JPH0527629B2 - - Google Patents
Info
- Publication number
- JPH0527629B2 JPH0527629B2 JP22657083A JP22657083A JPH0527629B2 JP H0527629 B2 JPH0527629 B2 JP H0527629B2 JP 22657083 A JP22657083 A JP 22657083A JP 22657083 A JP22657083 A JP 22657083A JP H0527629 B2 JPH0527629 B2 JP H0527629B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- reaction
- formula
- yield
- usually
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 238000006704 dehydrohalogenation reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 claims description 3
- 150000007657 benzothiazepines Chemical class 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- -1 p-methoxy-α-acetoxycinnamic acid Chemical compound 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000012345 acetylating agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- AOPNPZIOVIPWMF-UHFFFAOYSA-N 3-(4-methoxyphenyl)-2-oxopropanoic acid Chemical compound COC1=CC=C(CC(=O)C(O)=O)C=C1 AOPNPZIOVIPWMF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229940085242 benzothiazepine derivative selective calcium channel blockers with direct cardiac effects Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BTOJSYRZQZOMOK-UHFFFAOYSA-N 4-chloro-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=NC(Cl)=C2C=C1 BTOJSYRZQZOMOK-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、式
で表される２−（４−メトキシフエニル）−３−ア
セトキシ−５−（２−ジメチルアミノエチル）−
２，３−ジヒドロ−１，５−ベンゾチアゼピン−
４（5H）−オン及びその酸付加塩であるベンゾチ
アセピン誘導体の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the formula 2-(4-methoxyphenyl)-3-acetoxy-5-(2-dimethylaminoethyl)-
2,3-dihydro-1,5-benzothiazepine-
The present invention relates to a method for producing benzothiacepine derivatives, which are 4(5H)-one and its acid addition salt.
式〔〕の化合物及びその酸付加塩は、ベンゾ
チアゼピン誘導体の中でも特に重要な医薬品であ
り、抵抗うつ剤、精神神経安定剤、冠状血管抗張
剤等として臨床に供されている。 The compound of formula [] and its acid addition salt are particularly important pharmaceuticals among benzothiazepine derivatives, and are used clinically as anti-depressants, psychoneurol stabilizers, coronary vascular tonic agents, and the like.
本発明の目的は、上記ベンゾチアゼピン誘導体
を、簡便な反応操作で収率良く得られる新規な製
造法を提供することにある。以下、本発明製造法
について説明する。 An object of the present invention is to provide a novel method for producing the above-mentioned benzothiazepine derivatives with a high yield through simple reaction operations. The manufacturing method of the present invention will be explained below.
本発明によれば、式〔〕の化合物は、下記反
応工程式Ａに従つて製造される。 According to the present invention, the compound of formula [] is prepared according to reaction scheme A below.
〔上記一般式〔〕中は、Ｘはハロゲン原子を示
す。〕
即ち、一般式〔〕で表わされる化合物と式
〔〕で表わされる２−Ｎ−（２−ジメチルアミノ
エチル）アミノチオフエノールとを脱ハロゲン化
水素反応に付して生成する化合物〔〕を加熱す
ることにより目的の式〔〕の化合物が得られ
る。化合物〔〕は、式〔〕の化合物がＮ−ア
シル化された上記構造を有すると推定でき、これ
が加熱により閉環して目的化合物〔〕が得られ
るものと考えられる。 [In the above general formula [], X represents a halogen atom. ] That is, the compound represented by the general formula [] and the 2-N-(2-dimethylaminoethyl)aminothiophenol represented by the formula [] are subjected to a dehydrohalogenation reaction to produce a compound [], which is heated. By doing this, the desired compound of formula [] is obtained. It is presumed that the compound [] has the above structure in which the compound of the formula [] is N-acylated, and it is thought that this is ring-closed by heating to obtain the target compound [].
