JPS5817460B2 - Thiazoline Kanno Kaikanhouhou - Google Patents
Thiazoline Kanno KaikanhouhouInfo
- Publication number
- JPS5817460B2 JPS5817460B2 JP50033808A JP3380875A JPS5817460B2 JP S5817460 B2 JPS5817460 B2 JP S5817460B2 JP 50033808 A JP50033808 A JP 50033808A JP 3380875 A JP3380875 A JP 3380875A JP S5817460 B2 JPS5817460 B2 JP S5817460B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- oxo
- thia
- compound
- diazabicyclo
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
- C07D205/095—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4 and with a nitrogen atom directly attached in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
この発明は７−オキソ−４−チア−２，６−ジアザビシ
クロ〔３，２，０’：］ヘプ）−２−ニー／骨格を有す
る化合物に酸と水とを作用させて２−オキソ−３−アシ
ルアミノ−４−メルカプトアゼチジン骨格を有する化合
物を製造する方法に関する７−オキソ−４−チア−２，
６−ジアザビシクロ〔３，２，０〕ヘプト−２−エン骨
格を有する化合物のチアゾリン環を開環して２−オキソ
−３−アシルアミノ−４一置換チオアゼチジン骨格を有
する化合物を製造する方法は二、三種知られているが、
２−オキソ−３−アシルアミノ−４−メルカプトアゼチ
ジン化合物を製造する方法は記載されていない。DETAILED DESCRIPTION OF THE INVENTION The present invention involves the action of acid and water on a compound having a 7-oxo-4-thia-2,6-diazabicyclo[3,2,0':]hep)-2-ni/skeleton. 7-oxo-4-thia-2, which relates to a method for producing a compound having a 2-oxo-3-acylamino-4-mercaptoazetidine skeleton by
There are two methods for producing a compound having a 2-oxo-3-acylamino-4 monosubstituted thioazetidine skeleton by opening the thiazoline ring of a compound having a 6-diazabicyclo[3,2,0]hept-2-ene skeleton. Three types are known,
A method for producing 2-oxo-3-acylamino-4-mercaptoazetidine compounds is not described.
本発明者はチアゾリノアゼチジンの化学を研究中、たま
たま７−オキソ−４−チア−２，６−ジアザビシクロ〔
３，２，Ｏｌヘプト−２−エン骨格を有する化合物に酸
と水とを作用させたところ、合成化学上有利な２−オキ
ソ・−３−アシルアミノ−４−メルカプトアゼチジン骨
格を有する化合物が高収率で生成することを発見した。While researching the chemistry of thiazolinoazetidine, the present inventor happened to find 7-oxo-4-thia-2,6-diazabicyclo[
When a compound having a 3,2,Olhept-2-ene skeleton was reacted with acid and water, a compound having a 2-oxo-3-acylamino-4-mercaptoazetidine skeleton, which is advantageous in terms of synthetic chemistry, was It was discovered that the product was produced in high yield.
本発明はこの知見に基き、研究を発展させて完成したも
のである。The present invention was completed by developing research based on this knowledge.
この反応に用いる原料物質である７−オキソ−４−チア
−２，６−ジアザビシクロ〔３，２，０ヘプト−２−エ
ン骨格を有する化合物としては、この骨格を有し、開環
条件下に不都合な変化を起さない置換基を有し得る、す
べての化合物を用いることができる。A compound having a 7-oxo-4-thia-2,6-diazabicyclo[3,2,0hept-2-ene skeleton, which is a raw material used in this reaction, has this skeleton and under ring-opening conditions, All compounds can be used that can have substituents that do not result in undesirable changes.
３位には水素の他に、置換基を有していてもよい炭化水
素基（アルキル、アルケニル、アラルキル、複素環基を
含むアリール、アリールオキシアルキル、アリールチオ
アルキルなト）、天然または合成のペニシリン、セファ
ロスポリンの側鎖を構成するアシルアミノ基におけるア
シル基からカルボニルを除くことによって得られる基な
ど、一価の置換基を有し得る。In addition to hydrogen, the 3rd position is a hydrocarbon group that may have a substituent (alkyl, alkenyl, aralkyl, aryl including heterocyclic group, aryloxyalkyl, arylthioalkyl), natural or synthetic It may have a monovalent substituent, such as a group obtained by removing carbonyl from an acylamino group constituting the side chain of penicillin or cephalosporin.
また、６位には水素の他に、置換基を有していてもよい
炭化水素基（アルキル、アルケニル、アラルキル、アリ
ールなど）、有機まだは無機の酸から誘導さｔｌｆアシ
ル基、シリル基、スルフェニル基、そのほかの、一価の
アミノ保護基を有し得る。In addition to hydrogen, at the 6-position, a hydrocarbon group that may have a substituent (alkyl, alkenyl, aralkyl, aryl, etc.), a tlf acyl group derived from an organic or inorganic acid, a silyl group, It may have a sulfenyl group or other monovalent amino protecting group.
