JPS5823398B2 - Piperidylbenzimidazole - Google Patents

Piperidylbenzimidazole

Info

Publication number
JPS5823398B2
JPS5823398B2 JP50074813A JP7481375A JPS5823398B2 JP S5823398 B2 JPS5823398 B2 JP S5823398B2 JP 50074813 A JP50074813 A JP 50074813A JP 7481375 A JP7481375 A JP 7481375A JP S5823398 B2 JPS5823398 B2 JP S5823398B2
Authority
JP
Japan
Prior art keywords
group
piperidyl
chloroform
fluorobenzoyl
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
JP50074813A
Other languages
Japanese (ja)
Other versions
JPS52278A (en
Inventor
佐藤誠
上野勝次郎
有本昌弘
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.)
Daiichi Pharmaceutical Co Ltd
Original Assignee
Daiichi Pharmaceutical 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 Daiichi Pharmaceutical Co Ltd filed Critical Daiichi Pharmaceutical Co Ltd
Priority to JP50074813A priority Critical patent/JPS5823398B2/en
Publication of JPS52278A publication Critical patent/JPS52278A/en
Publication of JPS5823398B2 publication Critical patent/JPS5823398B2/en
Expired legal-status Critical Current

Links

Landscapes

  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

【発明の詳細な説明】 本発明は一般式(I) (式中Yはカルボニル基又は−CH−基、Arはハロフ
ェニル基)で表わされる新規なピペリジルベンゾイミダ
ゾール誘導体又はその塩類の製造法に関する。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a novel piperidylbenzimidazole derivative represented by the general formula (I) (wherein Y is a carbonyl group or a -CH- group and Ar is a halophenyl group) or a salt thereof.

(式中Qはカルボニル基、保護基で保護されたカルボニ
ル基又は−CH−基を、Arはハロフェニル基を、Rは
低級アルキル基、アラルキル基、ベンゾイル低級アルキ
ル基、低級アシル基又はアルコキシカルボニル基から選
択されるーSHの保護基を示す)で表わされるピペリジ
ン誘導体を酸又は塩基と反応させ一8Hの保護基を脱離
し、必要に応じて加水分解することにより製することが
出来る。
(In the formula, Q is a carbonyl group, a carbonyl group protected with a protecting group, or a -CH- group, Ar is a halophenyl group, and R is a lower alkyl group, an aralkyl group, a benzoyl lower alkyl group, a lower acyl group, or an alkoxycarbonyl group. It can be produced by reacting a piperidine derivative represented by -SH (representing a protecting group selected from -SH) with an acid or base to remove the -8H protecting group, and optionally hydrolyzing.

先に示した「カルボニルの保護基」としては例えばエチ
レンケタール等のケタール類、チオケタール類、ヘミチ
オケタール類、チアゾリジン類、エノールエーテル類、
エノールエステル類、アセタール類、シッフ塩基、オキ
シム等があり、中でも取扱いの容易さなどからエチレン
ケタールが好適に用いられる。
Examples of the above-mentioned "carbonyl protecting group" include ketals such as ethylene ketal, thioketals, hemithioketals, thiazolidines, enol ethers,
There are enol esters, acetals, Schiff bases, oximes, etc. Among them, ethylene ketal is preferably used because of its ease of handling.

一8Hの保護基の脱離に用いる酸としては、例えば臭化
水素酸、ヨウ化水素酸等のハロゲン化水素酸又は酪酸、
安息香酸、トリフルオロ酢酸、パラトルエンスルホン酸
等の有機酸又はそれらの混合物および塩化アルミニウム
、三臭化ホウ素等のルイス酸、更(こはピリジン塩酸塩
、ピリジン臭化水素酸塩等の強酸と弱塩基の塩類等があ
る。
Examples of acids used for removing the 18H protecting group include hydrohalic acids such as hydrobromic acid and hydroiodic acid, or butyric acid;
Organic acids such as benzoic acid, trifluoroacetic acid, para-toluenesulfonic acid, or mixtures thereof; Lewis acids such as aluminum chloride, boron tribromide; and strong acids such as pyridine hydrochloride, pyridine hydrobromide, etc. There are salts of weak bases.

