KR20150120772A - Novel preparation method of quinoline n-oxide derivative with amide group - Google Patents
Novel preparation method of quinoline n-oxide derivative with amide group Download PDFInfo
- Publication number
- KR20150120772A KR20150120772A KR1020140046863A KR20140046863A KR20150120772A KR 20150120772 A KR20150120772 A KR 20150120772A KR 1020140046863 A KR1020140046863 A KR 1020140046863A KR 20140046863 A KR20140046863 A KR 20140046863A KR 20150120772 A KR20150120772 A KR 20150120772A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- quinoline
- aryl
- heteroaryl
- hydrogen
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
- C07D241/52—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
- C07D215/60—N-oxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/08—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/36—Benzo-cinnolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
본 발명은 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 새로운 제조방법에 관한 것으로, 보다 상세하게는 선택적으로 퀴놀린 N-옥사이드 유도체의 C-8자리에 아미드 작용기를 도입하는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법 및 이에 따라 제조된 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체에 관한 것이다.The present invention relates to a novel process for preparing a quinoline N-oxide derivative having an amide functional group, and more particularly to a process for preparing a quinoline N-oxide derivative having an amide functional group introduced with an amide functional group at the C-8 position of a quinoline N- -Oxide derivatives and quinoline N-oxide derivatives incorporating the amide functional groups thus prepared.
헤테로원자를 하나이상 포함하는 헤테로아릴, 보다 구체적으로 퀴놀린은 의약 산업 및 재료 산업에 다양하게 적용될 수 있어 이들 유도체의 제조방법들이 다양하게 연구되어왔다.Heteroaryl containing at least one heteroatom, more specifically quinoline, has been extensively studied in the pharmaceutical industry and in the materials industry, and various methods for producing these derivatives have been studied.
그러나 이러한 퀴놀린 유도체의 제조방법은 대부분 복잡한 단계를 거치는 제조방법들로 보다 간단한 공정이 요구되어왔다.However, the production method of such quinoline derivatives has been demanded in a simpler process by the manufacturing methods which are mostly complicated.
이에 최근 퀴놀린과 퀴놀린으로 용이하게 전환가능한 퀴놀린 N-옥사이드의 C-H결합을 활성화시켜 탄소-탄소 결합과 탄소-할로겐 결합을 직접 형성할 수 있는 방법들이 제안되었다.Recently, a method has been proposed which can directly form a carbon-carbon bond and a carbon-halogen bond by activating C-H bonds of quinoline N-oxide which can be easily converted to quinoline and quinoline.
그러나 이러한 방법들은 모두 퀴놀린 또는 퀴놀린 N-옥사이드의 C-2자리에 작용기를 도입하는 방법들이다( Wu, J. L.; Cui, X. L.; Chen, L. M.; Jiang, G. J.; Wu, Y. J. J. Am. Chem. Soc. 2009, 131, 13888.; Campeau, L.-C.; Stuart, D. R.; Leclerc, J.-P.; Bertrand-Laperle, M.; Villemure, E.; Sun, H.-Y.; Lasserre, S.; Guimond, N.; Lecavallier, M.; Fagnou, K. J. Am. Chem. Soc. 2009, 131, 3291).However, all of these methods are methods for introducing a functional group at the C-2 position of quinoline or quinoline N-oxide (Wu, JL; Cui, XL; Chen, LM; Jiang, GJ; Wu, YJ J. Am. . 2009, 131, 13888 .; Campeau , L.-C .; Stuart, DR; Leclerc, J.-P .; Bertrand-Laperle, M .; Villemure, E .; Sun, H.-Y .; Lasserre, S .; Guimond, N .; Lecavallier, M .; Fagnou, K. J. Am. Chem. Soc., 2009 , 131 , 3291).
하지만 하기에 표시된 화합물과 같이 퀴놀린의 C-8자리에 아미드 작용기가 도입된 화합물이 다양한 분야에 사용되고 있어, C-2자리가 아닌 위치 선택적으로 C-8자리에 아미드 작용기를 도입하는 간단하고도 효율적인 방법이 요구된다.However, compounds having an amide functional group introduced at the C-8 position of the quinoline are used in various fields as in the compounds shown below, so that simple and efficient introduction of the amide functional group at the C-8 position, Method is required.
본 발명은 퀴놀린 N-옥사이드 유도체의 C-8 위치에 아미드 작용기를 도입하여 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법 및 이에 따라 제조된 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체를 제공한다. The present invention provides a process for preparing an amide functional group-introduced quinoline N-oxide derivative by introducing an amide functional group at the C-8 position of the quinoline N-oxide derivative and a quinoline N-oxide derivative having the amide functional group thus prepared .
본 발명자들은 이리튬 촉매 및 산 존재하에 퀴놀린 N-옥사이드 유도체를 아지드 화합물과 반응시킬 시 위치 선택적으로 C-8자리에 아미드기가 도입됨을 알아내어 본 발명을 완성하였다.The present inventors have found that an amide group is optionally introduced at the C-8 position when a quinoline N-oxide derivative is reacted with an azide compound in the presence of an erythium catalyst and an acid, thereby completing the present invention.
즉, 본 발명은 다양한 의약품 및 재료물질의 중간체 또는 원료물질로 사용가능한 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법 및 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체를 제공하는 것으로, 보다 상세하게는 이리듐 촉매 및 산 존재 하에서 하기 화학식 3의 퀴놀린 N-옥사이드 유도체와 하기 화학식 4의 아지드 화합물을 반응시켜 하기 화학식 1로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법을 제공한다.That is, the present invention provides a method for preparing an amide functional group-introduced quinoline N-oxide derivative, which can be used as an intermediate or raw material for various pharmaceuticals and materials, and a quinoline N-oxide derivative to which an amide functional group is introduced. Which comprises reacting a quinoline N-oxide derivative represented by the following formula (III) with an azide compound represented by the following formula (IV) in the presence of an iridium catalyst and an acid to produce an amide functional group-substituted quinoline N-oxide derivative.
[화학식 1][Chemical Formula 1]
[화학식 3](3)
[화학식 4][Chemical Formula 4]
[상기 화학식 1, 화학식 3 및 화학식 4에서, [In the above formulas (1), (3) and (4)
A1 및 A2는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며; A 1 and A 2 are independently each other N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R1 내지 R4는 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며; R 1 to R 4 are independently of each other hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z는 -S(O)2- 또는 -CO-이며;Z is -S (O) 2- or -CO-;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R1 내지 R4 및 R은 서로 독립적으로 인접한 치환체와 융합고리를 포함하거나 포함하지 않는 (C3-C12)알킬렌 또는 (C3-C12)알케닐렌으로 연결되어 지환족 고리 및 단일환 또는 다환의 방향족고리를 형성할 수 있으며;R 1 to R 4 and R 5 are each independently selected from the group consisting of (C3-C12) alkylene or (C3-C12) alkenylene which contains an adjacent substituent with or without a fused ring to form an alicyclic ring and a monocyclic or polycyclic aromatic May form a ring;
R1 내지 R4 및 R의 알킬, 알콕시, 알콕시카보닐, 아릴, 아릴옥시카보닐, 헤테로시클로알킬, 헤테로아릴, 지환족 고리 및 방향족 고리와 R11 내지 R15의 알킬은 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 및 (C1-C10)알킬(C6-C12)아릴에서 선택되는 하나이상으로 더 치환될 수 있다.]The alkyl, alkoxy, alkoxycarbonyl, aryl, aryloxycarbonyl, heterocycloalkyl, heteroaryl, alicyclic and aromatic rings of R 1 to R 4 and R and alkyl of R 11 to R 15 are independently selected from the group consisting of halogen, (C6-C12) aryl, (C3-C12) heteroaryl, 5 to 7 membered heterocycloalkyl, (C3-C12) (C1-C10) alkyl, (C1-C10) alkyl, (C2-C10) alkynyl, cyano, (C6-C12) aryl. ≪ / RTI >
또한 본 발명은 이리듐 촉매 및 산 존재 하에서 하기 화학식 5의 퀴놀린 N-옥사이드 유도체와 하기 화학식 4의 아지드 화합물을 반응시켜 하기 화학식 2로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법을 제공한다.The present invention also relates to a process for preparing a quinoline N-oxide derivative having an amide functional group represented by the following formula (2) by reacting a quinoline N-oxide derivative represented by the following formula (5) with an azide compound represented by the following formula to provide.
[화학식 2](2)
[화학식 5][Chemical Formula 5]
[화학식 4][Chemical Formula 4]
[상기 화학식 2, 화학식 4 및 화학식 5에서,[In the formulas (2), (4) and (5)
A1 및 A3는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15) 이며; A 1 and A 3 are independently from each other is N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R1 내지 R8은 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며; R 1 to R 8 are each independently hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C6- C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z는 -S(O)2- 또는 -CO-이며;Z is -S (O) 2- or -CO-;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R1 내지 R8 및 R은 서로 독립적으로 인접한 치환체와 융합고리를 포함하거나 포함하지 않는 (C3-C12)알킬렌 또는 (C3-C12)알케닐렌으로 연결되어 지환족 고리 및 단일환 또는 다환의 방향족고리를 형성할 수 있으며;R 1 to R 8 and R are independently selected from the group consisting of (C3-C12) alkylene or (C3-C12) alkenylene which contains an alicyclic ring and a monocyclic or polycyclic aromatic May form a ring;
R1 내지 R8 및 R의 알킬, 알콕시, 알콕시카보닐, 아릴, 아릴옥시카보닐, 헤테로시클로알킬, 헤테로아릴, 지환족 고리 및 방향족 고리와 R11 내지 R15의 알킬은 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 및 (C1-C10)알킬(C6-C12)아릴에서 선택되는 하나이상으로 더 치환될 수 있다.]The alkyl, alkoxy, alkoxycarbonyl, aryl, aryloxycarbonyl, heterocycloalkyl, heteroaryl, alicyclic and aromatic rings of R 1 to R 8 and R and alkyl of R 11 to R 15 are independently selected from the group consisting of halogen, (C6-C12) aryl, (C3-C12) heteroaryl, 5 to 7 membered heterocycloalkyl, (C3-C12) (C1-C10) alkyl, (C1-C10) alkyl, (C2-C10) alkynyl, cyano, (C6-C12) aryl. ≪ / RTI >
본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법은 이리듐 촉매와 산 존재하에 아미드화 반응을 진행시켜 C-2자리가 아닌 위치 선택적으로 C-8자리의 H를 활성화 시켜 C-8자리에 아미드 작용기를 도입한다.The method of preparing the quinoline N-oxide derivative having the amide functional group according to the present invention is characterized in that the amidation reaction is carried out in the presence of an iridium catalyst and an acid to activate C-8-position H selectively in place of C- Lt; / RTI > functional group.
본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법은 단순한 공정과 온화한 반응조건으로 높은 수율로 위치 선택적으로 C-8위치에 아미드 작용기가 도입된 생성물을 얻을 수 있는 매우 효과적인 방법이다.The process for preparing the quinoline N-oxide derivative having the amide functional group according to the present invention is a very effective method for obtaining a product in which the amide functional group is introduced at a C-8 position at a high yield in a simple process and mild reaction conditions.
본 발명의 메커니즘적 연구를 위해 하기 반응식 1에서 보이는 바와 같이 중수소로 치환된 화합물 1a로 비교실험한 결과 반응속도의 큰 차이가 없는 결과를 얻어 이 단계는 반응 속도 결정 단계는 아님을 확인하였다. 반응식 2에서 보이는 바와 같이 반응 중간체로 이리듐과 퀴놀린의 반응으로 얻어진 결정(8)을 얻었고 반응식 3에서 보이는 바와 같이 이를 촉매로 사용하여 최종 화합물을 얻을 수 있음을 증명하였다. 이와 같은 사실을 근거로 본 발명의 메커니즘은 상기 반응식 4에 나타낸 바와 같이 C-H 활성화 반응(I) 후 아지드 화합물과의 반응을 통해 반응 중간체 II와 III이 생성되고 산의 영향에 최종 촉매 반응이 완성되는 것으로 진행된다고 예상된다.For the mechanism study of the present invention, as shown in the following Reaction Scheme 1, the deuterium substituted compound 1a did not show a large difference in the reaction rate, confirming that this step was not the step of determining the reaction rate. As shown in Scheme 2, a crystal (8) obtained by the reaction of iridium and quinoline as a reaction intermediate was obtained, and as shown in Scheme 3, it was proved that the final compound could be obtained by using it as a catalyst. Based on these facts, the mechanism of the present invention is that the reaction intermediates II and III are produced through the reaction with the azide compound after the CH activation reaction (I) as shown in Scheme 4, and the final catalytic reaction is completed As well.