上記脱ハロゲン化水素反応の反応条件として
は、特に限定されず、この種の反応の通常の条件
と同様で良い。具体的には、化合物〔〕に対し
て化合物〔〕を通常0.5〜２倍モル程度の割合
で用い、非プロトン性溶媒中で反応させれは良
い。非プロトン性溶媒としては、例えば塩化メチ
レン、ジオキサン、アセトニトリル、クロロホル
ム、ジメチルスルホキシド等を挙げることがで
き、これらの少なくとも１種を用いる。反応は、
無触媒下でも進行するが、通常例えばピリジン、
コリジン、トリエチルアミン等の塩基性触媒の存
在下に行なうのが好ましい。触媒を使用する場合
の使用量は、化合物〔〕に対して通常0.5倍モ
ル以上程度、特に好ましくは１〜２倍モル程度と
するのが良い。反応温度は、特に限定されない
が、通常０〜50℃程度とするのが適当である。本
反応は、通常10分〜２時間程度で終了し、化合物
〔〕が生成する。 The reaction conditions for the dehydrohalogenation reaction are not particularly limited, and may be the same as usual conditions for this type of reaction. Specifically, it is preferable to use the compound [] in a ratio of about 0.5 to 2 times the mole of the compound [] and to react in an aprotic solvent. Examples of the aprotic solvent include methylene chloride, dioxane, acetonitrile, chloroform, dimethyl sulfoxide, and at least one of these is used. The reaction is
Although it can proceed without a catalyst, it is usually carried out using, for example, pyridine,
It is preferable to carry out the reaction in the presence of a basic catalyst such as collidine or triethylamine. When a catalyst is used, the amount used is usually about 0.5 times or more, particularly preferably about 1 to 2 times, by mole relative to the compound []. Although the reaction temperature is not particularly limited, it is usually appropriate to set it to about 0 to 50°C. This reaction usually ends in about 10 minutes to 2 hours, and the compound [ ] is produced.
本発明においては、化合物〔〕を特に精製す
る必要はなく、上記脱ハロゲン化水素反応終了
後、加熱して閉環させれば良い。閉環反応は、適
当な溶媒中、通常１〜10時間程度、通常50〜150
℃程度の温度に加熱すれば良い。溶媒としては、
例えばエタノール、プロパノール、ブタノール等
のアルコール、ベンゼン、トルエン、キシレン等
の芳香族系炭化水素等を挙げることができ、これ
らの少なくとも１種を用いる。 In the present invention, it is not necessary to particularly purify the compound [], and it is sufficient to heat the compound to close the ring after the above-mentioned dehydrohalogenation reaction is completed. The ring-closing reaction is carried out in an appropriate solvent, usually for about 1 to 10 hours, usually for 50 to 150 hours.
It is sufficient to heat it to a temperature of about ℃. As a solvent,
Examples include alcohols such as ethanol, propanol and butanol, and aromatic hydrocarbons such as benzene, toluene and xylene, and at least one of these may be used.
かくして得られる目的化合物〔〕は、慣用の
分離精製手段、例えば再結晶、各種クロマトグラ
フイー等により容易に単離できる。 The target compound [] thus obtained can be easily isolated by conventional separation and purification means such as recrystallization, various chromatography, etc.
本発明においては、上記で得られる目的化合物
〔〕を、常法によつて、塩酸塩等の酸付加塩に
することもできる。 In the present invention, the target compound [] obtained above can also be converted into an acid addition salt such as a hydrochloride by a conventional method.
上記反応工程式Ａにおける化合物〔〕は公知
の化合物であるが、化合物〔〕は新規化合物で
ある。化合物〔〕は、例えば下記反応工程式Ｂ
に従つて製造できる。 Compound [] in the above reaction scheme A is a known compound, but compound [] is a new compound. Compound [] is, for example, the following reaction scheme B
It can be manufactured according to
〔上記一般式〔〕中、Ｘはハロゲン原子を示
す。〕
即ち、式〔〕で表わされる公知化合物ｐ−メ
トキシフエニルピルビン酸をアセチル化して化合
物〔〕とし、次いでハロゲン化して化合物
〔〕を得る。尚、化合物〔〕、即ちｐ−メトキ
シ−α−アセトキシケイ皮酸も新規化合物であ
る。 [In the above general formula [], X represents a halogen atom. ] That is, the known compound p-methoxyphenylpyruvic acid represented by formula [] is acetylated to give compound [], and then halogenated to obtain compound []. Note that the compound [ ], ie, p-methoxy-α-acetoxycinnamic acid, is also a new compound.