又、この発明に用いる塩基としては、例えば水酸化ナト
IJウム、水酸化カリウムなどの金属水酸化物、ナトリ
ウムエチラート、カリウム第三ブチラードなどの金属ア
ルコラードなどがある。
Examples of the base used in this invention include metal hydroxides such as sodium hydroxide and potassium hydroxide, and metal alcoholades such as sodium ethylate and potassium tert-butylade.

又、この発明の反応は無溶媒でも行われるか水、アルコ
ール又はベンゼン、トルエン、キシレン、ニトロベンゼ
ン、テトラリン等の芳香族炭化水素類、ジクロルメタン
等のハロゲン化炭化水素類、石油類あるいはこれらの混
合物など反応原料、生成物に支障をきたさない溶媒を使
用することが出来る。
Furthermore, the reaction of the present invention may be carried out without a solvent, water, alcohol, aromatic hydrocarbons such as benzene, toluene, xylene, nitrobenzene, tetralin, halogenated hydrocarbons such as dichloromethane, petroleum, or mixtures thereof. Any solvent that does not harm the reaction raw materials and products can be used.

本発明の反応温度は室温〜200℃で、反応時間は30
分〜72時間で充分な場合が多く、一般に反応温度を上
昇させることによって反応を有効に促進させることが出
来る。
The reaction temperature of the present invention is room temperature to 200°C, and the reaction time is 30°C.
Minutes to 72 hours is often sufficient, and the reaction can generally be effectively promoted by increasing the reaction temperature.

又、本反応は常圧の他加圧下に行うことも出来る。Further, this reaction can be carried out under normal pressure as well as under increased pressure.

反応終了後は通常の手法によって目的物を単離すること
が出来る。
After the reaction is completed, the target product can be isolated by conventional techniques.

式(II)の原料化合物でカルボニル基が保護されてい
る場合、処理手段によっては反応と同時にカルボニルの
保護基がはずれることもあるが、保護基がはずれないと
きは公知の常法、例えば稀鉱酸で加水分解することによ
ってカルボニル基の保護基を除去することも出来る。
When the carbonyl group is protected in the starting compound of formula (II), the carbonyl protecting group may be removed at the same time as the reaction depending on the processing method, but if the protecting group cannot be removed, a known conventional method such as rare mineral The protective group for the carbonyl group can also be removed by hydrolysis with an acid.

なお、本発明の方法で製造される化合物(1)は塩酸、
硫酸等の無機酸又は酢酸、クエン酸等の有機酸と反応さ
せることによって、治療学的に有用な酸付加塩に変える
ことが出来る。
In addition, the compound (1) produced by the method of the present invention is hydrochloric acid,
They can be converted into therapeutically useful acid addition salts by reaction with inorganic acids such as sulfuric acid or organic acids such as acetic acid or citric acid.

なお、式け)の化合物は2−ベンゾイミダゾリンチオン
型と互変異性の関係にある。
Note that the compound of formula (2) has a tautomeric relationship with the 2-benzimidazolinthione type.

本発明によって製造される式(I)の化合物は興味ある
薬理作用を有する。
The compounds of formula (I) produced according to the invention have interesting pharmacological actions.

例えば顕著な自発運動抑制作用(マウス)、メタンフェ
タミン群居毒性抑制作用(マウス)、メタンフェタミン
常置行動抑制作用(ラット)、条件回避反応抑制作用(
ラット)、アポモルヒネ雷同行動抑制作用(ラット)を
示し、医薬特に向精神薬として有用な性質を有する。
For example, remarkable locomotor activity suppression effect (mice), methamphetamine group toxicity suppression effect (mice), methamphetamine permanent behavior suppression effect (rat), conditioned avoidance response suppression effect (
Apomorphine exhibits a behavioral inhibitory effect (in rats), and has properties that are useful as a medicine, especially as a psychotropic drug.

例えば本発明に係わる代表化合物の1つである1−(1
−(3−(4−フルオロベンゾイル)プロピル〕−4−
ピペリジル〕−2−メルカプトベンゾイミダゾールの薬
理効果を示せば下記の通りである。
For example, 1-(1
-(3-(4-fluorobenzoyl)propyl)-4-
The pharmacological effects of [piperidyl]-2-mercaptobenzimidazole are as follows.

なお、本発明の原料化合物は新規な化合物であり、例え
ば次に示す参考例の方法で容易に製することが出来る。
Note that the raw material compound of the present invention is a novel compound, and can be easily produced, for example, by the method of the following reference example.

