KR800000058B1 - Process for preparing benzocycloheptathiphene derivatives - Google Patents
Process for preparing benzocycloheptathiphene derivatives Download PDFInfo
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- KR800000058B1 KR800000058B1 KR7601503A KR760001503A KR800000058B1 KR 800000058 B1 KR800000058 B1 KR 800000058B1 KR 7601503 A KR7601503 A KR 7601503A KR 760001503 A KR760001503 A KR 760001503A KR 800000058 B1 KR800000058 B1 KR 800000058B1
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- 238000004519 manufacturing process Methods 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 206010003119 arrhythmia Diseases 0.000 description 5
- 230000006793 arrhythmia Effects 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- -1 3-amino-2-hydroxypropoxy Chemical class 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- VAQHTLMMCQIMBL-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzo[1,2]cyclohepta[3,4-b]thiophen-10-one Chemical compound C=1C2=CC=CC=C2C(=O)C=2C=CSC=2C=1OCC1CO1 VAQHTLMMCQIMBL-UHFFFAOYSA-N 0.000 description 2
- ZSGIVIUNURDDJL-UHFFFAOYSA-N 4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-one Chemical compound COC1=CC2=CC=CC=C2C(=O)C2=C1SC=C2 ZSGIVIUNURDDJL-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- MLSGWYGDGPOZMX-UHFFFAOYSA-N OC1=CC2=C(C(C3=C1SC=C3)=O)C=CC=C2 Chemical compound OC1=CC2=C(C(C3=C1SC=C3)=O)C=CC=C2 MLSGWYGDGPOZMX-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 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 description 2
- SDGKUVSVPIIUCF-KNVOCYPGSA-N (2r,6s)-2,6-dimethylpiperidine Chemical compound C[C@H]1CCC[C@@H](C)N1 SDGKUVSVPIIUCF-KNVOCYPGSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- YYTSGNJTASLUOY-UHFFFAOYSA-N 1-chloropropan-2-ol Chemical class CC(O)CCl YYTSGNJTASLUOY-UHFFFAOYSA-N 0.000 description 1
- FMRWQLAJBBKXDM-UHFFFAOYSA-N 2,2,5,5-tetramethylpyrrolidine Chemical compound CC1(C)CCC(C)(C)N1 FMRWQLAJBBKXDM-UHFFFAOYSA-N 0.000 description 1
- GTOLCXTWQDBGBN-UHFFFAOYSA-N 4-methoxy-10h-benzo[1,2]cyclohepta[3,4-b]thiophene Chemical compound COC1=CC2=CC=CC=C2CC2=C1SC=C2 GTOLCXTWQDBGBN-UHFFFAOYSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- AKYJPOPHGMQXHH-UHFFFAOYSA-N benzo[1,2]cyclohepta[3,4-b]thiophen-10-one Chemical compound C1=CC2=CC=CC=C2C(=O)C2=C1SC=C2 AKYJPOPHGMQXHH-UHFFFAOYSA-N 0.000 description 1
- 150000008617 benzocycloheptathiophenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
내용 없음.No content.
Description
본 발명은 부정맥 치료제로 유효한 다음 구조식(I)인 벤조사이클로 헵타티오펜의 유도체의 제조방법에 관한 것이다.The present invention relates to a method for preparing a derivative of benzocyclo heptathiophene, which is the following structural formula (I) effective as an arrhythmia therapeutic agent.
상기 구조식에서In the above structural formula
n은 1-3인 정수이고n is an integer of 1-3
R1은 수소 또는 원자번호 9-35인 할로겐원자이고R 1 is hydrogen or a halogen atom with atomic number 9-35
R2두개는 모두 같은 것으로 수소 또는 탄소수 1-4인 알킬이고Both R 2 are the same, hydrogen or alkyl having 1-4 carbons
R3두개는 모두 같은 것으로 수소 또는 탄소수 1-4인 알킬이고Both R 3 are the same, hydrogen or alkyl having 1-4 carbons
X는 카보닐 또는 메틸렌이다.X is carbonyl or methylene.
n은 2 또는 3이 바람직하고 할로겐은 염소 또는 취소가 바람직하고 특히 염소가 좋다. 알킬은 탄소수 1-2가 바람직하고 특히 탄소수 1개가 좋다. R1은 수소가 바람직하고 R1이 할로겐이면 트리사이클부분의 6 또는 7 위치에 붙는 것이 바람직하다.n is preferably 2 or 3 and halogen is preferably chlorine or cancellation, especially chlorine. The alkyl preferably has 1-2 carbon atoms, particularly preferably 1 carbon atom. R 1 is preferably hydrogen and is preferably attached at the 6 or 7 position of the tricycle moiety if R 1 is halogen.