[반응식 1][Reaction Scheme 1]
[반응식 2][Reaction Scheme 2]
[반응식 3][Reaction Scheme 3 ]
[반응식 4][Reaction Scheme 4]
바람직하게 본 발명에서 상기 화학식 1은 하기 화학식 6 내지 9로 표시될 수 있다.In the present invention, the formula (1) may be represented by the following formulas (6) to (9).
[화학식 6][Chemical Formula 6]
[화학식 7](7)
[화학식 8][Chemical Formula 8]
[화학식 9][Chemical Formula 9]
[상기 화학식 6 내지 9에서, [In the above formulas (6) to (9)
A1 및 A2는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15) 이며; A 1 and A 2 are independently each other N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R1 내지 R4는 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며; R 1 to R 4 are independently of each other hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z는 -S(O)2- 또는 -CO-이며;Z is -S (O) 2- or -CO-;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R21 내지 R25는 서로 독립적으로 수소, 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 또는 (C1-C10)알킬(C6-C12)아릴이다.]R 21 to R 25 independently from each other are hydrogen, halogen, hydroxy, amino, nitro, carboxy, (C 1 -C 10) alkyl, halo (C 1 -C 10) alkyl, (C 6 -C 12) (C2-C10) alkenyl, (C2-C10) alkynyl, cyano, (C6-C12) cycloalkyl, (C1-C10) alkyl or (C1-C10) alkyl (C6-C12) aryl.
바람직하게 본 발명의 일 실시예에 따른 상기 화학식 1 또는 2에서 T는 페닐렌, 나프탈렌 또는 안트라센일 수 있다.Preferably, T in Formula 1 or 2 according to an embodiment of the present invention may be phenylene, naphthalene, or anthracene.
보다 구체적으로 본 발명의 일 실시예에 따른 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체는 하기 화합물에서 선택될 수 있으나, 이에 한정이 있는 것은 아니다.More specifically, the quinoline N-oxide derivative to which an amide functional group is introduced according to an embodiment of the present invention may be selected from the following compounds, but is not limited thereto.
본 발명에 기재된 본 발명에 기재된 「알킬」, 「알콕시」 및 그 외 「알킬」부분을 포함하는 치환체는 직쇄 또는 분쇄 형태를 모두 포함한다. 또한 본 발명에 기재된 「아릴」은 하나의 수소 제거에 의해서 방향족 탄화수소로부터 유도된 유기 라디칼로, 각 고리에 적절하게는 4 내지 7개, 바람직하게는 5 또는 6개의 고리원자를 포함하는 단일 또는 융합고리계를 포함하며, 다수개의 아릴이 단일결합으로 연결되어 있는 형태까지 포함한다. 구체적인 예로 페닐, 나프틸, 비페닐, 안트릴, 인데닐(indenyl), 플루오레닐 등을 포함하지만, 이에 한정되지 않는다. The substituents including the "alkyl", "alkoxy" and other "alkyl" moieties described in the present invention described in the present invention include both linear and branched forms. The term " aryl " in the present invention means an organic radical derived from an aromatic hydrocarbon by the removal of one hydrogen, and may be a single or fused ring containing 4 to 7, preferably 5 or 6 ring atoms, A ring system, and a form in which a plurality of aryls are connected by a single bond. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, indenyl, fluorenyl, and the like.
본 발명에 기재된 「헤테로아릴」은 방향족 고리 골격 원자로서 B, N, O, S, P(=O), Si 및 P로부터 선택되는 1 내지 4개의 헤테로원자를 포함하고, 나머지 방향족 고리 골격 원자가 탄소인 아릴 그룹을 의미하는 것으로, 5 내지 6원 단환 헤테로아릴, 및 하나 이상의 벤젠환과 축합된 다환식 헤테로아릴이며, 부분적으로 포화될 수도 있다. 또한, 본 발명에서의 헤테로아릴은 하나 이상의 헤테로아릴이 단일결합으로 연결된 형태도 포함한다. "Heteroaryl" in the present invention includes 1 to 4 heteroatoms selected from B, N, O, S, P (= O), Si and P as aromatic ring skeletal atoms and the remaining aromatic ring skeletal atoms are carbon Means a 5 to 6 membered monocyclic heteroaryl and a polycyclic heteroaryl condensed with at least one benzene ring and may be partially saturated. The heteroaryl in the present invention also includes a form in which one or more heteroaryl is connected to a single bond.
본 발명에 기재된 「알케닐」은 2 내지 12개의 탄소 원자 및 1개 이상의 탄소 대 탄소 이중 결합을 함유하는 직쇄, 분지쇄 또는 사이클릭 탄화수소 라디칼을 의미한다.&Quot; Alkenyl " as used in the present invention means a straight, branched or cyclic hydrocarbon radical containing from 2 to 12 carbon atoms and at least one carbon to carbon double bond.
상기에 기재된 단독으로 또는 또다른 기의 일부분으로서 기재된 「시클로알킬」은 3 내지 9개의 탄소 원자의 완전히 포화 및 부분적으로 불포화된 탄화수소 고리를 의미하며, 아릴 또는 헤테로아릴이 융합되어 있는 경우도 포함하며, 일례로 본 발명의 
상기에 기재된「헤테로시클로알킬」은 헤테로원자로서 고리 내에 산소, 황 또는 질소를 포함하는 완전히 포화 및 부분적으로 불포화된 탄화수소 고리를 의미하며, 헤테로원자의 개수는 1-4이며, 바람직하게는 1-2이다. 헤테로시클로알킬에서 시클로알킬은 바람직하게는 모노시클로알킬 또는 비시클로알킬이며, 방향족고리리인 아릴 또는 헤테로아릴이 융합되어 있는 경우도 포함하며, 이중결합 또는 삼중결합으로 연결되어 있는 경우도 포함된다."Heterocycloalkyl" as described above means a fully saturated and partially unsaturated hydrocarbon ring containing oxygen, sulfur or nitrogen in the ring as a hetero atom, and the number of heteroatoms is 1-4, preferably 1- 2. Cycloalkyl in heterocycloalkyl is preferably monocycloalkyl or bicycloalkyl, including those in which an aromatic cyclic aryl or heteroaryl is fused and also includes a double bond or a triple bond.
본 발명의 일 실시예에 따른 이리듐 촉매는 [IrCp*Cl2]2, [IrCl(COD)]2 (Chloro-1,5-cyclooctadiene iridium(I) dimer), Ir(acac)3(Ir(acetylacetonate)3)(Iridium(III)acetylacetonate), [Ir(OMe)(COD)]2(1,5-Cyclooctadiene)(methoxy)iridium(I) dimer), IrCl(CO)(PPh3)2 (Bis(triphenylphosphine)iridium(I) carbonyl chloride)및 IrCl3(Iridium(III) chloride)에서 선택되는 어느 하나이상일 수 있으며, 반응효율측면에서 바람직하게 [IrCp*Cl2]2, [IrCl(COD)]2 및 [Ir(OMe)(COD)]2에서 선택되는 어느 하나이상일 수 있다.Iridium catalyst in accordance with one embodiment of the present invention [IrCp * Cl 2] 2, [IrCl (COD)] 2 (Chloro-1,5-cyclooctadiene iridium (I) dimer), Ir (acac) 3 (Ir (acetylacetonate ) 3 ) (Iridium (III) acetylacetonate), [Ir (OMe) (COD)] 2 (1,5-Cyclooctadiene) (methoxy) iridium IrCl (CO) (PPh 3) 2 (Bis (triphenylphosphine) iridium (I) carbonyl chloride) and IrCl 3 (Iridium (III) chloride ) preferably in the reaction efficiency, side, and be at least one selected from [IrCp * Cl 2 ] 2 , [IrCl (COD)] 2 and [Ir (OMe) (COD)] 2 .
본 발명의 일 실시예에 따른 이리듐 촉매는 상기 화학식 3 또는 화학식 5의 화합물 1몰에 대하여 0.01 내지 0.5 몰, 바람직하게는 0.02 내지 0.1 몰로 사용될 수 있다.The iridium catalyst according to an embodiment of the present invention may be used in an amount of 0.01 to 0.5 mole, preferably 0.02 to 0.1 mole per mole of the compound of Formula 3 or Formula 5. [
본 발명의 일 실시예에 따른 상기 반응은 은 촉매를 더 포함하여 수행될 수 있으며, 은 촉매의 구체적인 일례로 AgNTf2, AgSbF6, AgPF6, AgBF4, Ag2O 또는 이들의 혼합촉매를 들 수 있으나, 이에 한정이 있는 것은 아니다.The reaction according to an embodiment of the present invention may be performed by further comprising a silver catalyst, and examples of the silver catalyst include AgNTf 2 , AgSbF 6 , AgPF 6 , AgBF 4 , Ag 2 O, But is not limited thereto.
본 발명의 일 실시예에 따른 은 촉매는 반응효율면에서 바람직하게는 AgNTf2, AgSbF6, AgPF6 및 AgBF4 에서 선택되는 어느 하나이상일 수 있으며, 상기 화학식 3 또는 화학식 5의 화합물 1몰에 대하여 0.04 내지 2 몰로 사용될 수 있으며, 바람직하게는 0.08 내지 0.16 몰일 수 있다.The silver catalyst according to one embodiment of the present invention is preferably at least one selected from AgNTf 2 , AgSbF 6 , AgPF 6 and AgBF 4 in view of the reaction efficiency, May be used in an amount of 0.04 to 2 moles, preferably 0.08 to 0.16 moles.
본 발명의 산은 아세트산, 피발릭산, 벤조산 및 술폰산에서 선택되는 어느 하나 이상일 수 있으며, 바람직하게는 아세트산, 피발릭산, 벤조산 또는 이들의 혼합산일 수 있으며, 상기 화학식 3 또는 화학식 5의 화합물 1몰에 대해 0.1 내지 3 몰, 바람직하게는 0.2 내지 1 몰로 사용될 수 있다.The acid of the present invention may be at least one selected from acetic acid, pivalic acid, benzoic acid and sulfonic acid, preferably acetic acid, pivalic acid, benzoic acid or a mixed acid thereof. 0.1 to 3 moles, preferably 0.2 to 1 mole.
본 발명에 사용된 퀴놀린 N-옥사이드 유도체와 아지드 화합물은 통상적인 유기합성분야에서 사용되는 방법을 사용하여 제조될 수 있음은 물론이다.It is a matter of course that the quinoline N-oxide derivative and the azide compound used in the present invention can be produced by a method used in the field of ordinary organic synthesis.
본 발명의 일 실시예에 따른 상기 화학식 4의 아지드 화합물은 상기 화학식 3 또는 5로 표시되는 퀴놀린 N-옥사이드 1몰에 대하여 1.1 내지 2몰이 사용될 수 있다.The azide compound of Formula 4 according to an embodiment of the present invention may be used in an amount of 1.1 to 2 moles per mole of the quinoline N-oxide represented by Formula 3 or 5.