参考例 1 l−(1−フェノキシカルボニル−4−ピペリジル)−
2−フエノキシ力ルポニルメルカブトベンゾイミダゾー
ル12g、エタノール350m1及び10%水酸化ナト
リウム水溶液350m1の混合物を5時間加熱還流した
後、エタノールを留去し、水を加え、エーテル抽出し、
水層を酢酸酸性としエーテル抽出、水層をアンモニアア
ルカリ性としクロロホルムで抽出し、クロロホルム層を
乾燥、濃縮し、得られた粗結晶をクロロホルムより再結
晶して得た2−メルカプト−1−(4−ピペリジル)ベ
ンゾイミダゾール(融点252°C〜256℃)の4.
67gをメタノール100Tftlに溶解し、塩化水素
飽和エタノールを加え酸性とした後、濃縮乾固する。
Reference example 1 l-(1-phenoxycarbonyl-4-piperidyl)-
A mixture of 12 g of 2-phenoxylmercabutobenzimidazole, 350 ml of ethanol, and 350 ml of 10% aqueous sodium hydroxide solution was heated under reflux for 5 hours, the ethanol was distilled off, water was added, and the mixture was extracted with ether.
The aqueous layer was made acidic with acetic acid and extracted with ether. The aqueous layer was made alkaline with ammonia and extracted with chloroform. The chloroform layer was dried and concentrated, and the resulting crude crystals were recrystallized from chloroform. -piperidyl)benzimidazole (melting point 252°C to 256°C) 4.
Dissolve 67 g in 100 Tftl of methanol, make it acidic by adding ethanol saturated with hydrogen chloride, and then concentrate to dryness.

これをメタノール100TLlに溶解、ベンジルクロリ
ド2.6g加え6時間30分加熱還流し、更にベンジル
クロリド710■加え7時間加熱還流後減圧濃縮、アセ
トンを加え結晶化すれば、2−ベンジルチオ−1−(4
−ピペリジル)ベンゾイミダゾール塩酸塩の無色結晶を
得る。
Dissolve this in 100 TL of methanol, add 2.6 g of benzyl chloride, heat under reflux for 6 hours and 30 minutes, add 710 μl of benzyl chloride, heat under reflux for 7 hours, concentrate under reduced pressure, add acetone and crystallize, 2-benzylthio-1-( 4
-Piperidyl)benzimidazole hydrochloride colorless crystals are obtained.

融点185〜188℃(分解)、これにクロロホルム、
5%炭酸ナトリウム水溶液を加えかきまぜ、アルカリ性
条件下クロロホルム抽出、水洗し無水硫酸ナトリウムで
乾燥濾過、濃縮、エーテル−ノルマルヘキサンで結晶化
すれば2−ベンジルチオ−1−(4−ピペリジル)ベン
ゾイミダゾールの無色結晶を得る。
Melting point: 185-188°C (decomposition), followed by chloroform,
Add 5% aqueous sodium carbonate solution, stir, extract with chloroform under alkaline conditions, wash with water, dry over anhydrous sodium sulfate, filtrate, concentrate, and crystallize with ether-n-hexane to obtain colorless 2-benzylthio-1-(4-piperidyl)benzimidazole. Obtain crystals.

融点98〜102℃。参考例 2 2−(3−クロロプロピル)−2−(4−フルオロフェ
ニル)−1,3−ジオキソラン1.16.!li’、2
−ベンジルチオ−1−(4−ピペリジル)ベンゾイミダ
ゾール1.62g、炭酸カリウム420■、ヨウ化カリ
ウム50〜、ノルマルブクノール5mAの混合物を撹拌
下24時間加熱還流する。
Melting point: 98-102°C. Reference Example 2 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane 1.16. ! li', 2
A mixture of 1.62 g of -benzylthio-1-(4-piperidyl)benzimidazole, 420 g of potassium carbonate, 50 mA of potassium iodide, and 5 mA of n-buquinol is heated under reflux for 24 hours with stirring.

