JPH02149553A - Indane derivative and production thereof - Google Patents
Indane derivative and production thereofInfo
- Publication number
- JPH02149553A JPH02149553A JP25275489A JP25275489A JPH02149553A JP H02149553 A JPH02149553 A JP H02149553A JP 25275489 A JP25275489 A JP 25275489A JP 25275489 A JP25275489 A JP 25275489A JP H02149553 A JPH02149553 A JP H02149553A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- compound expressed
- compound
- nitrophenyl
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 125000003392 indanyl group Chemical class C1(CCC2=CC=CC=C12)* 0.000 title 1
- -1 trifluoromethylphenyl Chemical group 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000004799 bromophenyl group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
- 239000011593 sulfur Substances 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims description 6
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 5
- 150000002468 indanes Chemical class 0.000 claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 36
- 150000001875 compounds Chemical class 0.000 abstract description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002904 solvent Substances 0.000 abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract description 6
- 230000003042 antagnostic effect Effects 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 238000006482 condensation reaction Methods 0.000 abstract description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 abstract description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract description 3
- 229940127218 antiplatelet drug Drugs 0.000 abstract description 2
- 208000006673 asthma Diseases 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract description 2
- 229910006069 SO3H Inorganic materials 0.000 abstract 1
- 210000001772 blood platelet Anatomy 0.000 abstract 1
- 210000004204 blood vessel Anatomy 0.000 abstract 1
- 230000002490 cerebral effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000003449 preventive effect Effects 0.000 abstract 1
- 230000016160 smooth muscle contraction Effects 0.000 abstract 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 abstract 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- HGTBAIVLETUVCG-UHFFFAOYSA-M (methylthio)acetate Chemical compound CSCC([O-])=O HGTBAIVLETUVCG-UHFFFAOYSA-M 0.000 description 1
- XEHNLVMHWYPNEQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-amine;hydron;chloride Chemical compound Cl.C1=CC=C2CC(N)CC2=C1 XEHNLVMHWYPNEQ-UHFFFAOYSA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- XGYOEHBMGLNBGY-UHFFFAOYSA-N ethyl 2-(2-acetamido-2,3-dihydro-1h-inden-5-yl)acetate Chemical compound CCOC(=O)CC1=CC=C2CC(NC(C)=O)CC2=C1 XGYOEHBMGLNBGY-UHFFFAOYSA-N 0.000 description 1
- PYRXAKHVTIHCFE-UHFFFAOYSA-N ethyl 2-chloro-2-methylsulfanylacetate Chemical compound CCOC(=O)C(Cl)SC PYRXAKHVTIHCFE-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- OWANULLRPQLPKQ-UHFFFAOYSA-N methyl 2-(2-amino-2,3-dihydro-1h-inden-5-yl)acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=C2CC(N)CC2=C1 OWANULLRPQLPKQ-UHFFFAOYSA-N 0.000 description 1
- SOJSYOXMFGDLHY-UHFFFAOYSA-N methyl acetate;hydrochloride Chemical compound Cl.COC(C)=O SOJSYOXMFGDLHY-UHFFFAOYSA-N 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- UOOXDDHYFFXMJJ-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)acetamide Chemical compound C1=CC=C2C(NC(=O)C)CCC2=C1 UOOXDDHYFFXMJJ-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明はトロンボキサンＡ２拮抗作用を有するインダン
誘導体の新規合成中間体及びその製法に関する。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel synthetic intermediate of an indane derivative having thromboxane A2 antagonistic activity and a method for producing the same.
（従来の技術）
トロンボキサンＡ２（Ｔｈｒｏｍｂｏｘａｎ Ａ２＋以
下ＴｘＡｚと称する）は動物の各種臓器（例えば、肝臓
、腎臓、肺臓、脳等）に広く存在しているアラキドン酸
が代謝されて生成し、このＴｘＡｚが有する血小板凝集
作用に起因して、しばしば末梢動脈血栓症、肺塞栓症、
冠動脈閉塞症、心筋梗塞症、−過性脳虚血症等の各種血
栓症が引き起こされることが知られている。・このため
、ＴｘＡ、に基づく血小板凝集を抑制する物質として４
−（２−ベンゼンスルホニルアミノエチル）フェノキシ
酢酸が報告されている〔トロンボシス・リサーチ（Ｔｈ
ｒｏｍｂｏｓｉｓＲｅｓｅａｒｃｈ） 、第３５巻、
３７９−３９５頁（１９８４年）〕。(Prior Art) Thromboxan A2 (hereinafter referred to as TxAz) is produced by the metabolism of arachidonic acid, which is widely present in various organs of animals (e.g., liver, kidney, lung, brain, etc.), and this TxAz Due to its platelet aggregation effect, peripheral arterial thrombosis, pulmonary embolism,
It is known that various thromboses such as coronary artery occlusion, myocardial infarction, and hyperencephalic ischemia are caused.・For this reason, 4 is a substance that suppresses platelet aggregation based on TxA.
