JPS5846091A - Thinoindolidine compound and its preparation - Google Patents
Thinoindolidine compound and its preparationInfo
- Publication number
- JPS5846091A JPS5846091A JP56144893A JP14489381A JPS5846091A JP S5846091 A JPS5846091 A JP S5846091A JP 56144893 A JP56144893 A JP 56144893A JP 14489381 A JP14489381 A JP 14489381A JP S5846091 A JPS5846091 A JP S5846091A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- lower alkyl
- acid
- cyano
- 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
Links
Abstract
Description
【発明の詳細な説明】
本発明は新規なチイメインドリジン化合物及びその製造
法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel thiimeindrisine compound and a method for producing the same.
本発明のチイメインドリジン化合物は下記一般式(1)
で表わされる。The thiimeindolizine compound of the present invention has the following general formula (1):
It is expressed as
(式中Rは水素原子または低級アルキル基を、R1は低
級アルキル基を、Rはシアノ基または低級アルコキシカ
ルボニル基を意味スル)
上記一般式q)中、RおよびRで定義される低級アルキ
ル基の例として、炭素数1〜6のアルキル基、例えばメ
チル、エチル、プロピル、ブチル、ヘキシル基等を、ま
たR8で定義される低級アルコキシカルボニル基の低級
アルコキンの例として、炭素数1〜6のアルコキシ、例
えばメトキシ、エトキシ、プロポキシ、プ゛トキシ、ヘ
キシルオキン等をそれぞれ例示できる。(In the formula, R represents a hydrogen atom or a lower alkyl group, R1 represents a lower alkyl group, and R represents a cyano group or a lower alkoxycarbonyl group) In the above general formula q), a lower alkyl group defined by R and R. Examples include alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, hexyl groups, etc., and examples of lower alkoxycarbonyl groups defined by R8 include 1 to 6 carbon atoms. Examples of alkoxy include methoxy, ethoxy, propoxy, propoxy, and hexyl oxene.
本発明の上記一般式(1)で表わされるチイ′ツイント
リジン化合物は文献未載の新規化合物であり、抗アレル
ギー作用、血小板凝集抑制作用等を有し、医薬の分野に
おいて抗アンルギー剤、抗血栓剤等として有用である。The chi'twintolidine compound of the present invention represented by the above general formula (1) is a new compound that has not been described in any literature, and has antiallergic effects, platelet aggregation inhibitory effects, etc., and is used as an antianruginic agent, an antithrombotic agent, etc. in the pharmaceutical field. It is useful as a drug.
本発明の一般式(1)で示されるチイノインドリジン化
合物は、例えば下記反応行程式に示すように一般式(I
I)で表わされる2−アルキルチオインドリジン化合物
に酸を作用させることにより製造される。The thiinoindolizine compound represented by the general formula (1) of the present invention can be prepared by the general formula (I) as shown in the following reaction scheme, for example.
It is produced by reacting the 2-alkylthioindolizine compound represented by I) with an acid.
〈反応行程式〉
は低級アルキル基を意味する)
本発明において出発原料として用いられる一般式(!T
)で表わされる2−アルキルチオインドリジン化合物は
通常公知の化合物であり、例えばジャーナル オグ オ
ーガニック クミストリー(J。<Reaction scheme> means a lower alkyl group) General formula (!T
The 2-alkylthioindolizine compound represented by ) is a commonly known compound, for example, in Journal Og Organic Cumistry (J.
Org、 Chem、) 48,4837 (1978
)に記載の方法またはこれに準する方法により容易に製
造することができる。Org, Chem, ) 48,4837 (1978
) or a similar method.
本発明において、酸としては一般に塩酸、硫酸、硝酸、
臭化水素酸、ヨク化水素酸等の無機酸が好適に使用され
る。酸の使用量は広い範囲から選択できるが、通常は一
般式(It)の2−アルキルチオインドリジン化合物に
対して当モル〜過剰量用いるのが好ましい。本反応の反
応温度は特に限定されないが、好ましくは室温〜100
’C程度において実施される。In the present invention, acids generally include hydrochloric acid, sulfuric acid, nitric acid,
Inorganic acids such as hydrobromic acid and hydroioccic acid are preferably used. The amount of acid to be used can be selected from a wide range, but it is usually preferred to use an equivalent molar to excess amount relative to the 2-alkylthioindolizine compound of general formula (It). The reaction temperature of this reaction is not particularly limited, but is preferably room temperature to 100°C.
It is carried out at the 'C level.