上記アセチル化反応は、アセチル化剤として、
例えば無水酢酸、塩化アセチル等を用い、アセチ
ル化剤をそのまま溶媒としても用いるか又は前記
非プロトン性溶媒中で、行なわれる。アセチル化
剤の使用量は、化合物〔〕に対して通常0.5倍
モル以上、好ましくは等倍モル以上とするのが良
い。反応は、無触媒下でも進行するが、反応の
際、例えばｐ−トルエンスルホン酸等の触媒を、
化合物〔〕に対して0.1〜10％程度使用するの
が好ましい。反応温度は、特に限定されないが、
通常０〜200℃程度にすれば良い。反応時間は、
通常30分〜24時間程度である。 In the above acetylation reaction, as an acetylating agent,
For example, acetic anhydride, acetyl chloride, etc. are used, and the acetylating agent is used as a solvent as it is, or the reaction is carried out in the aprotic solvent described above. The amount of the acetylating agent to be used is usually 0.5 times or more, preferably 1 times or more by mole, relative to the compound []. The reaction proceeds even without a catalyst, but when a catalyst such as p-toluenesulfonic acid is used during the reaction,
It is preferable to use it in an amount of about 0.1 to 10% based on the compound []. The reaction temperature is not particularly limited, but
Normally, the temperature should be about 0 to 200°C. The reaction time is
Usually it takes about 30 minutes to 24 hours.
また、上記ハロゲン化反応は、ハロゲン化剤と
して、例えばオキサリルクロライド、チオニルク
ロライド、オキシ塩化燐、オキサリルブロマイド
等を用い、ハロゲン化剤をそのまま溶媒としても
用いるか又は前記非プロトン性溶媒中で、行なわ
れる。ハロゲン化剤の使用量は、化合物〔〕に
対して通常0.2倍モル程度以上、好ましくは0.5倍
モル以上とするのが良い。反応温度は、特に限定
されないが、通常０〜200℃程度とすれば良い。
反応時間は、通常10分〜12時間程度である。 Further, the above halogenation reaction is carried out using, for example, oxalyl chloride, thionyl chloride, phosphorus oxychloride, oxalyl bromide, etc. as a halogenating agent, and using the halogenating agent as it is as a solvent, or in the aprotic solvent described above. It will be done. The amount of the halogenating agent used is usually about 0.2 times or more, preferably 0.5 times or more by mole, relative to the compound []. The reaction temperature is not particularly limited, but may generally be about 0 to 200°C.
The reaction time is usually about 10 minutes to 12 hours.
かくして、化合物〔〕が得られ、これを前記
反応工程式Ａの原料とする。 In this way, compound [ ] is obtained, which is used as the raw material for reaction scheme A above.
本発明法によれば、目的化合物〔〕を、簡単
な反応操作で収率良く得ることができるため工業
上有利である。また、必要に応じて、塩酸塩等の
酸付加塩とすることもできる。 The method of the present invention is industrially advantageous because the target compound [] can be obtained in good yield through simple reaction operations. Moreover, if necessary, it can also be made into an acid addition salt such as a hydrochloride.
以下、参考例及び実施例を挙げて、本発明を更
に具体的に説明する。 Hereinafter, the present invention will be explained in more detail with reference to Reference Examples and Examples.
参考例 １
ｐ−メトキシ−α−アセトキシケイ皮酸の合成
ｐ−メトキシフエニルピルビン酸２ｇを無水酢
酸５mlに懸濁し、ｐ−トルエンスルホン酸0.1ｇ
を加え、撹拌下２時間還流した。反応終了後、冷
却し析出する結晶を取し、酢酸エチル洗浄後乾
燥した。収量２ｇ（収率82.2％）、mp.180〜181
℃、黄色結晶。Reference Example 1 Synthesis of p-methoxy-α-acetoxycinnamic acid 2 g of p-methoxyphenylpyruvic acid was suspended in 5 ml of acetic anhydride, and 0.1 g of p-toluenesulfonic acid was added.
was added, and the mixture was refluxed for 2 hours while stirring. After the reaction was completed, it was cooled, and the precipitated crystals were collected, washed with ethyl acetate, and then dried. Yield 2g (yield 82.2%), mp.180-181
°C, yellow crystals.
IR（cm-1）：1765（−Ｃ＝Ｃ−Ｏ−CO−）、1710（−
COOH）。IR (cm -1 ): 1765 (-C=C-O-CO-), 1710 (-
COOH).
元素分析値：C12H12O5として、 計算値（％）Ｃ：61.01、Ｈ：5.12 実験値（％）Ｃ：61.11、Ｈ：5.15。Elemental analysis values: As C 12 H 12 O 5 , calculated values (%) C: 61.01, H: 5.12, experimental values (%) C: 61.11, H: 5.15.
