KR101540623B1 - Novel preparation method of benzoxazole derivative - Google Patents
Novel preparation method of benzoxazole derivative Download PDFInfo
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Abstract
본 발명은 하기 화학식 1로 표시되는 알키닐레이션(alkynylation) 된 벤즈옥사졸(benzoxazole) 유도체의 제조방법에 관한 것으로, 보다 상세하게는, 팔라듐 촉매, 포스핀계 리간드로 1,3-bis(diphenylphosphino)propane 존재 하에서 은염(silver salt), 프로피올릭 산(propiolic acid) 및 벤즈옥사졸 화합물을 반응시켜 알키닐레이션(alkynylation) 된 벤즈옥사졸 유도체의 제조방법에 관한 것이다.The present invention relates to a process for preparing an alkynylated benzoxazole derivative represented by the following general formula (1), more specifically, to a process for producing a benzoxazole derivative represented by the following general formula (1) The present invention relates to a process for preparing benzoxazole derivatives which are alkynylated by reacting silver salt, propiolic acid and benzoxazole compounds in the presence of propane.
Description
본 발명은 새로운 벤즈옥사졸 유도체의 제조방법에 관한 것이다.The present invention relates to a process for the preparation of novel benzoxazole derivatives.
질소와 산소 원자를 모두 포함하는 오각고리 형태의 화합물인 벤즈옥사졸 유도체는 다양한 생물학적 활성을 가지고 있어 의약학 산업 및 재료 산업에 이용되고 있다. 따라서 이러한 벤즈옥사졸 유도체에 다양한 치환기를 도입하기 위해 많은 연구가 보고되었다. 특히, 탄소-수소 결합 활성화 반응을 통해 벤즈옥사졸 유도체의 2번 위치에 알키닐기를 도입하기 위해 다양한 반응들이 보고되었다(Angew . Chem . Int. Ed., 2009, 48, 9553; Org . Lett. 2009, 11, 4156; Org . Lett. 2010, 12, 2358; Org . Lett. 2010, 12, 4038; J. Org . Chem. 2010, 75, 1764; Org . Lett. 2011, 13, 1474; Adv . Synth . Catal . 2011, 353, 3085; Tetrahedron Lett. 2011, 52, 5617; J. Am . Chem . Soc. 2012, 77, 5381).Benzoxazole derivatives, which are pentachloro-type compounds containing both nitrogen and oxygen atoms, have various biological activities and are used in the pharmaceutical industry and in the materials industry. Therefore, many studies have been reported to introduce various substituents into these benzoxazole derivatives. In particular, various reactions have been reported to introduce an alkynyl group at position 2 of the benzoxazole derivative via a carbon-hydrogen bond activation reaction ( Angew . Chem . Int. Ed ., 2009 , 48 , 9553; Org . Lett . 2009, 11, 4156; Org Lett 2010, 12, 2358;.. Org Lett 2010, 12, 4038;.. J. Org Chem 2010, 75, 1764;.... Org Lett 2011, 13, 1474; Adv. Synth . Catal ., 2011 , 353 , 3085; Tetrahedron Lett . 2011 , 52 , 5617; J. Am . Chem . Soc . 2012 , 77 , 5381).
그러나, 프로피올릭 산 유도체로부터 탈탄산 반응을 통해 손쉽게 금속-아세틸라이드 친핵체를 제조하는 동시에 이를 탄소-수소 결합 활성화 반응을 통한 벤즈옥사졸 유도체의 2번 위치에 알키닐기를 도입하는 반응은 현재까지 보고된 바가 없다.However, the metal-acetylide nucleophile is easily produced through the decarboxylation reaction from the propiolic acid derivative, and the reaction of introducing the alkynyl group at the 2-position of the benzoxazole derivative through the carbon-hydrogen bond activation reaction has been reported There is no bar.