-(2-benzenesulfonylaminoethyl)phenoxyacetic acid has been reported [Thrombosis Research (Thrombosis Research)
rombosis Research), Volume 35,
pp. 379-395 (1984)].
（発明の構成及び効果）
本発明は一般式
（但し Ｒ１はブロモフェニル基、トリフルオロメチル
フェニル基、ニトロフェニル基、ナフチル基又は含硫複
素環式基、Ｒ２は低級アルコキシカルボニル基又はカル
ボキシル基を表す。）
で示されるインダン誘導体に関する。(Structure and Effects of the Invention) The present invention is based on the general formula (wherein R1 is a bromophenyl group, trifluoromethylphenyl group, nitrophenyl group, naphthyl group, or a sulfur-containing heterocyclic group, and R2 is a lower alkoxycarbonyl group or a carboxyl group). ) is related to an indane derivative represented by
本発明の目的化合物は、各種医薬化合物、例えば上記公
知化合物に較べて一層優れたＴｘＡｚ拮抗作用を有する
医薬化合物、の合成中間体として有用な新規化合物であ
る。かかる目的化合物の具体例としては、−数式（１）
において、Ｒ１がブロモフェニル基、トリフルオロメチ
ルフェニル基、ニトロフェニル基、ナフチル基又はチエ
ニル基である化合物があげられる。The object compound of the present invention is a novel compound useful as a synthetic intermediate for various pharmaceutical compounds, for example, a pharmaceutical compound having a TxAz antagonistic effect superior to that of the above-mentioned known compounds. Specific examples of such target compounds include - Formula (1)
Examples include compounds in which R1 is a bromophenyl group, a trifluoromethylphenyl group, a nitrophenyl group, a naphthyl group, or a thienyl group.
本発明の目的化合物（１）は１個の不斉炭素原子に基づ
く２種の光学異性体及びその混合物をいずれも包含する
ものである。The object compound (1) of the present invention includes both optical isomers based on one asymmetric carbon atom and mixtures thereof.
本発明によれば、目的化合物（１）は、例えば、−数式
（但し、Ｒ２は前記と同一意味を有する。）で示される
アミノインダン化合物又はその塩と一般式
％式％［）
（但し、Ｒ１は前記と同一意味を存する。）で示される
スルホン酸化合物又はその反応性誘導体とを縮合反応さ
せ、要すれば生成物を加水分解して製造することができ
る。According to the present invention, the target compound (1) is, for example, an aminoindan compound or a salt thereof represented by the formula - (wherein R2 has the same meaning as above) and the general formula % formula % [) (however, R1 has the same meaning as above) or a reactive derivative thereof, and the product can be produced by condensation reaction and, if necessary, hydrolysis of the product.
アミノインダン化合物（ＩＩ）又はその塩とスルポン酸
化合物（ＩＩＩ）又はその反応性誘導体との縮合反応は
脱酸剤の存在又は非存在下に実施することができる。化
合物（１１１１）の反応性誘導体としては、慣用の反応
性誘導体、例えば対応するスルホニルハライド化合物が
好適にあげられる。脱酸剤としては、例えば炭酸アルカ
リ金属、炭酸水素アルカリ金属、トリアルキルアミン、
ピリジンなど慣用のものをいずれも用いることができる
。またアミノインダン化合物（ＩＩ）の塩としては、鉱
酸塩及び有機酸塩を適宜用いることができる。本反応は
適当な溶媒（例えば、水、酢酸エチル）中冷却〜加温下
で実施するのが好ましい。The condensation reaction between aminoindan compound (II) or a salt thereof and sulfonic acid compound (III) or a reactive derivative thereof can be carried out in the presence or absence of a deoxidizing agent. Suitable examples of the reactive derivative of compound (1111) include conventional reactive derivatives, such as the corresponding sulfonyl halide compounds. Examples of deoxidizers include alkali metal carbonates, alkali metal hydrogen carbonates, trialkylamines,
Any conventional one such as pyridine can be used. Moreover, as the salt of aminoindan compound (II), mineral acid salts and organic acid salts can be used as appropriate. This reaction is preferably carried out in a suitable solvent (eg, water, ethyl acetate) under cooling to heating.