上記本発明の反応により一般式(1)で表わされるチイ
メインドリジン化合物が生成し、通常の方法により無機
酸塩として容易に単離可能であるが、本発明では引き続
き塩基性化合物を加えて中和することにより一般式(1
)で表わされるチイノイノドリジン化合物を遊離体とし
て単離することも可能である。この際中和に用いられる
塩基性化合物としては、例えば水酸化ナトリウム、水酸
化カリウム、炭酸ナトリウム、炭酸カリウム、炭酸水素
ナトリウム、炭酸水素カリウム等が挙げられる。The above reaction of the present invention produces a thiimeindolizine compound represented by the general formula (1), which can be easily isolated as an inorganic acid salt by a normal method, but in the present invention, a basic compound is subsequently added. By neutralization, the general formula (1
) It is also possible to isolate the thiinoinodorizine compound represented by the following as an educt. Examples of the basic compound used for neutralization include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, and the like.
本発明の化合物は通常公知の手段、例えば抽出、濃縮、
蒸留、再結晶゛、カラムクロマトグラフィー等により精
製される。The compounds of the present invention can be prepared by commonly known means such as extraction, concentration,
It is purified by distillation, recrystallization, column chromatography, etc.
以下本発明化合物の製造例を実施例として挙げる。Examples of the production of the compounds of the present invention are listed below as examples.
実施例1
l−(2−シアノ−2−エトキシカフレボニルビニルメ
チルチオインドリジン−3−カルボン酸エチルエステル
a5sq(1ミリモル)を濃塩酸20m1に加え、70
〜80″Cで1時間加熱した後、反応溶液を減圧濃縮す
る。残置をエタノールから再結晶して融点204−20
5°Cの2−イE/−2H−チイノ[3,2−a〕イン
ドリジン−311O−ジカルホ゛ン酸ジエチルエステル
塩酸塩を得る。この塩酸塩を水20m1に溶解し炭酸カ
リクム水溶液を加えて中和する。析出物を口取し、クロ
ロホルムから再結晶して、融点142〜145’Cの2
−イミ/−2H−チイ/ [3t2−a)イノトリジン
−3,10−ジカルボン酸ジエチルエステル230mg
を得る。Example 1 5 sq (1 mmol) of l-(2-cyano-2-ethoxycafflebonyl vinylmethylthioindolizine-3-carboxylic acid ethyl ester) was added to 20 ml of concentrated hydrochloric acid, and 70
After heating at ~80"C for 1 hour, the reaction solution is concentrated under reduced pressure. The residue is recrystallized from ethanol to give a melting point of 204-20.
2-IE/-2H-thiino[3,2-a]indolizine-311O-dicarboic acid diethyl ester hydrochloride is obtained at 5°C. This hydrochloride is dissolved in 20 ml of water and neutralized by adding an aqueous solution of potassium carbonate. The precipitate was collected and recrystallized from chloroform to give 2.
-Imi/-2H-Chii/ [3t2-a) Inotridine-3,10-dicarboxylic acid diethyl ester 230 mg
get.
融点 +42−+45°C(塩酸塩204−205°C
)収率 67%
IR分析結果 (KBr錠)
8250(NH)、 1670cm (CO)元
素分析値 (C10HI6 N204Sトシテ)計算値
(ト) C59,29H4,68N 8.14実測値
(@ C59,51H4,60N 8.02実施例
2
和尚する出発原料を用い、実施例Iと同様にして下記各
化合物を得る。Melting point +42-+45°C (hydrochloride 204-205°C
) Yield 67% IR analysis result (KBr tablet) 8250 (NH), 1670 cm (CO) Elemental analysis value (C10HI6 N204S) Calculated value (g) C59,29H4,68N 8.14 Actual value (@ C59,51H4, 60N 8.02 Example 2 The following compounds were obtained in the same manner as in Example I using the starting materials.
3−シアノ−2−イE/−2H−チイ/ [3,2−a
”Jインドリジン−10−カルボン酸エチルエステル融
点 268−270°C
収率 43%
IR分析結果 (KBr錠)
3250 (NH) 、 221 B (C’N) 、
1688cm (CO)元素分析値 (C+5H++
Na02Sとして)計算値(ト)C60,59H34a
N 14.+3実測値(ト)C60,40H3,L(
N 14.222−イミノ−7−メチル−2H−チイン
[3,2−a〕インドリジン−3,10−ジカルボン酸
ジエチルエステIし融点 202−205°C(塩酸塩
184−188’C)収率 57%
IR分析結果 (KBr錠)
8260(NH) 1680cm (Co)元素分
析値(Crs HI8 N2045として)計算値(ト
)C60,32H5,06N 7−.82実測値(ト)
C60,61H4−97N 7.013−シアノ−2−
イミノ−7〜メチル−2H−チイン(3,2−a)イン
ドリジン−10−カルボン酸エチルエステル
融点 264−267°C
収率 56%
IR分析結果 (KBr錠)
3250(NH)、2218(CN)、1685c晶’
(c6)元素分析値 (C1e H+a Na 02
Sとして)計算値(ト)C61,72H4,21N 1
3.50実測値(ト)C61,59H4,05,N 1
3.797−エチル−2−イ=ノー2H−チイノ〔3,
2−a〕インドリジン−3,10−ジカルボン酸ジエチ
ルエステル融点 r9ia−2t2°C (塩酸塩1
9 2 − 1 9 66C)収率 40%
IR分析結果 (KBr錠)
3260(NH)、 1680cm (CO)元素
分析値 ( C10 N20 N2 04 S (!:
シテ)計算値(ト) C 61.27 H 5.41