冷却下エタノール10m11濃塩酸5TLlを加え5分
間加熱還流し、冷却下10%水酸化ナトリウム水溶液で
アルカリ性とし、濃縮、クロロホルム抽出し水洗、無水
硫酸すトリウムで乾燥し濾過、濃縮、次にベンゼ゛ン、
クロロホルムを用いたシリカゲルクロマトで精製、クロ
ロホルム−エーテルの混合溶媒より再結晶すれば2−ベ
ンジルチオ−1−(l−(3−(4−フルオロベンゾイ
ル)フロビルシー4−ピペリジル〕ベンゾイミダゾール
の無色プリズム晶を得る。
While cooling, add 10 ml of ethanol and 5 TL of concentrated hydrochloric acid, heat under reflux for 5 minutes, make alkaline with 10% sodium hydroxide aqueous solution while cooling, concentrate, extract with chloroform, wash with water, dry over anhydrous sodium sulfate, filter, concentrate, and then add benzene. ,
Purification by silica gel chromatography using chloroform and recrystallization from a mixed solvent of chloroform and ether yields colorless prismatic crystals of 2-benzylthio-1-(l-(3-(4-fluorobenzoyl)furobilcy4-piperidyl)benzimidazole. obtain.

融点124〜126°C0参考例 3 参考例2に準じて1−クロロ−4,4−ビス(4−フル
オロフェニル)ブタンと2−メチルチオ−1−(4−ピ
ペリジル)ベンゾイミダゾール(2−メチルメルカプ1
−−1−(1−フェノキシカルボニル−4−ピペリジル
)−ベンゾイミダゾール4.16g、エタノール30m
1及び10%水酸化ナトリウム水溶液10m1の混合物
を45時間加熱還流して合成)より1−(1,−(4,
4−ビス−(4−フルオロフェニル)ブチルクー4−ピ
ペリジル〕−2−メチルチオベンゾイミダゾールの無色
プリズム晶を得る。
Melting point 124-126°C0 Reference Example 3 According to Reference Example 2, 1-chloro-4,4-bis(4-fluorophenyl)butane and 2-methylthio-1-(4-piperidyl)benzimidazole (2-methylmercap 1
--1-(1-phenoxycarbonyl-4-piperidyl)-benzimidazole 4.16g, ethanol 30m
1-(1,-(4,
Colorless prism crystals of 4-bis-(4-fluorophenyl)butylcou-4-piperidyl]-2-methylthiobenzimidazole are obtained.

(エーテル−ノルマルヘキサン混合溶媒から再結晶)。(Recrystallized from ether-n-hexane mixed solvent).

融点110.5〜111.5°C6実施例 1 2−ベンジルチオ−1−(1−(3−(4−フルオロベ
ンゾイル)フロビルシー4−ピペリジル〕ベンゾイミダ
ゾール490〜.48%臭化水素酸40TLlを7時間
加熱還流する。
Melting point 110.5-111.5°C6 Example 1 2-benzylthio-1-(1-(3-(4-fluorobenzoyl)furobylthi-4-piperidyl)benzimidazole 490-.48% hydrobromic acid 40TLl 7 Heat to reflux for an hour.

今後ベンゼン40m11水20m1を加えかきまぜベン
ゼン層を分液して除き、水層および結晶性物質を集める
Next, add 40 ml of benzene and 20 ml of water, stir, separate and remove the benzene layer, and collect the water layer and crystalline substance.

この結晶性物質をメタノールに溶解し5%炭酸す) I
Jウム水溶液でアルカリ性とし、先の水層と合せ再び5
%炭酸ナトリウム水溶液でアルカリ性とし、クロロホル
ム抽出する。
Dissolve this crystalline substance in methanol and add 5% carbonic acid) I
Make it alkaline with Jum aqueous solution and add it to the previous water layer again.
Make alkaline with % sodium carbonate aqueous solution and extract with chloroform.

クロロホルム層を水洗、無水硫酸ナトリウムで乾燥、濾
過、濃縮し、ベンゼン、クロロホルムを用いたシリカゲ
ルクロマトで精製し、アセトンから再結晶すれば1−(
1−(3−(4−フルオロベンゾイル)フロビル〕=4
−ピペリジル〕−2−メルカプトベンゾイミダゾールの
無色結晶を得る。
The chloroform layer is washed with water, dried over anhydrous sodium sulfate, filtered, concentrated, purified with silica gel chromatography using benzene and chloroform, and recrystallized from acetone to obtain 1-(
1-(3-(4-fluorobenzoyl)furovir)=4
-Piperidyl]-2-mercaptobenzimidazole colorless crystals are obtained.

