KR101020486B1 - Novel 1,3-butadien-2-yl methyl amine derivatives and a process for their preparation using indium reagents - Google Patents

Novel 1,3-butadien-2-yl methyl amine derivatives and a process for their preparation using indium reagents Download PDF

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KR101020486B1
KR101020486B1 KR1020080093293A KR20080093293A KR101020486B1 KR 101020486 B1 KR101020486 B1 KR 101020486B1 KR 1020080093293 A KR1020080093293 A KR 1020080093293A KR 20080093293 A KR20080093293 A KR 20080093293A KR 101020486 B1 KR101020486 B1 KR 101020486B1
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박용광
이태석
이필호
김현석
어재명
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Abstract

본 발명은 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체와 이의 제조방법에 관한 것이다.The present invention relates to a 1,3-butadien-2-yl methyl amine derivative represented by the following Chemical Formula 1 and a preparation method thereof.

[화학식 1][Formula 1]

Figure 112008066835369-pat00001
Figure 112008066835369-pat00001

보다 상세하게는, 본 발명의 1,3-부타다이엔-2-일 메틸 아민 유도체는 유기인듐 시약과 다양한 이민 화합물과의 첨가반응을 통해 아민 화합물 내에 알파 탄소 위치에 1,3-다이엔 치환체를 도입하여 제조되며, 상기 유기 인듐 시약은 1,4-다이브로모-2-부타인과 인듐(indium)을 반응시켜 제조된다. 본 발명의 1,3-부타다이엔-2-일 메틸 아민 유도체를 제조하는 다른 방법은 1,4-다이브로모-2-부타인, 인듐 및 다양한 이민 화합물을 바비어 타입(Barbier type)으로 반응시키는 방법이고, 또 다른 방법으로는 알데히드 유도체와 아민 유도체를 축합반응 시켜 얻어진 이민 화합물을 별도로 분리하지 않고 유기인듐 시약과의 첨가 반응시킨 방법이다.More specifically, the 1,3-butadien-2-yl methyl amine derivative of the present invention is a 1,3-diene substituent in the alpha carbon position in the amine compound through the addition reaction of the organic indium reagent and various imine compounds. The organic indium reagent is prepared by reacting 1,4-dibromo-2-butyne with indium. Another method for preparing the 1,3-butadien-2-yl methyl amine derivative of the present invention is the reaction of 1,4-dibromo-2-butyne, indium and various imine compounds in the Barbier type. Another method is a method in which an imine compound obtained by condensation of an aldehyde derivative and an amine derivative is added and reacted with an organic indium reagent without being separated separately.

인듐, 유기인듐, 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine), 1,4-다이브로모-2-부타인, 이민 (imine), 첨가반응 Indium, organoindium, 1,3-butadien-2-yl methyl amine, 1,4-dibromo-2-butyne, imine, addition reaction

Description

신규한 1,3-부타다이엔-2-일 메틸 아민 유도체 및 유기 인듐 시약을 이용한 이의 제조방법{Novel 1,3-butadien-2-yl methyl amine derivatives and a process for their preparation using indium reagents}Novel 1,3-butadien-2-yl methyl amine derivatives and a process for their preparation using indium reagents}

본 발명은 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체와 이의 제조방법에 관한 것이다. 보다 상세하게는, 본 발명의 1,3-부타다이엔-2-일 메틸 아민 유도체는 유기인듐 시약과 다양한 이민 화합물과의 첨가반응을 통해 아민 화합물 내에 알파 탄소 위치에 1,3-다이엔 치환체를 도입하여 제조되며, 상기 유기 인듐 시약은 1,4-다이브로모-2-부타인과 인듐(indium)을 반응시켜 제조된다. 본 발명의 1,3-부타다이엔-2-일 메틸 아민 유도체를 제조하는 다른 방법은 1,4-다이브로모-2-부타인, 인듐 및 다양한 이민 화합물을 바비어 타입(Barbier type)으로 반응시키는 방법이고, 또 다른 방법으로는 알데히드 유도체와 아민 유도체를 축합반응 시켜 얻어진 이민 화합물을 별도로 분리하지 않고 유기인듐 시약과의 첨가 반응시킨 방법이다.The present invention relates to a 1,3-butadien-2-yl methyl amine derivative represented by the following Chemical Formula 1 and a preparation method thereof. More specifically, the 1,3-butadien-2-yl methyl amine derivative of the present invention is a 1,3-diene substituent in the alpha carbon position in the amine compound through the addition reaction of the organic indium reagent and various imine compounds. The organic indium reagent is prepared by reacting 1,4-dibromo-2-butyne with indium. Another method for preparing the 1,3-butadien-2-yl methyl amine derivative of the present invention is the reaction of 1,4-dibromo-2-butyne, indium and various imine compounds in the Barbier type. Another method is a method in which an imine compound obtained by condensation of an aldehyde derivative and an amine derivative is added and reacted with an organic indium reagent without being separated separately.

[화학식 1] [Formula 1]

Figure 112008066835369-pat00002
Figure 112008066835369-pat00002

유기화학에서 아민 화합물은 이민 화합물과 친핵체와의 첨가반응을 통해 합성할 수 있으며, 특히 생화학적 활성을 지닌 아민 화합물을 합성하기 위한 아민 전구체의 개발 방법은 매우 유용하다. 일반적으로 카보닐 화합물과 친핵체와의 첨가반응을 통한 탄소-탄소 결합 방법은 널리 연구되고 활용되고 있지만 상대적으로 이민 화합물을 이용한 첨가반응은 이민의 낮은 반응성 때문에 많이 개발되지 못했다. 이민의 첨가반응으로는 유기금속 시약을 이용한 반응들이 보고 되어지고 있지만 이민 화합물이 쉽게 가수분해 되기 때문에 비양성자성 용매 (aprotic solvent)를 사용해야 하는 제한 점과 수득 률 또한 좋지 않다.In organic chemistry, amine compounds can be synthesized through addition reaction of imine compounds with nucleophiles, and in particular, a method of developing an amine precursor for synthesizing an amine compound having biochemical activity is very useful. In general, carbon-carbon bonding method through addition reaction of carbonyl compound and nucleophile has been widely studied and utilized, but addition reaction using imine compound has not been developed because of low reactivity of imine. Although addition reactions using organometallic reagents have been reported as imine addition reactions, the limitation and yield of using an aprotic solvent are also poor because the imine compounds are easily hydrolyzed.

유기 금속 시약으로 사용되는 인듐 (Indium) 금속은 다른 금속에 비해 공기 중에 안정하며, 독성이 낮은 장점을 지니고 있다. 인듐 (In)과 알릴 할라이드 또는 프로파질 할라이드 유도체와의 반응을 통해 얻어지는 유기 인듐 시약을 인-시츄 (in-situ)로 제조할 수 있으며, 좋은 친핵체로 사용된다. 최근 유기 인듐 시약을 이용한 이민 화합물의 첨가반응에 대한 연구가 활발히 이루어지고 있다. (Tetrahedron Lett . 1992, 33, 5959; Tetrahedron Lett . 1997, 38, 865; Tetrahedron Lett . 2000, 41, 9311; J. Org . Chem . 2001, 66, 7516; Tetrahedron Lett. 2001, 42, 9073; Tetrahedron Lett . 2003, 44, 6755; J. Org . Chem . 2007, 72, 923; Org . Lett . 2008, 10, 1259). 또한 이민화합물이 가수분해되기 쉬운 점을 극복하기 위해 알데히드 유도체와 아민 유도체의 축합반응을 통해 형성된 이민 화합물을 별도의 분리 없이 유기인듐 시약과의 첨가반응을 진행시켜 아민 화합물을 얻는 반응이 연구되고 있다. (Tetrahedron Lett. 2004, 45, 3413; Bull . Korean Chem . Soc . 2007, 28, 139). 특히 아민 화합물 내 1,3-다이엔 치환체를 도입하는 것은 매우 유용한 방법이 될 수 있으며, 생화학적 활성을 지닌 화합물을 합성하는데 중요한 전구체로 사용될 수 있다. 그러나, 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 화합물은 현재까지 많이 보고되지 않은 화합물로, 이의 제조방법 역시 거의 보고된 바가 없다.Indium metal, which is used as an organometallic reagent, is more stable in air than other metals, and has low toxicity. Organic indium reagents obtained through the reaction of indium (In) with allyl halides or propazyl halide derivatives can be prepared in-situ and used as good nucleophiles. Recently, studies on addition reactions of imine compounds using organic indium reagents have been actively conducted. ( Tetrahedron Lett . 1992 , 33 , 5959; Tetrahedron Lett . 1997 , 38 , 865; Tetrahedron Lett . 2000 , 41 , 9311; J. Org . Chem . 2001 , 66 , 7516; Tetrahedron Lett. 2001 , 42 , 9073; Tetrahedron Lett . 2003 , 44 , 6755; J. Org . Chem . 2007 , 72 , 923; Org . Lett . 2008 , 10 , 1259). In addition, in order to overcome the tendency that the imine compound is easily hydrolyzed, the reaction of obtaining an amine compound by proceeding an addition reaction with an indium reagent without separate separation of the imine compound formed through the condensation reaction between the aldehyde derivative and the amine derivative has been studied. . (Tetrahedron Lett 2004, 45, 3413 ;.. Bull Korean Chem . Soc . 2007 , 28 , 139). In particular, the introduction of 1,3-diene substituents in amine compounds can be a very useful method, and can be used as an important precursor for synthesizing compounds with biochemical activity. However, the 1,3-butadien-2-yl methyl amine compound represented by Chemical Formula 1 is a compound that has not been reported much until now, and its preparation method has also been hardly reported.