３位の置換基または６位のアミノ保護基中に有し得る置
換基は・・ロゲン（ふっ素、塩素、臭素など）、硫黄基
（メルカプト、アルキルチオ、アラルキルチオ、アリー
ルチオ、アシルチオ、チオキソ、スルホ、スルホニル、
スルフィニル、アルコキシスルホニル、アリールオキシ
スルフィニルなト）、酸素基（ヒドロキシ、アルコキシ
、アラルコキシ、アリールオキシ、アシルオキシ、オキ
ソなど）、窒素基（アミノ、ヒドラゾ、ジアゾ、アジド
、アルキルアミノ、ピペリジン−１−、イル、モルホリ
ン−４−イル、アラルキルアミノ、アリールアミノ、ア
シルアミノ、アルキリデンアミノ、アシルイミノ、イミ
ノ、アルキルイミノ、ニトロソ、ニトロなト）、炭素基
（アルキル、アルケニルアラルキル、芳香族異項環基を
含むアリール、カルボキシ、カルバモイル、カルボアル
コキシ、アルカノイル、アラルカッイル、アロイル、シ
アノなど）などの他に、りん基（ホスホニルなど）、そ
の他の置換基を含むものとする。The substituents that may be present in the substituent at position 3 or the amino protecting group at position 6 are: rogene (fluorine, chlorine, bromine, etc.), sulfur group (mercapto, alkylthio, aralkylthio, arylthio, acylthio, thioxo, sulfo, sulfonyl,
sulfinyl, alkoxysulfonyl, aryloxysulfinyl), oxygen groups (hydroxy, alkoxy, aralkoxy, aryloxy, acyloxy, oxo, etc.), nitrogen groups (amino, hydrazo, diazo, azide, alkylamino, piperidine-1-, yl) , morpholin-4-yl, aralkylamino, arylamino, acylamino, alkylideneamino, acylimino, imino, alkylimino, nitroso, nitro), carbon groups (alkyl, alkenylaralkyl, aryl including aromatic heterocyclic groups), In addition to carboxy, carbamoyl, carbalkoxy, alkanoyl, aralkayl, aroyl, cyano, etc.), phosphorus groups (phosphonyl, etc.) and other substituents are included.
これらの原料物質は、例えば対応するペニシリン−１−
オキシドエステルに亜りん酸メチルなどを作用させる方
法によって得られる化合物またはそれから公知方法など
を援用して製造することができる。These raw materials are, for example, the corresponding penicillin-1-
It can be produced from a compound obtained by a method of reacting methyl phosphite or the like with an oxide ester, or by using known methods.
本発明の反応においては、前記原料物質に酸と水とを作
用させる。In the reaction of the present invention, acid and water are allowed to act on the raw material.
水の作用は結果的にチアゾリン環をアゼチジン環の４−
メルカプト基と３−ア。The action of water results in the thiazoline ring becoming 4- of the azetidine ring.
Mercapto group and 3-a.
シルアミノ基に変化するためには必要なものである。It is necessary for converting into a cylamino group.
酸としては鉱酸（・・ロゲン化水素酸、硫酸、硝酸、り
ん酸、過塩素酸、塩素酸など）、スルホン酸（アルカン
スルホン酸、アリールスルホン酸、アラルキルスルホン
酸、特にα−ハロアルカンスルホン酸など）、α−ハロ
カルボン酸、ポリカルボン酸など、好ましくは解離恒数
約０．０１以上の酸を用いることができる。Acids include mineral acids (hydrogenic acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, chloric acid, etc.), sulfonic acids (alkanesulfonic acid, arylsulfonic acid, aralkylsulfonic acid, especially α-haloalkanesulfonic acid) etc.), α-halocarboxylic acids, polycarboxylic acids, etc. Preferably, acids having a dissociation constant of about 0.01 or more can be used.
特に過塩素酸、トリフルオロ酢酸、トリクロニ酢酸、ジ
クロロ酢酸、トリフルオロメタンスルホン酸、トリクロ
１−１メタンスルホン酸、はうふつ化水素酸、塩酸、ぶ
つ化水素酸、しゆう化水素酸、硝酸、りん酸、ベンゼン
スルホン酸、トルエンスルホン酸、ブロモベンゼンスル
ホン酸、メタンスルホン酸、エタンスルホン酸などの強
酸は効率よく利用できる。In particular, perchloric acid, trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, trifluoromethanesulfonic acid, trichloro-1-1methanesulfonic acid, hydrofluoric acid, hydrochloric acid, hydrobutic acid, hydrofluoric acid, nitric acid, Strong acids such as phosphoric acid, benzenesulfonic acid, toluenesulfonic acid, bromobenzenesulfonic acid, methanesulfonic acid, and ethanesulfonic acid can be used efficiently.