融点201〜203°00元素分析値 C22H24F
N30Sに対して計算値 C66,47,H6,09,
Nl O,57実測値 C66,42,H5,94,N
10.39実施例 2 l−(4−ピペリジル)−2−メチルメルカプトベンゾ
イミタソール990■、γ−クロロー4−フルオロブチ
ロフェノン810mg、無水炭酸ナトリウム2707n
?、ノルマル・ブチルアルコール9m1.の混液を撹拌
下56時間加熱還流し、反応波溶媒を留去し、この残渣
に水を加えクロロホルムで抽出、水洗、乾燥し、クロロ
ホルムを留去し、次いでシリカゲルカラムクロマトに付
し、クロロホルム:ベンゼン(1:1)及びクロロホル
ムで流出する部分を集め濃縮、エーテル−ノルマル・ヘ
キサンから再結晶して得られる1−(1−(3−(4−
フルオロベンゾイル)フロビル)−4−ピペリジルコ−
2−メチルメルカプトベンゾイミダゾール(融点98〜
98,5°C)の塩酸塩500〜、安息香酸10yの混
合物を160℃の油浴上28時間加熱撹拌する。
Melting point 201-203°00 Elemental analysis value C22H24F
Calculated value for N30S C66, 47, H6, 09,
Nl O, 57 actual measurement value C66, 42, H5, 94, N
10.39 Example 2 l-(4-piperidyl)-2-methylmercaptobenzimitazole 990■, γ-chloro-4-fluorobutyrophenone 810mg, anhydrous sodium carbonate 2707n
? , normal butyl alcohol 9ml 1. The mixture was heated to reflux for 56 hours with stirring, the reaction wave solvent was distilled off, water was added to the residue, extracted with chloroform, washed with water, dried, chloroform was distilled off, and then subjected to silica gel column chromatography. Collect and concentrate the effluent with benzene (1:1) and chloroform, and recrystallize from ether-n-hexane to obtain 1-(1-(3-(4-
fluorobenzoyl)furovir)-4-piperidylco-
2-Methylmercaptobenzimidazole (melting point 98~
A mixture of 500 to 10 y of hydrochloride (98.5° C.) and 10 y of benzoic acid is heated and stirred on a 160° C. oil bath for 28 hours.

器壁についた安息香酸をかき取り除く。Scrape off the benzoic acid that adheres to the walls of the vessel.

次いで10%水酸化す) IJウム水溶液を加えアルカ
リ性とし、クロロホルム抽出、水洗、無水硫酸ナトリウ
ムで乾燥し、濾過、濃縮、アセトンから再結晶すれば1
−(1−C3−(4−フルオロベンゾイル)プロピル〕
−4−ピペリジル〕−2−メルカプトベンゾイミダゾー
ルの無色結晶を得る。
Then, the mixture is made alkaline by adding an aqueous IJ solution, extracted with chloroform, washed with water, dried over anhydrous sodium sulfate, filtered, concentrated, and recrystallized from acetone to obtain 1.
-(1-C3-(4-fluorobenzoyl)propyl)
-4-Piperidyl]-2-mercaptobenzimidazole colorless crystals are obtained.

融点201〜203°C6実施例 3 1−(1−(3−(4−フルオロベンゾイル)プロピル
〕−4−ピペリジル〕−2−メチルチオベンゾイミダゾ
ール塩酸塩250mI?、ピリジン塩酸塩5gの混合物
を160℃の油浴上16時間加熱撹拌する。
Melting point 201-203°C6 Example 3 A mixture of 250 mI? of 1-(1-(3-(4-fluorobenzoyl)propyl]-4-piperidyl]-2-methylthiobenzimidazole hydrochloride and 5 g of pyridine hydrochloride was heated at 160°C Heat and stir on an oil bath for 16 hours.

器壁(こ昇華したピリジン塩酸塩をかき取り除く。Scrape off the sublimated pyridine hydrochloride from the vessel wall.