N 7.52実測値(ト) C B1.18 H 5
.49 N 7.583−シアノ−7−エチル−2−イ
ミノ−2Hーチイノ(3.2−a)インドリジン−10
−カルボン酸エチルエステル融点 192−195’C
(塩酸塩+54−1s7”C)収率 68%
IR分析結果 (KBr’錠)
8260(NH)、2218(CN)、1687cm
(CO)元素分析値 (C10HI5 Na 02 S
として)計算値C@、 C62,75H4,65N 1
2.92実測値(4) C62,97H4,70N 1
2.58(以上)3-cyano-2-iE/-2H-chii/[3,2-a
"J indolizine-10-carboxylic acid ethyl ester Melting point 268-270°C Yield 43% IR analysis result (KBr tablet) 3250 (NH), 221 B (C'N),
1688cm (CO) elemental analysis value (C+5H++
Calculated value (as Na02S) C60,59H34a
N 14. +3 Actual measurement value (G) C60, 40H3, L (
N 14.222-Imino-7-methyl-2H-thiine[3,2-a]indolizine-3,10-dicarboxylic acid diethyl ester I, melting point 202-205°C (hydrochloride 184-188'C) Yield Rate 57% IR analysis result (KBr tablet) 8260 (NH) 1680 cm (Co) Elemental analysis value (as Crs HI8 N2045) Calculated value (g) C60,32H5,06N 7-. 82 actual measurement value (g)
C60,61H4-97N 7.013-cyano-2-
Imino-7-methyl-2H-thiine (3,2-a) indolizine-10-carboxylic acid ethyl ester Melting point 264-267°C Yield 56% IR analysis results (KBr tablets) 3250 (NH), 2218 (CN) ), 1685c crystal'
(c6) Elemental analysis value (C1e H+a Na 02
S) Calculated value (g) C61,72H4,21N 1
3.50 Actual value (g) C61,59H4,05,N 1
3.797-ethyl-2-y=no2H-thiino[3,
2-a] Indolizine-3,10-dicarboxylic acid diethyl ester melting point r9ia-2t2°C (hydrochloride 1
9 2 - 1 9 66C) Yield 40% IR analysis result (KBr tablet) 3260 (NH), 1680 cm (CO) Elemental analysis value (C10 N20 N2 04 S (!:
C) Calculated value (G) C 61.27 H 5.41
N 7.52 Actual value (g) C B1.18 H 5
.. 49 N 7.583-cyano-7-ethyl-2-imino-2H-thiino(3.2-a) indolizine-10
-Carboxylic acid ethyl ester melting point 192-195'C
(Hydrochloride +54-1s7”C) Yield 68% IR analysis results (KBr' tablets) 8260 (NH), 2218 (CN), 1687 cm
(CO) elemental analysis value (C10HI5 Na 02 S
) Calculated value C@, C62,75H4,65N 1
2.92 actual value (4) C62,97H4,70N 1
2.58 (or more)
Claims (1)
アルキル基を、Rはシアン基または低級アルコキシカル
ボニル基を意味する)で示されるチイノインドリジン化
合物。 (式中Rは水素原子または低級アルキル基を、R1およ
びRは低級アルキル基を、Rはシアノ基または低級アル
コキンカルボニル基を意味する)で示される2−アルキ
ルチオインドリジン化合物に酸を作用させることを特徴
とする一般式(式中JRおよびRは前記と同じである)
で示されるチイメインドリジン化合物の製造法。(1) A thiinoindolizine compound represented by the general formula (in the formula, R represents a hydrogen atom or a lower alkyl group, R represents a lower alkyl group, and R represents a cyan group or a lower alkoxycarbonyl group). (In the formula, R represents a hydrogen atom or a lower alkyl group, R1 and R represent a lower alkyl group, and R represents a cyano group or a lower alkoxycarbonyl group) with an acid. (wherein JR and R are the same as above)
A method for producing a thiimeindolizine compound shown in
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP56144893A JPS5846091A (en) | 1981-09-14 | 1981-09-14 | Thinoindolidine compound and its preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP56144893A JPS5846091A (en) | 1981-09-14 | 1981-09-14 | Thinoindolidine compound and its preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5846091A true JPS5846091A (en) | 1983-03-17 |
JPH0161111B2 JPH0161111B2 (en) | 1989-12-27 |
Family
ID=15372788
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP56144893A Granted JPS5846091A (en) | 1981-09-14 | 1981-09-14 | Thinoindolidine compound and its preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5846091A (en) |
-
1981
- 1981-09-14 JP JP56144893A patent/JPS5846091A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPH0161111B2 (en) | 1989-12-27 |
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