前記反応は好ましくは溶媒中で行なわれる。The reaction is preferably carried out in a solvent.
反応溶媒としては炭化水素（ペンタン、ヘキサン、ベン
ゼン、トルエンナト）、・・ロゲン化炭化水素（塩化メ
チレン、クロロホルム、四塩化炭素、ジクロロベンゼン
なト）、エステル（酢酸エチル、酢酸メチル、安息香酸
メチルなど）、ケトン（アセトン、ンクロヘキサノン、
ベンゾフェノンなａ１エーテル（ジエチルエーテル、エ
チレンクリコール・ジメチルエーテル テトラヒドロフ
ラン テトラヒドロピラン、ジオキサン、アニソールな
トリ、アルコール（メタノール、エタノール、エチレン
クリコール、ベンジルアルコールなト）、カルボン酸（
酢酸、プロピオン酸など）、アミド（ジメチルホルムア
ミド、ジメチルアセトアミド、ヘキサメチルホスホロト
リアミドなど）、ニトリル（アセトニトリル、ベンゾニ
トリルなど）、ニトロ炭化水素、スルホキシド（ジメチ
ルスルホキシドなど）、水などおよびそれらの混合物が
用いられる。Reaction solvents include hydrocarbons (pentane, hexane, benzene, toluene), logenated hydrocarbons (methylene chloride, chloroform, carbon tetrachloride, dichlorobenzene, etc.), esters (ethyl acetate, methyl acetate, methyl benzoate, etc.) ), ketones (acetone, nclohexanone,
Benzophenone a1 ether (diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, tetrahydropyran, dioxane, anisole tri, alcohol (methanol, ethanol, ethylene glycol, benzyl alcohol), carboxylic acid (
Acetic acid, propionic acid, etc.), amides (dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide, etc.), nitriles (acetonitrile, benzonitrile, etc.), nitrohydrocarbons, sulfoxides (dimethylsulfoxide, etc.), water, etc. and mixtures thereof. used.
特に水と酸とをとかし得るエーテル、ケトン、アルコー
ル、アミド、スルホキシド、水などの極性溶媒、ハロゲ
ン化炭化水素、エステル、エーテル、ケトンなと原料物
質をとかし得る溶媒、またはそれらの混合物は有利であ
る。Particularly advantageous are ethers, ketones, alcohols, amides, sulfoxides, polar solvents such as water which are capable of dissolving water and acids, solvents which are capable of dissolving raw materials such as halogenated hydrocarbons, esters, ethers and ketones, or mixtures thereof. be.
強酸を用いる場合にアゼチジノン環の分解など、副反応
が起きる場合には濃度、温度、反応時間などの条件を適
宜選択すれば高収率で目的とする化合物を製造できる。If a side reaction occurs when a strong acid is used, such as decomposition of the azetidinone ring, the desired compound can be produced in high yield by appropriately selecting conditions such as concentration, temperature, and reaction time.
一般に、反応は室温でも速やかに進行し、場合によって
は１０分ないし１時間で目的物を高吟収率で得ることが
できる。Generally, the reaction proceeds rapidly even at room temperature, and depending on the case, the desired product can be obtained in a high yield in 10 minutes to 1 hour.
このようにして製造した目的化合物は反応混合物から未
反応原料、酸、副産物、溶媒などを常法に従って除去す
れば容易に取得できる。The target compound thus produced can be easily obtained by removing unreacted raw materials, acids, by-products, solvents, etc. from the reaction mixture according to conventional methods.
単離、精製法としては分別抽出、濃縮、乾燥、吸着、溶
離、沈澱、濾過、再結晶、グロマトグラフイー、向流分
配などを適宜組合わせて用いる。As isolation and purification methods, appropriate combinations of fractional extraction, concentration, drying, adsorption, elution, precipitation, filtration, recrystallization, chromatography, countercurrent distribution, etc. are used.
この目的化合物は溶液中、特にアルカリ性と酸化に対し
て不安定であって、すべての処理には中性、弱塩基性、
または酸性で低温で行なうなど不安定性に対する通常の
注意が必要である。The target compound is unstable in solution, especially towards alkalinity and oxidation, and all treatments require neutral, weakly basic,
Ordinary precautions against instability, such as carrying out the process in acidic conditions and at low temperatures, are required.
反応中に酸または水の作用で分子の一部が原料とは異な
るアゼチジン誘導体が生成することもあるが、このよう
な場合もこの発明の定義内に含めるものとする。During the reaction, an azetidine derivative having a part of the molecule different from that of the raw material may be produced due to the action of acid or water, but such cases are also included within the definition of the present invention.