따라서, 본 발명은 신규 화합물로서 1,3-부타다이엔-2-일 메틸 아민 유도체를 제공하는데 그 목적이 있다.It is therefore an object of the present invention to provide 1,3-butadien-2-yl methyl amine derivatives as novel compounds.

또한, 본 발명은 1,4-다이브로모 부타인 화합물과 인듐(indium)을 반응시켜 제조된 유기인듐 시약을 다양한 이민 유도체와 반응시켜 1,3-부타다이엔-2-일 메틸 아민 유도체를 제조하는 방법을 제공하는데 다른 목적이 있다.In addition, the present invention is to prepare a 1,3-butadien-2-yl methyl amine derivative by reacting an organic indium reagent prepared by reacting a 1,4-dibromo butyne compound and indium with various imine derivatives There is another purpose to provide a way to do this.

또한, 본 발명은 1,4-다이브로모-2-부타인, 인듐 및 다양한 이민 화합물을 바비어 타입(Barbier type)으로 반응시켜 1,3-부타다이엔-2-일 메틸 아민 유도체를 제조하는 방법을 제공하는데 다른 목적이 있다.In addition, the present invention is to prepare a 1,3-butadien-2-yl methyl amine derivative by reacting 1,4-dibromo-2-butyne, indium and various imine compounds in the Barbier type (Barbier type) There is another purpose in providing a method.

또한, 본 발명은 알데히드 유도체와 아민 유도체를 축합반응 시켜 얻어진 이민 화합물을 별도로 분리하지 않고 한 반응용기 안에서 상기 유기인듐 시약과 첨가 반응시켜 1,3-부타다이엔-2-일 메틸 아민 유도체를 제조하는 방법을 제공하는데 또 다른 목적이 있다.The present invention also provides a 1,3-butadien-2-yl methyl amine derivative by adding and reacting an imine compound obtained by condensation of an aldehyde derivative and an amine derivative with the organoindium reagent in a reaction vessel without separate separation. Another purpose is to provide a way to do this.

본 발명은 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체와 이의 제조방법에 관한 것이다.The present invention relates to a 1,3-butadien-2-yl methyl amine derivative represented by the following formula (1) and a preparation method thereof.

[화학식 1][Formula 1]

Figure 112008066835369-pat00003
Figure 112008066835369-pat00003

[상기 화학식 1에서, A는 (C1-C10)알킬, (C3-C9)시클로알킬, (C6-C12)아릴, (C1-C10)알콕시카보닐 또는 (C3-C7)헤테로아릴이고; B는 (C6-C12)아릴, (C6-C12)아르(C1-C10)알킬 또는 (C6-C12)아르(C1-C10)알콕시이고; 상기 A 및 B의 알킬, 시클로알킬, 아릴, 알콕시카보닐, 헤테로아릴, 아르알킬 또는 아르알콕시는 (C1-C10)알킬, (C1-C10)알콕시, 할로겐 또는 히드록시로부터 선택되는 하나 이상의 치환기가 더 치환될 수 있다.][In Formula 1, A is (C1-C10) alkyl, (C3-C9) cycloalkyl, (C6-C12) aryl, (C1-C10) alkoxycarbonyl or (C3-C7) heteroaryl; B is (C6-C12) aryl, (C6-C12) ar (C1-C10) alkyl or (C6-C12) ar (C1-C10) alkoxy; Alkyl, cycloalkyl, aryl, alkoxycarbonyl, heteroaryl, aralkyl or aralkoxy of A and B may have one or more substituents selected from (C1-C10) alkyl, (C1-C10) alkoxy, halogen or hydroxy. May be further substituted.]

상기 화학식 1에서, '알킬'는 직쇄상 또는 분쇄상의 탄소사슬을 모두 포함하며, '알콕시'는 직쇄상 또는 분쇄상의 탄소사슬에 산소가 치환된 그룹을 모두 포함한다.In Formula 1, 'alkyl' includes all linear or pulverized carbon chains, and 'alkoxy' includes all groups substituted with oxygen in the linear or pulverized carbon chain.

상기 화학식 1에서, A는 메틸, 에틸, 프로필, 이소프로필, n-부틸, tert-부틸, 펜틸, 이소펜틸, n-헥실, 시클로헥실, 클로로페닐, 메틸페닐, 히드록시페닐, 브로모페닐, 요오드페닐, 에톡시카보닐, 퓨릴 또는 피리딜로부터 선택되어지고; B는 요오드페닐, 벤질, 메톡시벤질 또는 벤질옥시로부터 선택되어진다.In Formula 1, A is methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, pentyl, isopentyl, n-hexyl, cyclohexyl, chlorophenyl, methylphenyl, hydroxyphenyl, bromophenyl, iodine Phenyl, ethoxycarbonyl, furyl or pyridyl; B is selected from iodinephenyl, benzyl, methoxybenzyl or benzyloxy.

본 발명의 1,3-부타다이엔-2-일 메틸 아민 유도체는 하기 화합물로부터 선택 되나, 이에 한정되는 것은 아니다.The 1,3-butadien-2-yl methyl amine derivative of the present invention is selected from the following compounds, but is not limited thereto.

Figure 112008066835369-pat00004
Figure 112008066835369-pat00004

본 발명에 따른 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 유도체는 이민 화합물과의 첨가반응으로부터 유도되는 화합물로서, 아민 화합물내 알파-위치에 1,3-다이엔 치환체를 포함하고 있다.The 1,3-butadien-2-yl methyl amine derivative represented by Chemical Formula 1 according to the present invention is a compound derived from an addition reaction with an imine compound, and has a 1,3-diene at an alpha-position in the amine compound. It contains a substituent.

또한, 본 발명은 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 유도체의 제조방법을 권리범위로 포함하는 바, 본 발명에 따른 제조방법은 다음과 같은 두 단계의 제조과정으로 이루어진다.In addition, the present invention includes a method for producing a 1,3-butadien-2-yl methyl amine derivative represented by Chemical Formula 1 as a right scope, the production method according to the present invention is prepared in the following two steps The process takes place.

1) 하기 화학식 2로 표시되는 1,4-다이브로모-2-부타인(1,4-dibromo-2-butyne) 화합물과 인듐(Indium; In)과 반응시켜 하기 화학식 3으로 표시되는 유기인듐 시약을 제조하는 단계; 및1) an organic indium reagent represented by the following Chemical Formula 3 by reacting 1,4-dibromo-2-butyne (1,4-dibromo-2-butyne) compound represented by Chemical Formula 2 with Indium (In) Preparing a; And

Figure 112008066835369-pat00005
Figure 112008066835369-pat00005

2) 하기 화학식 3으로 표시되는 유기인듐 시약과 하기 화학식 4로 표시되는 이민 화합물을 반응시켜 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체를 제조하는 단계.2) 1,3-butadien-2-yl methyl amine (1,3-butadien-2 represented by Chemical Formula 1) by reacting an organoindium reagent represented by Chemical Formula 3 with an imine compound represented by Chemical Formula 4 -yl methyl amine) derivative.

Figure 112008066835369-pat00006
Figure 112008066835369-pat00006

[상기 식에서, A 및 B는 상기 화학식 1에서 정의한 바와 같다.][Wherein, A and B are as defined in Formula 1 above.]

본 발명에 따른 제조방법에서는 상기 화학식 2로 표시되는 1,4-다이브로모-2-부타인 화합물과 인듐을 반응시켜 얻어지는 상기 화학식 3으로 표시되는 유기인듐 시약을 별도의 제조시간을 필요로 하지 않는 바비어 타입(Barbier type) 방법으로 반응을 수행할 수 있다. '바비어 타입 (Barbier type)'이라 함은 상기 화학식 3으로 표시되는 유기인듐 시약을 별도의 제조 과정을 거치지 않고 상기 화학식 4로 표시되는 이민 화합물과 인듐, 상기 화학식 2로 표시되는 1,4-다이브로모-2-부타인 화합물을 동시에 첨가하여 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 유도체를 합성하는 방법을 의미한다.In the preparation method according to the present invention, the organic indium reagent represented by the formula (3) obtained by reacting the 1,4-dibromo-2-butyne compound represented by the formula (2) with indium does not require a separate preparation time. The reaction can be performed by the Barbier type method. 'Barbier type' refers to the imine compound represented by the formula (4) and indium, represented by the formula (2) without undergoing a separate manufacturing process of the organic indium reagent represented by the formula (3) A method of synthesizing a 1,3-butadien-2-yl methyl amine derivative represented by Chemical Formula 1 by simultaneously adding a dibromo-2-butyne compound.

상기 제조방법에서 사용되는 인듐 금속은 상기 화학식 4로 표시되는 이민에 대하여 1.5 내지 2.5 당량 범위로 사용하고, 상기 화학식 2로 표시되는 1,4-다이브로모-2-부타인 화합물은 화합물은 상기 화학식 4로 표시되는 이민 화합물에 대하여 1.0 내지 2.0 당량 범위로 사용하는 것이 좋다.The indium metal used in the preparation method is used in the range of 1.5 to 2.5 equivalents based on the imine represented by the formula (4), and the 1,4-dibromo-2-butyne compound represented by the formula (2) is a compound represented by the formula The imine compound represented by 4 is preferably used in the range of 1.0 to 2.0 equivalents.