본 발명의 일 실시예에 따른 반응은 유기 용매 하에서 이루어 질 수 있으며, 상기 반응물질을 용해할 수 있는 것이라면 유기용매에 제한을 둘 필요는 없다. 상기 유기용매의 일례로는 다이옥산, 테트라하이드로퓨란, 다이메틸포름아마이드, 다이클로로메탄, 다이클로로에탄, 벤젠, 톨루엔 및 이들의 혼합물로 이루어진 군에서 선택되며 반응물의 용해성 및 제거의 용이성 또한 반응 효율면을 고려할 때 클로로포름을 사용하는 것이 더욱 바람직하다.The reaction according to an embodiment of the present invention can be carried out in an organic solvent, and it is not necessary to limit the organic solvent as long as it can dissolve the reactant. Examples of the organic solvent include organic solvents selected from the group consisting of dioxane, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, benzene, toluene, and mixtures thereof, It is more preferable to use chloroform.
반응온도는 30 내지 100℃ 범위에서 수행하며, 50 내지 80℃ 범위에서 수행하는 것이 바람직하다. 반응시간은 4시간 내지 24시간, 바람직하게는 8시간 내지 15시간 동안 반응하는 것이 유리하다. 이는 반응시간이 지나치게 길어지거나 부산물이 발생하여 반응 수율이 저하될 수 있기 때문이다.The reaction is carried out at a temperature ranging from 30 to 100 ° C, preferably from 50 to 80 ° C. The reaction time is advantageously from 4 hours to 24 hours, preferably from 8 hours to 15 hours. This is because the reaction time may become excessively long or by-products may occur and the reaction yield may be lowered.
본 발명의 일 실시예에 따른 반응은 TLC 등을 통하여 출발물질인 화학식 3 또는 화학식 5의 퀴놀린 N-옥사이드가 모두 소모되었음을 확인 후 반응을 완결시키도록 한다. 반응이 완결되면 감압 하에서 용매를 증류시킨 후, 관 크로마토그래피 등의 통상의 방법을 통하여 목적물을 분리 정제할 수 있다.The reaction according to an embodiment of the present invention is accomplished by confirming that the starting quinoline N-oxide of formula (3) or (5) is exhausted through TLC or the like. When the reaction is completed, the solvent can be distilled off under reduced pressure, and the desired product can be separated and purified through a conventional method such as column chromatography.
또한 본 발명은 본 발명의 제조방법에 따라 제조된 상기 화학식 1 또는 화학식 2로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체를 제공한다.The present invention also provides a quinoline N-oxide derivative to which an amide functional group is introduced, which is represented by the above formula (1) or (2), prepared according to the production method of the present invention.
바람직하게는 본 발명의 상기 화학식 1로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체는 상기 화학식 6 내지 9로 표시될 수 있다.Preferably, the quinoline N-oxide derivative having the amide functional group represented by the formula (1) of the present invention may be represented by the above formulas (6) to (9).
본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체는 하기 구조식에서 선택될 수 있으나, 이에 한정이 있는 것은 아니다.The quinoline N-oxide derivative to which the amide functional group of the present invention is introduced may be selected from the following structural formulas, but is not limited thereto.
본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체는 의약 산업등의 다양한 분야의 원료물질 또는 중간체로 매우 유용하게 사용가능하다.The quinoline N-oxide derivative to which the amide functional group of the present invention is introduced can be very useful as a raw material or an intermediate in various fields such as the pharmaceutical industry.
본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법은 종래의 방법과는 달리 C-2자리가 아니라 위치선택적으로 C-8자리에 아미드 작용기를 도입할 수 있다.Unlike the conventional method, the amide functional group-introduced quinoline N-oxide derivative of the present invention can introduce an amide functional group at the C-8 position in place of the C-2 position.
또한 본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법은 간단한 공정과 온화한 조건으로 C-8자리에 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체를 높은 수율로 얻을 수 있는 매우 효과적인 방법이다.Also, the process for preparing the quinoline N-oxide derivative having the amide functional group of the present invention is a very effective method for obtaining a quinoline N-oxide derivative having an amide functional group introduced at the C-8 position in a simple process and a mild condition at a high yield .
또한 본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법은 용이하게 위치선택적으로 C-8위치에 아미드 작용기를 도입할 수 있어 다양한 분야의 중간체 합성에 매우 유용하게 적용할 수 있다.In addition, the process for preparing the quinoline N-oxide derivative to which the amide functional group is introduced according to the present invention can easily and selectively introduce the amide functional group at the C-8 position, and thus can be very usefully applied to the synthesis of intermediates in various fields.
본 발명의 제조방법에 따라 제조된 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체 또한 천연물 기본골격으로 사용될 뿐만 아니라 신약 및 다양한 의약품등의 개발에 유용하게 사용가능하다.The quinoline N-oxide derivative having an amide functional group prepared according to the production method of the present invention can be used not only as a natural skeleton but also in the development of new drugs and various medicines.
이하, 실시예를 통하여 본 발명의 구성을 보다 구체적으로 설명하지만, 하기의 실시예들은 본 발명에 대한 이해를 돕기 위한 것으로서, 본 발명의 범위가 여기에 국한된 것은 아니다.
Hereinafter, the structure of the present invention will be described in more detail with reference to examples. However, the following examples are provided to aid understanding of the present invention, and the scope of the present invention is not limited thereto.
[제조예 1] 아지드 화합물의 제조[Preparation Example 1] Preparation of azide compound
10 mL의 증류수에 30.0 mmol의 NaN3를 녹인 후 0℃로 온도를 낮추어 20 mL의 아세톤에 녹아 있는 20.0 mmol의 sulfonyl chloride(
After dissolving 30.0 mmol of NaN 3 in 10 mL of distilled water, the temperature was lowered to 0 ° C, and 20.0 mmol of sulfonyl chloride dissolved in 20 mL of acetone
[제조예 2] 아지드 화합물의 제조[Preparation Example 2] Preparation of azide compound
2.5mL 의 아세톤에 5.0 mmol의 4-nitrobenzoyl chloride를 녹인 후 2.5 mL의 증류수에 녹아 있는 8.1 mmol의 sodium azide를 0℃에서 천천히 넣어 주었다. 고체 침전물이 즉시 생성되었고, 30분 동안 상온에서 교반한 뒤 2.5 mL의 증류수를 더 넣어준 후 30분동안 더 교반하였다. 생성된 고체를 모아 건조시켜 무색 고체인 4-nitrobenzoyl azide를 90%의 수율로 얻었다.
After dissolving 5.0 mmol of 4-nitrobenzoyl chloride in 2.5 mL of acetone, 8.1 mmol of sodium azide dissolved in 2.5 mL of distilled water was added slowly at 0 ° C. A solid precipitate was formed immediately, stirred for 30 minutes at room temperature, then added 2.5 mL of distilled water, and then stirred for an additional 30 minutes. The resulting solid was collected and dried to give 4-nitrobenzoyl azide as a colorless solid in 90% yield.
[제조예 3] 퀴놀린 화합물의 제조[Preparation Example 3] Preparation of quinoline compound
3 mL의 THF에 녹아 있는 2.5 mmol의 6-aminoquinoline에 2.67 mL의 1.9 M NaHMDS(Sodium Hexamethyldisilazide)의 THF 용액을 상온에서 넣어주고 30분동안 교반시켰다. 교반 후 2 mL의 THF에 녹아 있는 5.0 mmol의 di-tert-butyl dicarbonate 를 상온에서 첨가하였고 상온에서 12시간동안 더 교반시켰다. 교반 후 10 mL의 물을 넣어 반응을 종료시켰고 50 mL의 NaHCO3의 포화 수용액을 넣어 주었다. 수용액 층을 ethyl acetate로 20 mL씩 3회 추출하였고 MgSO4로 건조시킨 뒤 고체를 걸러낸 후 유기 용매를 감압 건조기로 제거하였다. 반응 혼합물을 실리카겔 관 크로마토그라피로 정제하여 (EtOAc/n-hexane, 2:1) 백색 고체의 6-[bis(tert-butoxycarbonyl)amino]quinoline 을 34%의 수율로 얻었다.2.67 mL of THF solution of 1.9 M NaHMDS (sodium hexamethyldisilazide) was added to 2.5 mmol of 6-aminoquinoline dissolved in 3 mL of THF at room temperature and stirred for 30 minutes. After stirring, 5.0 mmol of di-tert-butyl dicarbonate dissolved in 2 mL of THF was added at room temperature and further stirred at room temperature for 12 hours. After stirring, 10 mL of water was added to complete the reaction, and 50 mL of a saturated aqueous solution of NaHCO 3 was added. The aqueous layer was extracted three times with ethyl acetate (20 mL each), dried over MgSO 4 , filtered, and the organic solvent was removed by vacuum drying. The reaction mixture was purified by silica gel column chromatography (EtOAc / n- hexane, 2: 1) to give 6- [bis ( tert- butoxycarbonyl) amino] quinoline as white solid in 34% yield.
m.p. 148~149 ℃m.p. 148 ~ 149 ℃
1H NMR (600 MHz, CDCl3) δ 8.93 (dd, J = 4.2, 1.7 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.9 Hz, 1H), 7.61 (d, J = 2.3 Hz, 1H), 7.50 (dd, J = 9.0, 2.3 Hz, 1H), 7.42 (dd, J = 8.3, 4.2 Hz, 1H), 1.42 (s, 18H) 1 H NMR (600 MHz, CDCl 3) δ 8.93 (dd, J = 4.2, 1.7 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.9 Hz, 1H), 7.61 (d, J = 2.3 Hz, 1H), 7.50 (dd, J = 9.0, 2.3 Hz, 1H), 7.42 (dd, J = 8.3, 4.2 Hz, 1H), 1.42 (s, 18H)
13C NMR (150 MHz, CDCl3) δ 151.7, 150.8, 147.2, 137.3, 136.0, 130.1, 130.0, 128.1, 126.0, 121.3, 83.1, 27.9; 13 C NMR (150 MHz, CDCl 3) δ 151.7, 150.8, 147.2, 137.3, 136.0, 130.1, 130.0, 128.1, 126.0, 121.3, 83.1, 27.9;
IR (diamond) 2979, 2934, 1748, 1712, 1367, 1273, 1249, 1151, 1097, 858IR (diamond) 2979, 2934, 1748, 1712, 1367, 1273, 1249, 1151, 1097, 858
HRMS (EI) m/z calcd. for C19H24N2O4 [M]+: 344.1736, found: 344.1738.
HRMS (EI) m / z calcd. for C 19 H 24 N 2 O 4 [M] +: 344.1736, found: 344.1738.
[제조예 4] 퀴놀린 화합물의 제조[Preparation Example 4] Preparation of quinoline compound
10 mL의 dimethylformamide에 녹아 있는 1.5 mmol의 5-hydroxyquinoline에 3.75 당량의 imidazole과 1.5 당량의 triisopropylsilyyl chlloride를 넣어 주고 상온에서 24시간동안 교반시켰다. 교반 후 20 mL의 증류수를 넣어주었고, 20 mL의 dichloromethane으로 3회 추출한 후 MgSO4로 건조시키고 나서 고체를 걸러낸 후 유기 용매를 감압 건조기로 제거하였다. 얻어진 반응 혼합물을 실리카겔 관 크로마토그래피로 정제하여 (EtOAc/n-hexane, 1:5) 무색 액체의 5-(triisopropylsilyloxy)quinoline을 90%의 수율로 얻었다. 3.75 equivalents of imidazole and 1.5 equivalents of triisopropylsilyyl chloranide were added to 1.5 mmol of 5-hydroxyquinoline dissolved in 10 mL of dimethylformamide and stirred at room temperature for 24 hours. After stirring, 20 mL of distilled water was added, and the mixture was extracted three times with 20 mL of dichloromethane, dried over MgSO 4 , filtered, and the organic solvent was removed by vacuum drying. The resulting reaction mixture was purified by silica gel column chromatography (EtOAc / n- hexane, 1: 5) to give a colorless liquid 5- (triisopropylsilyloxy) quinoline in 90% yield.