また、加水分解は例えばアルカリ試薬又は酸で処理する
ことにより実施することができる。アルカリ試薬として
は例えば水酸化アルカリ金属を、酸としては例えば鉱酸
を適宜用いることができる。本加水分解は適当な溶媒（
例えば、水、低級アルカノール）中冷却〜加温下で実施
するのが好ましい。Hydrolysis can also be carried out, for example, by treatment with an alkaline reagent or an acid. For example, an alkali metal hydroxide can be used as the alkaline reagent, and a mineral acid can be used as the acid. This hydrolysis is carried out using an appropriate solvent (
For example, it is preferable to carry out the reaction under cooling to heating in water, lower alkanol).
上記反応はすべてラセミ化を伴わずに進行するため、光
学活性な原料化合物からは光学活性な目的化合物（１）
を得ることができる。All of the above reactions proceed without racemization, so the optically active starting compound can be converted into the optically active target compound (1).
can be obtained.
上記の如くして得られる本発明化合物（１）は、Ｍ離カ
ルボン酸またはその塩のいずれの形ででも合成中間体と
して使用でき、かかる塩としては、例えばアルカリ金属
塩、アルカリ土類金属塩、トリエチルアミン塩、ピリジ
ン塩、塩基性アミノ酸塩の如き有機アミン塩があげられ
る。The compound (1) of the present invention obtained as described above can be used as a synthetic intermediate in the form of an M-free carboxylic acid or a salt thereof. Examples of such salts include alkali metal salts and alkaline earth metal salts. , triethylamine salts, pyridine salts, and basic amino acid salts.
また、かかる目的化合物（Ｉ）及びその塩は、例えば、
−数式Ｒ’−Ｎｌ＋、 （但し、Ｒ３は低級アルコキシ
カルボニル低級アルキル基又はカルボキシ低級アルキル
基を表す。）で示される化合物とペプチド縮合させれば
、−数式
（１９８４年）記載の化合物に較べてより強力なＴＸＡ
２拮抗作用を有し、血小板凝集抑制剤、血栓症の予防・
治療剤、冠・脳血管などの平滑筋子線及び喘息の予防・
治療剤として有用な医薬化合物である。Moreover, such target compound (I) and its salts are, for example,
- If the peptide is condensed with a compound represented by the formula R'-Nl+, (where R3 represents a lower alkoxycarbonyl lower alkyl group or a carboxy lower alkyl group), - compared to the compound described in the formula (1984), more powerful TXA
2 antagonistic effects, platelet aggregation inhibitor, prevention of thrombosis,
Therapeutic agents, smooth muscle cells such as coronary and cerebrovascular vessels, and prevention and treatment of asthma.
It is a pharmaceutical compound useful as a therapeutic agent.
なお、本発明の原料化合物（ＩＩ）は、例えば２−アミ
ノインゲンとアセチルクロリドとを溶媒中脱酸剤の存在
下反応させて２−アセチルアミノインゲンとし、該化合
物とハロ（メチルチオ）酢酸低級アルキルエステルとを
溶媒中反応させた後還元剤で処理して、２−アセチルア
ミノ−５−低級アルコキシカルボニルメチル−インダン
とシ、Ｈｆｉ化合物を加水分解後、常法により脱アセチ
ル化して製造することができる。In addition, the raw material compound (II) of the present invention can be obtained by, for example, reacting 2-aminoingene and acetyl chloride in a solvent in the presence of a deoxidizing agent to obtain 2-acetylaminoingene, and then reacting the compound with lower alkyl halo(methylthio)acetate. It can be produced by reacting the compound with ester in a solvent and then treating it with a reducing agent to hydrolyze the 2-acetylamino-5-lower alkoxycarbonylmethyl-indane and Hfi compounds, followed by deacetylation by a conventional method. can.