본 발명은 팔라듐 촉매로 PdCl2, 포스핀계 리간드로 1,3-bis(diphenylphosphino)propane 존재 하에서 프로피올릭 산 유도체의 탈탄산 반응과 탄소-수소 결합 활성화 반응을 통해 벤즈옥사졸 2번 위치에 알키닐기를 도입하는 제조방법을 제공한다.The present invention relates to a process for the production of PdCl 2 as a palladium catalyst, a decarbonation reaction of a propiolic acid derivative in the presence of 1,3-bis (diphenylphosphino) propane as a phosphine ligand and an alkynyl Group is introduced.
본 발명은 다양한 생물학적 활성을 가져 다양한 의약품 및 재료물질의중간체로 사용가능한 벤즈옥사졸 유도체의 제조방법을 제공하는 것으로, 보다 상세하게는 팔라듐 촉매로 PdCl2, 포스핀계 리간드로 1,3-bis(diphenylphosphino)propane 존재 하에서 하기 화학식 2의 프로피올릭산 유도체, 하기 화학식 3의 은염 및 하기 화학식 4의 벤즈옥사졸 화합물을 반응시켜 하기 화학식 1로 표시되는 벤즈옥사졸 유도체를 제공한다.The invention 1,3-bis as PdCl 2, phosphine ligand pingye a variety of different biologically active brought to provide a method of manufacturing a benzoxazole derivative usable as an intermediate of pharmaceuticals and material substance, and more particularly, a palladium catalyst ( diphenylphosphino) propane represented by the following general formula (2), a silver salt represented by the following general formula (3), and a benzoxazole compound represented by the following general formula (4) to provide a benzoxazole derivative represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
[화학식 2](2)
[화학식 3](3)
(Ag)nX1 (Ag) nX 1
[화학식 4][Chemical Formula 4]
[상기 화학식 1 내지 화학식 4에서 [In the formulas (1) to (4)
R1 내지 R4는 수소, 할로겐 및 (C1~C7)알킬기로부터 선택되고;R은 (C1~C7)알킬기, (C6~C20)아릴기, (C1-C7)알킬기 또는 (C1-C7)알콕시로 치환된 (C6~C20)아릴기로부터 선택되고;R 1 To R 4 is selected from hydrogen, halogen and (C1 ~ C7) alkyl group and; R is (C1 ~ C7) alkyl, (C6 ~ C20) aryl, optionally substituted with (C1-C7) alkyl or (C1-C7) alkoxy (C6-C20) aryl group;
X1은 Cl, Br, I, NO2, OTf, CO3 또는 O에서 선택되며;X 1 is selected from Cl, Br, I, NO 2 , OTf, CO 3 or O;
n은 X1의 산화수이다.]n is an oxidation number of X < 1 & gt ;.
본 발명의 벤즈옥사졸 유도체의 제조방법은 상기 화학식 2의 프로피올릭산의 탈탄산반응이 진행되어 유기은염이 제조되고 제조된 유기은염이 벤즈옥사졸 화합물의 탄소-수소 결합 활성화를 통해 탄소-탄소 결합반응으로 제조되는 것으로 one-pot에 in-suit로 일어나 여러 단계를 거치지 않는 간단한 공정으로 알키닐 기가 도입된 벤즈옥사졸 유도체의 제조가 가능하다.The method for preparing the benzoxazole derivative of the present invention is characterized in that the decarbonation of the propiolic acid of Formula 2 proceeds and the organic silver salt is prepared and the prepared silver salt is reacted with the carbon- And it is possible to prepare a benzoxazole derivative in which an alkynyl group is introduced by a simple process in which one-pot is carried out in situ without any steps.