1H NMR (600 MHz, CDCl3) δ 8.93 - 8.86 (m, 1H), 8.58 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.42-7.33 (m, 1H), 6.92 (d, J = 7.6 Hz, 1H), 1.46-1.36 (m, 3H), 1.15 (d, J = 7.6 Hz, 18H) 1 H NMR (600 MHz, CDCl 3) δ 8.93 - 8.86 (m, 1H), 8.58 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.54 (t, J = J = 7.6 Hz, 1H), 1.46-1.36 (m, 3H), 1.15 (d, J = 7.6 Hz,
13C NMR (150 MHz, CDCl3) δ 151.8, 150.5, 149.5, 131.3, 129.3, 122.9, 122.0, 120.2, 112.2, 18.0, 13.0; IR (diamond) 2943, 2865, 1466, 1393, 1269, 1085, 915, 881, 795, 676 cm-1 13 C NMR (150 MHz, CDCl 3) δ 151.8, 150.5, 149.5, 131.3, 129.3, 122.9, 122.0, 120.2, 112.2, 18.0, 13.0; IR (diamond) 2943, 2865, 1466, 1393, 1269, 1085, 915, 881, 795, 676 cm -1
HRMS (EI) m/z calcd. for C18H27NOSi [M]+: 301.1862, found: 301.1864
HRMS (EI) m / z calcd. for C 18 H 27 NOSi [M ] +: 301.1862, found: 301.1864
[제조예 5] 퀴놀린 화합물의 제조[Preparation Example 5] Preparation of quinoline compound
5 mL의 dichloromethane에 녹아 있는 2.0 mmol의 4-quinolinol에 2.2 mmol의 benzoyl chloride를 상온에서 첨가한 후 3 시간동안 교반시켰다. 교반 후 5 mL의 증류수를 넣어 반응을 종료시켰고, 30 mL의 포화 NaHCO3 수용액에 넣었다. 수용액 층을 30 mL의 dichloromethane으로 3회 추출하였고 MgSO4로 건조시킨 뒤 고체를 걸러낸 후 유기 용매를 감압 건조기로 제거하였다. 얻어진 4-(benzyloxy)quinoline은 더 이상의 정제 없이 해당하는 N-oxide를 만드는 데 사용되었다.
2.2 mmol of benzoyl chloride was added to 2.0 mmol of 4-quinolinol dissolved in 5 mL of dichloromethane at room temperature, followed by stirring for 3 hours. After stirring, 5 mL of distilled water was added to terminate the reaction, and the solution was added to 30 mL of a saturated aqueous solution of NaHCO 3 . The aqueous layer was extracted three times with 30 mL of dichloromethane, dried over MgSO 4 , filtered, and the organic solvent was removed by vacuum drying. The resulting 4- (benzyloxy) quinoline was used to make the corresponding N-oxide without further purification.
[제조예 6] 퀴놀린 화합물의 제조[Preparation Example 6] Preparation of quinoline compound
Dean-Stark 증류기가 장착된 two-neck round bottom flask에 4.0 mmol의 3-quinolinecarboxaldehyde 와 0.4 mmol의 p-toluenesulfonic acid monohydrate 를 넣어준 후 40 mL의 벤젠과 8.0 mmol의 ethylene glycol을 넣어주었다. TLC로 확인하여 반응이 완료될 때까지 환류시킨 후 상온으로 식힌 다음 감압 증류기로 유기 용매를 제거하였다. 반응 혼합물을 포화 NaHCO3 수용액에 넣은 뒤 수용액 층을 20 mL의 dichloromethane으로 3회 추출한 후 MgSO4로 건조시킨 다음 고체를 걸러내었다. 유기 용매를 감압 건조기로 제거하여 얻어진 반응 혼합물을 실리카겔 관 크로마토그래피로 정제하여 (EtOAc/n-hexane, 1:4) 백색 고체의 3-(1,3-Dioxolan-2-yl)quinoline을 91%의 수율로 얻었다.4.0 mmol of 3-quinolinecarboxaldehyde and 0.4 mmol of p- toluenesulfonic acid monohydrate were added to a two-neck round bottom flask equipped with a Dean-Stark distiller and 40 mL of benzene and 8.0 mmol of ethylene glycol were added. After confirming with TLC and refluxing until the reaction was completed, the reaction mixture was cooled to room temperature and the organic solvent was removed with a vacuum distillation apparatus. The reaction mixture was poured into a saturated aqueous solution of NaHCO 3 , and the aqueous layer was extracted three times with 20 mL of dichloromethane, dried over MgSO 4 , and filtered. The reaction mixture was purified by silica gel column chromatography (EtOAc / n- hexane, 1: 4) to yield 91% of 3- (1,3-dioxolan-2-yl) quinoline as a white solid. . ≪ / RTI >
[제조예 7] 퀴놀린 화합물의 제조[Preparation Example 7] Preparation of quinoline compound
5 mL의 메탄올에 녹아 있는 2.0 mmol의 6-quinolinecarboxylic acid에 6.0 mmol의 thionyl chloride를 0℃에서 천천히 넣어 준 후 50℃에서 12 시간 동안 교반시켰다. 30 mL의 포화 NaHCO3 수용액을 넣어 반응을 종료시킨 후 수용액 층을 30 mL의 dichloromethane으로 3회 추출하였다. MgSO4로 건조시킨 뒤 고체를 걸러낸 후 유기 용매를 감압 건조기로 제거하여 백색 고체의 6-(methoxycarbonyl)quinoliine을 98 %의 수율로 얻었다.6.0 mmol of thionyl chloride was slowly added to 2.0 mmol of 6-quinolinecarboxylic acid dissolved in 5 mL of methanol at 0 ° C, followed by stirring at 50 ° C for 12 hours. 30 mL of a saturated aqueous solution of NaHCO 3 was added to terminate the reaction, and the aqueous layer was extracted three times with 30 mL of dichloromethane. After drying with MgSO 4 , the solid was filtered off and the organic solvent was removed in a vacuum dryer to obtain a white solid, 6- (methoxycarbonyl) quinoliine, in a yield of 98%.
[제조예 8] 퀴놀린 화합물의 제조[Preparation Example 8] Preparation of quinoline compound
25 mL의 톨루엔에 녹아 있는 5.0 mmol의 2-chloroquinoline, 7.5 mmol의 naphthalen-1-ylboronic acid, 0.25 mmol의 tetrakis(triphenylphosphine)palladium 에 5 mL의 2.0 M sodium carbonate 수용액을 넣어준 후 80℃에서 24 시간 동안 교반시켰다. 교반 후 반응 혼합물을 상온으로 식힌 후 셀라이트와 실리카에 통과시키고 나서 20 mL의 ethyl acetate로 3회 추출하였다. MgSO4로 건조시킨 뒤 고체를 걸러낸 후 유기 용매를 감압 건조기로 제거하였다. 반응 혼합물을 실리카겔 관 크로마토그라피로 정제하여 (n-hexane/EtOAc, 3:1, R f = 0.5) 2-(naphthalen-1-yl)quinoline을 76%의 수율로 얻었다.
5 mL of 2.0 M sodium carbonate aqueous solution was added to 5.0 mmol of 2-chloroquinoline, 7.5 mmol of naphthalen-1-ylboronic acid and 0.25 mmol of tetrakis (triphenylphosphine) palladium dissolved in 25 mL of toluene, ≪ / RTI > After stirring, the reaction mixture was cooled to room temperature, passed through celite and silica, and then extracted three times with 20 mL of ethyl acetate. After drying with MgSO 4 , the solid was filtered off and the organic solvent was removed by vacuum drying. The reaction mixture was purified by a silica gel tube chromatography (n- hexane / EtOAc, 3: 1, R f = 0.5) to give the 2- (naphthalen-1-yl) quinoline in 76% yield.
퀴놀린 N-옥사이드 유도체의 일반적인 제조General Preparation of Quinoline N-oxide Derivatives
5 mL의 클로로포름에 녹아 있는 3.0 mmol의 quinoline에 2.5 당량의 m-Chloroperoxybenzoic acid(Mcpba)를 넣은 뒤 4 시간 동안 환류시켰다. 반응 혼합물을 상온으로 식힌 후 포화 NaHCO3 수용액을 넣어 주었다. 수용액 층을 10 mL의 dichloromethane으로 3회 추출한 후 유기 용매를 감압 건조기로 제거한 후 실리카겔 관 크로마토그라피로 정제하여 N-oxide들을 얻었다.2.5 equivalents of m- Chloroperoxybenzoic acid (Mcpba) was added to 3.0 mmol of quinoline dissolved in 5 mL of chloroform and refluxed for 4 hours. The reaction mixture was cooled to room temperature and saturated aqueous NaHCO 3 solution was added thereto. The aqueous layer was extracted three times with 10 mL of dichloromethane, the organic solvent was removed with a vacuum dryer, and purified by silica gel column chromatography to obtain N- oxides.
상기와 같은 방법으로 제조된 퀴놀린 N-옥사이드는 하기와 같다.
The quinoline N-oxides prepared by the above process are as follows.
[제조예 9] 6-Bromo-2-methylquinoline N-oxide (1i) 의 제조[Preparation Example 9] Preparation of 6-Bromo-2-methylquinoline N- oxide (1i)
[제조예 10] 3-(1,3-Dioxolan-2-yl)quinoline N-oxide (1m) 의 제조[Production Example 10] Preparation of 3- (1,3-Dioxolan-2-yl) quinoline N- oxide (1m)
[제조예 11] 5-(Triisopropylsilyloxy)quinoline N-oxide (1o) 의 제조[Preparation Example 11] Preparation of 5- (Triisopropylsilyloxy) quinoline N- oxide (1o)
[제조예 12] 6-[Bis(tert-butoxycarbonyl)amino]quinoline N-oxide (1p)의 제조[Preparation Example 12] Preparation of 6- [Bis ( tert- butoxycarbonyl) amino] quinoline N- oxide (1p)
[제조예 13] 3-Formylquinoline N-oxide( 1q) 의 제조[Preparation Example 13] Preparation of 3-Formylquinoline N- oxide (1q)
3 mL의 tetrahydrofuran에 녹아 있는 0.7 mmol의 3-(1,3-dioxolan-2-yl)quinoline N-oxide에 1.5 mL의 37 wt % formaldehyde 수용액과 0.7 mmol의 p-toluenesulfonic acid monohydrate(p-TSA)를 넣어준 후 상온에서 36시간 동안 교반시켰다. 교반 후 20 mL의 포화 NaHCO3 수용액으로 반응을 종료시킨 후 수용액 층을 20 mL의 dichloromethane으로 3회 추출한 다음 MgSO4로 건조시킨 후 감압 건조기로 유기 용매를 제거하였다. 얻어진 혼합물을 실리카겔 관 크로마토그라피로 정제하여 (EtOAc/n-hexane, 3:1) 노란색 고체의 3-formylquinoline N-oxide를 80%의 수율로 얻었다.1.5 mL of a 37 wt% formaldehyde aqueous solution and 0.7 mmol of p- toluenesulfonic acid monohydrate (p-TSA) were added to 0.7 mmol of 3- (1,3-dioxolan-2-yl) quinoline N- oxide dissolved in 3 mL of tetrahydrofuran, And the mixture was stirred at room temperature for 36 hours. After stirring, 20 mL of saturated NaHCO 3 solution was added to the reaction mixture. The aqueous layer was extracted three times with 20 mL of dichloromethane, dried over MgSO 4, and then the organic solvent was removed using a reduced pressure drier. The resulting mixture was purified by silica gel column chromatography (EtOAc / n- hexane, 3: 1) to give the yellow solid 3-formylquinoline N- oxide in 80% yield.
m.p. 205~206 oCmp 205-206 o C
1H NMR (600 MHz, CDCl3) δ 10.09 (s, 1H), 8.92 (s, 1H), 8.80 (d, J = 8.7 Hz, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.93 (t, J = 7.9 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H) 1 H NMR (600 MHz, CDCl 3) δ 10.09 (s, 1H), 8.92 (s, 1H), 8.80 (d, J = 8.7 Hz, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.93 (t, J = 7.9 Hz, 1H), 7.78 (t, J = 7.6 Hz,
13C NMR (150 MHz, CDCl3) δ 188.1, 143.9, 133.2, 132.9, 130.1, 129.9, 129.9, 129.3, 129.1, 120.3; IR (diamond) 3008, 2861, 1692, 1576, 1357, 1331, 1219, 993, 775, 573 cm-1 13 C NMR (150 MHz, CDCl 3) δ 188.1, 143.9, 133.2, 132.9, 130.1, 129.9, 129.9, 129.3, 129.1, 120.3; IR (diamond) 3008, 2861, 1692, 1576, 1357, 1331, 1219, 993, 775, 573 cm -1
HRMS (EI) m/z calcd. for C10H7NO2 [M]+: 173.0477, found: 173.0476.