この発明により製造できる２−オキソ−３−アシルアミ
ノ−４−メルカプトアゼチジン骨格を有する化合物はペ
ニシリン・セファロスポリンなど有用な化合物の合成中
間体として用いられる。The compound having a 2-oxo-3-acylamino-4-mercaptoazetidine skeleton that can be produced according to the present invention is used as a synthetic intermediate for useful compounds such as penicillin and cephalosporin.
以下に実施例を示して本発明実施の態様を説明する。Examples are shown below to explain embodiments of the present invention.
例１
３−フェノキシメチル−７−オキソ−４−チア−２，６
−シアザービシクロ（３，２，０）ヘプト−２−エン２
００■ヲシクロロメタン８ｍｌとアセトン８ｍｌとの混
液にとかし、これ［３０％過塩素酸水溶液１．０７７２
１を加えて室温にて４０分間かきまぜる。Example 1 3-phenoxymethyl-7-oxo-4-thia-2,6
-Searazerbicyclo(3,2,0)hept-2-ene 2
00 ■ Dissolve in a mixture of 8 ml of chloromethane and 8 ml of acetone, and add this [30% aqueous perchloric acid solution 1.0772
Add 1 and stir at room temperature for 40 minutes.
過剰の水を加えてのち、反応液をジクロロメタンで抽出
する。After adding excess water, the reaction solution is extracted with dichloromethane.
抽出液を水洗し、無水硫酸ナトリウム上乾燥したのち溶
媒留去する。The extract was washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off.
残留物１５８ｍ１は４β−メルカプト−３β−フェノキ
シアセトアミド−２−オキソアゼチジンの白色結晶であ
る。The residue (158 ml) is white crystals of 4β-mercapto-3β-phenoxyacetamido-2-oxoazetidine.
ｍｐ１３７〜１３８℃。例２
α−（３一置換（Ｒ’） −７−オキソ−４−チア−２
，６−ジアザビシクロ（３，２，０，１ヘプト−２−エ
ン−６−イル）−α一置換（Ｒ２）酢酸エステル（Ｒ３
）（Ｉ）を溶媒にとかし、これに酸を加えて所定温度に
て所定時間かきまぜる。mp137-138°C. Example 2 α-(3-monosubstituted (R')-7-oxo-4-thia-2
,6-diazabicyclo(3,2,0,1hept-2-en-6-yl)-α monosubstituted (R2) acetic acid ester (R3
) (I) is dissolved in a solvent, an acid is added thereto, and the mixture is stirred at a predetermined temperature for a predetermined time.
反応液を水で希釈し、ジクロロメタンで抽出する。The reaction solution was diluted with water and extracted with dichloromethane.
抽出液を水で洗い、無水硫酸ナトリウム上乾燥したのち
、溶媒留去すれば目的とするα−（４−メルカプト−３
一置換アミノ（Ｒ’Ｃ０ＮＨ−）−２−オキソアゼチジ
ン−１−イル）−α一置換（Ｒ２）酢酸エステル（Ｒ３
）（Ｉ［）を得る。The extract is washed with water, dried over anhydrous sodium sulfate, and the solvent is distilled off to obtain the desired α-(4-mercapto-3
Monosubstituted amino (R'C0NH-)-2-oxoazetidin-1-yl)-α monosubstituted (R2) acetate (R3
)(I[) is obtained.
反応条件を第１表に、生成物（ｎ）の性状を第■表にそ
れぞれ示す。The reaction conditions are shown in Table 1, and the properties of the product (n) are shown in Table 2.
第１表中、粗収量は反応生成物の重量である。In Table 1, the crude yield is the weight of the reaction product.
この生成物は薄層クロマトグラムおよびＮＭＲ−スペク
トルから殆ど純粋な目的化合物であることが明らかであ
る。The thin layer chromatogram and NMR spectrum reveal that this product is almost pure target compound.
一部については更に精製して結晶化させた。A portion was further purified and crystallized.
反応Ａ３とＡ６とでは目的物は低収率で生成するが多量
の原料および副生成物を回収する。In reactions A3 and A6, the target products are produced in low yields, but large amounts of raw materials and by-products are recovered.
例３
α−（３−フェノキシメチル−７−オキソ−４−チア−
２，６−ジアザビシクロ〔３，２，０〕ヘプト−２−エ
ン−６−１ル）−α−イソプロペニル酢酸ｐ−ニトロベ
ンジル２００ＴＩｇヲテトラヒドロンラン５Ｔｌｌにと
かし、これにしゆう酸２００■と水０．５ ｍｌとを加
えて３時間室温でかきまぜる。Example 3 α-(3-phenoxymethyl-7-oxo-4-thia-
200 TI of p-nitrobenzyl 2,6-diazabicyclo[3,2,0]hept-2-en-6-1)-α-isopropenylacetate was dissolved in 5 TL of tetrahydrone, and this was mixed with 200 μl of cylic acid and 0 μl of water. .5 ml and stir at room temperature for 3 hours.