水を加えクロロホルム抽出し、クロロホルム層を10%
水酸化すl−IJウム水溶液でかきまぜ、アルカリ性と
しクロロホルム抽出、水洗、無水硫酸ナトl)ラムで乾
燥、濾過、濃縮、アセトンから再結晶すれば1−(1−
(3−(4−フルオロベンゾイル)プロピルクー4−ピ
ペリジル〕−2−メルカプトベンゾイミダゾールの無色
結晶を得る。
Add water, extract with chloroform, and remove 10% chloroform layer.
Stir with an aqueous solution of sulfur hydroxide, make alkaline, extract with chloroform, wash with water, dry with anhydrous sodium sulfate ram, filter, concentrate, and recrystallize from acetone.
Colorless crystals of (3-(4-fluorobenzoyl)propyl-4-piperidyl)-2-mercaptobenzimidazole are obtained.

融点201〜203°c。実施例 4 1−(1−(3−(4−フルオロベンゾイル)プロピル
クー4−ピペリジル〕−2−メチルチオベンゾイミダゾ
ール塩酸塩500η、47%臭化水素酸10m11ノル
マル酪酸10Tllの混合物を160℃の油浴上15時
間加熱還流する。
Melting point 201-203°C. Example 4 A mixture of 1-(1-(3-(4-fluorobenzoyl)propyl-4-piperidyl)-2-methylthiobenzimidazole hydrochloride 500η, 47% hydrobromic acid 10ml11 n-butyric acid 10Tll was heated to oil at 160°C Heat to reflux on the bath for 15 hours.

水冷下5%炭酸ナトリウム水溶液でアルカリ性としクロ
ロホルム抽出、水洗後無水硫酸ナトリウムで乾燥、濾過
、濃縮する。
While cooling with water, the mixture is made alkaline with a 5% aqueous sodium carbonate solution, extracted with chloroform, washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated.

これをアセトンから再結晶すれば1−CI−(3−(4
−フルオロベンゾイル)プロピルクー4−ピペリジル〕
−2−メルカプトベンゾイミダゾールの無色結晶を得る
If this is recrystallized from acetone, 1-CI-(3-(4
-fluorobenzoyl)propyl-4-piperidyl]
- Obtain colorless crystals of 2-mercaptobenzimidazole.

融点201〜203℃。Melting point: 201-203°C.

実施例 5 実施例4に準じ、1−(1−(4,4−ビス−(4−フ
ルオロフェニル)ブチルシー4−ピペリジル〕−2−メ
チルチオベンゾイミダゾールより1−CI−(4,4−
ビス−(4−フルオロフェニル)フチル〕−4−ピペリ
ジル〕−2−メルカプトベンゾイミダゾールの無色プリ
ズム晶を得る。
Example 5 According to Example 4, 1-CI-(4,4-
Colorless prismatic crystals of bis-(4-fluorophenyl)phthyl]-4-piperidyl]-2-mercaptobenzimidazole are obtained.

融点224〜227°C(エーテルより再結晶)。Melting point 224-227°C (recrystallized from ether).

実施例 6 実施例4に準じ、1−(1−(3−(4−フルオロベン
ゾイル)プロピルクー4−ピペリジル〕−2−メチルチ
オベンゾイミダゾール・エチレンケタールより1−(1
−(3−(4−フルオロベンゾイル)フロビルシー4−
ピペリジル)−2−メルカプトベンゾイミダゾールの無
色結晶を得る。
Example 6 According to Example 4, 1-(1-(3-(4-fluorobenzoyl)propyl-4-piperidyl)-2-methylthiobenzimidazole ethylene ketal was
-(3-(4-fluorobenzoyl)furobylcy4-
Colorless crystals of (piperidyl)-2-mercaptobenzimidazole are obtained.

融点201〜203°C(アセトンから再結晶)。Melting point 201-203°C (recrystallized from acetone).

実施例 7 実施例4に準じて2−(4−クロロフェナシルチオ)−
1−〔1−(3−(4−フルオロベンゾイル)プロピル
〕4−ピペリジル〕ベンゾイミダゾールより1−(1−
(3−(4−フルオロベンゾイル)フロビルシー4−ピ
ペリジル〕−2−メルカプトベンゾイミダゾールの無色
結晶を得る。
Example 7 According to Example 4, 2-(4-chlorophenacylthio)-
1-[1-(3-(4-fluorobenzoyl)propyl]4-piperidyl]benzimidazole to 1-(1-
Colorless crystals of (3-(4-fluorobenzoyl)furobylcy4-piperidyl)-2-mercaptobenzimidazole are obtained.