HRMS (EI) m / z calcd. for C 10 H 7 NO 2 [ M] +: 173.0477, found: 173.0476.
[제조예 13] benzo[c]cinnoline N-oxide (6e)의 제조[Preparation Example 13] Preparation of benzo [ c ] cinnoline N- oxide (6e)
25 mL의 40% NaOH 수용액과 1.0 mmol의 2,2'-dinitrobiphenyl의 혼합물에 1.2 mmol의 acetophenone을 넣은 후 155 ℃에서 4 시간 30 분 동안 환류시켰다. 환류 후 반응 혼합물을 상온으로 식힌 후 100 mL의 증류수와 50 mL의 ethyl acetate로 천천히 묽힌 다음 셀라이트에 통과시켜 검은색 고체를 제거하였다. 얻어진 혼합물을 20 mL의 ethyl acetate로 3회 추출한 뒤 Na2SO4로 건조시키고 고체를 걸러낸 다음 감압 건조기로 유기 용매를 제거하였다. 얻어진 혼합물을 실리카겔 관 크로마토그라피로 정제하여 (CH2Cl2/acetone, 30:1, Rf = 0.5) 백색 고체의 benzo[c]cinnoline N-oxide를 95%의 수율로 얻었다.
1.2 mmol of acetophenone was added to a mixture of 25 mL of 40% NaOH aqueous solution and 1.0 mmol of 2,2'-dinitrobiphenyl, and the mixture was refluxed at 155 ° C for 4 hours and 30 minutes. After refluxing, the reaction mixture was cooled to room temperature, diluted slowly with 100 mL of distilled water and 50 mL of ethyl acetate, and then passed through a celite to remove the black solid. The resulting mixture was extracted three times with 20 mL of ethyl acetate, dried over Na 2 SO 4 , filtered and the organic solvent was removed using a vacuum dryer. The resulting mixture was purified by silica gel column chromatography (CH2Cl2 / acetone, 30: 1, Rf = 0.5) to give benzo [ c ] cinnoline N- oxide as a white solid in a yield of 95%.
[실시예] 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법EXAMPLES Preparation of Quinoline N-oxide Derivatives Having Amide Functional Groups
1 mL 리액션 바이알에 0.2 mmol의 quinolone N-oxide, 0.22 mmol의 azide, 0.004 mmol의 [IrCp*Cl2]2, 0.016 mmol의 AgNTf2, 0.06 mmol의 AcOH, 0.5 mL의 1,2-dichloroethane을 넣은 후 50 ℃에서 12 시간동안 교반시켰다. 교반 후 셀라이트에 통과시키고 10 mL의 dichloromethane으로 3회 씻어준 후 유기 용매를 감압 건조기로 제거하였다. 얻어진 반응 혼합물을 실리카겔 관 크로마토그라피로 정제하여 생성물을 얻었다.To a 1 mL reaction vial was added 0.2 mmol of quinolone N- oxide, 0.22 mmol of azide, 0.004 mmol of [IrCp * Cl 2 ] 2 , 0.016 mmol of AgNTf 2 , 0.06 mmol of AcOH and 0.5 mL of 1,2-dichloroethane Followed by stirring at 50 ° C for 12 hours. After stirring, the mixture was passed through celite, washed with 10 mL of dichloromethane three times, and then the organic solvent was removed by vacuum drying. The obtained reaction mixture was purified by silica gel column chromatography to obtain a product.
위와 동일한 방법으로 하기의 아미드 작용기가 도입된 퀴놀린 N-옥사이드를 제조하였다.In the same manner as above, quinoline N-oxide having the following amide functional group introduced therein was prepared.
[실시예 1] 8-(4-Methylphenylsulfonamido)quinoline N-oxide (3a)의 제조 [Example 1] Preparation of 8- (4-Methylphenylsulfonamido) quinoline N- oxide (3a)
[실시예 2] 6-Methyl-8-(4-methylphenylsulfonamido)quinoline N-oxide (3b)의 제조 Example 2 Preparation of 6-Methyl-8- (4-methylphenylsulfonamido) quinoline N- oxide (3b)
[실시예 3] 2,6-Dimethyl-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3c)의 제조 [Example 3] Preparation of 2,6-Dimethyl-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3c )
[실시예 4] 3-Methyl-8-(4-methylphenylsulfonamido)quinoline N- oxide (3d)의 제조 Example 4 Preparation of 3-Methyl-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3d )
[실시예 5] 5-Chloro-8-(4-methylphenylsulfonamido)quinoline N- oxide (3e) 의 제조 Example 5 Preparation of 5-Chloro-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3e )
[실시예 6] 6-Chloro-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3f) 의 제조 [Example 6] Preparation of 6-Chloro-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3f )
[실시예 7] 4-Chloro-8-(4-methylphenylsulfonamido)quinoline N- oxide (3g)의 제조 [Example 7] Preparation of 4-Chloro-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3 g )
[실시예 8] 6-Bromo-8-(4-methylphenylsulfonamido)quinoline N- oxide (3h)의 제조 Example 8 Preparation of 6-Bromo-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3h )
[ 실시예 9] 6- Bromo -2- methyl -8-(4- methylphenylsulfonamido ) quinoline N- oxide (3i)의 제조 [ Example 9] 6- Bromo -2- methyl -8- (4- methylphenylsulfonamido ) quinoline N- oxide ( 3i )
[실시예 10] 8-(4-Methylphenylsulfonamido)-5-nitroquinoline N- oxide (3j)의 제조 [Example 10] Preparation of 8- (4-Methylphenylsulfonamido) -5-nitroquinoline N- oxide ( 3j )
[실시예 11] 6-(Methoxycarbonyl)-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3k)의 제조 [Example 11] Preparation of 6- (Methoxycarbonyl) -8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3k )
[실시예 12] 4-(Benzoyloxy)-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3l)의 제조 [Example 12] Preparation of 4- (Benzoyloxy) -8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3l )
[실시예 13] 3-(1,3-Dioxolan-2-yl)-8-(4-methylphenylsulfonamido)quinoline N- oxide (3m)의 제조 Example 13 Preparation of 3- (1,3-Dioxolan-2-yl) -8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3m )
[실시예 14]6-Methoxy-8-(4-methylphenylsulfonamido)quinoline N- oxide (3n)의 제조 [Example 14] Preparation of 6-Methoxy-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3n )
[실시예 15] 8-(4-Methylphenylsulfonamido)-5-(triisopropylsilyloxy)quinoline N- oxide (3o)의 제조 [Example 15] Preparation of 8- (4-Methylphenylsulfonamido) -5- (triisopropylsilyloxy) quinoline N- oxide ( 3o )
[실시예 16] 6-[Bis( tert- butoxycarbonyl)amino]-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3p)의 제조 [Example 16] Preparation of 6- [Bis ( tert- butoxycarbonyl) amino] -8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3p )
[실시예 17] 3-Formyl-8-(4-methylphenylsulfonamido)quinoline N- oxide ( 3q)의 제조 [Example 17] Preparation of 3-Formyl-8- (4-methylphenylsulfonamido) quinoline N- oxide ( 3q )
[실시예 18] 8-(Methylsulfonamido)quinoline N- oxide (5a)의 제조 [Example 18] Preparation of 8- (Methylsulfonamido) quinoline N- oxide ( 5a )
[실시예 19] 8-(Phenylmethylsulfonamido)quinoline N-oxide ( 5b)의 제조 [Example 19] Preparation of 8- (phenylmethylsulfonamido) quinoline N-oxide ( 5b )
[실시예 20] 8-[(7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methylsulfonamido]quinoline N- oxide (5c)의 제조 Example 20 Preparation of 8 - [(7,7-Dimethyl-2-oxobicyclo [2.2.1] heptan-1-yl) methylsulfonamido] quinoline N- oxide ( 5c )
[실시예 21] 8-(2-Bromophenylsulfonamido)quinoline N- oxide (5d)의 제조 [Example 21] Preparation of 8- (2-Bromophenylsulfonamido) quinoline N- oxide ( 5d )
[실시예 22] 8-(4-Methoxyphenylsulfonamido)quinoline N- oxide (5e)의 제조 [Example 22] Preparation of 8- (4-Methoxyphenylsulfonamido) quinoline N- oxide ( 5e )
[ 실시예 23] 8-( Naphthalene -1- sulfonamido ) quinoline N- oxide (5f)의 제조 [ Example 23] 8- ( Naphthalene -1- sulfonamido ) quinoline N- oxide ( 5f )
[실시예 24] 8-(4-Nitrobenzamido)quinoline N- oxide (5g)의 제조 [Example 24] Preparation of 8- (4-Nitrobenzamido) quinoline N- oxide ( 5 g )
[실시예 25][Example 25] 4-(4-Methylphenylsulfonamido)acridine 10-oxide (7a)의 제조Preparation of 4- (4-Methylphenylsulfonamido) acridine 10-oxide (7a)
[실시예 26][Example 26] 5-(4-Methylphenylsulfonamido)benzo[5- (4-Methylphenylsulfonamido) benzo [ ff ]quinoline 4-oxide (7b)의 제조] quinoline 4-oxide (7b)
[[ 실시예Example 27] 27] 4-(4-4- (4- MethylphenylsulfonamidoMethylphenylsulfonamido )) phenanthridine피탄 히드INE 5- 5- oxideoxide (7c)의 제조 (7c)
[실시예 28][Example 28] 4-(4-Methylphenylsulfonamido)phenazine 5-oxide (7d)의 제조Preparation of 4- (4-Methylphenylsulfonamido) phenazine 5-oxide (7d)
[실시예 29][Example 29] 4-(4-Methylphenylsulfonamido)benzo[4- (4-Methylphenylsulfonamido) benzo [ cc ]cinnoline 5-oxide (7e)의 제조] Preparation of cinnoline 5-oxide (7e)
[[ 실시예Example 30]8,8'- 30] 8,8'- BisBis (4-(4- methylphenylsulfonamidomethylphenylsulfonamido )-2,2'-) -2,2'- biquinolinebiquinoline 1,1'- 1,1'- dioxidedioxide (7f)의 제조 (7f)
[실시예 31]8-(4-Methylphenylsulfonamido)-2-phenylquinoline [Example 31] 8- (4-Methylphenylsulfonamido) -2-phenylquinoline N-N- oxide (7g)의 제조Preparation of oxide (7g)
[실시예 32][Example 32] 8-(4-Methylphenylsulfonamido)-2-(naphthalen-1-yl)quinoline 8- (4-Methylphenylsulfonamido) -2- (naphthalen-1-yl) quinoline N-N- oxide (7h)의 제조Preparation of oxide (7h)
[비교예 1] 아미드 작용기가 도입된 퀴놀린 N옥사이드 유도체의 제조[Comparative Example 1] Production of quinoline Noxide derivative into which an amide functional group was introduced
실시예 1에서 [IrCp*Cl2]2 대신 [RhCp*Cl2]2를 사용한 것을 제외하고는 실시예 1과 동일하게 퀴놀린 N-옥사이드 유도체에 아미드 작용기를 도입하였다.In Example 1 [IrCp * Cl 2] and is in the same manner as in Example 1 except that instead of 2 [RhCp * Cl 2] 2 An amide functional group was introduced into the quinoline N-oxide derivative.