反応液のクロマトグラムはα−（４−メルカプト−３−
フェノキシアセトアミド−２−オキソアゼチジン−１−
イル）−α−イソプロペニル酢酸ｐ−ニトロベンジルお
よび原料物質の存在を示す。The chromatogram of the reaction solution shows α-(4-mercapto-3-
Phenoxyacetamide-2-oxoazetidine-1-
yl)-α-isopropenylacetate and the presence of the starting material.
例４ 例２と同様な方法で次の化合物を製造できる。Example 4 The following compounds can be prepared in a similar manner to Example 2.
（１） ６−アセチル−３−チェニルメチル−７−オ
キソ−４−チア−２，６−ジアザビシクロ〔３゜２．０
〕ヘプト−２−エンより４−メルカプト−３−チェニル
アセトアミド−２−オキソ−１＝アセチルアゼチジン；
（２） ６− ト＋）フルオロアセチル−３−フェニ
ル−７−オキソ−４−チア−２，６−ジアザビシクロ（
３，２，０〕ヘプト−２−エンより４−メルカプト−３
−ベンズアミド−２−オキソ−１−トリフルオロアセチ
ルアゼチジン；
（３）３．６−シメチルー７−オキノー４−チア−２，
６−ジアザビシクロ［３，２，０］ヘプト−２−エンよ
り４−メルカプト−３−アセトアミド−２−オキソ−１
−メチルアゼチジン；（４） ６− カルヘトキシカ
ルボニル−３−フェニルクロロメチル−７−オキソ−４
−チア−２，６−ジアザビシクロ（３，２，Ｏ’３ヘプ
ト−２−エンより４−メルカプト−３−（α−フェニル
−α−クロロアセトアミド）−２−オキソ−１−カルベ
トキシカルボニルアゼチジン；
（５）α−（７−オキソ−４−チア−２，６−ジアザビ
シクロ（３，２，０）ヘプト−２−エン−６−イル）−
α−インプロピリデン酢酸よりα−（４−メルカプト−
３−ホルムアミド−２−オキソアゼチジン−１−イル）
−α−イソプロピリデン酢酸；
（６） ３−ベンジルチオ−６−
ニル−７−オキソ−４−チア−２，６−ジアザ〔３，２
，Ｏｆヘプト−２−エンより４−メルカプト−３−ベン
ジルチオカルボニルアミノ−２−、ｔ キソ−１−ｐ
−トルエンスルホニルアゼチジン。(1) 6-acetyl-3-thenylmethyl-7-oxo-4-thia-2,6-diazabicyclo [3°2.0
[Hept-2-ene to 4-mercapto-3-chenylacetamido-2-oxo-1=acetylazetidine; (2) 6-t+)fluoroacetyl-3-phenyl-7-oxo-4-thia- 2,6-diazabicyclo(
3,2,0]hept-2-ene to 4-mercapto-3
-benzamido-2-oxo-1-trifluoroacetylazetidine; (3) 3,6-dimethyl-7-okino-4-thia-2,
6-diazabicyclo[3,2,0]hept-2-ene to 4-mercapto-3-acetamido-2-oxo-1
-Methylazetidine; (4) 6-carhethoxycarbonyl-3-phenylchloromethyl-7-oxo-4
-thia-2,6-diazabicyclo(3,2,O'3hept-2-ene to 4-mercapto-3-(α-phenyl-α-chloroacetamide)-2-oxo-1-carbetoxycarbonylazetidine (5) α-(7-oxo-4-thia-2,6-diazabicyclo(3,2,0)hept-2-en-6-yl)-
α-(4-mercapto-
3-formamido-2-oxoazetidin-1-yl)
-α-isopropylideneacetic acid; (6) 3-benzylthio-6-yl-7-oxo-4-thia-2,6-diaza [3,2
, Of hept-2-ene to 4-mercapto-3-benzylthiocarbonylamino-2-,t xo-1-p
-Toluenesulfonyl azetidine.
１２１− １２２−121- 122-
Claims (1)
、，２、０）ヘプト−２−エン骨格を有する化合物に酸
と水とを作用させて２−オキソ−３−アシルアミノ−４
−メルカプトアゼチジン骨格を有する化合物を製造する
ことを特徴とするチアゾリン環の開環方法。17-okino 4-thia-2,6-diazabicyclo(3
,,2,0) A compound having a hept-2-ene skeleton is reacted with acid and water to form 2-oxo-3-acylamino-4
- A method for opening a thiazoline ring, which comprises producing a compound having a mercaptoazetidine skeleton.
