JPH02167268A - Novel heterocyclic compound - Google Patents
Novel heterocyclic compoundInfo
- Publication number
- JPH02167268A JPH02167268A JP32046888A JP32046888A JPH02167268A JP H02167268 A JPH02167268 A JP H02167268A JP 32046888 A JP32046888 A JP 32046888A JP 32046888 A JP32046888 A JP 32046888A JP H02167268 A JPH02167268 A JP H02167268A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- chloroform
- added
- formula
- reaction
- 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.)
- Pending
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract 4
- 150000002367 halogens Chemical class 0.000 claims abstract 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims abstract 2
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 2
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 45
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 abstract description 5
- 230000000767 anti-ulcer Effects 0.000 abstract description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 239000003699 antiulcer agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- -1 dry Chemical compound 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- LHUHAARPMJISMM-UHFFFAOYSA-N 2,5-dichloro-1,3-benzothiazole Chemical compound ClC1=CC=C2SC(Cl)=NC2=C1 LHUHAARPMJISMM-UHFFFAOYSA-N 0.000 description 1
- JVIHSTYYPRUSFG-UHFFFAOYSA-N 2-(1h-benzimidazol-2-ylsulfinylmethyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1CS(=O)C1=NC2=CC=CC=C2N1 JVIHSTYYPRUSFG-UHFFFAOYSA-N 0.000 description 1
- AZQOTRRSHMSXFJ-UHFFFAOYSA-N 2-ethylsulfanylethanamine;hydron;chloride Chemical compound Cl.CCSCCN AZQOTRRSHMSXFJ-UHFFFAOYSA-N 0.000 description 1
- RAFAYWADRVMWFA-UHFFFAOYSA-N 4,6-dimethyl-1h-pyrimidine-2-thione Chemical compound CC1=CC(C)=NC(S)=N1 RAFAYWADRVMWFA-UHFFFAOYSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 229940121819 ATPase inhibitor Drugs 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000002467 anti-pepsin effect Effects 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
- 229960004633 pirenzepine Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、優れた抗潰瘍作用を有する、新規な複素環式
化合物に関するものである。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel heterocyclic compound having excellent anti-ulcer activity.
（従来の技術）
従来、抗潰瘍薬としては、「重曹」、「アルミニウム剤
」などの制酸剤あるいは抗ペプシン剤、抗コリン剤が用
いられるか、または「シメチジン」で代表されるＲ２−
受容体拮抗薬や「ピレンゼピン」のようなムスカリン受
容体遮断薬が用いられている。さらに新しい作用機序を
もつものとして、Ｈ”／ Ｋ ’″−ＡＴＰアーゼ阻害
薬であるベンズイミダゾール誘導体の「オメプラゾール
Ｊ （２−［２−（３，５−ジメチル−４−メトキシ
）−ピリジルメチルスルフィニル］ −（５−メトキシ
）−ベンズイミダゾール）やｒＮＣ−１３００Ｊ （
２−（２−ジメチルアミノベンジルスルフィニル）−ベ
ンズイミダゾール）が現在開発中である。一方、ベンゾ
チアゾール誘導体、ベンゾキサゾール誘導体にもＨ”／
Ｋ”−ＡＴＰアーゼ阻害作用があることが、最近報告さ
れている（ Ｊ 、Ｍｅｄ、Ｃｈｅｍ、、 １９８８゜
３１、１７７８−１７８５）。(Prior Art) Conventionally, as anti-ulcer drugs, antacids such as "baking soda" and "aluminum agents", anti-pepsin agents, and anti-cholinergic agents have been used, or R2-
Receptor antagonists and muscarinic receptor blockers such as pirenzepine are used. Furthermore, a new drug with a new mechanism of action is omeprazole J (2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethyl), a benzimidazole derivative that is an H"/K'"-ATPase inhibitor. sulfinyl] -(5-methoxy)-benzimidazole) and rNC-1300J (
2-(2-dimethylaminobenzylsulfinyl)-benzimidazole) is currently under development. On the other hand, benzothiazole derivatives and benzoxazole derivatives also have H”/
It has recently been reported that it has a K''-ATPase inhibitory effect (J. Med. Chem., 1988.31, 1778-1785).
（本発明が解決しようとする問題点）
本発明者らは、さらに優れた抗潰瘍作用を有する複素環
式化合物検索を行った結果、下記−形式（Ｉ）の複素環
部分の２位に特異な側鎖を有する、有効な複素環式化合
物を見出した。(Problems to be Solved by the Present Invention) As a result of searching for a heterocyclic compound having even better anti-ulcer activity, the present inventors found that: We have discovered an effective heterocyclic compound having a side chain.