그 결과 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 수율은 1%미만이었다.
As a result, the yield of the quinoline N-oxide derivative into which the amide functional group was introduced was less than 1%.
[비교예 2] 아미드 작용기가 도입된 퀴놀린 N옥사이드 유도체의 제조[Comparative Example 2] Production of quinoline Noxide derivative into which an amide functional group was introduced
실시예 1에서 [IrCp*Cl2]2 대신 [Ru(p-cymene)Cl2]2를 사용한 것을 제외하고는 실시예 1과 동일하게 퀴놀린 N-옥사이드 유도체에 아미드 작용기를 도입하였다.Except that [Ru ( p- cymene) Cl 2 ] 2 was used instead of [IrCp * Cl 2 ] 2 in Example 1 An amide functional group was introduced into the quinoline N-oxide derivative.
그 결과 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 수율은 1%미만이었다.
As a result, the yield of the quinoline N-oxide derivative into which the amide functional group was introduced was less than 1%.
[비교예 3] 아미드 작용기가 도입된 퀴놀린 N옥사이드 유도체의 제조[Comparative Example 3] Production of quinoline Noxide derivative into which an amide functional group was introduced
실시예 1에서 [IrCp*Cl2]2 대신 Pd(OAc)2를 사용한 것을 제외하고는 실시예 1과 동일하게 퀴놀린 N-옥사이드 유도체에 아미드 작용기를 도입하였다.Except for using Pd (OAc) 2 instead of [IrCp * Cl 2 ] 2 in Example 1, An amide functional group was introduced into the quinoline N-oxide derivative.
그 결과 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 수율은 1%미만이었다.
As a result, the yield of the quinoline N-oxide derivative into which the amide functional group was introduced was less than 1%.
[비교예 4] 아미드 작용기가 도입된 퀴놀린 N옥사이드 유도체의 제조[Comparative Example 4] Preparation of quinoline Noxide derivative into which an amide functional group was introduced
실시예 1에서 아세트산 대신 CHCOONa를 사용한 것을 제외하고는 실시예 1과 동일하게 퀴놀린 N-옥사이드 유도체에 아미드 작용기를 도입하였다.In the same manner as in Example 1 except that CHCOONa was used instead of acetic acid in Example 1 An amide functional group was introduced into the quinoline N-oxide derivative.
그 결과 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 수율은 24%였다.
As a result, the yield of the quinoline N-oxide derivative into which the amide functional group was introduced was 24%.
[비교예 5] 아미드 작용기가 도입된 퀴놀린 N옥사이드 유도체의 제조[Comparative Example 5] Preparation of quinoline Noxide derivative into which an amide functional group was introduced
실시예 1에서 아세트산 대신 CSA(camphorsulfonic acid)를 사용한 것을 제외하고는 실시예 1과 동일하게 퀴놀린 N-옥사이드 유도체에 아미드 작용기를 도입하였다.In the same manner as in Example 1 except that CSA (camphorsulfonic acid) was used instead of acetic acid in Example 1 An amide functional group was introduced into the quinoline N-oxide derivative.
그 결과 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 수율은 18%였다.
As a result, the yield of the quinoline N-oxide derivative into which the amide functional group was introduced was 18%.
[실시예 33] 진퀸(Zinquin)에틸에스터의 제조[Example 33] Preparation of Zinquin ethyl ester
(1) Ethyl 2-(2-methylquinolin-6-yloxy)acetate (9)의 제조(1) Preparation of Ethyl 2- (2-methylquinolin-6-yloxy) acetate (9)
K2CO3 (460 mg, 3.3 mmol)와 2-methyl-6-hydroxyquinoline (318.4 mg, 2.0 mmol)을 DMF (20 mL)에 넣은 후 ethyl bromoacetate (367 mg, 2.2 mmol)를 천천히 적가한 후 상온에서 12시간 동안 교반시켰다. 반응물에 H2O (20 mL)을 투입한 후 ethyl acetate (20 mL x 3)로 추출하고 유기층을 포화 소금물로 세척한 후 Na2SO4로 물을 제거하고 감압조건에서 농축하였다. 얻어진 화합물을 컬럼크로마토그래피로 분리하여(CH2Cl2/acetone, 10:1, R f = 0.3) ethyl 2-(2-methylquinolin-6-yloxy)acetate를 얻었다. (461 mg, 94%); yellow solid; m.p. 44~46℃; 1H NMR (600 MHz, CDCl3) δ 7.97 - 7.90 (m, 2H), 7.41 (dd, J = 9.2, 2.8 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 2.8 Hz, 1H), 4.73 (s, 2H), 4.29 (q, J = 7.1 Hz, 2H), 2.70 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 168.6, 157.0, 155.3, 144.3, 135.1, 130.4, 127.0, 122.4, 121.7, 106.8, 65.7, 61.5, 25.1, 14.2; IR (diamond) 3043, 2984, 2947, 2911, 2869, 1747, 1620, 1598, 1499, 1446, 1377, 1201, 1164, 1074, 1021, 832 cm-1; HRMS (EI) m/z calcd. for C14H15NO3 [M+H+]+: 246.1125, found: 246.1129.
Ethyl bromoacetate (367 mg, 2.2 mmol) was slowly added dropwise to K 2 CO 3 (460 mg, 3.3 mmol) and 2-methyl-6-hydroxyquinoline (318.4 mg, 2.0 mmol) Lt; / RTI > for 12 hours. H 2 O (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic layer was washed with saturated brine, water was removed with Na 2 SO 4 and concentrated under reduced pressure. The obtained compound was separated by column chromatography to obtain ethyl 2- (2-methylquinolin-6-yloxy) acetate (CH 2 Cl 2 / acetone, 10: 1, R f = 0.3). (461 mg, 94%); yellow solid; mp 44-46 [deg.] C; 1 H NMR (600 MHz, CDCl 3) δ 7.97 - 7.90 (m, 2H), 7.41 (dd, J = 9.2, 2.8 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 2.8 Hz, 1H), 4.73 (s, 2H), 4.29 (q, J = 7.1 Hz, 2H), 2.70 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 ) 隆 168.6, 157.0, 155.3, 144.3, 135.1, 130.4, 127.0, 122.4, 121.7, 106.8, 65.7, 61.5, 25.1, 14.2; IR (diamond) 3043, 2984, 2947, 2911, 2869, 1747, 1620, 1598, 1499, 1446, 1377, 1201, 1164, 1074, 1021, 832 cm -1 ; HRMS (EI) m / z calcd. for C 14 H 15 NO 3 [ M + H +] +: 246.1125, found: 246.1129.
(2) 6-(2-ethoxy-2-oxoethoxy)-2-methyl-8-(4-methylphenylsulfonamido) quinoline N-oxide (11)의 제조(2) Preparation of 6- (2-ethoxy-2-oxoethoxy) -2-methyl-8- (4-methylphenylsulfonamido) quinoline N-oxide (11)
ethyl 2-(2-methylquinolin-6-yloxy)acetate (123 mg, 0.5 mmol)를 크로로름 (10 mL)에 녹인 후 m-chloroperbenzoic acid (168 mg, 0.75 mmol) 를 분할 투입하고 50 ℃에서 5시간 동안 교반시켰다. 50 mL 의 크로로포름을 투입한 후 포화 탄산수소나트륨 수용액으로 세척하였다. (10 mL x 3). MgSO4 로 물을 제거한 후 감압 증류하여 ethyl 2-(2-methylquinolin-6-yloxy)acetate ethyl 2-(2-methylquinolin-6-yloxy)acetate (10)를 얻었고 추가 정제 없이 다음 반응에 사용하였다. 10 (129.8 mg, 5.0 mmol), [IrCp*Cl2]2 (15.9 mg, 0.02 mmol), AgNTf2 (31.0 mg, 0.08 mmol) 및 아세트산 (9.0 mg, 0.15 mmol)을 1,2-dichloroethane (2.0 mL)에 넣은 후 p-toluenesulfonyl azide (108 mg, 0.55 mmol)를 투입하고 50 ℃에서 5시간동안 교반하였다. 반응물을 셀라이트를 통과하여 여과한 후 감압 농축하였다. 얻어진 화합물은 컬럼크로마토그램으로 분리하여(CH2Cl2/acetone, 10:1, R f = 0.5) 6-(2-ethoxy-2-oxoethoxy)-2-methyl-8-(4-methylphenylsulfonamido)quinoline N-oxide(11)를 얻었다. (164 mg, 76%); 10 : 1H NMR (600 MHz, CDCl3) δ 8.72 (d, J = 9.4 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.44 (dd, J = 9.5, 2.7 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 4.74 (s, 2H), 4.30 (q, J = 7.1 Hz, 2H), 2.68 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 168.2, 156.9, 144.1, 137.8, 130.3, 124.0, 123.7, 122.0, 121.7, 107.5, 65.6, 61.6, 18.5, 14.1; 11 : yellow solid; m.p. 155~157 ℃; 1H NMR (600 MHz, CDCl3) δ 14.91 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.51 (d, J = 2.7 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.21 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.6 Hz, 1H), 6.63 (d, J = 2.6 Hz, 1H), 4.65 (s, 2H), 4.28 (q, J = 7.2 Hz, 2H), 2.56 (s, 3H), 2.33 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 168.0, 156.6, 145.2, 143.5, 136.9, 135.1, 132.0, 129.5, 127.3, 127.1, 123.5, 107.9, 102.5, 65.4, 61.6, 21.4, 18.4, 14.1; IR (diamond) 3084, 2981, 2922, 2643, 1760, 1609, 1578, 1418, 1369, 1325, 1283, 1155, 1077, 841, 657 cm-1; HRMS (EI) m/z calcd. for C21H22N2O6S [M]+: 430.1199, found: 430.1199.ethyl 2- (2-methylquinolin-6 -yloxy) acetate was dissolved in flow (10 mL) a (123 mg, 0.5 mmol) by dividing the croissant m- chloroperbenzoic acid (168 mg, 0.75 mmol) is added at 50 ℃ 5 Lt; / RTI > 50 mL of chloroform was added thereto, followed by washing with a saturated aqueous solution of sodium hydrogencarbonate. (10 mL x 3). After removing water with MgSO 4 , ethyl 2- (2-methylquinolin-6-yloxy) acetate ethyl 2- (2-methylquinolin-6-yloxy) acetate ( 10 ) was obtained. 10 (129.8 mg, 5.0 mmol) , [IrCp * Cl 2] 2 (15.9 mg, 0.02 mmol), AgNTf 2 (31.0 mg, 0.08 mmol) and acetic acid (9.0 mg, 0.15 mmol) to 1,2-dichloroethane (2.0 mL), p- toluenesulfonyl azide (108 mg, 0.55 mmol) was added thereto, and the mixture was stirred at 50 ° C for 5 hours. The reaction was filtered through celite and concentrated under reduced pressure. The obtained compound was separated by column chromatograph (CH 2 Cl 2 / acetone, 10: 1, R f = 0.5) 6- (2-ethoxy-2-oxoethoxy) -2-methyl-8- (4-methylphenylsulfonamido) quinoline N- oxide (11) was obtained. (164 mg, 76%); 10: 1 H NMR (600 MHz , CDCl 3) δ 8.72 (d, J = 9.4 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.44 (dd, J = 9.5, 2.7 Hz, 1H) , 7.27 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 4.74 (s, 2H), 4.30 (q, J = 7.1 Hz, 2H), 2.68 (s, 3H) , 1.30 (t, J = 7.1 Hz, 3 H); 13 C NMR (150 MHz, CDCl 3 )? 168.2, 156.9, 144.1, 137.8, 130.3, 124.0, 123.7, 122.0, 121.7, 107.5, 65.6, 61.6, 18.5, 14.1; 11 : yellow solid; mp 155-157 C; 1 H NMR (600 MHz, CDCl 3) δ 14.91 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.51 (d, J = 2.7 Hz, 1H), 7.44 (d, J = 8.6 Hz , 1H), 7.21 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.6 Hz, 1H), 6.63 (d, J = 2.6 Hz, 1H), 4.65 (s, 2H), 4.28 (q J = 7.2 Hz, 2H), 2.56 (s, 3H), 2.33 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13 C NMR (150 MHz, CDCl 3) δ 168.0, 156.6, 145.2, 143.5, 136.9, 135.1, 132.0, 129.5, 127.3, 127.1, 123.5, 107.9, 102.5, 65.4, 61.6, 21.4, 18.4, 14.1; IR (diamond) 3084, 2981, 2922, 2643, 1760, 1609, 1578, 1418, 1369, 1325, 1283, 1155, 1077, 841, 657 cm -1 ; HRMS (EI) m / z calcd. for C 21 H 22 N 2 O 6 S [M] +: 430.1199, found: 430.1199.