Priority Applications (77)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP50033808A JPS5817460B2 (en) | 1975-03-20 | 1975-03-20 | Thiazoline Kanno Kaikanhouhou |
| CA000245317A CA1136132A (en) | 1975-02-17 | 1976-02-09 | Cyclization to form cephem ring and intermediates therefor |
| PT64806A PT64806B (en) | 1975-02-17 | 1976-02-16 | Process of cyclization to form cephem ring and intermediate products for same |
| SE7601715A SE421691B (en) | 1975-02-17 | 1976-02-16 | NEW AZETID COMPOUNDS FOR USE AS INTERMEDIATES FOR THE MANUFACTURE OF 3-CEFEM SOCIETIES |
| IL57541A IL57541A (en) | 1975-02-17 | 1976-02-16 | 7-oxo-alpha-4-thia-2,6-diazabicyclo(3,2,0)heptene derivatives,process for their preparation and their cyclization to form cephem compounds and pharmaceutical compositions comprising said cephem compounds |
| DK061976A DK156575C (en) | 1975-02-17 | 1976-02-16 | METHOD OF PREPARING 3-HYDROXY-3-CEPHEM OR 3-OXO-CEPHAM CARBOXYLIC ACID DERIVATIVES |
| IL49048A IL49048A (en) | 1975-02-17 | 1976-02-16 | Cyclization process to form a cephem ring and intermediates therefor |
| MX76898U MX3818E (en) | 1975-02-17 | 1976-02-17 | PROCEDURE FOR THE PREPARATION OF ENAMINES OF HYDROXI-3-CEFEM COMPOUNDS |
| NZ184640A NZ184640A (en) | 1975-02-17 | 1976-02-17 | Derivatives of 7-oxo-4-thia-2,6-diazo-bicyclic-hept-2-enes |
| MX890276U MX6597E (en) | 1975-03-20 | 1976-02-17 | PROCEDURE FOR PREPARING DERIVATIVES OF 4-MERCAPTO-3-CARBOXILICO ACILAMINO-2-OXOACETIDINA |
| IE313/76A IE42479B1 (en) | 1975-02-17 | 1976-02-17 | Cyclization to form a cephem ring and intermediates therefor |
| NZ184641A NZ184641A (en) | 1975-02-17 | 1976-02-17 | Mercaptoazetidines, intermediates for cephem ring compounds |
| AU11181/76A AU508160B2 (en) | 1975-02-17 | 1976-02-17 | Cyclization |
| GB41074/78A GB1548643A (en) | 1975-02-17 | 1976-02-17 | Thiazoline ring cleavage |
| RO7694587A RO74958A (en) | 1975-02-17 | 1976-02-17 | PROCESS FOR THE PREPARATION OF CEPHALOSPORINS |
| HU76SI1594A HU174387B (en) | 1975-03-20 | 1976-02-17 | Process for producing 2-oxo-3-acylamino-4-mercapto-azetidine derivatives |
| GB41073/78A GB1548642A (en) | 1975-02-17 | 1976-02-17 | 2-oxo-azetidine acetic acids |
| DD7600195993A DD127899A5 (en) | 1975-02-17 | 1976-02-17 | PROCESS FOR THE PREPARATION OF CEPHEM COMPOUNDS |
| NZ184639A NZ184639A (en) | 1975-02-17 | 1976-02-17 | Azetidinones, intermediates for cephem compounds |
| BE164401A BE838656A (en) | 1975-02-17 | 1976-02-17 | CYCLING PROCESS LEADING TO THE CYCLE OF CEPHEME AND INTERMEDIARIES FOR ITS EXECUTION |
| RO7694586A RO75006A (en) | 1975-02-17 | 1976-02-17 | PROCESS FOR THE PREPARATION OF MERCAPTOAZETIDINONE |
| BG034106A BG25216A3 (en) | 1975-02-17 | 1976-02-17 | A method of obtaining mercaptoazetidyne derivatives |
| DD7600195997A DD127901A5 (en) | 1975-02-17 | 1976-02-17 | METHOD FOR PRODUCING MERCAPTOAZETIDINE DERIVATIVES |
| IE167/80A IE42481B1 (en) | 1975-03-20 | 1976-02-17 | Thiazoline ring cleavage |
| GB6187/76A GB1548641A (en) | 1975-02-17 | 1976-02-17 | Cyclization to form a cephem ring and intermediates therefor |
| RO7684836A RO68460A (en) | 1975-02-17 | 1976-02-17 | PROCEDURE FOR THE PREPARATION OF AZETIDINONE DERIVATIVES |
| YU384/76A YU40272B (en) | 1975-02-17 | 1976-02-17 | Process for producing beta-lactamine compounds |
| FR7604318A FR2334669A1 (en) | 1975-02-17 | 1976-02-17 | CYCLING PROCESS FOR FORMING A CORE OF CEPHEM AND NEW PRODUCTS THUS OBTAINED |
| BG034108A BG25076A3 (en) | 1975-02-17 | 1976-02-17 | A method of obtaining mercapto-azetidine derivatives |