（問題点を解決するだめの手段）
本発明は、下記−形式（Ｉ）
し式中、Ｘ、Ｙ、Ｒ’、Ｒ”、ｍは上記と同様の定義を
有す。１で示される化合物は次のＡ法またはＢ法により
製造することができる。(Means for Solving the Problems) The present invention provides a compound represented by the following formula (I) in which X, Y, R', R'', and m have the same definitions as above. can be produced by the following method A or B.
Ａ法ニ
一般式（ＩＩ）の化合物
［式中、Ｘ又はＹはＮ、Ｏ又はＳを示し、Ｒ１は水素原
子、ハロゲン原子又は低級アルコキシ基を示し、Ｒ２は
低級アルキル基、低級アルフキジカルボニルアルキル基
、複素環、又はベンゼン環あるいは複素環で置換された
低級アルキル基を示し、ｍは１〜３の整数、ｎはＯ〜２
の整数を示す。１で表される複素環式化合物を提供する
ものである。Method A - compound of general formula (II) [wherein, It represents an alkyl group, a heterocycle, or a lower alkyl group substituted with a benzene ring or a heterocycle, m is an integer of 1 to 3, and n is O to 2.
indicates an integer. The present invention provides a heterocyclic compound represented by 1.
上記−形式（Ｉ）で表される化合物のうち、−形式（Ｉ
ａ）
を−形式（ＩＩりの化合物
Ｘ ”（ＣＨｉ）ｍ−３−Ｒ” （ｍ ）１
式中、Ｙ、Ｒ’、Ｒ”、ｍは上記と同様の定義を有し、
２つの基ＸＩおよびｘ２は、−形式［１ａｌにおいてＸ
がＮまたはＯの場合、ｘｌはハロゲン原子、ｘ２は−Ｎ
Ｈ，基または一〇Ｈ基を示す。また−形式［１ａｌにお
いてＸがＳの場合、ＸＩは一５Ｈ基、Ｘ２はハロゲン原
子を示す。］と反応させることにより、−形式［１ａｌ
の化合物を生皮する。Among the compounds represented by the above-format (I), -format (I)
a) Compound X of the form (II) ``(CHi)m-3-R'' (m )1
In the formula, Y, R', R'', m have the same definitions as above,
The two groups XI and x2 are of the form [X in 1al
is N or O, xl is a halogen atom, x2 is -N
Indicates H, group or 10H group. Further, when X is S in the -form [1al, XI represents a -5H group and X2 represents a halogen atom. ] By reacting with -form [1al
rawhide compound.
反応溶媒としては、例えばテトラヒドロフランもしくは
ジメチルホルムアミドなどの非プロトン性極性溶媒が挙
げられる。使用する塩基としては、例えばトリエチルア
ミン、水素化ナトリウムなどが挙げられる。反応割合は
、化合物［１１に対して、化合物［ＩＩＩ］ を１〜２
モル当量、塩基をｌ〜１．２モル当量とする。反応温度
は３０〜７０°ｃ１反応時間は２〜２４時間とする。Examples of the reaction solvent include aprotic polar solvents such as tetrahydrofuran and dimethylformamide. Examples of the base used include triethylamine and sodium hydride. The reaction ratio is 1 to 2 of compound [III] to compound [11].
The molar equivalent is 1 to 1.2 molar equivalents of the base. The reaction temperature is 30 to 70°C and the reaction time is 2 to 24 hours.
ｌ迭ニ
一般式（ＩＶ）の化合物
基を１〜１．２倍モル量とする。反応温度は３０〜１０
０°Ｃ１反応時間は２〜２４時間とする。The molar amount of the compound group of general formula (IV) is 1 to 1.2 times. The reaction temperature is 30-10
The reaction time at 0°C is 2 to 24 hours.