（但し、記号は前記と同一意味を有する。）とすること
ができる（特願昭６３−２８９８０１）。(However, the symbols have the same meanings as above.) (Japanese Patent Application No. 63-289801).
この化合物（ＩＶ）は、トロンボシス・リサーチ（Ｔｈ
ｒｏｍｂｏｓｉｓ Ｒｅ５ｅａｒｃｈ）、第３５巻、、
３７９−３９５ ’ｆ４実施例１
（１）（２−アミノインダン−５−イル）酢酸メチルエ
ステル・塩酸塩４．８３ｇ、炭酸カリウム８．２９ｇ、
水４０ｍ１．酢酸エチル１００ｍ１及び４−ニトロフェ
ニルスルホニルクロリド４．４３ｇの混合物を室温で１
時間撹拌する。反応混合物から酢酸エチル層を分取し、
食塩水で洗浄、乾燥後減圧下に溶媒を留去する。得られ
る粗製物を酢酸エチル−イソプロピルエーテル−ｎ−ベ
キ４Ｊ−ン混液から再結晶して（２−（（４−ニトロフ
ェニル）スルホニルアミノコ−インダン−５−イル）酢
酸メチルエステル７．４３ｇを得る。This compound (IV) was manufactured by Thrombosis Research (Th
Rombosis Research), Volume 35,
379-395'f4 Example 1 (1) (2-aminoindan-5-yl)acetic acid methyl ester hydrochloride 4.83g, potassium carbonate 8.29g,
Water 40ml1. A mixture of 100 ml of ethyl acetate and 4.43 g of 4-nitrophenylsulfonyl chloride was mixed with 1 ml of ethyl acetate at room temperature.
Stir for an hour. Separate the ethyl acetate layer from the reaction mixture,
After washing with brine and drying, the solvent is distilled off under reduced pressure. The obtained crude product was recrystallized from a mixture of ethyl acetate-isopropyl ether-n-benzene to give 7.43 g of (2-((4-nitrophenyl)sulfonylaminoco-indan-5-yl)acetic acid methyl ester). obtain.
ｍ、ｐ、 １２２〜１２４°Ｃ
ＭＳ （ｍ／ｅ）： ３９Ｑ （Ｍ ” ）（２）本
品７．３２ｇのメタノール７０ｍ１溶液にＩＮ水酸化ナ
トリウム水溶液３７ｍ１を加え室温で１時間撹拌後、減
圧下に溶媒を留去する。残香を水に溶解し、１０％塩酸
で約ｐＨ１とした後酢酸エチルで抽出する。抽出液を乾
燥後減圧下に溶媒を留去する。得られる粗製物を酢酸エ
チル−ｎ−ヘキサン混液から再結晶して（２−（（４−
ニトロフェニル）スルホニルアミノコ−インダン−５−
イル）酢酸６．７１ｇを得る。m, p, 122-124°C MS (m/e): 39Q (M '') (2) Add 37 ml of IN sodium hydroxide aqueous solution to a solution of 7.32 g of this product in 70 ml of methanol, stir at room temperature for 1 hour, and then reduce the pressure. The solvent is distilled off.The residual aroma is dissolved in water, the pH is adjusted to about 1 with 10% hydrochloric acid, and then extracted with ethyl acetate.After drying the extract, the solvent is distilled off under reduced pressure.The resulting crude product is dissolved in acetic acid. Recrystallized from ethyl-n-hexane mixture (2-((4-
nitrophenyl)sulfonylaminoco-indane-5-
6.71 g of acetic acid are obtained.
ｍ、ｐ、 １７３−１７４°Ｃ
ＭＳ （ｍ／ｅ）： ３７６ （Ｍ” ）ナトリウム塩
： ｍ、ｐ、 １７３−１７６°Ｃ（イソプロピルア
ルコール−水から再結晶）
実施例２〜５
（１） 対応原料化合物を実施例１−（１）と同様に処
理して下記第１表記載化合物を得る。m, p, 173-174°C MS (m/e): 376 (M”) Sodium salt: m, p, 173-176°C (recrystallized from isopropyl alcohol-water) Examples 2-5 (1) The corresponding starting compounds were treated in the same manner as in Example 1-(1) to obtain the compounds listed in Table 1 below.