또한, 제조과정 중에서 화학식 4로 표시되는 이민 화합물이 가수분해되는 것을 방지하고 수율을 향상시킬 목적으로 건조제를 추가사용할 수 있다. 상기 반응에 사용되는 건조제는 수분을 제거할 수 있는 물질로, 구체적으로 마그네슘 설페이트 (MgSO4) 이다. 상기 건조제는 상기 화학식 4로 표시되는 이민에 대하여 0.5 내지 1.5 당량 범위로 사용하도록 한다. In addition, a drying agent may be further used for the purpose of preventing hydrolysis of the imine compound represented by the formula (4) during the manufacturing process and improving the yield. Desiccant used in the reaction is a material capable of removing moisture, specifically magnesium sulfate (MgSO 4 ). The drying agent is to be used in the range of 0.5 to 1.5 equivalents relative to the imine represented by the formula (4).

또한, 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 유도체의 또 다른 제조방법으로, 하기 화학식 5로 표시되는 알데히드 유도체와 하기 화학식 6로 표시되는 아민 유도체의 축합반응을 통해 얻어진 이민 화합물을 별도로 분리하지 않고, 한 반응용기 안에서 화학식 3으로 표시되는 1,3-부타다이엔-2-일 인듐 시약과의 첨가반응을 통해 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체를 제조하는 방법이 있다.In addition, as another method for preparing the 1,3-butadien-2-yl methyl amine derivative represented by Formula 1, the condensation reaction of the aldehyde derivative represented by the following formula (5) and the amine derivative represented by the following formula (6) The imine compound obtained through the reaction was not separately separated, but was added to the 1,3-butadien-2-yl indium reagent represented by the formula (3) in one reaction vessel, and the 1,3-butadiide represented by the following formula (1) There is a method of preparing an 1,3-butadien-2-yl methyl amine derivative.

[상기 식에서, A 및 B는 상기 화학식 1에서 정의한 바와 같다.][Wherein, A and B are as defined in Formula 1 above.]

상기 알데히드 화합물을 사용하는 제조방법에서 상기 화학식 6으로 표시되는 아민 유도체는 상기 화학식 5로 표시되는 알데히드 유도체에 대하여 1.0 내지 2.0 당량 범위로 사용된다. 또한 이민 화합물을 생성하는 축합반응의 수율을 향상시킬 목적으로 산을 추가사용할 수 있으며, 상기 반응에 사용되는 산은 알데히드를 활성화시키는 역할을 하는 물질로, 구체적으로 아세트산 (AcOH)을 사용하는 것이 좋다. 아세트산은 상기 화학식 5로 표시되는 알데히드 유도체에 대하여 0.5 내지 1.5 당량을 범위로 추가 사용할 수 있다.In the preparation method using the aldehyde compound, the amine derivative represented by Chemical Formula 6 is used in the range of 1.0 to 2.0 equivalents relative to the aldehyde derivative represented by Chemical Formula 5. In addition, an acid may be additionally used for the purpose of improving the yield of the condensation reaction to generate an imine compound, and the acid used in the reaction is a substance that activates aldehyde, and specifically, acetic acid (AcOH) may be used. Acetic acid may be additionally used in the range of 0.5 to 1.5 equivalents relative to the aldehyde derivative represented by Formula 5.

본 발명의 2가지 제조방법에서 사용되는 반응 용매는 탄소수 1 내지 7의 저급 알코올성 용매로서, 메탄올 (MeOH), 에탄올 (EtOH)를 사용하며, 바람직하기로는 에탄올 (EtOH)을 사용한다. 반응 온도는 상온에서 상기반응을 수행하며, 바람직하기로는 25도 에서 수행한다. 반응 시간은 반응물질, 용매의 종류 및 용매의 양에 따라 달라질 수 있으며, TLC 등을 통하여 출발물질인 이민 화합물이 모두 소모되었음을 확인 후 반응을 완결시키도록 한다. 반응이 완결되면, 추출과정을 통해 감압 하에서 용매를 증류시킨 후 관 크로마토그래피 등의 통상의 방법을 통하여 목적물을 분리 정제할 수도 있다.The reaction solvent used in the two production methods of the present invention is a lower alcoholic solvent having 1 to 7 carbon atoms, methanol (MeOH), ethanol (EtOH) is used, preferably ethanol (EtOH). The reaction temperature is carried out at room temperature, preferably at 25 degrees. The reaction time may vary depending on the reactants, the type of solvent, and the amount of solvent. The TLC may be used to complete the reaction after confirming that all the imine compounds as starting materials have been consumed. When the reaction is completed, the solvent may be distilled off under reduced pressure through the extraction process, and then the target product may be separated and purified through conventional methods such as column chromatography.

이상에서 설명한 바와 같이, 본 발명에 따른 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체는 현재까지 어느 문헌에도 보고된 바 없는 신규 화합물이며, 1,4-다이브로모-2-부타인 화합물과 인듐 금속의 반응으로부터 얻어지는 유기 인듐 시약을 별도의 제조시간을 필요로 하지 않는 바비어 타입(Barbier type) 반응으로, 상기 화학식 4로 표시되는 이민 화합물에 반응시켜 상기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체 화합물을 우수한 수득률로 합성할 수 있다. 또한 알데히드 유도체와 아민 유도체의 축합반응을 통해 형성된 이민 화합물을 별도의 분리 없이 유기인듐 시약과의 첨가반응을 진행시켜 동일한 화합물인 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체 화합물을 우수한 수득률로 합성할 수 있다.As described above, the 1,3-butadien-2-yl methyl amine derivative according to the present invention is a novel compound that has not been reported in any literature so far. , An organic indium reagent obtained from the reaction of a 1,4-dibromo-2-butyne compound and an indium metal, is a Barbier type reaction that does not require a separate production time, and is represented by Formula 4 By reacting with the compound, a 1,3-butadien-2-yl methyl amine derivative compound represented by Chemical Formula 1 may be synthesized with excellent yield. In addition, the imine compound formed through the condensation reaction between the aldehyde derivative and the amine derivative is subjected to the addition reaction with the organoindium reagent without further separation, and thus the same compound 1,3-butadien-2-yl methyl amine (1,3- butadien-2-yl methyl amine) derivative compounds can be synthesized with good yield.

또한, 본 발명의 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체는 생화학적 활성을 가지는 아민 화합물의 합성을 위한 전구체로서 유용하게 사용되어 질 수 있다.In addition, the 1,3-butadien-2-yl methyl amine derivative of the present invention is usefully used as a precursor for the synthesis of amine compounds having biochemical activity. Can lose.

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 configuration of the present invention in more detail through examples, the following examples are provided to help the understanding of the present invention, the scope of the present invention is not limited thereto.

[실시예 1] (1-시클로헥실-2-메틸렌-부트-3-엔일)-페닐-아민 ((1- Cyclohexyl-2-methylene-but-3-enyl)-phenyl-amine)의 제조Example 1 Preparation of (1-cyclohexyl-2-methylene-but-3-enyl) -phenyl-amine ((1-Cyclohexyl-2-methylene-but-3-enyl) -phenyl-amine)

Figure 112008066835369-pat00008
Figure 112008066835369-pat00008

질소분위기 하에서 N-(시클로헥실메틸리덴)페닐아민 (N-(cyclohexylmethylidene)phenylamine) (56.2mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 7시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (1-시클로헥실-2-메틸렌-부트-3-엔일)-페닐-아민 (42 mg, 58%)을 얻었다.N- (cyclohexylmethylidene) phenylamine (56.2 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and reaction solvent under nitrogen atmosphere Add EtOH (1.2 mL) and stir. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 7 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (1-cyclohexyl-2-methylene-but-3-enyl) -phenyl-amine (42 mg, 58%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.12 (t, J = 7.5 Hz, 2H), 6.64 (t, J = 7.5 Hz, 1H), 6.51 (d, J = 7.5 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 5.09 (s, 1H), 3.89 (d, J = 5.6 Hz, 1H), 3.85(s, 1H), 1.88-1.85(m, 1H), 1.81-1.55(m, 5H), 1.31-1.10(m, 4H), 1.06-0.95(m, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.12 (t, J = 7.5 Hz, 2H), 6.64 (t, J = 7.5 Hz, 1H), 6.51 (d, J = 7.5 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 5.09 (s, 1H), 3.89 (d, J = 5.6 Hz, 1H), 3.85 (s, 1H), 1.88-1.85 (m, 1H), 1.81-1.55 (m, 5H), 1.31-1.10 (m, 4H), 1.06-0.95 (m, 1H).

[실시예 2] (2-메틸렌-1-페닐-부트-3-엔일)-페닐-아민 ((2-Methylene-1-phenyl-but-3-enyl)-phenyl-amine)의 제조Example 2 Preparation of (2-Methylene-1-phenyl-but-3-enyl) -phenyl-amine ((2-Methylene-1-phenyl-but-3-enyl) -phenyl-amine)

Figure 112008066835369-pat00009
Figure 112008066835369-pat00009

질소분위기 하에서 N-벤질리덴-페닐-아민 (N-benzylidene-phenyl-amine) (54.4 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 ml)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인(95.4 mg. 0.45 mmol)을 첨가 후 상온에서 2시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (2-메틸렌-1-페닐-부트-3-엔일)-페닐-아민 (60.7 mg, 86%)을 얻었다.N-benzylidene-phenyl-amine (54.4 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and reaction solvent EtOH under nitrogen atmosphere (1.2 ml) is added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (2-methylene-1-phenyl-but-3-enyl) -phenyl-amine (60.7 mg, 86%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.41-7.26 (m, 5H), 7.14 (t, J = 7.6 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 7.6 Hz, 2H), 6.42 (dd, J = 17.8, J = 11.1 Hz, 1H) 5.33 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 3.99 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.41-7.26 (m, 5H), 7.14 (t, J = 7.6 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 7.6 Hz, 2H), 6.42 (dd, J = 17.8, J = 11.1 Hz, 1H) 5.33 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 3.99 (s, 1H).