−形式（１）で表される化合物のうち一般式（Ｉｂ）１
式中、Ｘ、Ｙ、Ｒ’、Ｒ”、ｍは上記と同様の定義を有
す。１
あるいは−形式（Ｉｃ）
を−形式（ｖ）の化合物
ＨａＱ−Ｒ” （Ｖ）［式中Ｘ、Ｙ
、Ｒ’、Ｒ”、ｍは上記と同様の定義を有し、ＨａＱは
ハロゲン原子を示す。１ と反応させることにより、−
形式［１ａｌの化合物を生成する。反応溶媒としては、
例えばテトラヒドロフラン、ジメチルホルムアミドなど
が挙げられる。使用する塩基としては例えばトリエチル
アミン、水素化ナトリウムなどが挙げられる。反応割合
は化合物［ＩＶ］に対して化合物１ｖｌ を等モル量、
塩［式中、Ｘ、Ｙ、Ｒ’、Ｒ”、ｍは上記と同様の定義
を有す。〕で示される化合物は、−形式（ｌａ）で表さ
れる化合物に適当量の酸化剤を作用させることにより得
られる。即ち一般式（ｌａ）の化合物に酸化剤を１〜１
．２モル当量作用させると一役式（Ｉｂ）の化合物が主
生成物として得られ、酸化剤を２〜２．２モル当量作用
させると一般式（Ｉｃ）の化合物が得られる。- General formula (Ib) 1 among compounds represented by format (1)
In the formula, X, Y, R', R", m have the same definition as above. 1 or - form (Ic) - a compound of form (v) HaQ-R" ,Y
, R', R", m have the same definitions as above, and HaQ represents a halogen atom. By reacting with 1, -
A compound of the form [1al is produced. As a reaction solvent,
Examples include tetrahydrofuran and dimethylformamide. Examples of the base used include triethylamine and sodium hydride. The reaction ratio is an equimolar amount of 1 vol of compound to compound [IV],
The compound represented by the salt [wherein X, Y, R', R'', and m have the same definitions as above] is prepared by adding an appropriate amount of an oxidizing agent to the compound represented by the -form (la). It can be obtained by reacting the compound of general formula (la) with 1 to 1 oxidizing agent.
．． When 2 molar equivalents of the oxidizing agent are applied, a compound of formula (Ib) is obtained as the main product, and when 2 to 2.2 molar equivalents of the oxidizing agent are applied, a compound of general formula (Ic) is obtained.
反応溶媒としては例えばクロロホルムもしくはジクロロ
メタンなどのハロゲン化炭化水素類、あるいは酢酸など
が挙げられる。酸化剤としては例えばメタクロロ過安息
香酸、過酸化水素などが挙げられる。反応温度は０〜３
０’Ｏ１反応時間は３０分間〜２時間程度とする。Examples of the reaction solvent include halogenated hydrocarbons such as chloroform and dichloromethane, and acetic acid. Examples of the oxidizing agent include metachloroperbenzoic acid and hydrogen peroxide. Reaction temperature is 0-3
The 0'O1 reaction time is approximately 30 minutes to 2 hours.
（発明の効果） 本願化合物は抗潰瘍薬としての効果が期待される。(Effect of the invention) The compound of the present application is expected to be effective as an anti-ulcer drug.
本発明の一般式（１）で表される化合物の具体例として
は、例えば後記第１表に記載された化合物を挙げること
ができるが１本発明はこれらの化合物に限定されるもの
ではない。Specific examples of the compound represented by the general formula (1) of the present invention include the compounds listed in Table 1 below, but the present invention is not limited to these compounds.
実施例１（化合物ＮＯ，１９）
２−（エチルチオ）エチルアミン塩酸塩０．４２ ｇを
無水テトラヒドロ７ラン５ｍ１２に懸濁させ、これにト
リエチルアミン０−８３ｍｆｆと２．５−ジクロロベン
ゾチアゾール０．５０ｇを加え、１時間環流下撹拌した
。Example 1 (Compound No. 19) 0.42 g of 2-(ethylthio)ethylamine hydrochloride was suspended in 5 ml of anhydrous tetrahydro7rane, and 0-83 mff of triethylamine and 0.50 g of 2,5-dichlorobenzothiazole were added thereto. The mixture was added and stirred under reflux for 1 hour.
反応混合物に水を加え、クロロホルムで抽出、乾燥後、
クロロホルムを減圧留去した。残渣をカラムクロマトグ
ラフィー（溶出液：ｎ−ヘキサン／酢酸エチル−５／ｌ
）で精製し、白色粉末として標題化合物０．３９ ｇを
得た。Add water to the reaction mixture, extract with chloroform, dry,
Chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (eluent: n-hexane/ethyl acetate-5/l
) to obtain 0.39 g of the title compound as a white powder.