1) 일반적인 탄소간의 공유결합을 형성하는 촉매 짝지움 반응은 미리 활성화된 친전자체 (예를 들어 아릴 할라이드 또는 아릴 트리플레이트 등)를 사용한다. 따라서 이 때 사용하는 활성화된 친전자체들은 가격이 상대적으로 고가이며 합성하기 위해서 추가 단계가 요구되기 때문에 다양한 치환기를 가진 생성물을 얻기가 어려운 단점이 있다. 또한 짝지움 반응시 유기금속 화합물을 사용하기 때문에 반드시 독성이 큰 금속 염화물들이 당량 이상 부산물로 생성된다는 단점이 있다. 이러한 단점을 극복하기 위해서 최근 탄소-수소 결합 활성화 (activation) 반응을 이용하여 탄소간 혹은 탄소와 헤테로 원자간의 공유결합 합성법 연구가 전세계적으로 활발하게 이루어지고 있다. 이 반응의 장점은 탄소-수소 결합을 미리 반응성이 높은 작용기로 활성화 시키지 않고 직접 탄소-수소 결합을 활성화 하기 때문에 기존 방법에 비하여 큰 장점을 가지고 있다. 따라서 이 방법의 이용시 전통적인 유기합성법으로 합성하기 어려운 화합물들을 손쉽게 합성할 수 있는 장점이 있다. 일반적으로 지금까지 벤즈옥사졸 유도체의 2번 위치에 알키닐 기를 도입하는 방법에는 세가지가 있다(하기 반응식 1에 도시).Terminal alkyne을 사용하는 경우 : 이 경우 출발물질을 얻기는 쉬우나 tert-BuOLi 와 같은 강염기를 과량 (적어도 3 당량) 사용하기 때문에 작용기 선택성이 매우 나쁘며 또한 독성을 가지는 Li 염화물이 부생성물로 과량 생성되는 단점이 있다. 1) The catalytic coupling reaction, which forms a common carbon-carbon covalent bond, uses a preactivated electrophile (such as an aryl halide or aryl triflate). Therefore, the activated electrophiles used at this time are relatively expensive and require additional steps to synthesize, which makes it difficult to obtain products having various substituents. In addition, since organometallic compounds are used in the coupling reaction, there is a disadvantage that metal chlorides which are highly toxic are produced as by-products more than equivalents. In order to overcome these disadvantages, researches on the synthesis of covalent bonds between carbon atoms or carbon and heteroatoms using carbon - hydrogen bond activation reaction have been actively carried out all over the world. The advantage of this reaction is that it has a great advantage over the conventional method because it directly activates the carbon-hydrogen bond without activating the carbon-hydrogen bond to a highly reactive functional group in advance. Therefore, when this method is used, it is possible to easily synthesize compounds which are difficult to synthesize by a conventional organic synthesis method. In general, there are three methods for introducing an alkynyl group at the 2-position of a benzoxazole derivative (as shown in the following Reaction Scheme 1). In the case of using the terminal alkyne: In this case, it is easy to obtain the starting material, (Such as at least 3 equivalents) of the same strong base, there is a disadvantage in that the selectivity of the functional group is very poor and the toxic Li chloride is excessively produced as a by-product.
2)Alkynyl bromide를 사용하는 경우 : 이 경우 alkynyl bromide를 따로 만들어야 하는 단점이 있으며 이 화합물은 불안정하다. 또한 이때도 tert-BuOLi 와 같은 강 염기를 과량 (적어도 3 당량) 사용하기 때문에 작용기 선택성이 매우 나쁘며 또한 독성을 가지는 LiBr가 부생성물로 과량 생성되는 단점이 있다. 또한 이때 bromide 화합물을 사용하기 때문에 mass balance 관점에서 문제점을 가지고 있다.2) When using Alkynyl bromide: In this case, alkynyl bromide must be prepared separately and this compound is unstable. Also, at this time, since a strong base such as tert-BuOLi is used in excess (at least 3 equivalents), the functional group selectivity is very poor and the toxic LiBr is excessively produced as an by-product. Also, since bromide compounds are used at this time, they have problems in view of mass balance.
3)Dichloroalkene를 사용하는 경우 : Alkynyl bromide의 단점을 보완하고자 대신 dichloroalkene 화합물을 이용하는 경우가 보고되었다. 그러나 이 경우도 tert-BuOLi 와 같은 강 염기를 과량 (적어도 3 당량)을 사용하며 chloro 기 두개가 떨어저 나가기 때문에 mass balance 관점에서 문제점이 잇다. 3) When dichloroalkene is used: dichloroalkene compounds have been reported to replace the disadvantages of Alkynyl bromide. In this case, however, there is a problem in terms of mass balance because two or more chloro groups are used in excess (at least 3 equivalents) of strong bases such as tert-BuOLi.