[실시예 3] [1-(4-클로로-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 ([1-(4- Chloro-phenyl)-2-methylene-but-3-enyl]-phenyl-amine)의 제조Example 3 [1- (4-Chloro-phenyl) -2-methylene-but-3-enyl] -phenyl-amine ([1- (4-Chloro-phenyl) -2-methylene-but-3- enyl] -phenyl-amine)

Figure 112008066835369-pat00010
Figure 112008066835369-pat00010

질소분위기 하에서 N-(4-클로로벤질리덴)-페닐-아민 (N-(4-chlorobenzylidene)-phenyl-amine) (64.7mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 2시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 [1-(4-클로로-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 (60.7 mg, 75%)을 얻었다.N- (4-chlorobenzylidene) -phenyl-amine (64.7 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36) under nitrogen atmosphere mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) are added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and the residue was separated by column chromatography to obtain the title compound [1- (4-chloro-phenyl) -2-methylene-but-3-enyl] -phenyl-amine (60.7 mg, 75%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.34-7.31 (m, 4H), 7.14 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.7 Hz, 1H), 6.52 (d, J = 7.7 Hz, 2H), 6.40 (dd, J = 17.8 Hz, J = 11.1 Hz, 1H) 5.32 (s, 1H), 5.26 (d, J =17.8 Hz, 1H), 5.20 (s, 1H), 5.14 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 3.96 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.34-7.31 (m, 4H), 7.14 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.7 Hz, 1H), 6.52 (d, J = 7.7 Hz, 2H), 6.40 (dd, J = 17.8 Hz, J = 11.1 Hz, 1H) 5.32 (s, 1H), 5.26 (d, J = 17.8 Hz, 1H), 5.20 (s , 1H), 5.14 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 3.96 (s, 1H).

[실시예 4] (2-메틸렌-1-p-톨릴-부트-3-엔일)-페닐-아민 ((2-methylene-1- p-tolylbut-3-enyl)-phenyl-amine)의 제조Preparation of amines ((2-methylene-1- p -tolylbut-3-enyl) -phenyl-amine) - [ Example 4] (2-methylene -1- p-tolyl-but-3-enyl) -phenyl

Figure 112008066835369-pat00011
Figure 112008066835369-pat00011

질소분위기 하에서 N-(4-메틸-벤질리덴)-페닐-아민 (N-(4-methylbenzylidene)-phenyl-amine) (58.6mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 2시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (2-메틸렌-1-p-톨릴-부트-3-엔일)-페닐-아민 (53.9 mg, 72%)을 얻었다.N- (4-methylbenzylidene) -phenyl-amine (58.6 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (N- (4-methylbenzylidene) -phenyl-amine) 36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (2-methylene-1- p -tolyl-but-3-enyl) -phenyl-amine (53.9 mg, 72%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.27 (d, J = 7.6 Hz, 2H), 7.15-7.11 (m, 4H), 6.68 (t, J = 7.6 Hz, 1H), 6.52 (d, J = 7.6 Hz, 2H), 6.41 (dd, J = 17.7, J = 11.1 Hz, 1H) 5.31 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.11 (s, 1H), 5.07 (d, J = 11.1 Hz, 1H), 3.95 (s, 1H), 2.33 (s, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.27 (d, J = 7.6 Hz, 2H), 7.15-7.11 (m, 4H), 6.68 (t, J = 7.6 Hz, 1H), 6.52 (d, J = 7.6 Hz, 2H), 6.41 (dd, J = 17.7, J = 11.1 Hz, 1H) 5.31 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.11 (s, 1H), 5.07 (d, J = 11.1 Hz, 1H), 3.95 (s, 1H), 2.33 (s, 3H).

[실시예 5] 3-(2-메틸렌-1-페닐아미노-부트-3-엔일)-페놀 (3-(2-Methylene- 1-phenylamino-but-3-enyl)-phenol)의 제조 Example 5 Preparation of 3- (2-methylene-1-phenylamino-but-3-enyl) -phenol (3- (2-Methylene-1-phenylamino-but-3-enyl) -phenol)

Figure 112008066835369-pat00012
Figure 112008066835369-pat00012

질소분위기 하에서 3-페닐이미노메틸-페놀 (59.1mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 3시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 3-(2-메틸렌-1-페닐아미노-부트-3-엔일)-페놀 (56.5 mg, 75%) 얻었다.Under a nitrogen atmosphere, 3-phenyliminomethyl-phenol (59.1 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added thereto and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 3 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound 3- (2-methylene-1-phenylamino-but-3-enyl) -phenol (56.5 mg, 75%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.21-7.09 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 6.70 (t, J =7.6 Hz, 2H), 6.52 (d, J = 7.6 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.29 (s, 1H), 5.27 (d, J = 17.6 Hz, 1H), 5.24 (s, 1H), 5.09 (s, 1H), 5.08 (d, J = 11.1 Hz, 1H), 3.98 (br, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.21-7.09 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 6.70 (t, J = 7.6 Hz, 2H), 6.52 (d, J = 7.6 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.29 (s, 1H), 5.27 (d, J = 17.6 Hz , 1H), 5.24 (s, 1H), 5.09 (s, 1H), 5.08 (d, J = 11.1 Hz, 1H), 3.98 (br, 1H).

[실시예 6] [1-(3-브로모-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 ([1-(3- Bromo-phenyl)-2-methylene-but-3-enyl]-phenyl-amine)의 제조 Example 6 [1- (3-Bromo-phenyl) -2-methylene-but-3-enyl] -phenyl-amine ([1- (3- Bromo-phenyl) -2-methylene-but-3 -enyl] -phenyl-amine)

Figure 112008066835369-pat00013
Figure 112008066835369-pat00013

질소분위기 하에서 N-(3-브로모-벤질리덴)-페닐-아민 (N-(3-bromobenzylidene)-phenyl-amine) (78 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 3시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 [1-(3-브로모-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 (56.6 mg, 60%)을 얻었다.N- (3-bromobenzylidene) -phenyl-amine (78 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate under nitrogen atmosphere (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 3 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and the residue was separated by column chromatography to obtain the title compound [1- (3-bromo-phenyl) -2-methylene-but-3-enyl] -phenyl-amine (56.6 mg, 60%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.54 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H) 7.15 (t, J = 7.5 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.40 (dd, J = 17.7, J = 11.1 Hz, 1H), 5.33 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.20 (s, 1H), 5.13 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 3.96 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.54 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.20 ( t, J = 7.8 Hz, 1H) 7.15 (t, J = 7.5 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.40 (dd, J = 17.7, J = 11.1 Hz, 1H), 5.33 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.20 (s, 1H), 5.13 (s, 1H), 5.11 (d, J = 11.1 Hz, 1 H), 3.96 (s, 1 H).

[실시예 7] (2-메틸렌-1-톨릴-부트-3-엔일)-페닐-아민 ((2-Methylene-1-o-tolyl-but-3-enyl)-phenyl-amine)의 제조Example 7 Preparation of (2-Methylene-1-tolyl-but-3-enyl) -phenyl-amine ((2-Methylene-1-o-tolyl-but-3-enyl) -phenyl-amine)

Figure 112008066835369-pat00014
Figure 112008066835369-pat00014

질소분위기 하에서 N-(2-메틸-벤질리덴)-페닐-아민 (N-(2-methylbenzylidene)-phenyl-amine) (58.7 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 4시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (2-메틸렌-1-톨릴-부트-3-엔일)-페닐-아민 (50.1 mg, 67%)을 얻었다.N- (2-methylbenzylidene) -phenyl-amine (58.7 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate ( 36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 4 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (2-methylene-1-tolyl-but-3-enyl) -phenyl-amine (50.1 mg, 67%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.36 (d, J = 7.1 Hz, 1H), 7.21-7.11 (m, 5H), 6.68 (t, J = 7.5 Hz, 1H), 6.50 (d, J = 7.5 Hz, 2H), 6.47 (dd, J = 17.7, J = 11.1 Hz, 1H), 5.34 (s, 1H), 5.28 (s, 1H), 5.19 (s, 1H), 5.14 (d, J = 17.7 Hz, 1H), 5.07 (d, J = 11.1 Hz, 1H), 3.87 (s, 1H), 2.34 (s, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.36 (d, J = 7.1 Hz, 1H), 7.21-7.11 (m, 5H), 6.68 (t, J = 7.5 Hz, 1H), 6.50 (d, J = 7.5 Hz, 2H), 6.47 (dd, J = 17.7, J = 11.1 Hz, 1H), 5.34 (s, 1H), 5.28 (s, 1H), 5.19 (s, 1H), 5.14 (d, J = 17.7 Hz, 1H), 5.07 (d, J = 11.1 Hz, 1H), 3.87 (s, 1H), 2.34 (s, 3H).