実施例２（化合物Ｎ ｏ、２０）
実施例１で得られた化合物０．３９ ｇに酢酸２ａ＋（
２，３０％過酸化水素水０．２ｍ１２、タングステン酸
ナトリウム触媒量を加えて室温で１時間撹拌した。反応
混合物に水を加え、炭酸水素ナトリウムでｐＨ７に中和
後、クロロホルムで抽出した。抽出液を乾燥し、クロロ
ホルムを減圧留去して、残渣をカラムクロマトグラフィ
ー（溶出液：ｎ−ヘキサン／アセトン−２７３）にかけ
て精製、白色粉末として標題化合物０．１９ｇを得た。Example 2 (Compound No. 20) 0.39 g of the compound obtained in Example 1 was added with acetic acid 2a+ (
0.2 ml of 2.30% hydrogen peroxide solution and a catalytic amount of sodium tungstate were added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, neutralized to pH 7 with sodium hydrogen carbonate, and extracted with chloroform. The extract was dried, chloroform was distilled off under reduced pressure, and the residue was purified by column chromatography (eluent: n-hexane/acetone-273) to obtain 0.19 g of the title compound as a white powder.
実施例３（化合物Ｎ ｏ、２１）
実施例１で得られた化合物０．３９ｇに酢酸２ｍα、３
０％過酸化水素水０−３６ｍＱ１ タングステン酸ナト
リウム触媒量を加えて室温で１時間撹拌しｔ；。反応混
合物に水を加え、炭酸水素ナトリウムでｐＨ７に中和後
、クロロホルムで抽出した。抽出液を乾燥し、クロロホ
ルムを減圧留去して、残渣をカラムクロマトグラフィー
（溶出液：ｎ−ヘキサン／アセト／−２／ｌ）にかけて
精製、白色粉末として標題化合物０．４０ｇを得た。Example 3 (Compound No. 21) To 0.39 g of the compound obtained in Example 1, 2 mα, 3 acetic acid was added.
Add a catalytic amount of 0% hydrogen peroxide solution 0-36 mQ1 sodium tungstate and stir at room temperature for 1 hour. Water was added to the reaction mixture, neutralized to pH 7 with sodium hydrogen carbonate, and extracted with chloroform. The extract was dried, chloroform was distilled off under reduced pressure, and the residue was purified by column chromatography (eluent: n-hexane/acet/-2/l) to obtain 0.40 g of the title compound as a white powder.
５−クロロ−２−［２−（メトキシ力ルボニルメ５−ク
ロロ−２−メルカプトベンゾチアゾール１ 、２５ ｇ
を無水ジメチルホルムアミド６ 、 ３ｍＩ２に溶かし
、水素化ナトリウム０．１８ｇを少しずつ加え、室温で
１時間撹拌した。これに（２−クロロエチル）チオグリ
コール酸メチル１．０４ｇを加えて室温で２４時間撹拌
した。反応混合物に水を加え、クロロホルムで抽出、乾
燥後、クロロホルムを減圧留去した。残渣をカラムクロ
マトグラフィー（溶出液：クロロホルム）で精製し、黄
色油状物として、原題化合物１．８０ｇを得た。5-chloro-2-[2-(methoxycarbonylmercaptobenzothiazole 1, 25 g
was dissolved in 6.3ml of anhydrous dimethylformamide, 0.18g of sodium hydride was added little by little, and the mixture was stirred at room temperature for 1 hour. To this was added 1.04 g of methyl (2-chloroethyl)thioglycolate, and the mixture was stirred at room temperature for 24 hours. Water was added to the reaction mixture, extracted with chloroform, dried, and then chloroform was distilled off under reduced pressure. The residue was purified by column chromatography (eluent: chloroform) to obtain 1.80 g of the title compound as a yellow oil.
実施例５（化合物Ｎ ｏ．２５）
ル：
実施例４で得られた化合物１．８０ｇに酢酸９ｍＱ，３
０％過酸化水素水０．６ｍＬタングステン酸ナトリウ実
施例４（化合物Ｎ ｏ．２４）
ム触媒量を加え、室温で１時間撹拌した。反応混合物に
水を加え、炭酸水素すトリウムでｐＨ７に中和後、クロ
ロホルムで抽出した。抽出液を乾燥し、クロロホルムを
減圧留去して、残渣をカラムクロマトグラフィー（溶出
液＝クロロホルム／メタノール＝ ５０／ ｌ ）にか
けて精製、淡黄色粉末として標題化合物１．３３ｇを得
た。Example 5 (Compound No. 25): To 1.80 g of the compound obtained in Example 4 was added 9 mQ of acetic acid, 3
0% hydrogen peroxide solution 0.6 mL Sodium tungstate Example 4 (Compound No. 24) A catalyst amount was added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, neutralized to pH 7 with sodium bicarbonate, and extracted with chloroform. The extract was dried, chloroform was distilled off under reduced pressure, and the residue was purified by column chromatography (eluent = chloroform/methanol = 50/l) to obtain 1.33 g of the title compound as a pale yellow powder.