[반응식 1][Reaction Scheme 1]
따라서 이러한 문제점을 개선하기 위해 본 발명은안정하고 가격이 저렴하고 손쉽게 구할 수 있는 프로피올릭 산을 이용하여 무해한 이산화탄소가 부산물로 생성되는 매우 환경 친화적인 반응을 개발하였다. 또한 본 발명의 벤즈옥사졸 유도체의 제조방법은 강한 염기를 사용하지 않는다는 장점을 가지고 있기 때문에 기존 방법에 비하여 매우 효과적이며, 또한 친전자체를 미리 활성화할 필요가 없고 벤즈옥사졸을 바로 직접 출발물질로 사용하기 때문에 매우 효율적인 방법이다.In order to solve these problems, the present invention has developed a highly environmentally friendly reaction in which harmless carbon dioxide is produced as a by-product using propiolic acid which is stable, cheap and easily available. In addition, since the method for preparing the benzoxazole derivative of the present invention has an advantage that strong bases are not used, it is very effective as compared with the conventional method, and it is not necessary to activate the electrophile beforehand and benzoxazole is directly used as a direct starting material It is a very efficient way to use.
또한 상기와 같은 친전자체는 반응 후 독성이 있는 금속염화물들이 부산물로 배출되는 단점이 있어 친환경적이지 않다.In addition, the above electrophiles themselves are not environmentally friendly since they have the disadvantage that toxic metal chlorides are discharged as by-products after the reaction.
그러나 본 발명의 벤즈옥사졸 유도체의 제조방법은 상기와 같은 친전자체를 사용하지 않아 다양한 치환기를 가진 벤즈옥사졸 유도체를 합성할 수 있으며, 반응후 독성물질이 배출되지 않아 매우 친환경적이다.However, since the benzoxazole derivative of the present invention does not use the above electrophile, the benzoxazole derivative having various substituents can be synthesized, and toxic substances are not discharged after the reaction, which is very environmentally friendly.
또한 본 발명의 벤즈옥사졸 유도체의 제조방법은 상기와 같은 친전자체를 사용하지 않아 미리 활성화 시킬 필요가 없어 여러단계의 공정이 필요하지 않아 매우 효율적이며 경제적이다. In addition, since the benzoxazole derivative of the present invention does not use the electrophile as described above, it is not necessary to activate the benzoxazole derivative in advance, so that it is very efficient and economical because it does not require a multi-step process.
본 발명의 일 실시예에 따른 상기 화학식 1에서 바람직하게 R1 및 R4는 수소이며; R2는 수소 및 (C1~C7)알킬기로부터 선택되고; R3은 수소, (C1~C7)알킬기 및 할로겐으로부터 선택될 수 있다.In Formula 1 according to an embodiment of the present invention, preferably, R 1 and R 4 are hydrogen; R 2 is selected from hydrogen and (C 1 -C 7) alkyl groups; R 3 can be selected from hydrogen, (C 1 -C 7) alkyl, and halogen.
보다 바람직하게는 상기 화학식 2는 하기 화학식 5로 표시될 수 있다. More preferably, the formula (2) may be represented by the following formula (5).
[화학식 5][Chemical Formula 5]
[상기 화학식 5에서,[In the formula (5)
R11 내지 R15는 수소, (C1-C7)알킬 또는 (C1-C7)알콕시이거나, 서로 인접한 치환체들은 (C2-C7)알케닐렌 또는 (C2-C7)알키닐렌으로 연결되어 방향족고리를 형성할 수 있다.]R 11 to R 15 are hydrogen, (C 1 -C 7) alkyl or (C 1 -C 7) alkoxy, or adjacent substituents are connected by (C 2 -C 7) alkenylene or (C 2 -C 7) alkynylene to form an aromatic ring Can be.]