[실시예 8] [1-(2-아이오도-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 ([1-(2-Iodo-phenyl)-2-methylene-but-3-enyl]-phenyl-amine)의 제조 Example 8 [1- (2-Iodo-phenyl) -2-methylene-but-3-enyl] -phenyl-amine ([1- (2-Iodo-phenyl) -2-methylene-but-3 -enyl] -phenyl-amine)

Figure 112008066835369-pat00015
Figure 112008066835369-pat00015

질소분위기 하에서 N-(2-아이오도-벤질리덴)-페닐-아민 (N-(2-iodobenzylidene)-phenyl-amine) (92.1 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 5시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 [1-(2-아이오도-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 (62.9 mg, 58%)을 얻었다.N- (2-iodobenzylidene) -phenyl-amine (92.1 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate under nitrogen atmosphere (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred for 5 hours at room temperature. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and the residue was separated by column chromatography to obtain the title compound [1- (2-iodo-phenyl) -2-methylene-but-3-enyl] -phenyl-amine (62.9 mg, 58%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.89 (d, J = 7.6 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H) 7.14 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 6.70 (t, J = 7.6 Hz, 1H), 6.49 (d, J = 7.5 Hz, 2H), 6.50-6.43 (m, 1H), 5.34 (s, 2H), 5.26 (d, J = 17.7 Hz, 1H), 5.14 (d, J = 11.1 Hz, 1H), 5.01 (s, 1H), 3.96 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.89 (d, J = 7.6 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H) 7.14 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 6.70 (t, J = 7.6 Hz, 1H), 6.49 (d, J = 7.5 Hz, 2H), 6.50-6.43 (m, 1H), 5.34 (s, 2H), 5.26 (d, J = 17.7 Hz, 1H), 5.14 (d, J = 11.1 Hz, 1H), 5.01 (s, 1H), 3.96 (s , 1H).

[실시예 9] (1-퓨란-2-일-2-메틸렌-부트-3-엔일)-페닐-아민 ((1-Furan-2-yl-2-methylene-but-3-enyl)-phenyl-amine)의 제조 Example 9 (1-furan-2-yl-2-methylene-but-3-enyl) -phenyl-amine ((1-Furan-2-yl-2-methylene-but-3-enyl) -phenyl -amine)

Figure 112008066835369-pat00016
Figure 112008066835369-pat00016

질소분위기 하에서 N-((퓨란-2-일)메틸리덴)-페닐-아민 (N-((furan-2-yl)methylidene)-phenyl-amine) (51.4 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 2시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (1-퓨란-2-일-2-메틸렌-부트-3-엔일-페닐-아민 (45.3 mg, 67%)을 얻었다.N-((furan-2-yl) methylidene) -phenyl-amine (N-((furan-2-yl) methylidene) -phenyl-amine) (51.4 mg, 0.3 mmol), indium (68.9 mg) under nitrogen atmosphere , 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added thereto and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (1-furan-2-yl-2-methylene-but-3-enyl-phenyl-amine (45.3 mg, 67%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.38 (dd, J = 3.3 Hz, J =1.8 Hz, 1H), 7.16 (t, J = 7.5 Hz, 2H), 6.73 (t, J = 7.5 Hz, 1H), 6.57 (d, J = 7.5 Hz, 2H), 6.44 (dd, J = 17.7, J = 11.1 Hz, 1H), 6.32 (dd, J = 1.8 Hz, J = 3.3 Hz, 1H), 6.24(d, J = 3.3 Hz, 1H), 5.33 (d, J = 17.7 Hz, 1H), 5.31 (s, 1H), 5.28 (s, 1H), 5.13 (d, J = 11.1 Hz, 1H), 4.11 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.38 (dd, J = 3.3 Hz, J = 1.8 Hz, 1H), 7.16 (t, J = 7.5 Hz, 2H), 6.73 (t, J = 7.5 Hz, 1H), 6.57 (d, J = 7.5 Hz, 2H), 6.44 (dd, J = 17.7, J = 11.1 Hz, 1H), 6.32 (dd, J = 1.8 Hz, J = 3.3 Hz, 1H), 6.24 (d, J = 3.3 Hz, 1H), 5.33 (d, J = 17.7 Hz, 1H), 5.31 (s, 1H), 5.28 (s, 1H), 5.13 (d, J = 11.1 Hz, 1H), 4.11 (s, 1 H).

[실시예 10] (4-아이오도-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 ((4-Iodo-phenyl)-(2-methylene-1-phenyl-but-3-enyl)-amine)의 제조 Example 10 (4-iodo-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine ((4-Iodo-phenyl)-(2-methylene-1-phenyl-but -3-enyl) -amine)

Figure 112008066835369-pat00017
Figure 112008066835369-pat00017

질소분위기 하에서 N-벤질리덴-(4-아이오도-페닐)-아민 (N-benzylidene-(4-iodo-phenyl)-amine) (92.1 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 1시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (4-아이오도-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 (80.2 mg, 74%)을 얻었다.N-benzylidene- (4-iodo-phenyl) -amine (92.1 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), under nitrogen atmosphere Magnesium sulfate (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) are added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 1 hour. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (4-iodo-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine (80.2 mg, 74%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.39-7.33 (m, 6H), 7.32-7.29 (m, 1H), 6.40 (dd, J = 17.6, J = 11.1 Hz, 1H), 6.31 (d, J = 8.9 Hz, 2H), 5.32 (s, 1H), 5.25 (d, J = 17.6 Hz, 1H), 5.23 (s, 1H), 5.10 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 4.02 (s , 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.39-7.33 (m, 6H), 7.32-7.29 (m, 1H), 6.40 (dd, J = 17.6, J = 11. 1 Hz, 1H) , 6.31 (d, J = 8.9 Hz, 2H), 5.32 (s, 1H), 5.25 (d, J = 17.6 Hz, 1H), 5.23 (s, 1H), 5.10 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 4.02 (s, 1H).

[실시예 11] (4-메톡시-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 ((4-Methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl)-amine)의 제조 Example 11 (4-methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine ((4-Methoxy-phenyl)-(2-methylene-1-phenyl-but -3-enyl) -amine)

Figure 112008066835369-pat00018
Figure 112008066835369-pat00018

질소분위기 하에서 N-벤질리덴-(4-메톡시-페닐)-아민 (N-benzylidene-(4-methoxy-phenyl)-amine) (63.4 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 4시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (4-메톡시-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 (60.5 mg, 76%)을 얻었다.N-benzylidene- (4-methoxy-phenyl) -amine (63.4 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), under nitrogen atmosphere Magnesium sulfate (36 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) are added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, followed by stirring at room temperature for 4 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (4-methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine (60.5 mg, 76%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.40-7.25 (m, 5H), 6.74 (d, J = 8.9 Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 6.41 (dd, J = 17.8, J = 11.1 Hz, 1H), 5.31 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.08 (d, J = 11.1 Hz, 1H), 5.08 (s, 1H), 3.77 (br, 1H), 3.71 (s, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.40-7.25 (m, 5H), 6.74 (d, J = 8.9 Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 6.41 (dd, J = 17.8, J = 11.1 Hz, 1H), 5.31 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.08 (d, J = 11.1 Hz , 1H), 5.08 (s, 1H), 3.77 (br, 1H), 3.71 (s, 3H).

[실시예 12] 벤질-(2-메틸렌-1-페닐-부트-3-엔일)-아민 (Benzyl-(2-methylene-1-phenyl-but-3-enyl)-amine)의 제조 Example 12 Preparation of Benzyl- (2-methylene-1-phenyl-but-3-enyl) -amine (Benzyl- (2-methylene-1-phenyl-but-3-enyl) -amine)

Figure 112008066835369-pat00019
Figure 112008066835369-pat00019

질소분위기 하에서 벤질-벤질리덴-아민 (benzyl-benzylidene-amine) (58.6 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인(95.4 mg. 0.45 mmol)을 첨가 후 상온에서 6시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 벤질-(2-메틸렌-1-페닐-부트-3-엔일)-아민 (44.1 mg, 59%)을 얻었다.Benzyl-benzylidene-amine (58.6 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and reaction solvent EtOH (1.2 mL) under nitrogen atmosphere Add and stir. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 6 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound benzyl- (2-methylene-1-phenyl-but-3-enyl) -amine (44.1 mg, 59%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.40 (d, J = 7.2 Hz, 2H), 7.33-7.29 (m, 6H), 7.26-7.22 (m, 2H), 6.31 (dd, J = 17.7, J = 11.1 Hz, 1H) 5.40 (s, 1H), 5.30 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.00 (d, J = 11.1 Hz, 1H), 4.52 (s, 1H), 3.7-3.69 (m, 2H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.40 (d, J = 7.2 Hz, 2H), 7.33-7.29 (m, 6H), 7.26-7.22 (m, 2H), 6.31 (dd) , J = 17.7, J = 11.1 Hz, 1H) 5.40 (s, 1H), 5.30 (s, 1H), 5.26 (d, J = 17.7 Hz, 1H), 5.00 (d, J = 11.1 Hz, 1H), 4.52 (s, 1 H), 3.7-3.69 (m, 2 H).