R2과 R3의 4개의 기는 같은 것이 바람직하고 알킬기가 좋다.The four groups of R 2 and R 3 are preferably the same and have an alkyl group.
만약 R2가 R3와 같지 않으면 R3는 수소가 바람직하다.If R 2 is not equal to R 3 then R 3 is preferably hydrogen.
X는 카보닐이 바람직하다.X is preferably carbonyl.
본 발명은 다음 구조식(Ⅱ) 화합물 또는 그의 반응활성기를 가진 유도체를 다음 구조식(Ⅲ)인 화합물과 반응시켜 상기 언급한 구조식(I)화합물을 제조하는 방법이다.The present invention is a method for preparing the above-mentioned compound of formula (I) by reacting a compound of formula (II) or a derivative having a reactive active group thereof with a compound of formula (III).
상기 구조식에서In the above structural formula
X, R1, R2, R3와 n은 상기와 같다.X, R 1 , R 2 , R 3 and n are the same as above.
유사한 3-아미노-2-하이드록시프로폭시 유도체의 제조를 위한 반응은 통상의 방법으로 할 수 있으며 적합한 구조식(Ⅱ)화합물의 반응 활성기를 가진 유도체에는 구조식(Ⅱ)화합물과 구조식HY(Y는 할로겐 또는 R4-SO2-O-그룹이고 여기서 R4는 페닐, 토릴, 또는 저급알킬임) 화합물과의 부가생성물이 포함된다. 바람직한 Y는 염소 또는 취소이다. 구조식(Ⅲ)인 아민은 편리한대로 구조식(Ⅱ)화합물에 대해 과량 존재시킨다. 임의로 불활성 유기용매를 쓸 수 있다.Reactions for the preparation of similar 3-amino-2-hydroxypropoxy derivatives can be carried out in a conventional manner. Derivatives having reactive activating groups of suitable formula (II) compounds include those of formula (II) and Or a R 4 -SO 2 -O- group wherein R 4 is phenyl, toryl, or lower alkyl). Preferred Y is chlorine or cancellation. An amine of formula III is present in excess of the compound of formula II as convenient. Optionally, an inert organic solvent can be used.
R2가 R3와 같지 않을때는 구조식(I)화합물은 시스 또는 트랜스이성체로 존재하며 반응물질로 사용되는 구조식(Ⅲ)화합물이 시스 또는 트랜스에 따라 이에 상응하는 이성체를 각각 생성한다.When R 2 is not the same as R 3 , the compound of formula (I) exists as a cis or trans isomer, and the compound of formula (III) used as a reactant generates corresponding isomers according to the cis or trans, respectively.
구조식(Ⅱ)화합물은 신규의 것이다. 통상의 방법에 따라 실시예로서 예를들면 상응하는 10-메톡시-4H-벤조[4,5-]사이클로헵타[1,2-b]티오펜-4-온으로부터 제조한다.The compound of formula II is novel. According to the usual method it is prepared, for example, from the corresponding 10-methoxy-4H-benzo [4,5-] cyclohepta [1,2-b] thiophen-4-one.
출발물질의 제조에 관해 특별히 기술하지 않았으면 이러한 화합물은 기지의 것이나 기지의 방법에 의해 제조 및 정제하거나 여기 실시예에 기술된 유사한 방법으로 제조할 수 있다.Unless specifically stated for the preparation of starting materials, these compounds can be prepared and purified by known or known methods or by analogous methods described in the Examples herein.
구조식(I)화합물의 유리 염기를 통상의 방법으로 산부가염으로 전환시키고 다시 유리염기로 복귀시킨다. 염형성에 적당한 산은 염산이다.The free base of the compound of formula (I) is converted to the acid addition salt in a conventional manner and back to the free base. Acids suitable for salt formation are hydrochloric acid.