第 １ 表
（２）上記（１）の生成物を実施例１− （２）と同様
に処理して下記第２表記載化合物を得る。Table 1 (2) The product of (1) above is treated in the same manner as in Example 1-(2) to obtain the compounds listed in Table 2 below.
第２表
〔原料化合物（Ｉｔ）の調製〕
（１） ２−アミノインダン塩酸塩１０．４０ｇ、炭酸
カリウム３４．２ｇ、水１００ｍ１及び酢酸エチル１５
０ｍ１の混合物に水冷下塩化アセチル９６８ｇを滴下す
る。混合物をＯ″Ｃで１．５時間撹拌した後酢酸エチル
層を分取し、洗浄、乾燥後減圧下に溶媒を留去する。残
金を酢酸エチル−ｎ−ヘキサン混液から再結晶して２−
アセチルアミノインダン９．５ｇを無色結晶として得る
。Table 2 [Preparation of raw material compound (It)] (1) 10.40 g of 2-aminoindan hydrochloride, 34.2 g of potassium carbonate, 100 ml of water, and 15 ml of ethyl acetate.
968 g of acetyl chloride was added dropwise to 0 ml of the mixture under water cooling. After stirring the mixture at O''C for 1.5 hours, the ethyl acetate layer was separated, washed, dried, and the solvent was distilled off under reduced pressure.The residue was recrystallized from an ethyl acetate-n-hexane mixture to give 2-
9.5 g of acetylaminoindan are obtained as colorless crystals.
ｍ、ｐ、 １２６．５〜１２７．５°Ｃ（２） 本島
１３．０６ｇ、クロロ（メチルチオ）酢酸エチルエステ
ル１３．３５ｇ及び塩化メチレン１００ｍ１の混合物に
塩化第二スズ４０．０ｇの塩化メチレン５０ｍ１溶液を
水冷上滴下する。混合物を０°Ｃ〜室温で２時間撹拌後
、氷に江別し酢酸エチルで抽出する。抽出液を１０％塩
酸、炭酸水素ナトリウム水溶液及び食塩水で順次洗浄し
、乾燥後減圧下に溶媒を留去する。残金（２４，３ｇ）
を酢酸１５０ｍ１に溶解し、亜鉛末１００ｇを加え２時
間加熱還流する。冷後、混合物をろ過し、ろ液を減圧下
に濃縮して酢酸を留去する。残金に水と酢酸エチルを加
え、酢酸エチル層を分取する。酢酸エチル液を炭酸水素
ナトリウム水溶液及び食塩水で洗浄し、乾燥後減圧下に
溶媒を留去する。得られる粗結晶をエーテル−ｎ−ヘキ
サン混液から再結晶して（２−アセチルアミノインダン
−５−イル）酢酸エチルエステル１５．６７ｇを無色結
晶として得る。m, p, 126.5 - 127.5 °C (2) A solution of 40.0 g of stannic chloride in 50 ml of methylene chloride in a mixture of 13.06 g of Honjima, 13.35 g of chloro(methylthio)acetic acid ethyl ester and 100 ml of methylene chloride. Drop onto water cooling. After stirring the mixture at 0°C to room temperature for 2 hours, it was poured onto ice and extracted with ethyl acetate. The extract is washed successively with 10% hydrochloric acid, an aqueous sodium bicarbonate solution, and brine, and after drying, the solvent is distilled off under reduced pressure. Remaining amount (24.3g)
was dissolved in 150 ml of acetic acid, 100 g of zinc powder was added, and the mixture was heated under reflux for 2 hours. After cooling, the mixture is filtered, and the filtrate is concentrated under reduced pressure to remove acetic acid. Add water and ethyl acetate to the residue, and separate the ethyl acetate layer. The ethyl acetate solution is washed with an aqueous sodium hydrogen carbonate solution and brine, and after drying, the solvent is distilled off under reduced pressure. The resulting crude crystals were recrystallized from a mixture of ether and n-hexane to obtain 15.67 g of ethyl (2-acetylaminoindan-5-yl)acetate as colorless crystals.