[실시예 13] 2-벤질옥시아미노-3-메틸렌-펜트-4-에노익 엑시드 에틸 에스터 (2-Benzyloxyamino-3-methylene-pent-4-enoic acid ethyl ester)의 제조 Example 13 Preparation of 2-Benzyloxyamino-3-methylene-pent-4-enoic acid ethyl ester (2-Benzyloxyamino-3-methylene-pent-4-enoic acid ethyl ester)

Figure 112008066835369-pat00020
Figure 112008066835369-pat00020

질소분위기 하에서 벤질옥시이미노-아세틱 엑시드 에틸 에스터 (62.2 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 6시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 2-벤질옥시아미노-3-메틸렌-펜트-4-에노익 엑시드 에틸 에스터 (60.4 mg, 77%)을 얻었다.Benzyloxyimino-acetic acid ethyl ester (62.2 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and reaction solvent EtOH (1.2 mL) were added and stirred under a nitrogen atmosphere. . 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 6 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound 2-benzyloxyamino-3-methylene-pent-4-enoic acid ethyl ester (60.4 mg, 77%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.38-7.28 (m, 5H), 6.29 (dd, J = 17.5, J = 11.0 Hz, 1H), 6.04 (d, J = 9.0 Hz, 1H), 5.25 (d, J = 17.5 Hz, 1H), 5.23 (s, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.0 Hz, 1H), 4.78-4.70 (m, 2H), 4.45 (d, J = 9.0 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.38-7.28 (m, 5H), 6.29 (dd, J = 17.5, J = 11.0 Hz, 1H), 6.04 (d, J = 9.0 Hz , 1H), 5.25 (d, J = 17.5 Hz, 1H), 5.23 (s, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.0 Hz, 1H), 4.78-4.70 (m, 2H) , 4.45 (d, J = 9.0 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[실시예 14] 2-(4-메톡시-페닐아미노)-3-메틸렌-펜트-4-에노익 엑시드 에틸 에스터 (2-(4-Methoxy-phenylamino)-3-methylene-pent-4-enoic acid ethyl ester)의 제조 Example 14 2- (4-Methoxy-phenylamino) -3-methylene-pent-4-enoic acid ethyl ethyl (2- (4-Methoxy-phenylamino) -3-methylene-pent-4-enoic acid ethyl ester)

Figure 112008066835369-pat00021
Figure 112008066835369-pat00021

질소분위기 (4-메톡시-페닐이미도)-아세틱 엑시드 에틸 에스터 (62.2 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 6시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 2-(4-메톡시-페닐아미노)-3-메틸렌-펜트-4-에노익 엑시드 에틸 에스터 (51 mg, 65%)을 얻었다.Nitrogen atmosphere (4-methoxy-phenylimido) -acetic acid ethyl ester (62.2 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) and reaction solvent EtOH (1.2 mL) and add to stirring. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 6 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound 2- (4-methoxy-phenylamino) -3-methylene-pent-4-enoic acid ethyl ester (51 mg, 65%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 6.76 (d, J = 8.9, Hz 2H), 6.56 (d, J = 8.9 Hz, 2H), 6.42 (dd, J = 17.6, J = 11.2 Hz, 1H), 5.54 (d, J = 17.6 Hz, 1H), 5.36 (s, 1H), 5.31 (s, 1H), 5.21 (d, J = 11.2 Hz, 1H), 4.74 (s, 1H), 4.35 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.73 (s, 3H), 1.25 (t, J = 7.1Hz, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 6.76 (d, J = 8.9, Hz 2H), 6.56 (d, J = 8.9 Hz, 2H), 6.42 (dd, J = 17.6, J = 11.2 Hz, 1H), 5.54 (d, J = 17.6 Hz, 1H), 5.36 (s, 1H), 5.31 (s, 1H), 5.21 (d, J = 11.2 Hz, 1H), 4.74 (s, 1H ), 4.35 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.73 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H).

[실시예 15] 4-(2-메틸렌-1-페닐아미노-부트-3-엔일)-벤조익 엑시드 메틸 에스터 (4-(2-Methylene-1-phenylamino-but-3-enyl)-benzoic acid methyl ester)의 제조Example 15 4- (2-Methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester (4- (2-Methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester)

Figure 112008066835369-pat00022
Figure 112008066835369-pat00022

질소분위기하에서 4-페닐이미노메틸-벤조익 엑시드 메틸 에스터 (4-phenyliminomethyl-benzoic acid methyl ester) (71.8 mg, 0.3 mmol), 인듐 (68.9 mg, 0.6 mmol), 마그네슘 설페이트 (36 mg, 0.3 mmol)와 반응 용매 EtOH (1.2 mL)을 넣고 교반한다. 반응 혼합물에 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 1시간 교반 시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 4-(2-메틸렌-1-페닐아미노-부트-3-엔일)-벤조익 엑시드 메틸 에스터 (57.2 mg, 65%)을 얻었다.4-phenyliminomethyl-benzoic acid methyl ester (71.8 mg, 0.3 mmol), indium (68.9 mg, 0.6 mmol), magnesium sulfate (36 mg, 0.3 mmol) under nitrogen atmosphere ) And the reaction solvent EtOH (1.2 mL) are added and stirred. 1,4-Dibromo-2-butane (95.4 mg. 0.45 mmol) was added to the reaction mixture, which was then stirred at room temperature for 1 hour. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound 4- (2-methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester (57.2 mg, 65%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 8.01 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.14 (t, J = 7.5 Hz, 2H), 6.71 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.41 (dd, J = 17.7 Hz, J = 11.1 Hz, 1H), 5.33 (s, 1H), 5.28 (d, J = 17.7 Hz, 1H), 5.22 (s, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 4.03 (s, 1H), 3.90 (s, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 8.01 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.14 (t, J = 7.5 Hz, 2H), 6.71 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.41 (dd, J = 17.7 Hz, J = 11.1 Hz, 1H), 5.33 (s, 1H) , 5.28 (d, J = 17.7 Hz, 1H), 5.22 (s, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 4.03 (s, 1H), 3.90 (s, 3H).

[실시예 16] (1-시클로헥실-2-메틸렌-부트-3-엔일-)-페닐-아민 ((1-Cyclohexyl-2-methylene-but-3-enyl)-phenyl-amine)의 제조Example 16 Preparation of (1-Cyclohexyl-2-methylene-but-3-enyl-)-phenyl-amine ((1-Cyclohexyl-2-methylene-but-3-enyl) -phenyl-amine)

Figure 112008066835369-pat00023
Figure 112008066835369-pat00023

질소분위기 하에서 시클로헥산카브알데히드 (33.7 mg, 0.3 mmol), 아닐린 (41.1 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간 동안 교반한다. 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 6시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (1-시클로헥실-2-메틸렌-부트-3-엔일-)-페닐-아민 (31.1 mg, 43%)을 얻었다.In a nitrogen atmosphere, cyclohexanecarbaldehyde (33.7 mg, 0.3 mmol), aniline (41.1 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and a reaction solvent EtOH (1.2 mL) were added and stirred for 1 hour. After stirring, indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butane (95.4 mg. 0.45 mmol) were added to the reaction mixture, followed by stirring at room temperature for 6 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (1-cyclohexyl-2-methylene-but-3-enyl-)-phenyl-amine (31.1 mg, 43%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.12 (t, J = 7.5 Hz, 2H), 6.64 (t, J = 7.5 Hz, 1H), 6.51 (d, J = 7.5 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 5.09 (s, 1H), 3.89 (d, J = 5.6 Hz, 1H), 3.85(s, 1H), 1.88-1.85(m, 1H), 1.81-1.55(m, 5H), 1.31-1.10(m, 4H), 1.06-0.95(m, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.12 (t, J = 7.5 Hz, 2H), 6.64 (t, J = 7.5 Hz, 1H), 6.51 (d, J = 7.5 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 5.09 (s, 1H), 3.89 (d, J = 5.6 Hz, 1H), 3.85 (s, 1H), 1.88-1.85 (m, 1H), 1.81-1.55 (m, 5H), 1.31-1.10 (m, 4H), 1.06-0.95 (m, 1H).

[실시예 17] (2-메틸렌-1-페닐-부트-3-엔일)-페닐-아민 ((2-Methylene-1-phenyl-but-3-enyl)-phenyl-amine) 의 제조Example 17 Preparation of (2-Methylene-1-phenyl-but-3-enyl) -phenyl-amine ((2-Methylene-1-phenyl-but-3-enyl) -phenyl-amine)

Figure 112008066835369-pat00024
Figure 112008066835369-pat00024

질소분위기 하에서 벤즈알데히드 (31.8 mg, 0.3 mmol), 아닐린 (41.1 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간 동안 교반한다. 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 2시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (2-메틸렌-1-페닐-부트-3-엔일)-페닐-아민 (41.7 mg, 59%)을 얻었다.Benzaldehyde (31.8 mg, 0.3 mmol), aniline (41.1 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added under a nitrogen atmosphere and stirred for 1 hour. After stirring, indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butane (95.4 mg. 0.45 mmol) were added to the reaction mixture, followed by stirring at room temperature for 2 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (2-methylene-1-phenyl-but-3-enyl) -phenyl-amine (41.7 mg, 59%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.41-7.26 (m, 5H), 7.14 (t, J = 7.6 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 7.6 Hz, 2H), 6.42 (dd, J = 17.8, J = 11.1 Hz, 1H) 5.33 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 3.99 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.41-7.26 (m, 5H), 7.14 (t, J = 7.6 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 7.6 Hz, 2H), 6.42 (dd, J = 17.8, J = 11.1 Hz, 1H) 5.33 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.16 (s, 1H), 5.09 (d, J = 11.1 Hz, 1H), 3.99 (s, 1H).

[실시예 18] [1-(4-클로로-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 ([1-(4-Chloro-phenyl)-2-methylene-but-3-enyl]-phenyl-amine)의 제조Example 18 [1- (4-Chloro-phenyl) -2-methylene-but-3-enyl] -phenyl-amine ([1- (4-Chloro-phenyl) -2-methylene-but-3- enyl] -phenyl-amine)

Figure 112008066835369-pat00025
Figure 112008066835369-pat00025

질소분위기 하에서 4-클로로벤즈알데히드 (42.2 mg, 0.3 mmol), 아닐린 (41.1 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간 동안 교반한다. 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 5시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 [1-(4-클로로-페닐)-2-메틸렌-부트-3-엔일]-페닐-아민 (48.4 mg, 60%)을 얻었다.In a nitrogen atmosphere, 4-chlorobenzaldehyde (42.2 mg, 0.3 mmol), aniline (41.1 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and a reaction solvent EtOH (1.2 mL) were added and stirred for 1 hour. After stirring, indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butane (95.4 mg. 0.45 mmol) were added to the reaction mixture, followed by stirring at room temperature for 5 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound [1- (4-chloro-phenyl) -2-methylene-but-3-enyl] -phenyl-amine (48.4 mg, 60%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.34-7.31 (m, 4H), 7.14 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.7 Hz, 1H), 6.52 (d, J = 7.7 Hz, 2H), 6.40 (dd, J = 17.8 Hz, J = 11.1 Hz, 1H) 5.32 (s, 1H), 5.26 (d, J =17.8 Hz, 1H), 5.20 (s, 1H), 5.14 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 3.96 (s, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.34-7.31 (m, 4H), 7.14 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.7 Hz, 1H), 6.52 (d, J = 7.7 Hz, 2H), 6.40 (dd, J = 17.8 Hz, J = 11.1 Hz, 1H) 5.32 (s, 1H), 5.26 (d, J = 17.8 Hz, 1H), 5.20 (s , 1H), 5.14 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 3.96 (s, 1H).