구조식(I)화합물은 약학적 활성을 가진다. 특히 본 화합물은 부정맥 치료작용을 가지며 이에 대한 예를 들어보면 참조의 원리에 따라 3-50mg/kg의 양을 클로로포름으로 유도된 부정맥을 앓는 쥐에게 복강내 주사하여 이 부정맥을 치유케 함으로 입증할 수 있다. [참조:J.W. Lawson, J. Pharmacol,Exp.Therap.(1968) 160, 22-31]Structural formula (I) compounds have pharmaceutical activity. In particular, the compound has a therapeutic effect on arrhythmia, for example, according to the principle of reference can be proved by the intraperitoneal injection of rats with arrhythmia induced by chloroform-induced amount to heal this arrhythmia have. [See: J.W. Lawson, J. Pharmacol, Exp. Therap. (1968) 160, 22-31].
그러므로 본 화합물은 부정맥 치료제로 쓰인다.Therefore, the compound is used as a treatment for arrhythmia.
이 용도를 위한 일일 상용량은 10-100mg이며 편리한대로 2-50mg의 투여단위 용량으로 하루에 2-4번으로 분복 또는 서방출형 제제로 하여 투여한다.The daily normal dose for this use is 10-100 mg and is conveniently administered as a divided or sustained release formulation 2-4 mg per day, at a dosage of 2-50 mg.
구조식(I)화합물은 약학적 가능한 염류로도 투여할 수 있다. 이러한 산 부가염은 유리염기와 작용하는 정도가 같고 쉽게 통상의 방법에 의해 제조되어진다. 본 발명에 따른 유리 염기형태 또는 약학적 가능한 염의 형태인 구조식(I)화합물과 약학적 담체 또는 희석제를 함유하는 약학적 제제로 본 발명과 관련이 있다.Structural formula (I) compounds may also be administered as pharmaceutically acceptable salts. These acid addition salts have the same degree of function as the free base and are easily prepared by conventional methods. A pharmaceutical formulation containing a compound of formula (I) in the free base form or in the form of a pharmaceutically acceptable salt according to the invention and a pharmaceutical carrier or diluent is relevant for the present invention.
이러한 제제로는 예를들면 액제, 정제가 있다.Such formulations include, for example, liquids and tablets.
본 화합물의 바람직한 화합물은 X가 카보닐이고 R1이 수소, 염소 또는 취소이며 6 또는 7위치에 있는 것이고 R2와 R3는 탄소수 1-2인 알킬이고 n은 2 또는 3인 것이다.Preferred compounds of this compound are those wherein X is carbonyl, R 1 is hydrogen, chlorine or cancelled and is at the 6 or 7 position, R 2 and R 3 are alkyl having 1-2 carbon atoms and n is 2 or 3.
실시예 1화합물은 특히 흥미로운 성질을 보여준다.Example 1 Compounds show particularly interesting properties.
다음 실시예는 본 발명을 상술하며 온도는 섭씨이며 실측치 그대로이다.The following examples detail the invention and the temperature is in degrees Celsius and is as measured.
[실시예 1]Example 1
10-[2-하이드록시-3-(2,2,5,5-데트라메틸-1-피로디닐)-프로폭시]-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온 20.0g의 10-(2,3-에폭시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온과 10-(3-클로로-2-하이드록시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온의 혼합물을 65ml의 2,2,5,5-테트라메틸피로리딘과 200ml의 메탄올중에서 5시간동안 가열, 환류시킨다. 반응혼합물을 증발건조하고 잔사를 600ml의 클로로포름과 150ml의 3N-가성소오다 용액으로 처리한다. 유기층을 분리해내고 3N-가성소오다 용액으로 3회 세척한다. 물로 중성이 될때까지 세척한 후에 용액을 황산나트륨으로 탈수하고 증발 농축한다. 잔사는 5%메탄올을 함유한 클로로포름 혼액으로 600g의 실리카겔상에 크로마토그래피하여 유리 염기 형태로 상기 제목의 화합물을 얻는다. (융점 : 104°-107°)이소프로판올로 재결정한 것임.10- [2-hydroxy-3- (2,2,5,5-detramethyl-1-pyridinyl) -propoxy] -4H-benzo [4,5] cyclohepta [1,2-b] 20.0 g of thiophen-4-one 10- (2,3-epoxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one and 10- (3- To a mixture of chloro-2-hydroxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one, 65 ml of 2,2,5,5-tetramethylpyrrolidine And refluxed in 200 ml of methanol for 5 hours. The reaction mixture is evaporated to dryness and the residue is treated with 600 ml of chloroform and 150 ml of 3N-caustic soda solution. The organic layer is separated and washed three times with 3N-caustic soda solution. After washing until neutral with water, the solution is dehydrated with sodium sulfate and concentrated by evaporation. The residue is chromatographed on 600 g of silica gel with a chloroform mixture containing 5% methanol to give the title compound in free base form. (Melting point: 104 ° -107 °) Recrystallized from isopropanol.