구체적으로, 상기 화학식 1 또는 4에서 R2은 수소 및 메틸기로부터 선택되고;Specifically, in Formula 1 or 4, R 2 is selected from hydrogen and a methyl group;
R3는 수소, 메틸기, t부틸기 및 클로린기로부터 선택되며;R 3 is selected from hydrogen, a methyl group, a t- butyl group and a chlorine group;
R는 펜틸기, 페닐기, 메틸페닐기, 메톡시페닐기, 나프틸기 및 클로로페닐기로부터 선택될 수 있다.R may be selected from a pentyl group, a phenyl group, a methylphenyl group, a methoxyphenyl group, a naphthyl group and a chlorophenyl group.
본 발명의 일 실시예에 따른 상기 화학식 1의 벤즈옥사졸 유도체는 보다 구체적으로 하기의 화합물일 수 있다.The benzoxazole derivative of Formula 1 according to an embodiment of the present invention may be more specifically the following compounds.
본 발명의 제조방법에서 사용되는 반응용기는 둥근바닥 플라스크, 테스트튜브 (test tube) 및 V-바이알로 이루어진 군에서 선택되는 것이 바람직하며, V-바이알을 사용하는 것이 더욱 바람직하다. V-바이알을 사용하는 이유는 열에너지를 효과적으로 전달하기 위함이고 보통의 플라스크에서도 반응이 진행한다.The reaction vessel used in the production method of the present invention is preferably selected from the group consisting of a round bottom flask, a test tube, and a V-vial, more preferably a V-vial. The reason for using V-vial is to effectively transfer heat energy and the reaction proceeds even in a normal flask.
본 발명의 제조방법에서 사용되는 촉매는 팔라듐 촉매로 PdCl2이며,The catalyst used in the production process of the present invention is PdCl 2 as a palladium catalyst,
상기 팔라듐 촉매의 사용량은 상기 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 0.1 몰 내지 1.0 몰 범위로 사용하도록 하며, 가장 바람직하기로는 0.1 당량을 사용하는 것이 좋다.The amount of the palladium catalyst to be used is in the range of 0.1 mole to 1.0 mole per mole of the benzoxazole compound of Formula 4, and most preferably 0.1 mole equivalent.
본 발명의 제조방법에서 사용되는 포스핀계 리간드로는 dppp [1,3-bis(diphenylphosphino)propane 이며Examples of the phosphine-based ligand used in the production method of the present invention include dppp [1,3-bis (diphenylphosphino) propane
상기 포스핀계 리간드의 사용량은 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 0.2 몰 내지 2.0 몰 범위로 사용하도록 하며 상기 범위가 수율 및 경제성 측면에서 바람직하고, 0.2 몰을 사용하는 것이 더욱 바람직하다. The amount of the phosphine-based ligand to be used is in the range of 0.2 to 2.0 mol per 1 mol of the benzoxazole compound of the formula (4). The range is preferred from the viewpoints of yield and economy, more preferably 0.2 mol.
본 발명의 제조방법에서 사용되는 상기 화학식 2의 프로피올릭 산의 사용량은 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 1.0 몰 내지 3.0 몰 범위로 사용하도록 하며, 1.5 몰을 사용하는 것이 더욱 바람직하다.The amount of the propiolic acid of Formula 2 used in the production method of the present invention is preferably in the range of 1.0 mol to 3.0 mol based on 1 mol of the benzoxazole compound of Formula 4, more preferably 1.5 mol .
본 발명의 제조방법에서 사용되는 상기 화학식 3의 은염의 사용량은 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 1.0 몰 내지 3.0 몰 범위로 사용하도록 하며, 3.0 몰을 사용하는 것이 더욱 바람직하다.The amount of the silver salt of Formula 3 used in the production method of the present invention is preferably in the range of 1.0 mol to 3.0 mol per mol of the benzoxazole compound of Formula 4, more preferably 3.0 mol.
본 발명의 제조방법에서 사용되는 상기 화학식 3의 은염은 산화은(I)(Ag2O)을 사용하는 것이 가장 바람직하다.The silver salt of Formula 3 used in the production method of the present invention is most preferably silver (I) oxide (Ag 2 O).