参考例 ２
ｐ−メトキシ−α−アセトキシケイ皮酸クロラ
イドの合成
ｐ−メトキシ−α−アセトキシケイ皮酸３ｇ
をオキサリルクロライド10mlに加え、撹拌下40
分間還流した。反応終了後、反応液を減圧にて
濃縮した。更に、残存するオキサリルクロライ
ドを除去するために塩化メチレンを加え、再
度、減圧で濃縮した。残渣にｎ−ヘキサンを加
えて、結晶化させ、結晶を取した。収量2.6
ｇ（収率80％）、m.p.124〜127℃（分解）、赤色
針状結晶。Reference Example 2 Synthesis of p-methoxy-α-acetoxycinnamic acid chloride 3 g of p-methoxy-α-acetoxycinnamic acid
was added to 10 ml of oxalyl chloride and stirred for 40 minutes.
Refluxed for minutes. After the reaction was completed, the reaction solution was concentrated under reduced pressure. Furthermore, methylene chloride was added to remove residual oxalyl chloride, and the mixture was again concentrated under reduced pressure. N-hexane was added to the residue to crystallize it, and the crystals were collected. Yield 2.6
g (80% yield), mp 124-127°C (decomposed), red needle-shaped crystals.
IR（cm-1）：1810（−COCl）。IR (cm -1 ): 1810 (-COCl).
元素分析値：C12H11ClO4として、 計算値（％）Ｃ：56.59、Ｈ：4.35、 実験値（％）Ｃ：56.70、Ｈ：4.40。Elemental analysis values: As C12H11ClO4 , calculated values (%) C: 56.59, H: 4.35, experimental values (%) C: 56.70, H: 4.40.
実施例 １
２−（４−メトキシフエニル）−３−アセトキシ
−５−（２−ジメチルアミノエチル）−２，３−
ジヒドロ−１，５−ベンゾチアゼビン−４
（5H）−オン〔〕及びその塩酸塩の合成
ｐ−メトキシ−α−アセトキシケイ皮酸クロラ
イド２ｇを塩化メチレン20mlに溶解した。これを
塩化メチレン40mlに溶解した２−Ｎ−（２−ジメ
チルアミノエチル）アミノチオフエノール1.55ｇ
及びピリジン２ml中に撹拌下室温にて加えた。更
に、30分間撹拌し、反応の終了後、減圧にて濃縮
した。残渣にエタノール20mlを加え、撹拌下６時
間還流した。その後、反応液を減圧下に濃縮し
た。この粗生組成物をシリカゲルカラムクロマト
グラフイー（クロロホルム・メタノール混液にて
溶出）により精製した。得られた結晶をイソプロ
ピルエーテルから再結晶した。収量1.7ｇ（収率
53.1％）、m.p.135〜136℃、白色結晶。Example 1 2-(4-methoxyphenyl)-3-acetoxy-5-(2-dimethylaminoethyl)-2,3-
Dihydro-1,5-benzothiazebin-4
Synthesis of (5H)-one [] and its hydrochloride 2 g of p-methoxy-α-acetoxycinnamic acid chloride was dissolved in 20 ml of methylene chloride. 1.55 g of 2-N-(2-dimethylaminoethyl)aminothiophenol dissolved in 40 ml of methylene chloride
and 2 ml of pyridine at room temperature under stirring. The mixture was further stirred for 30 minutes, and after the reaction was completed, it was concentrated under reduced pressure. 20 ml of ethanol was added to the residue, and the mixture was refluxed for 6 hours while stirring. Thereafter, the reaction solution was concentrated under reduced pressure. This crude composition was purified by silica gel column chromatography (eluted with a chloroform/methanol mixture). The obtained crystals were recrystallized from isopropyl ether. Yield 1.7g (yield
53.1%), mp135-136℃, white crystals.
IR（cm-1）：1740、1215（COCH3）1678（−CO−Ｎ
）、1250、1030（Ｃ−Ｓ）。IR (cm -1 ): 1740, 1215 (COCH 3 ) 1678 (-CO-N
), 1250, 1030 (C-S).
元素分析値：C22H26O4N2Sとして、 計算値（％）Ｃ：63.75、Ｈ：6.32、Ｎ：6.76、 実験値（％）Ｃ：63.81、Ｈ：6.34、Ｎ：6.79。Elemental analysis values: As C 22 H 26 O 4 N 2 S, calculated values (%) C: 63.75, H: 6.32, N: 6.76, experimental values (%) C: 63.81, H: 6.34, N: 6.79.
これをアセトンに溶解させ、塩酸・エタノール
を加え放置して塩酸塩を析出させた。これを
取、乾燥した。収量1.5ｇ（収率42.8％）、m.p.190
〜191℃、白色結晶。 This was dissolved in acetone, and hydrochloric acid and ethanol were added and allowed to stand to precipitate the hydrochloride. This was taken and dried. Yield 1.5g (yield 42.8%), mp190
~191℃, white crystals.