출발물질로 쓰이는 10-(2,3-에폭시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온과 10-(3-클로로-2-하이드록시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온의 혼합물을 다음과 같이 제조한다.10- (2,3-epoxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one and 10- (3-chloro-2-hydric as starting materials A mixture of oxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one is prepared as follows.
a) 20.0g의 10-메톡시-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온을 200ml의 6N염산으로 2.5시간동안 가열 환류시킨 후 20°로 냉각한다. 생성된 침전을 여과해낸다. 10-하이드록시-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온은 융점이 213°(에탄올로 부터 재결정한 것임)a) 20.0 g of 10-methoxy-4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one was heated to reflux for 2.5 hours with 200 ml of 6N hydrochloric acid and then cooled to 20 ° do. The resulting precipitate is filtered off. 10-hydroxy-4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one has a melting point of 213 ° (recrystallized from ethanol)
b) 15.0g의 10-하이드록시-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온, 150ml의 에피클로로히드린과 0.7ml의 피페리딘을 30분간 비등시킨다.b) 15.0 g of 10-hydroxy-4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one, 150 ml of epichlorohydrin and 0.7 ml of piperidine for 30 minutes Boil.
감압하에서 증발 농축시킨 후에 혼합물을 40°에서 건조시켜 10-(2,3-에폭시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온과 10-(3-클로로-2-하이드록시프로폭시)-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온의 혼합물을 얻으며 계속해서 이 혼합물 상태로 사용되어진다.After evaporation and concentration under reduced pressure, the mixture was dried at 40 ° to give 10- (2,3-epoxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one and 10 A mixture of-(3-chloro-2-hydroxypropoxy) -4H-benzo [4,5] cyclohepta [1,2-b] thiophen-4-one is obtained and subsequently used in this mixture state .
실시예 1에서 기술된 유사한 방법으로 다음과 같은 구조식(I)인 화합물을 상응하는 구조식(Ⅱ)인 상응하는 에폭사이드 및/또는 상응하는 3-클로로-2-프로판올 유도체를 구조식(Ⅲ)인 적당한 화합물과 반응시켜 제조한다.In a similar manner as described in Example 1, a compound of formula (I) is prepared according to the corresponding epoxide and / or corresponding 3-chloro-2-propanol derivative of formula (II). Prepared by reaction with a compound.
a) 중간체로 필요한 10-메톡시-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜(융점 : 94°-96°)을 무수상태로 하여 10-메톡시-4H-벤조[4,5] 사이클로헵타[1,2-b] 티오펜-4-온을 리튬 알루미늄 하이드라이드와 염화 알루미늄 존재하의 에텔중에서 반응혼합물을 실온에서 최종적으로 1.5시간 교반하여 제조한다.a) 10-methoxy-4H- in anhydrous state with 10-methoxy-4H-benzo [4,5] cyclohepta [1,2-b] thiophene (melting point: 94 ° -96 °) required as an intermediate The benzo [4,5] cyclohepta [1,2-b] thiophen-4-one is prepared by stirring the reaction mixture in lithium ether hydride and ether in the presence of aluminum chloride, finally stirring for 1.5 hours at room temperature.
b) R2그룹이 모두 각각에 대해 시스일때 사용되는 구조식(Ⅲ)화합물은 시스-2,6-디메틸 피페리딘이다.b) The structural formula (III) compound used when all R 2 groups are cis for each is cis-2,6-dimethyl piperidine.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR7601503A KR800000058B1 (en) | 1976-06-16 | 1976-06-16 | Process for preparing benzocycloheptathiphene derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR7601503A KR800000058B1 (en) | 1976-06-16 | 1976-06-16 | Process for preparing benzocycloheptathiphene derivatives |
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| Publication Number | Publication Date |
|---|---|
| KR800000058B1 true KR800000058B1 (en) | 1980-01-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR7601503A Expired KR800000058B1 (en) | 1976-06-16 | 1976-06-16 | Process for preparing benzocycloheptathiphene derivatives |
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| KR (1) | KR800000058B1 (en) |
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1976
- 1976-06-16 KR KR7601503A patent/KR800000058B1/en not_active Expired
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