(3) zinquin ethyl ester (12)의 제조(3) Preparation of zinquin ethyl ester (12)
6-(2-ethoxy-2-oxoethoxy)-2-methyl-8-(4methylphenylsulfonamido)-6- (2-ethoxy-2-oxoethoxy) -2-methyl-8- (4-methylphenylsulfonamido) -
quinoline N-oxide (43.1 mg, 0.1 mmol)을 THF (1.5 mL)에 넣은 후 30% 염화암모늄 수용액(1.5 mL) 과 아연가루(59 mg, 0.9 mmol)를 순차적으로 투입하고 상온에서 1시간 동안 교반시켰다. 물(20 mL)을 투입한 후 Ethyl acetate (20 mL x 3)로 추출하고 MgSO4로 물을 제거하였다. 감압증류로 얻어진 화합물을 컬럼크로마토그래피(CH2Cl2/MeOH, 20:1, R f = 0.3)로 정제하여 zinquin ethyl ester를 얻었다. (32 mg, 76%); white solid; m.p. 106~108 ℃; 1H NMR (600 MHz, CDCl3) δ 9.27 (s, 1H), 7.83 - 7.79 (m, 3H), 7.50 (d, J = 2.6 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 8.1 Hz, 2H), 6.63 (d, J = 2.6 Hz, 1H), 4.66 (s, 2H), 4.28 (q, J = 7.1 Hz, 2H), 2.64 (s, 3H), 2.31 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 168.5, 155.6, 155.5, 143.7, 136.5, 135.2, 134.5, 134.4, 129.5, 127.2, 126.8, 123.3, 106.8, 101.2, 65.7, 61.5, 24.8, 21.4, 14.1; IR (diamond) 3271, 2980, 2916, 1765, 1627, 1605, 1577, 1501, 1424, 1378, 1340, 1203, 1157, 1089, 840 cm-1; HRMS (EI) m/z calcd. for C21H22N2O5S [M]+: 414.1249, found: 414.1248.
quinoline N- oxide (43.1 mg, 0.1 mmol) was added to THF (1.5 mL), and then 30% ammonium chloride aqueous solution (1.5 mL) and zinc powder (59 mg, 0.9 mmol) were sequentially added thereto and stirred at room temperature for 1 hour . Water (20 mL) was added, extracted with ethyl acetate (20 mL × 3), and water was removed with MgSO 4 . The compound obtained by vacuum distillation was purified by column chromatography (CH 2 Cl 2 / MeOH, 20: 1, R f = 0.3) to obtain zinquin ethyl ester. (32 mg, 76%); white solid; mp 106-108 C; 1 H NMR (600 MHz, CDCl 3) δ 9.27 (s, 1H), 7.83 - 7.79 (m, 3H), 7.50 (d, J = 2.6 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H) , 7.18 (d, J = 8.1 Hz, 2H), 6.63 (d, J = 2.6 Hz, 1H), 4.66 (s, 2H), 4.28 (q, J = 7.1 Hz, 2H), 2.64 (s, 3H) , 2.31 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 )? 168.5, 155.6, 155.5, 143.7, 136.5, 135.2, 134.5, 134.4, 129.5, 127.2, 126.8, 123.3, 106.8, 101.2, 65.7, 61.5, 24.8, 21.4, 14.1; IR (diamond) 3271, 2980, 2916, 1765, 1627, 1605, 1577, 1501, 1424, 1378, 1340, 1203, 1157, 1089, 840 cm < -1 >; HRMS (EI) m / z calcd. for C 21 H 22 N 2 O 5 S [M] +: 414.1249, found: 414.1248.
실시예 33에서 제조된 바와 같이 본 발명의 아미드 작용기가 도입된 퀴놀린 N-옥사이드의 제조방법에 따라 아연 검출용 염료인 진퀸 에틸 에스터를 용이하게 제조할 수 있다.According to the process for preparing quinoline N-oxide having an amide functional group introduced according to the present invention as described in Example 33, jinquin ethyl ester, a dye for detecting zinc, can be easily prepared.
Claims (15)
[화학식 1]
[화학식 3]
[화학식 4]
[상기 화학식 1, 화학식 3 및 화학식 4에서,
A1 및 A2는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R1 내지 R4는 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;
Z는 -S(O)2- 또는 -CO-이며;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;
R1 내지 R4 및 R은 서로 독립적으로 인접한 치환체와 융합고리를 포함하거나 포함하지 않는 (C3-C12)알킬렌 또는 (C3-C12)알케닐렌으로 연결되어 지환족 고리 및 단일환 또는 다환의 방향족고리를 형성할 수 있으며;
R1 내지 R4 및 R의 알킬, 알콕시, 알콕시카보닐, 아릴, 아릴옥시카보닐, 헤테로시클로알킬, 헤테로아릴, 지환족 고리 및 방향족 고리와 R11 내지 R15의 알킬은 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 및 (C1-C10)알킬(C6-C12)아릴에서 선택되는 하나이상으로 더 치환될 수 있다.]A process for preparing a quinoline N-oxide derivative having an amide functional group represented by the following formula (1) by reacting a quinoline N-oxide derivative represented by the following formula (3) with an azide compound represented by the following formula (4) in the presence of an iridium catalyst and an acid.
[Chemical Formula 1]
(3)
[Chemical Formula 4]
[In the above formulas (1), (3) and (4)
A 1 and A 2 are independently each other N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R 1 to R 4 are independently of each other hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z is -S (O) 2- or -CO-;
T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R 1 to R 4 and R 5 are each independently selected from the group consisting of (C3-C12) alkylene or (C3-C12) alkenylene which contains an adjacent substituent with or without a fused ring to form an alicyclic ring and a monocyclic or polycyclic aromatic May form a ring;
The alkyl, alkoxy, alkoxycarbonyl, aryl, aryloxycarbonyl, heterocycloalkyl, heteroaryl, alicyclic and aromatic rings of R 1 to R 4 and R and alkyl of R 11 to R 15 are independently selected from the group consisting of halogen, (C6-C12) aryl, (C3-C12) heteroaryl, 5 to 7 membered heterocycloalkyl, (C3-C12) (C1-C10) alkyl, (C1-C10) alkyl, (C2-C10) alkynyl, cyano, (C6-C12) aryl. ≪ / RTI >
[화학식 2]
[화학식 5]
[화학식 4]
[상기 화학식 2, 화학식 4 및 화학식 5에서,
A1 및 A3는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15) 이며;
R1 내지 R8은 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;
Z는 -S(O)2- 또는 -CO-이며;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;
R1 내지 R8 및 R은 서로 독립적으로 인접한 치환체와 융합고리를 포함하거나 포함하지 않는 (C3-C12)알킬렌 또는 (C3-C12)알케닐렌으로 연결되어 지환족 고리 및 단일환 또는 다환의 방향족고리를 형성할 수 있으며;
R1 내지 R8 및 R의 알킬, 알콕시, 알콕시카보닐, 아릴, 아릴옥시카보닐, 헤테로시클로알킬, 헤테로아릴, 지환족 고리 및 방향족 고리와 R11 내지 R15의 알킬은 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 및 (C1-C10)알킬(C6-C12)아릴에서 선택되는 하나이상으로 더 치환될 수 있다.]A process for preparing a quinoline N-oxide derivative having an amide functional group represented by the following formula (2) by reacting a quinoline N-oxide derivative represented by the following formula (5) with an azide compound represented by the following formula (4) in the presence of an iridium catalyst and an acid.
(2)
[Chemical Formula 5]
[Chemical Formula 4]
[In the formulas (2), (4) and (5)
A 1 and A 3 are independently from each other is N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R 1 to R 8 are each independently hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C6- C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z is -S (O) 2- or -CO-;
T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R 1 to R 8 and R are independently selected from the group consisting of (C3-C12) alkylene or (C3-C12) alkenylene which contains an alicyclic ring and a monocyclic or polycyclic aromatic May form a ring;
The alkyl, alkoxy, alkoxycarbonyl, aryl, aryloxycarbonyl, heterocycloalkyl, heteroaryl, alicyclic and aromatic rings of R 1 to R 8 and R and alkyl of R 11 to R 15 are independently selected from the group consisting of halogen, (C6-C12) aryl, (C3-C12) heteroaryl, 5 to 7 membered heterocycloalkyl, (C3-C12) (C1-C10) alkyl, (C1-C10) alkyl, (C2-C10) alkynyl, cyano, (C6-C12) aryl. ≪ / RTI >
상기 화학식 1은 하기 화학식 6 내지 9로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.
[화학식 6]
[화학식 7]
[화학식 8]
[화학식 9]
[상기 화학식 6 내지 9에서,
A1 및 A2는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15) 이며;
R1 내지 R4는 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;
Z는 -S(O)2- 또는 -CO-이며;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;
R21 내지 R25는 서로 독립적으로 수소, 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 또는 (C1-C10)알킬(C6-C12)아릴이다.]The method according to claim 1,
Wherein the formula 1 is represented by the following formulas 6 to 9, wherein the amide functional group is introduced into the quinoline N-oxide derivative.
[Chemical Formula 6]
(7)
[Chemical Formula 8]
[Chemical Formula 9]
[In the above formulas (6) to (9)
A 1 and A 2 are independently each other N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R 1 to R 4 are independently of each other hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z is -S (O) 2- or -CO-;
T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R 21 to R 25 independently from each other are hydrogen, halogen, hydroxy, amino, nitro, carboxy, (C 1 -C 10) alkyl, halo (C 1 -C 10) alkyl, (C 6 -C 12) (C2-C10) alkenyl, (C2-C10) alkynyl, cyano, (C6-C12) cycloalkyl, (C1-C10) alkyl or (C1-C10) alkyl (C6-C12) aryl.
상기 T는 페닐렌, 나프탈렌 또는 안트라센인 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
Wherein T is a phenylene, naphthalene or anthracene amide functional group-introduced quinoline N-oxide derivative.
상기 화학식 1은 하기 화합물에서 선택되는 아미드작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.
Wherein the compound represented by Formula 1 is an amide functional group selected from the following compounds.
상기 이리듐 촉매는 [IrCp*Cl2]2, [IrCl(COD)]2, Ir(acac)3, [Ir(OMe)(COD)]2, IrCl(CO)(PPh3)2 및 IrCl3에서 선택되는 어느 하나이상인 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
The iridium catalyst [IrCp * Cl 2] 2, [IrCl (COD)] 2, Ir (acac) 3, [Ir (OMe) (COD)] 2, IrCl (CO) (PPh 3) 2 and a method for producing the quinoline N- oxide derivatives are introduced one or more amide functional groups selected from IrCl 3.
상기 반응은 은 촉매를 더 포함하여 수행되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
Wherein the reaction is carried out by further comprising a silver catalyst, wherein the amide functional group is introduced.
상기 은 촉매는 AgNTf2, AgSbF6, AgPF6, AgBF4, Ag2O 에서 선택되는 하나이상인 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.8. The method of claim 7,
The catalyst is AgNTf 2, AgSbF 6, AgPF6, AgBF4, method for producing the quinoline N- oxide derivative is introduced at least one amide functional group is selected from Ag 2 O.