| BG032385A BG24948A3 (en) | 1975-02-17 | 1976-02-17 | A method of obtaining beta-lactam compounds |
| US05/658,665 US4079181A (en) | 1975-02-17 | 1976-02-17 | Certain 7-oxo-4-thio-2,6-diazabicyclo-3,2,0-hept-2-ene compounds |
| PL21210976A PL114456B1 (en) | 1975-03-20 | 1976-02-17 | Process for preparing novel derivatives of mercaptoazetidine |
| IE166/80A IE42480B1 (en) | 1975-03-20 | 1976-02-17 | 2-oxo-azetidine acetic acids |
| DE19762606278 DE2606278A1 (en) | 1975-02-17 | 1976-02-17 | AZETIDINE DERIVATIVES AND METHOD FOR THEIR PRODUCTION |
| DD7600195995A DD127900A5 (en) | 1975-02-17 | 1976-02-17 | METHOD FOR PRODUCING MERCAPTOAZETIDINE DERIVATIVES |
| BG034105A BG24949A3 (en) | 1975-02-17 | 1976-02-17 | A method of obtaining mercaptoazetidine derivatives |
| NZ184637A NZ184637A (en) | 1975-02-17 | 1976-02-17 | Method of cleaving a thiazoline ring |
| CH191876A CH627160A5 (en) | 1975-02-17 | 1976-02-17 | Process for preparing halogenated azetidinone or thiazolinoazetidinone derivatives |
| AR262283A AR225878A1 (en) | 1975-02-17 | 1976-02-17 | NEW DERIVATIVES OF 3-AMINO-2-AZETIDINON-1 - ((2-HALO-ACETIL OR 2-HALOETILIDEN)) - ACETIC, PROCEDURE TO PREPARE THEM AND PROCEDURE TO OBTAIN 3-CEFEM COMPOUNDS FROM SUCH DERIVATIVES |
| DD191283A DD124986A5 (en) | 1975-02-17 | 1976-02-17 | |
| NZ180037A NZ180037A (en) | 1975-02-17 | 1976-02-17 | Derivetives of2-azetidinone and cyclisation to form cephemring |
| BG034107A BG27557A4 (en) | 1975-02-17 | 1976-02-17 | Method of obtaining of cephemic compounds |
| NL7601613A NL190721C (en) | 1975-02-17 | 1976-02-17 | Process for the preparation of 3-hydroxy-cephem derivatives. |
| NZ184638A NZ184638A (en) | 1975-02-17 | 1976-02-17 | Derivatives of 7-oxo-4-thia-2,6-diazobicylic-hept-2-enes |
| DD7600195998A DD127902A5 (en) | 1975-02-17 | 1976-02-17 | METHOD FOR PRODUCING MERCAPTOAZETIDINE DERIVATIVES |
| ES445250A ES445250A1 (en) | 1975-02-17 | 1976-02-17 | Certain 7-oxo-4-thio-2,6-diazabicyclo-3,2,0-hept-2-ene compounds |
| GR50078A GR60437B (en) | 1975-02-17 | 1976-02-17 | Process for cyclization to form cephem ring and intermediates therefor |
| PH18164A PH18022A (en) | 1975-02-17 | 1976-03-03 | Cyclization to form cephem ring and intermediate thereof |
| RO197694535A RO74936A (en) | 1975-02-17 | 1976-07-17 | PROCESS FOR THE PREPARATION OF MERCAPTOAZETIDIONES |
| FR7701588A FR2334670A1 (en) | 1975-03-20 | 1977-01-20 | 3-Hydroxy-cephem cpds. prepn. - via new alpha-substd. 3-amino-4-mercapto-2-azetidinone-1-acetic acid derivs |
| SU772446154A SU795463A4 (en) | 1975-03-07 | 1977-01-26 | Method of preparing 2-oxo-3-acylamino-4-mercaptoazetidines |
| US05/856,806 US4160085A (en) | 1975-02-17 | 1977-12-01 | Cyclization to form cephem ring and intermediates therefor |
| CS78971A CS207656B2 (en) | 1975-03-20 | 1978-02-15 | Method of preparation of 2-oxo-3-acylamino-4-mercap-toazetidins |
| AT417178A AT351044B (en) | 1975-03-07 | 1978-06-08 | PROCESS FOR THE PRODUCTION OF NEW AZETIDE DERIVATIVES |
| IL56049A IL56049A0 (en) | 1975-02-17 | 1978-11-26 | Thiazoline ring cleavage |
| IL56050A IL56050A0 (en) | 1975-02-17 | 1978-11-26 | Azetidinones |
| IL57418A IL57418A0 (en) | 1975-02-17 | 1979-05-28 | 7-oxo-4-thia-2,6-diazabicyclo(3,2,0)heptene derivatives |
| IL57541A IL57541A0 (en) | 1975-02-17 | 1979-06-11 | 7-oxo- -4-thia-2,6-diazabicyclo(3,2,0)heptene derivatives,process for their preparation and pharmaceutical compositons comprising the same |
| SE7907813A SE434637B (en) | 1975-02-17 | 1979-09-20 | OZONIZATION PROCEDURE FOR PREPARATION OF ALFA- (AZETIDINYL) -ALFA- (HYDROXYTHYLIDE) -THETIC ACID SUBSTANCES |