融点201〜203°C(アセトンから再結晶)。Melting point 201-203°C (recrystallized from acetone).

実施例 8 2−エトキシカルボニルチオ−1−(l−(3−(4−
フルオロベンゾイル)プロピル)−4−ピペリジルコベ
ンゾイミダゾール470m9、エタノール30m1,1
0%水酸化すl−IJウム水溶液10m1の混液を2時
間加熱還流後濃縮する。
Example 8 2-ethoxycarbonylthio-1-(l-(3-(4-
Fluorobenzoyl)propyl)-4-piperidylcobenzimidazole 470m9, ethanol 30ml1,1
A mixed solution of 10 ml of a 0% sulfur hydroxide aqueous solution was heated under reflux for 2 hours and then concentrated.

次いで水を加えクロロホルム抽出、水洗後無水硫酸ナト
リウムで乾燥、濾過、濃縮し、アセトンより再結晶すれ
ば、1−〔1−(3−(4−フルオロベンゾイル)プロ
ピルクー4−ピペリジル)−2−メルカプトベンゾイミ
ダゾールの無色結晶を得る。
Next, water was added, extracted with chloroform, washed with water, dried over anhydrous sodium sulfate, filtered, concentrated, and recrystallized from acetone to obtain 1-[1-(3-(4-fluorobenzoyl)propyl-4-piperidyl)-2- Colorless crystals of mercaptobenzimidazole are obtained.

融点201〜203°c。Melting point 201-203°C.

実施例 9 実施例8に準じ、1−1:1−(3−(4−フルオロベ
ンゾイル)プロピルクー4−ピペリジル〕−2−ノルマ
ル・ヘプタノイルチオベンゾイミダゾール塩酸塩よりl
−41−43−(4−フルオロベンゾイル)フロビルシ
ー4−ピペリジル〕−2−メルカプトベンゾイミダゾー
ルの無色結晶を得る。
Example 9 According to Example 8, 1-1:1-(3-(4-fluorobenzoyl)propyl-4-piperidyl)-2-n-heptanoylthiobenzimidazole hydrochloride
Colorless crystals of -41-43-(4-fluorobenzoyl)furobilcy4-piperidyl]-2-mercaptobenzimidazole are obtained.

融点201〜203℃(アセトンから再結晶)。Melting point 201-203°C (recrystallized from acetone).

Claims (1)

【特許請求の範囲】 1 一般式 (式中Qはカルボニル基、保護基で保護されたカルボニ
ル基又は−CH−基を、Arはハロフェニル基を、Rは
低級アルキル基、アラルキル基、ベンゾイル低級アルキ
ル基、アルカノイル基又はアルコキシカルボニル基から
選択される一8Hの保護基を示す。 )で示されるピペリジン誘導体を酸又は塩基と反応させ
−SHの保護基を脱離し、必要に応じて加水分解するこ
とを特徴とする一般式 (式中Yはカルボニル基又は−CH−基、Arは前記に
同じ)で表わされるピペリジルベンゾイミダゾール誘導
体又はその塩類の製造法。
[Claims] 1 General formula (wherein Q is a carbonyl group, a carbonyl group protected with a protecting group, or a -CH- group, Ar is a halophenyl group, and R is a lower alkyl group, an aralkyl group, a benzoyl lower alkyl group) -SH protecting group selected from alkanoyl group, alkanoyl group, or alkoxycarbonyl group. A method for producing a piperidylbenzimidazole derivative or a salt thereof represented by the general formula (wherein Y is a carbonyl group or -CH- group, and Ar is the same as above), characterized by:
JP50074813A 1975-06-19 1975-06-19 Piperidylbenzimidazole Expired JPS5823398B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP50074813A JPS5823398B2 (en) 1975-06-19 1975-06-19 Piperidylbenzimidazole

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP50074813A JPS5823398B2 (en) 1975-06-19 1975-06-19 Piperidylbenzimidazole

Publications (2)

Publication Number Publication Date
JPS52278A JPS52278A (en) 1977-01-05
JPS5823398B2 true JPS5823398B2 (en) 1983-05-14

Family

ID=13558116

Family Applications (1)

