2002-04-12 2009-03-24 Showa Denko K.K. Stabilized ascorbic acid derivative

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4977264A (en) * 1988-11-21 1990-12-11 Lonza Ltd. Process for the production of 4,5-dichloro-6-ethylpyrimidine
US7507750B2 (en) 2002-04-12 2009-03-24 Showa Denko K.K. Stabilized ascorbic acid derivative

Also Published As

Publication number Publication date
JPH0375545B2 (en) 1991-12-02
CH657613A5 (en) 1986-09-15

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