[실시예 19] 3-(2-메틸렌-1-페닐아미노-부트-3-엔일)-페놀 (3-(2-Methylene-1-phenylamino-but-3-enyl)-phenol)의 제조 Example 19 Preparation of 3- (2-methylene-1-phenylamino-but-3-enyl) -phenol (3- (2-Methylene-1-phenylamino-but-3-enyl) -phenol)

Figure 112008066835369-pat00026
Figure 112008066835369-pat00026

질소분위기 하에서 3-히드록시벤즈알데히드 (36.6 mg, 0.3 mmol), 아닐린 (41.1 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간동안 교반한다. 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 5시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 3-(2-메틸렌-1-페닐아미노-부트-3-엔일)-페놀 (40.7 mg, 54%) 얻었다.In a nitrogen atmosphere, 3-hydroxybenzaldehyde (36.6 mg, 0.3 mmol), aniline (41.1 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred for 1 hour. . After stirring, indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butane (95.4 mg. 0.45 mmol) were added to the reaction mixture, followed by stirring at room temperature for 5 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and the residue was separated by column chromatography to obtain 3- (2-methylene-1-phenylamino-but-3-enyl) -phenol (40.7 mg, 54%) as a title compound.

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.21-7.09 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 6.70 (t, J =7.6 Hz, 2H), 6.52 (d, J = 7.6 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.29 (s, 1H), 5.27 (d, J = 17.6 Hz, 1H), 5.24 (s, 1H), 5.09 (s, 1H), 5.08 (d, J = 11.1 Hz, 1H), 3.98 (br, 1H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.21-7.09 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 6.70 (t, J = 7.6 Hz, 2H), 6.52 (d, J = 7.6 Hz, 2H), 6.39 (dd, J = 17.6, J = 11.1 Hz, 1H), 5.29 (s, 1H), 5.27 (d, J = 17.6 Hz , 1H), 5.24 (s, 1H), 5.09 (s, 1H), 5.08 (d, J = 11.1 Hz, 1H), 3.98 (br, 1H).

[실시예 20] (4-메톡시-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 ((4-Methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl)-amine)의 제조 Example 20 (4-methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine ((4-Methoxy-phenyl)-(2-methylene-1-phenyl-but -3-enyl) -amine)

Figure 112008066835369-pat00027
Figure 112008066835369-pat00027

질소분위기 하에서 벤즈알데히드 (31.8 mg, 0.3 mmol), p-아니시딘(55.4 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간동안 교반한다. 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 6시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 (4-메톡시-페닐)-(2-메틸렌-1-페닐-부트-3-엔일)-아민 (40.6 mg, 51%)을 얻었다.Benzaldehyde (31.8 mg, 0.3 mmol), p -anisidine (55.4 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added under a nitrogen atmosphere and stirred for 1 hour. After stirring, indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butane (95.4 mg. 0.45 mmol) were added to the reaction mixture, followed by stirring at room temperature for 6 hours. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound (4-methoxy-phenyl)-(2-methylene-1-phenyl-but-3-enyl) -amine (40.6 mg, 51%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 7.40-7.25 (m, 5H), 6.74 (d, J = 8.9 Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 6.41 (dd, J = 17.8, J = 11.1 Hz, 1H), 5.31 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.08 (d, J = 11.1 Hz, 1H), 5.08 (s, 1H), 3.77 (br, 1H), 3.71 (s, 3H). 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 7.40-7.25 (m, 5H), 6.74 (d, J = 8.9 Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 6.41 (dd, J = 17.8, J = 11.1 Hz, 1H), 5.31 (s, 1H), 5.29 (s, 1H), 5.28 (d, J = 17.8 Hz, 1H), 5.08 (d, J = 11.1 Hz , 1H), 5.08 (s, 1H), 3.77 (br, 1H), 3.71 (s, 3H).

[실시예 21] 4-(2-메틸렌-1-페닐아미노-부트-3-엔일)-벤조익 엑시드 메틸 에스터 (4-(2-Methylene-1-phenylamino-but-3-enyl)-benzoic acid methyl ester)의 제조Example 21 4- (2-Methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester (4- (2-Methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester)

Figure 112008066835369-pat00028
Figure 112008066835369-pat00028

질소분위기 하에서 메틸 4-포밀벤조에이트 (49.3 mg, 0.3 mmol), 아닐린 (41.1 mg, 0.45 mmol), 아세틱 엑시드 (18 mg, 0.3 mmol)와 반응용매 EtOH (1.2 mL)를 넣고 1시간 동안 교반 후 반응 혼합물에 인듐 (68.9 mg, 0.6 mmol)과 1,4-다이브로모-2-부타인 (95.4 mg. 0.45 mmol)을 첨가 후 상온에서 1시간 교반시킨다. 물 (3 mL)을 첨가해 반응을 종결 시킨 후 Et2O (10 mL × 3)로 유기층을 추출하고 NaCl-수용액 (10 mL)으로 씻어준다. 추출한 유기층은 무수 MgSO4로 건조 뒤 여과한다. 용매를 감압 증류하고 관크로마토그래피로 분리하여 표제화합물인 4-(2-메틸렌-1-페닐아미노-부트-3-엔일)-벤조익 엑시드 메틸 에스터 (46.6 mg, 53%)을 얻었다.In a nitrogen atmosphere, methyl 4-formylbenzoate (49.3 mg, 0.3 mmol), aniline (41.1 mg, 0.45 mmol), acetic acid (18 mg, 0.3 mmol) and the reaction solvent EtOH (1.2 mL) were added and stirred for 1 hour. After adding indium (68.9 mg, 0.6 mmol) and 1,4-dibromo-2-butyne (95.4 mg. 0.45 mmol) to the reaction mixture, the mixture was stirred at room temperature for 1 hour. Terminate the reaction by adding water (3 mL), extract the organic layer with Et 2 O (10 mL × 3), and wash with NaCl-aqueous solution (10 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain the title compound 4- (2-methylene-1-phenylamino-but-3-enyl) -benzoic acid methyl ester (46.6 mg, 53%).

1H NMR (400 MHz, CDCl3 , 25℃, TMS): δ 8.01 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.14 (t, J = 7.5 Hz, 2H), 6.71 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.41 (dd, J = 17.7 Hz, J = 11.1 Hz, 1H), 5.33 (s, 1H), 5.28 (d, J = 17.7 Hz, 1H), 5.22 (s, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 4.03 (s, 1H), 3.90 (s, 3H) 1 H NMR (400 MHz, CDCl 3 , 25 ° C., TMS): δ 8.01 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.14 (t, J = 7.5 Hz, 2H), 6.71 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 7.5 Hz, 2H), 6.41 (dd, J = 17.7 Hz, J = 11.1 Hz, 1H), 5.33 (s, 1H) , 5.28 (d, J = 17.7 Hz, 1H), 5.22 (s, 1H), 5.17 (s, 1H), 5.11 (d, J = 11.1 Hz, 1H), 4.03 (s, 1H), 3.90 (s, 3H)

Claims (11)