ａ、ｐ、 ８２〜８４°Ｃ
（３） 本島１６．６９ｇ及び２Ｎ塩酸１００ｍ１の混
合物を１８時間加熱還流する０反応後、減圧下に溶媒を
留去し、残香にメタノール１００ｍ１を加え１時間加熱
還流する。冷後、減圧下に溶媒を留去し、得られる粗結
晶をメタノールーイソプロビルアルコールーイソロピル
エーテル混液から再結晶して（２−アミノインダン−５
−イル）酢酸メチルエステル塩酸塩１５．１４ｇを無色
結晶として得る。a, p, 82-84°C (3) A mixture of 16.69 g of Honjima and 100 ml of 2N hydrochloric acid was heated under reflux for 18 hours. After the reaction, the solvent was distilled off under reduced pressure, and 100 ml of methanol was added to the residual aroma and heated for 1 hour. Reflux. After cooling, the solvent was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from a methanol-isopropyl alcohol-isolopyl ether mixture (2-aminoindan-5
15.14 g of methyl acetate hydrochloride are obtained as colorless crystals.
ｍ、ｐ、 １４５〜１４８°Ｃm, p, 145-148°C
Claims (1)
ルフェニル基、ニトロフェニル基、ナフチル基又は含硫
複素環式基、Ｒ＾２は低級アルコキシカルボニル基又は
カルボキシル基を表す。） で示されるインダン誘導体。 ２、一般式 ▲数式、化学式、表等があります▼ （但し、Ｒ＾２は低級アルコキシカルボニル基又はカル
ボキシル基を表す。） で示されるアミノインダン化合物又はその塩と一般式 Ｒ＾１ＳＯ＿３Ｈ （但し、Ｒ＾１はブロモフェニル基、トリフルオロメチ
ルフェニル基、ニトロフェニル基、ナフチル基又は含硫
複素環式基を表す。） で示されるスルホン酸化合物又はその反応性誘導体とを
縮合反応させることを特徴とする一般式▲数式、化学式
、表等があります▼ （但し、記号は前記と同一意味を有する。）で示される
インダン誘導体の製法。 ３、一般式 ▲数式、化学式、表等があります▼ （但し、Ｒ＾１はブロモフェニル基、トリフルオロメチ
ルフェニル基、ニトロフェニル基、ナフチル基又は含硫
複素環式基、Ｒ＾２＾１は低級アルコキシカルボニル基
を表す。） で示されるインダン誘導体を加水分解することを特徴と
する一般式 ▲数式、化学式、表等があります▼ （但し、記号は前記と同一意味を有する。）で示される
インダン誘導体の製法。[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (However, R^1 is a bromophenyl group, trifluoromethylphenyl group, nitrophenyl group, naphthyl group, or sulfur-containing heterocyclic group) , R^2 represents a lower alkoxycarbonyl group or a carboxyl group). 2. Aminoindan compound or its salt represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. R^1 represents a bromophenyl group, a trifluoromethylphenyl group, a nitrophenyl group, a naphthyl group, or a sulfur-containing heterocyclic group. A method for producing indane derivatives represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, the symbols have the same meanings as above.) 3. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (However, R^1 is a bromophenyl group, trifluoromethylphenyl group, nitrophenyl group, naphthyl group, or sulfur-containing heterocyclic group, R^2^1 represents a lower alkoxycarbonyl group.) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, the symbols have the same meanings as above.) A method for producing indane derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25275489A JPH02149553A (en) | 1989-09-28 | 1989-09-28 | Indane derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25275489A JPH02149553A (en) | 1989-09-28 | 1989-09-28 | Indane derivative and production thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63289801A Division JPH02138248A (en) | 1987-11-18 | 1988-11-16 | Indane derivative, its production and synthetic intermediate thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02149553A true JPH02149553A (en) | 1990-06-08 |
| JPH0524148B2 JPH0524148B2 (en) | 1993-04-06 |
Family
ID=17241822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25275489A Granted JPH02149553A (en) | 1989-09-28 | 1989-09-28 | Indane derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02149553A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6323853A (en) * | 1986-07-16 | 1988-02-01 | ドクトル カ−ル ト−メ− ゲゼルシヤフト ミツト ベシユレンクテル ハフツンク | Novel benzenesulfonamideindanyl compound |
-
1989
- 1989-09-28 JP JP25275489A patent/JPH02149553A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6323853A (en) * | 1986-07-16 | 1988-02-01 | ドクトル カ−ル ト−メ− ゲゼルシヤフト ミツト ベシユレンクテル ハフツンク | Novel benzenesulfonamideindanyl compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0524148B2 (en) | 1993-04-06 |
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