Application Number Title Priority Date Filing Date
JP50074813A Expired JPS5823398B2 (en) 1975-06-19 1975-06-19 Piperidylbenzimidazole

Country Status (1)

Country Link
JP (1) JPS5823398B2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63122151U (en) * 1987-02-04 1988-08-09

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5485678A (en) * 1977-12-20 1979-07-07 Canon Inc High accuracy alignment method for air bearing guide system xy stage
MA19091A1 (en) * 1980-03-10 1981-10-01 Janssen Pharmaceutica Nv NEW I- (4-ARYL-CYCLOHEXYL) PIPERIDINE DERIVATIVES.
JPS57114344A (en) * 1980-12-27 1982-07-16 Hitachi Ltd Apparatus for precise positioning
JPS6119502A (en) * 1985-06-19 1986-01-28 Matsushita Electric Ind Co Ltd Spindle device
JPS6338902U (en) * 1986-08-29 1988-03-12
JPS6434634A (en) * 1987-07-29 1989-02-06 Okuma Machinery Works Ltd Feed mechanism free from influence of deviation of feed screw
DE19952146A1 (en) * 1999-10-29 2001-06-07 Boehringer Ingelheim Pharma Arylalkanes, arylalkenes and aryl-azaalkanes, medicaments containing these compounds and process for their preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63122151U (en) * 1987-02-04 1988-08-09

Also Published As

Publication number Publication date
JPS52278A (en) 1977-01-05

Similar Documents

Publication Publication Date Title
US4565882A (en) Substituted dihydrobenzopyran-2-carboxylates
US5391754A (en) Process for preparing 1,2,5,6-tetrahydropyridin-3-carboxaldehyde oxime compounds
JPH04338386A (en) Benzodioxole, benzodioxane, and benzodioxepin derivative
DE69224115T2 (en) Heteroaryl substituted hydroxylamine derivatives as lipoxygenase inhibitors
EP0254329B1 (en) Substituted dihydrobenzopyranones
Harvill et al. Haloalkyltetrazole and aminoalkyltetrazole derivatives
US3120540A (en) Bis (polymethyl)-4-piperidinol alkanoates
NO163619B (en) ANALOGUE PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY ACTIVE TETRAHYDRO-2-HETEROCYCLOYLKYLPYRIDO (4,3) INDOLES.
JPS5823398B2 (en) Piperidylbenzimidazole
JPH0383979A (en) New benzopyran and benzothio- pyran derivatives
JPH0633254B2 (en) N-substituted diphenylpiperidines
BR112014030126B1 (en) processes for producing certain 2- (pyridin-3-yl) thiazoles
FI57261C (en) FOERFARANDE FOER FRAMSTAELLNING AV PAO CENTRALNERVSYSTEMET VERKANDE N- (HETEROARYL-METHYL) -6,14-ENDOETENO / ENDOETANO-7ALFA-HYDROXYLALKYLTETRAHYDRONORORIPAVIN OCH -TEBAY OCH DTEBAYRA OCH
JPS63185948A (en) Substitured aminopropionamide and manufacture
US3324139A (en) 3-(3-hydroxyphenyl)-1-phenacylpiperidine compounds
NL8105623A (en) NEW HYDROXYPHENYLTETRAHYDROPYRIDINE COMPOUNDS, THEIR SALTS, PROCESS FOR THEIR PREPARATION AND INTERMEDIATES IN THE PREPARATION, USE AS MEDICINAL PRODUCTS AND COMPOSITIONS CONTAINING THEM.
US2485662A (en) Alpha-(aminoalkyl)-stilbenes
EP0011282B1 (en) Thienylbenzoic-acid derivatives, process for their production, and pharmaceutical preparations containing these compounds
US4432984A (en) Anti-hypertensive benzodioxan derivatives
JPS5813540B2 (en) 1,2,3,4- Tetrahydroisoquinoline luino
NO137998B (en) ANALOGICAL PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY ACTIVE TEBAIN AND ORIPAVIN DERIVATIVES
US4060550A (en) Novel n'-acylated phenyl-hydrazine and -hydrazone derivatives
Marion et al. The Synthesis of l-Roemerine1
NO137695B (en) ANALOGICAL PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY ACTIVE N-THENYLMETHYL-HETEROCYCLIC COMPOUNDS
JPS5811873B2 (en) Piperidylbenzimidazole