| SE7907811A SE444811B (en) | 1975-02-17 | 1979-09-20 | AZETIDINYL SUBSTANCE FOR THE PREPARATION OF 3-HYDROXY-CEFEM SUBSTANCES AND PROCEDURE FOR ITS PREPARATION |
| SE7907812A SE434950B (en) | 1975-02-17 | 1979-09-20 | PROCEDURE FOR PREPARING 3-HYDROXY-CEPHALOSPORO COMPOUNDS |
| CA000337975A CA1095026A (en) | 1975-02-17 | 1979-10-19 | Cyclization to form cephem ring and intermediates therefor |
| CA000337973A CA1144924A (en) | 1975-02-17 | 1979-10-19 | Cyclization to form cephem ring and intermediates therefor |
| CA000337974A CA1077936A (en) | 1975-02-17 | 1979-10-19 | Cyclization to form cephem ring and intermediates therefor |
| CA000338132A CA1132547A (en) | 1975-02-17 | 1979-10-22 | Cyclization to form cephem ring and intermediates therefor |
| CH74980A CH634579A5 (en) | 1975-02-17 | 1980-01-30 | Process for preparing cephem compounds |
| CH74880A CH630074A5 (en) | 1975-02-17 | 1980-01-30 | Process for preparing an acetidinone compound |
| CH75080A CH628030A5 (en) | 1975-02-17 | 1980-01-30 | Process for the preparation of an enamine compound |
| CH75180A CH628031A5 (en) | 1975-02-17 | 1980-01-30 | Process for the preparation of azetidinone compounds |
| US06/125,233 US4346218A (en) | 1975-02-17 | 1980-02-27 | Cyclization process to form cephem ring |
| US06/125,232 US4332722A (en) | 1975-02-17 | 1980-02-27 | Cyclization to form cephem ring and intermediates therefor |
| US06/338,651 US4440683A (en) | 1975-02-17 | 1982-01-11 | Cyclization to form cephem ring and azetidinone intermediates therefor |
| DK76882A DK76882A (en) | 1975-02-17 | 1982-02-22 | INTERMEDIATES FOR THE CREATION OF A SEPHREATHER AND PROCEDURES FOR PRODUCING THEREOF |
| YU1739/82A YU40412B (en) | 1975-02-17 | 1982-08-10 | Process for producing mercapto azetidine compounds |
| YU1742/82A YU40414B (en) | 1975-02-17 | 1982-08-10 | Process for obtaining new azetidinone derivatives |
| YU1738/82A YU40411B (en) | 1975-02-17 | 1982-08-10 | Process for obtaining mrcapto azetidine compounds |
| YU1741/82A YU40413B (en) | 1975-02-17 | 1982-08-10 | Process for obtaining cephem compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP50033808A JPS5817460B2 (en) | 1975-03-20 | 1975-03-20 | Thiazoline Kanno Kaikanhouhou |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51108056A JPS51108056A (en) | 1976-09-25 |
| JPS5817460B2 true JPS5817460B2 (en) | 1983-04-07 |
Family
ID=12396765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50033808A Expired JPS5817460B2 (en) | 1975-02-17 | 1975-03-20 | Thiazoline Kanno Kaikanhouhou |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS5817460B2 (en) |
| FR (1) | FR2334670A1 (en) |
| HU (1) | HU174387B (en) |
| PL (1) | PL114456B1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0623189B2 (en) * | 1988-05-19 | 1994-03-30 | 大塚化学薬品株式会社 | Process for producing azetidinone derivative |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE794659A (en) * | 1972-01-28 | 1973-07-30 | Glaxo Lab Ltd | PROCESS FOR PREPARING INTERMEDIATE COMPOUNDS FOR OBTAINING BETA-LACTAM TYPE ANTIBIOTICS |
-
1975
- 1975-03-20 JP JP50033808A patent/JPS5817460B2/en not_active Expired
-
1976
- 1976-02-17 PL PL21210976A patent/PL114456B1/en unknown
- 1976-02-17 HU HU76SI1594A patent/HU174387B/en unknown
-
1977
- 1977-01-20 FR FR7701588A patent/FR2334670A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| HU174387B (en) | 1979-12-28 |
| PL114456B1 (en) | 1981-01-31 |
| FR2334670B1 (en) | 1979-08-24 |
| FR2334670A1 (en) | 1977-07-08 |
| JPS51108056A (en) | 1976-09-25 |
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