IR（cm-1）：1740、1213（COCH3）1680（−CO−Ｎ
）、1250、1028（Ｃ−Ｓ）。IR (cm -1 ): 1740, 1213 (COCH 3 ) 1680 (-CO-N
), 1250, 1028 (C-S).
元素分析値：C22H26O4N2S・HClとして、 計算値（％）Ｃ：58.60、Ｈ：6.04、Ｎ：6.21、 実験値（％）Ｃ：58.65、Ｈ：6.01、Ｎ：6.27。Elemental analysis value: As C 22 H 26 O 4 N 2 S・HCl, calculated value (%) C: 58.60, H: 6.04, N: 6.21, experimental value (%) C: 58.65, H: 6.01, N: 6.27 .
Claims (1)
ル）アミノチオフエノールとを脱ハロゲン化水素
反応に付して得られる生成物を加熱して、式 で表わされる２−（４−メトキシフエニル）−３−
アセトキシ−５−（２−ジメチルアミノエチル）−
２，３−ジヒドロ−１，５−ベンゾチアゼピン−
４（5H）−オンを得、更に必要に応じて酸付加塩
とすることを特徴とするベンゾチアゼピン誘導体
の製造法。[Claims] 1. General formula [In the formula, X represents a halogen atom. ] Compounds and formulas represented by The product obtained by subjecting 2-N-(2-dimethylaminoethyl)aminothiophenol represented by the formula to a dehydrohalogenation reaction is heated, and the product obtained by the formula 2-(4-methoxyphenyl)-3- represented by
Acetoxy-5-(2-dimethylaminoethyl)-
2,3-dihydro-1,5-benzothiazepine-
1. A method for producing a benzothiazepine derivative, which comprises obtaining 4(5H)-one and, if necessary, converting it into an acid addition salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22657083A JPS60116677A (en) | 1983-11-30 | 1983-11-30 | Production of benzothiazepine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22657083A JPS60116677A (en) | 1983-11-30 | 1983-11-30 | Production of benzothiazepine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60116677A JPS60116677A (en) | 1985-06-24 |
| JPH0527629B2 true JPH0527629B2 (en) | 1993-04-21 |
Family
ID=16847232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP22657083A Granted JPS60116677A (en) | 1983-11-30 | 1983-11-30 | Production of benzothiazepine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60116677A (en) |
-
1983
- 1983-11-30 JP JP22657083A patent/JPS60116677A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60116677A (en) | 1985-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0527629B2 (en) | ||
| CA1331602C (en) | Preparation process of acemetacin | |
| JPH0231075B2 (en) | ||
| US5578728A (en) | Process for the preparation of a benzo(a)quinolizione derivative | |
| JP2980992B2 (en) | Method for producing 6-halogeno-2-oxapregna-4,6-dien-3-one compound | |
| JPS60109541A (en) | Diarylindan-1,3-dione, preparation and use | |
| JPS6078973A (en) | Production of 1,5-benzothiazepine derivative | |
| JPS61165378A (en) | Production of benzothiazepine derivative | |
| JP3655311B2 (en) | Method for producing phthalide compound | |
| JPS6287599A (en) | Production of oxime derivative of erythromycin | |
| JP2676720B2 (en) | Method for producing 1,5-benzothiazepine derivative | |
| JPH051053A (en) | New process for producing 6-(3-dimethylamino-propionyl) forskolin | |
| KR900008171B1 (en) | Process for preparing benzodiazepine acetate | |
| JPS59212500A (en) | Novel process for preparation of 4'-demethyl- epipodophyllotoxin-beta-d-ethylydene glucoside | |
| JPS6345675B2 (en) | ||
| JPS61178947A (en) | Manufacture of arylalkyl ketone | |
| JPH041736B2 (en) | ||
| JPS60246384A (en) | Chromone-8-carboxamide derivative | |
| JPS61165363A (en) | Cinnamic acid amide derivative and production thereof | |
| JPH11302216A (en) | Production of dialkoxy-substituted indanone derivative | |
| JPS61158962A (en) | Production of 1,4-dihydropyridine derivative | |
| JPH0527617B2 (en) | ||
| JP2001199933A (en) | One-pot process for production of caffeic acid ester derivative | |
| JPH029572B2 (en) | ||
| JPH0651697B2 (en) | Method for purifying 2- (10,11-dihydro-10-oxodibenzo [b, f] thiepin-2-yl) propionic acid |