実施例６（化合物Ｎｏ、２６）
実施例４で得られた化合物１．８０ｇに酢酸９ｍ１２．
３０％過酸化水素水１．２２ｍＬ タングステン酸ナト
リウム触媒量を加え、室温で１時間撹拌しｌ；。反応混
合物に水を加え、炭酸水素ナトリウムでｐＨ７に中和後
、クロロホルムで抽出しｔこ。抽出液を乾燥し、クロロ
ホルムを減圧留去して、残渣をカラムクロマトグラフィ
ー（溶出液：クロロホルム／メタノール−８０／ ｌ
）にかけて精製、白色粉末として標題化合物１．４０ｇ
を得た。Example 6 (Compound No. 26) To 1.80 g of the compound obtained in Example 4 was added 9 ml of acetic acid.
Add 1.22 mL of 30% hydrogen peroxide solution and a catalytic amount of sodium tungstate, and stir at room temperature for 1 hour. Water was added to the reaction mixture, neutralized to pH 7 with sodium hydrogen carbonate, and extracted with chloroform. The extract was dried, chloroform was distilled off under reduced pressure, and the residue was subjected to column chromatography (eluent: chloroform/methanol-80/l
) to obtain 1.40 g of the title compound as a white powder.
I got it.
実施例７（化合物Ｎ ｏ、３２）
４．６−シメチル−２−メルカプトピリミジン０．５３
ｇを無水ジメチルホルムアミド２．７ｍＱに溶かし、水
素化ナトリウム０．ｌ１ｇを少しずつ加え、室温で１時
間撹拌した。これに５−クロロ−２−（クロロエチルチ
オ）ベンゾチアゾール１．ｏｏｇを加え、室温で１５時
間撹拌した。反応混合物に水を加え、クロロホルムで抽
出、乾燥後、クロロホルムを減圧留去した。残渣をカラ
ムクロマトグラフィー（溶出液：ｎ−ヘキサン／酢酸エ
チル−５／ｌ）で精製し、無色油状物として標題化合物
１．２６ｇを得た。Example 7 (Compound No, 32) 4.6-dimethyl-2-mercaptopyrimidine 0.53
g was dissolved in 2.7 mQ of anhydrous dimethylformamide, and 0.0 mQ of sodium hydride was added. 1 g was added little by little, and the mixture was stirred at room temperature for 1 hour. This was followed by 1.5-chloro-2-(chloroethylthio)benzothiazole. oog was added and stirred at room temperature for 15 hours. Water was added to the reaction mixture, extracted with chloroform, dried, and then chloroform was distilled off under reduced pressure. The residue was purified by column chromatography (eluent: n-hexane/ethyl acetate - 5/l) to obtain 1.26 g of the title compound as a colorless oil.
実施例８（化合物Ｎ ｏ、３３）
実施例７で得られた化合物１．２６ｇに塩化メチレン２
５ｍＱとメタクロロ過安息香酸０．７０ｇを加え、室温
で２時間撹拌した。反応混合物に水を加え、クロロホル
ムで抽出、乾燥後、クロロホルムを減圧留去した。残渣
をカラムクロマトグラフィー（溶出液：クロロホルム／
メタノール−７０／ ｌ ） Ｉ：ｎかけて精製、白色
粉末として標題化合物０．９３ｇを得た。Example 8 (Compound No. 33) 1.26 g of the compound obtained in Example 7 was added with methylene chloride 2
5 mQ and 0.70 g of metachloroperbenzoic acid were added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, extracted with chloroform, dried, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (eluent: chloroform/
Purification using methanol (70/l) I:n gave 0.93 g of the title compound as a white powder.
次の表１に示す、上記実施例１〜８以外の化合物につい
ても、これらのいずれかの方法を用いて同様に製造する
ことができる。Compounds other than those in Examples 1 to 8 shown in Table 1 below can also be produced in the same manner using any of these methods.