하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체:1,3-butadien-2-yl methyl amine derivative represented by Formula 1 below: [화학식 1][Formula 1]
Figure 112010068609172-pat00029
Figure 112010068609172-pat00029
 [상기 화학식 1에서, A는 (C3-C9)시클로알킬, (C6-C12)아릴, (C1-C10)알콕시카보닐 또는 퓨릴이고; B는 (C6-C12)아릴, (C6-C12)아르(C1-C10)알킬 또는 (C6-C12)아르(C1-C10)알콕시이고; 상기 A 및 B의 시클로알킬, 아릴, 알콕시카보닐, 퓨릴, 아르알킬 또는 아르알콕시는 (C1-C10)알킬, (C1-C10)알콕시, 할로겐 또는 히드록시로부터 선택되는 하나 이상의 치환기가 더 치환될 수 있다.][In Formula 1, A is (C3-C9) cycloalkyl, (C6-C12) aryl, (C1-C10) alkoxycarbonyl or furyl; B is (C6-C12) aryl, (C6-C12) ar (C1-C10) alkyl or (C6-C12) ar (C1-C10) alkoxy; The cycloalkyl, aryl, alkoxycarbonyl, furyl, aralkyl or aralkoxy of A and B may be further substituted with one or more substituents selected from (C1-C10) alkyl, (C1-C10) alkoxy, halogen or hydroxy. Can be] 제 1항에 있어서,The method of claim 1, 상기 A는 시클로헥실, 클로로페닐, 메틸페닐, 히드록시페닐, 브로모페닐, 요오드페닐, 에톡시카보닐 또는 퓨릴이고; B는 요오드페닐, 벤질, 메톡시벤질 또는 벤질옥시인 것을 특징으로 하는 1,3-부타다이엔-2-일 메틸 아민 유도체.A is cyclohexyl, chlorophenyl, methylphenyl, hydroxyphenyl, bromophenyl, iodinephenyl, ethoxycarbonyl or furyl; B is iodinephenyl, benzyl, methoxybenzyl or benzyloxy; 1,3-butadien-2-yl methyl amine derivative. 제 1항에 있어서,The method of claim 1, 하기 화합물로부터 선택되는 것을 특징으로 하는 1,3-부타다이엔-2-일 메틸 아민 유도체. 1,3-butadien-2-yl methyl amine derivative, characterized in that it is selected from the following compounds:
Figure 112010068609172-pat00030
Figure 112010068609172-pat00030
 하기 화학식 3으로 표시되는 유기인듐 시약과 하기 화학식 4로 표시되는 이민 화합물을 반응시켜 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체를 제조하는 방법.1,3-butadien-2-yl methyl amine (1,3-butadien-2-yl represented by the following Chemical Formula 1 by reacting an indium compound represented by the following Chemical Formula 3 with an imine compound represented by the following Chemical Formula 4 to prepare methyl amine derivatives. [화학식 1] [Formula 1]
Figure 112010068609172-pat00031
Figure 112010068609172-pat00031
 [화학식 3](3)
Figure 112010068609172-pat00032
Figure 112010068609172-pat00032
 [화학식 4][Formula 4]
Figure 112010068609172-pat00033
Figure 112010068609172-pat00033
 [상기 화학식 1 및 4에서, A는 (C3-C9)시클로알킬, (C6-C12)아릴, (C1-C10)알콕시카보닐 또는 퓨릴이고; B는 (C6-C12)아릴, (C6-C12)아르(C1-C10)알킬 또는 (C6-C12)아르(C1-C10)알콕시이고; 상기 A 및 B의 시클로알킬, 아릴, 알콕시카보닐, 퓨릴, 아르알킬 또는 아르알콕시는 (C1-C10)알킬, (C1-C10)알콕시, 할로겐 또는 히드록시로부터 선택되는 하나 이상의 치환기가 더 치환될 수 있다.][In Formulas 1 and 4, A is (C3-C9) cycloalkyl, (C6-C12) aryl, (C1-C10) alkoxycarbonyl or furyl; B is (C6-C12) aryl, (C6-C12) ar (C1-C10) alkyl or (C6-C12) ar (C1-C10) alkoxy; The cycloalkyl, aryl, alkoxycarbonyl, furyl, aralkyl or aralkoxy of A and B may be further substituted with one or more substituents selected from (C1-C10) alkyl, (C1-C10) alkoxy, halogen or hydroxy. Can be] 제 4항에 있어서,The method of claim 4, wherein 하기 화학식 3으로 표시되는 유기인듐 시약은 하기 화학식 2로 표시되는 1,4-다이브로모-2-부타인(1,4-dibromo-2-butyne) 화합물과 인듐(Indium; In)과 반응시켜 제조되는 것을 특징으로 하는 방법.The organic indium reagent represented by the following Chemical Formula 3 is prepared by reacting a 1,4-dibromo-2-butyne compound represented by the following Chemical Formula 2 with an indium (Indium). Characterized in that the method. [화학식 2][Formula 2]
Figure 112008066835369-pat00034
Figure 112008066835369-pat00034
 [화학식 3](3)
Figure 112008066835369-pat00035
Figure 112008066835369-pat00035
 하기 화학식 2로 표시되는 1,4-다이브로모-2-부타인(1,4-dibromo-2-butyne) 화합물, 인듐(Indium; In) 및 화학식 4로 표시되는 이민 화합물을 반응시켜 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민(1,3-butadien-2-yl methyl amine) 유도체를 제조하는 방법.To 1,4-dibromo-2-butyne (1,4-dibromo-2-butyne) compound, Indium (In) and the imine compound represented by the formula (4) represented by the formula (2) A method for producing a 1,3-butadien-2-yl methyl amine (1,3-butadien-2-yl methyl amine) derivative represented by. [화학식 1][Formula 1]
Figure 112010068609172-pat00036
Figure 112010068609172-pat00036
 [화학식 2][Formula 2]
Figure 112010068609172-pat00037
Figure 112010068609172-pat00037
 [화학식 3](3)
Figure 112010068609172-pat00038
Figure 112010068609172-pat00038
 [화학식 4][Formula 4]
Figure 112010068609172-pat00039
Figure 112010068609172-pat00039
 [상기 화학식 1 및 4에서, A는 (C3-C9)시클로알킬, (C6-C12)아릴, (C1-C10)알콕시카보닐 또는 퓨릴이고; B는 (C6-C12)아릴, (C6-C12)아르(C1-C10)알킬 또는 (C6-C12)아르(C1-C10)알콕시이고; 상기 A 및 B의 시클로알킬, 아릴, 알콕시카보닐, 퓨릴, 아르알킬 또는 아르알콕시는 (C1-C10)알킬, (C1-C10)알콕시, 할로겐 또는 히드록시로부터 선택되는 하나 이상의 치환기가 더 치환될 수 있다.][In Formulas 1 and 4, A is (C3-C9) cycloalkyl, (C6-C12) aryl, (C1-C10) alkoxycarbonyl or furyl; B is (C6-C12) aryl, (C6-C12) ar (C1-C10) alkyl or (C6-C12) ar (C1-C10) alkoxy; The cycloalkyl, aryl, alkoxycarbonyl, furyl, aralkyl or aralkoxy of A and B may be further substituted with one or more substituents selected from (C1-C10) alkyl, (C1-C10) alkoxy, halogen or hydroxy. Can be] 제 5항 또는 제 6항에 있어서, The method according to claim 5 or 6, 인듐 (Indium; In)은 상기 화학식 4로 표시되는 이민 화합물에 대하여 1.5 내지 2.5 당량 범위로 사용되는 것을 특징으로 하는 방법.Indium (In) is a method characterized in that it is used in the range of 1.5 to 2.5 equivalents relative to the imine compound represented by the formula (4). 제 5항 또는 제 6항에 있어서, The method according to claim 5 or 6, 상기 화학식 2로 표시되는 1,4-다이브로모 부타인 화합물은 상기 화학식 4로 표시되는 이민 화합물에 대하여 1.0 내지 2.0 당량 범위로 사용되는 것을 특징으로 하는 방법.The 1,4-dibromo butyne compound represented by Formula 2 is used in the range of 1.0 to 2.0 equivalents relative to the imine compound represented by the formula (4). 제 5항 또는 제 6항에 있어서, The method according to claim 5 or 6, 건조제인 마그네슘 설페이트(MgSO4)를 상기 화학식 4로 표시되는 이민 화합물에 대하여 0.5 내지 1.5 당량 범위로 더 첨가시키는 것을 특징으로 하는 제조방법.Magnesium sulfate (MgSO 4 ) is a drying agent, characterized in that the addition of 0.5 to 1.5 equivalents to the imine compound represented by the formula ( 4 ). 하기 화학식 5로 표시되는 알데히드 유도체와 하기 화학식 6로 표시되는 아민 유도체의 축합반응을 통해 얻어진 이민 화합물을 별도로 분리하지 않고 아세트산(AcOH) 존재하에서, 화학식 3으로 표시되는 1,3-부타다이엔-2-일 인듐 시약과의 첨가반응을 통해 하기 화학식 1로 표시되는 1,3-부타다이엔-2-일 메틸 아민 (1,3-butadien-2-yl methyl amine) 유도체를 제조하는 방법.1,3-butadiene- represented by the formula (3) in the presence of acetic acid (AcOH) without separately separating the imine compound obtained through the condensation reaction of the aldehyde derivative represented by the formula (5) and the amine derivative represented by the formula (6) Method of preparing a 1,3-butadien-2-yl methyl amine derivative represented by the following formula (1) through a reaction with a 2-yl indium reagent. [화학식 1][Formula 1]
Figure 112010068609172-pat00040
Figure 112010068609172-pat00040
 [화학식 3](3)
Figure 112010068609172-pat00041
Figure 112010068609172-pat00041
 [화학식 5][Chemical Formula 5]
Figure 112010068609172-pat00042
Figure 112010068609172-pat00042
 [화학식 6][Formula 6]
Figure 112010068609172-pat00043
Figure 112010068609172-pat00043
 [상기 화학식 1, 5 및 6에서, A는 (C3-C9)시클로알킬, (C6-C12)아릴, (C1-C10)알콕시카보닐 또는 퓨릴이고; B는 (C6-C12)아릴, (C6-C12)아르(C1-C10)알킬 또는 (C6-C12)아르(C1-C10)알콕시이고; 상기 A 및 B의 시클로알킬, 아릴, 알콕시카보닐, 퓨릴, 아르알킬 또는 아르알콕시는 (C1-C10)알킬, (C1-C10)알콕시, 할로겐 또는 히드록시로부터 선택되는 하나 이상의 치환기가 더 치환될 수 있다.][In Formulas 1, 5 and 6, A is (C3-C9) cycloalkyl, (C6-C12) aryl, (C1-C10) alkoxycarbonyl or furyl; B is (C6-C12) aryl, (C6-C12) ar (C1-C10) alkyl or (C6-C12) ar (C1-C10) alkoxy; The cycloalkyl, aryl, alkoxycarbonyl, furyl, aralkyl or aralkoxy of A and B may be further substituted with one or more substituents selected from (C1-C10) alkyl, (C1-C10) alkoxy, halogen or hydroxy. Can be] 제 10항에 있어서, The method of claim 10, 아세트산(AcOH)은 상기 화학식 5로 표시되는 알데히드 유도체에 대하여 0.5 내지 1.5 당량 범위로 첨가되는 것을 특징으로 하는 방법.Acetic acid (AcOH) is added in the range of 0.5 to 1.5 equivalents based on the aldehyde derivative represented by the formula (5).
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