상기 산은 아세트산, 피발릭산, 벤조산 및 술폰산에서 선택되는 어느 하나 이상인 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
Wherein the acid is at least one selected from the group consisting of acetic acid, pyruvic acid, benzoic acid and sulfonic acid.
상기 이리듐 촉매는 상기 화학식 3 또는 화학식 5의 화합물 1몰에 대하여 0.01 내지 0.5 몰로 사용되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
Wherein the iridium catalyst is used in an amount of 0.01 to 0.5 mol based on 1 mol of the compound of the formula (3) or (5).
상기 산은 상기 화학식 3 또는 화학식 5의 화합물 1몰에 대하여 0.1 내지 3몰로 사용되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체의 제조방법.3. The method according to claim 1 or 2,
Wherein the acid is used in an amount of 0.1 to 3 moles per mole of the compound of the formula (3) or (5).
[화학식 1]
[화학식 2]
[상기 화학식 1에서,
A1, A2 및 A3은 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R1 내지 R8은 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;
Z는 -S(O)2- 또는 -CO-이며;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;
R10은 수소, 할로겐, 니트로, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;
R1 내지 R8 및 R은 서로 독립적으로 인접한 치환체와 융합고리를 포함하거나 포함하지 않는 (C3-C12)알킬렌 또는 (C3-C12)알케닐렌으로 연결되어 지환족 고리 및 단일환 또는 다환의 방향족고리를 형성할 수 있으며;
R1 내지 R8 및 R의 알킬, 알콕시, 알콕시카보닐, 아릴, 아릴옥시카보닐, 헤테로시클로알킬, 헤테로아릴, 지환족 고리 및 방향족 고리와 R11 내지 R15의 알킬은 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 및 (C1-C10)알킬(C6-C12)아릴에서 선택되는 하나이상으로 더 치환될 수 있다.]An amide functional group-introduced quinoline N-oxide derivative represented by the following general formula (1) or (2)
[Chemical Formula 1]
(2)
[In the above formula (1)
A 1, A 2 and A 3 are independently N or CR to each other, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or - N (R 14) (R 15 ) a;
R 1 to R 8 are each independently hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6-C12) aryl, (C6- C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z is -S (O) 2- or -CO-;
T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R 10 is selected from the group consisting of hydrogen, halogen, nitro, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, (C 6 -C 12) aryloxycarbonyl C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R 1 to R 8 and R are independently selected from the group consisting of (C3-C12) alkylene or (C3-C12) alkenylene which contains an alicyclic ring and a monocyclic or polycyclic aromatic May form a ring;
The alkyl, alkoxy, alkoxycarbonyl, aryl, aryloxycarbonyl, heterocycloalkyl, heteroaryl, alicyclic and aromatic rings of R 1 to R 8 and R and alkyl of R 11 to R 15 are independently selected from the group consisting of halogen, (C6-C12) aryl, (C3-C12) heteroaryl, 5 to 7 membered heterocycloalkyl, (C3-C12) (C1-C10) alkyl, (C1-C10) alkyl, (C2-C10) alkynyl, cyano, (C6-C12) aryl. ≪ / RTI >
상기 화학식 1은 하기 화학식 6 내지 9로 표시되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체.
[화학식 6]
[화학식 7]
[화학식 8]
[화학식 9]
[상기 화학식 6 내지 9에서,
A1 및 A2는 서로 독립적으로 N 또는 CR이며, R은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15) 이며;
R1 내지 R4는 서로 독립적으로 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬, (C3-C12)헤테로아릴, -OSi(R11)(R12)(R13) 또는 -N(R14)(R15)이며;
R11 내지 R15는 서로 독립적으로 수소 또는 (C1-C10)알킬이며;
Z는 단일결합, -S(O)2- 또는 -CO-이며;
T는 (C1-C10)알킬렌, (C6-C12)아릴렌 또는 (C6-C12)헤테로아릴렌이며;
R10은 수소, 할로겐, 니트로, 포밀, (C1-C10)알킬, (C1-C10)알콕시, (C1-C10)알콕시카보닐, (C6-C12)아릴, (C6-C12)아릴옥시카보닐, (C3-C12)헤테로시클로알킬 또는 (C3-C12)헤테로아릴이며;
R21 내지 R25는 서로 독립적으로 수소, 할로겐, 하이드록시, 아미노, 니트로, 카르복시, (C1-C10)알킬, 할로(C1-C10)알킬, (C6-C12)아릴, (C3-C12)헤테로아릴, 5원 내지 7원의 헤테로시클로알킬, (C3-C12)시클로알킬, (C3-C12)시클로알킬, (C2-C10)알케닐, (C2-C10)알키닐, 시아노, (C6-C12)아르(C1-C10)알킬 또는 (C1-C10)알킬(C6-C12)아릴이다.]13. The method of claim 12,
The formula 1 is a quinoline N-oxide derivative having an amide functional group represented by the following formulas (6) to (9).
[Chemical Formula 6]
(7)
[Chemical Formula 8]
[Chemical Formula 9]
[In the above formulas (6) to (9)
A 1 and A 2 are independently each other N or CR, R is hydrogen, halogen, nitro, formyl, (C1-C10) alkyl, (C1-C10) alkoxy, (C1-C10) alkoxycarbonyl, (C6- C12) aryl, (C6-C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14 ) (R < 15 >);
R 1 to R 4 are independently of each other hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, C12) aryloxy-carbonyl, (C3-C12) heterocycloalkyl, (C3-C12) heteroaryl, -OSi (R 11) (R 12) (R 13) or -N (R 14) (R 15 ) , and ;
R 11 to R 15 independently from each other are hydrogen or (C 1 -C 10) alkyl;
Z is a single bond, -S (O) 2- or -CO-;
T is (C1-C10) alkylene, (C6-C12) arylene or (C6-C12) heteroarylene;
R 10 is selected from the group consisting of hydrogen, halogen, nitro, formyl, (C 1 -C 10) alkyl, (C 1 -C 10) alkoxy, (C 1 -C 10) alkoxycarbonyl, (C 6 -C 12) aryl, , (C3-C12) heterocycloalkyl or (C3-C12) heteroaryl;
R 21 to R 25 independently from each other are hydrogen, halogen, hydroxy, amino, nitro, carboxy, (C 1 -C 10) alkyl, halo (C 1 -C 10) alkyl, (C 6 -C 12) (C2-C10) alkenyl, (C2-C10) alkynyl, cyano, (C6-C12) cycloalkyl, (C1-C10) alkyl or (C1-C10) alkyl (C6-C12) aryl.
상기 T는 페닐렌, 나프탈렌 또는 안트라센인 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체.13. The method of claim 12,
Wherein T is phenylene, naphthalene or anthracene.
상기 화학식 1 또는 화학식 2는 하기 화합물에서 선택되는 아미드 작용기가 도입된 퀴놀린 N-옥사이드 유도체.
Wherein the formula (1) or (2) is a quinoline N-oxide derivative having an amide functional group selected from the following compounds.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140046863A KR101578504B1 (en) | 2014-04-18 | 2014-04-18 | - Novel preparation method of quinoline -oxide derivative with amide group |
| PCT/KR2015/003364 WO2015160125A1 (en) | 2014-04-18 | 2015-04-03 | Novel preparation method of quinoline n-oxide derivative with amide group |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140046863A KR101578504B1 (en) | 2014-04-18 | 2014-04-18 | - Novel preparation method of quinoline -oxide derivative with amide group |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150120772A true KR20150120772A (en) | 2015-10-28 |
| KR101578504B1 KR101578504B1 (en) | 2015-12-17 |
Family
ID=54324267
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020140046863A KR101578504B1 (en) | 2014-04-18 | 2014-04-18 | - Novel preparation method of quinoline -oxide derivative with amide group |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR101578504B1 (en) |
| WO (1) | WO2015160125A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110491996A (en) * | 2019-07-09 | 2019-11-22 | 中南民族大学 | A kind of Two-dimensional Carbon based perovskite solar battery based on aminoquinolines ionic liquid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4425155A (en) * | 1982-07-26 | 1984-01-10 | E. I. Du Pont De Nemours And Company | Herbicidal sulfonamide N-oxides |
| JP2012020960A (en) | 2010-07-14 | 2012-02-02 | Daiichi Sankyo Co Ltd | New medicine containing 2,5-disubstituted pyrrole derivative |
-
2014
- 2014-04-18 KR KR1020140046863A patent/KR101578504B1/en active IP Right Grant
-
2015
- 2015-04-03 WO PCT/KR2015/003364 patent/WO2015160125A1/en active Application Filing
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110491996A (en) * | 2019-07-09 | 2019-11-22 | 中南民族大学 | A kind of Two-dimensional Carbon based perovskite solar battery based on aminoquinolines ionic liquid |
| CN110491996B (en) * | 2019-07-09 | 2022-08-05 | 中南民族大学 | Two-dimensional carbon-based perovskite solar cell based on aminoquinoline ionic liquid |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2015160125A1 (en) | 2015-10-22 |
| KR101578504B1 (en) | 2015-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Villuendas et al. | Primary amines as directing groups in the Ru-catalyzed synthesis of isoquinolines, benzoisoquinolines, and thienopyridines | |
| CN105001028A (en) | Synthesis method for asymmetric conjugate diyne compound | |
| EP3245191A1 (en) | Quinolines and process for the preparation thereof | |
| Chen et al. | Oxidative aromatization of 3, 4-dihydroquinolin-2 (1 H)-ones to quinolin-2 (1 H)-ones using transition-metal-activated persulfate salts | |
| Harayama et al. | Aryl–Aryl Coupling Reaction Using a Novel and Highly Active Palladium Reagent Prepared from Pd (OAc) 2, 1, 3-Bis [diphenylphosphino] propane (DPPP), and Bu3P | |
| CN104844601A (en) | Method for synthesizing optical activity spiro-oxindole tetrahydroquinoline derivative | |
| CN103804432B (en) | Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof | |
| KR101578504B1 (en) | - Novel preparation method of quinoline -oxide derivative with amide group | |
| US9670240B2 (en) | Cyclic phosphinate derivatives and method of preparing the same | |
| JP6530807B2 (en) | Process for the preparation of indenoisoquinoline derivatives | |
| JP2017171603A (en) | Manufacturing method of condensed polycyclic compound | |
| CN111484436A (en) | Method for introducing isopentenyl group to C3 position of indole | |
| CN106366035B (en) | Synthesis method of quinoline derivative | |
| CN109134351B (en) | Synthesis method of S-3- (4-aminophenyl) piperidine | |
| KR101885084B1 (en) | Novel amidation of N-acyl indole derivatives | |
| Cikotiene et al. | The First Tandem Acetalization/5-exo-dig Cyclization of 6-Phenylethynylpyrimidine-5-carbaldehydes: Efficient Synthesis of 5-Alkoxy-(7Z)-7-benzylidene-5, 7-dihydrofuro [3, 4-d] pyrimidines | |
| CN106866348B (en) | A kind of polycyclic aromatic hydrocarbon compounds, synthetic method and purposes | |
| EP3782977A1 (en) | Cyclopropanation method and reagent | |
| CN106957318B (en) | Condensed polycyclic indoline compound, preparation method, pharmaceutical composition and application thereof | |
| CN107011251B (en) | Synthesis method and application of 2- (2-chlorophenoxy) pyridine compound | |
| CN104860881A (en) | Methods for synthesizing 8-(nitro methyl) quinoline compounds and 8-methylamino tetrahydroquinoline compounds | |
| CN112979529B (en) | Aromatic amine indole naphthoquinone derivative and preparation method thereof | |
| EP0479161A1 (en) | Synthesis of heterocyclic compounds | |
| CN117756950A (en) | Bio-based carbonylation reagent and application thereof | |
| KR102327657B1 (en) | Novel azulene compounds and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20181211 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20191204 Year of fee payment: 5 |