Claims (1)
原子、ハロゲン原子又は低級アルコキシ基を示し、Ｒ＾
２は低級アルキル基、低級アルコキシカルボニルアルキ
ル基、複素環又はベンゼン環あるいは複素環で置換され
た低級アルキル基を示し、ｍは１〜３の整数、ｎは０〜
２の整数を示す。］で表される複素環式化合物。[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, X or Y represents N, O or S, and R^1 represents a hydrogen atom or a halogen Indicates an atom or lower alkoxy group, R^
2 represents a lower alkyl group, a lower alkoxycarbonyl alkyl group, a heterocycle or a lower alkyl group substituted with a benzene ring or a heterocycle, m is an integer of 1 to 3, and n is 0 to
Indicates an integer of 2. ]Heterocyclic compound represented by.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32046888A JPH02167268A (en) | 1988-12-21 | 1988-12-21 | Novel heterocyclic compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32046888A JPH02167268A (en) | 1988-12-21 | 1988-12-21 | Novel heterocyclic compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02167268A true JPH02167268A (en) | 1990-06-27 |
Family
ID=18121789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP32046888A Pending JPH02167268A (en) | 1988-12-21 | 1988-12-21 | Novel heterocyclic compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02167268A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997003970A1 (en) * | 1995-07-17 | 1997-02-06 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds |
| FR2767828A1 (en) * | 1997-08-06 | 1999-03-05 | Ciba Geigy Ag | HETEROCYCLIC THIOETHERS AS ADDITIVES FOR LUBRICATING AGENTS |
| WO2004078345A1 (en) * | 2003-03-03 | 2004-09-16 | General Electric Company | Method for producing bisphenol catalysts and bisphenols |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4349555A (en) * | 1978-11-30 | 1982-09-14 | John Wyeth & Brother Limited | Dithiocompounds |
| JPS57158767A (en) * | 1981-03-26 | 1982-09-30 | Otsuka Pharmaceut Co Ltd | Antiulcer agent |
| JPS60149567A (en) * | 1984-01-13 | 1985-08-07 | Kyorin Pharmaceut Co Ltd | Novel imidazole derivative and preparation thereof |
| JPS60149569A (en) * | 1984-01-13 | 1985-08-07 | Kyorin Pharmaceut Co Ltd | Novel benzazole derivative and preparation thereof |
-
1988
- 1988-12-21 JP JP32046888A patent/JPH02167268A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4349555A (en) * | 1978-11-30 | 1982-09-14 | John Wyeth & Brother Limited | Dithiocompounds |
| JPS57158767A (en) * | 1981-03-26 | 1982-09-30 | Otsuka Pharmaceut Co Ltd | Antiulcer agent |
| JPS60149567A (en) * | 1984-01-13 | 1985-08-07 | Kyorin Pharmaceut Co Ltd | Novel imidazole derivative and preparation thereof |
| JPS60149569A (en) * | 1984-01-13 | 1985-08-07 | Kyorin Pharmaceut Co Ltd | Novel benzazole derivative and preparation thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997003970A1 (en) * | 1995-07-17 | 1997-02-06 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds |
| US5998456A (en) * | 1995-07-17 | 1999-12-07 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds containing 1,2,4-triazole ring, and compositions and methods of use containing the same |
| US6174907B1 (en) | 1995-07-17 | 2001-01-16 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds containing 1,2,4-triazole ring, and compositions and methods of use containing the same |
| US6288236B1 (en) | 1995-07-17 | 2001-09-11 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds containing a benzoxazole or benzothiazole ring, and compositions and methods of use containing the same |
| FR2767828A1 (en) * | 1997-08-06 | 1999-03-05 | Ciba Geigy Ag | HETEROCYCLIC THIOETHERS AS ADDITIVES FOR LUBRICATING AGENTS |
| NL1009793C2 (en) * | 1997-08-06 | 2000-05-31 | Ciba Sc Holding Ag | Heterocyclic thioethers as additives for lubricants. |
| BE1012345A5 (en) * | 1997-08-06 | 2000-10-03 | Ciba Sc Holding Ag | Thioethers heterocyclic as additives for s agents lubricants. |
| WO2004078345A1 (en) * | 2003-03-03 | 2004-09-16 | General Electric Company | Method for producing bisphenol catalysts and bisphenols |
| JP2006513848A (en) * | 2003-03-03 | 2006-04-27 | ゼネラル・エレクトリック・カンパニイ | Bisphenol catalyst and method for producing bisphenol |
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