상기 화학식 2의 프로피올릭 산 화합물과 상기 화학식 4의 벤즈옥사졸 유도체의 반응은 유기 용매 하에서 이루어 질 수 있으며, 상기 반응물질을 용해할 수 있는 것이라면 유기용매에 제한을 둘 필요는 없다. 상기 유기용매로는 다이옥산, 테트라하이드로퓨란, 다이메틸포름아마이드, 다이클로로메탄, 다이클로로에탄, 벤젠, 톨루엔 및 이들의 혼합물로 이루어진 군에서 선택되며 반응물의 용해성 및 제거의 용이성 또한 반응 효율면을 고려할 때 극성이 낮은, 벤젠을 사용하는 것이 더욱 바람직하다.The reaction between the propiolic acid compound of Formula 2 and the benzoxazole derivative of Formula 4 may be carried out in an organic solvent, and the organic solvent may be any organic solvent as long as it can dissolve the reactant. The organic solvent may be selected from the group consisting of dioxane, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, benzene, toluene, and mixtures thereof. It is more preferable to use benzene having a low polarity.
반응온도는 50 내지 100℃ 범위에서 수행하며, 60 내지 80℃ 범위에서 수행하는 것이 바람직하다. 반응시간은 10시간 내지 18시간, 바람직하게는 10시간 내지 12시간 동안 반응하는 것이 유리하다. 이는 반응시간이 지나치게 길어지거나 부산물이 발생하여 반응 수율이 저하될 수 있기 때문이다. TLC 등을 통하여 출발물질인 화학식 4의 벤즈옥사졸 화합물이 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 temperature is preferably in the range of 50 to 100 ° C and preferably in the range of 60 to 80 ° C. The reaction time is advantageously 10 hours to 18 hours, preferably 10 hours to 12 hours. This is because the reaction time may become excessively long or by-products may occur and the reaction yield may be lowered. After confirming that the benzoxazole compound of formula (4) as a starting material is consumed through TLC or the like, the reaction is completed. 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.
본 발명에 따른 벤즈옥사졸 유도체들은 천연물의 기본골격으로 사용될 뿐만 아니라 이를 통해 신약 및 다양한 의약품의 개발이 가능하다. 본 발명에서는 기존에 활성화된 알카인을 이용한 벤즈옥사졸 유도체들에 대한 알키닐레이션 반응이 아니라 안정하고 값이 저렴한 프로피올릭 산 유도체를 은염과의 탈탄산 반응을 통해 손쉽게 유기은염을 제조한 후 이를 벤즈옥사졸 유도체에 대한 알키닐레이션 반응에 이용하여 매우 효율적이고 경제적으로 2번 위치에 알키닐기가 도입된 벤즈옥사졸 유도체를 제조할 수 있다. 또한 본 발명은 강 염기 사용 없이 프로피올릭 산의 탈탄산 반응을 통해서 진행되었고 인체에 무해한 이산화탄소가 부산물로 배출된다는 장점이 있다.The benzoxazole derivatives according to the present invention can be used not only as a basic skeleton of natural products but also through the development of new drugs and various medicines. In the present invention, instead of the alkynylation reaction for the benzoxazole derivatives using the previously activated alkane, the stable and low-cost propiolic acid derivative can be easily produced through the decarboxylation reaction with the silver salt, It is possible to prepare a benzoxazole derivative in which an alkynyl group is introduced at the 2-position in a very efficient and economical manner by using the alkynylation reaction for the benzoxazole derivative. Further, the present invention proceeds through the decarbonation reaction of propiolic acid without the use of a strong base, and carbon dioxide which is harmless to the human body is discharged as a by-product.
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.
[[ 실시예Example 1] 2-( 1] 2- ( 페닐에티닐Phenylethynyl )) 벤즈옥사졸Benzoxazole [2-( [2-( phenylethynylphenylethynyl )) benzoxazolebenzoxazole ]의 제조]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 페닐프로피올릭산 (65.8 mg, 0.45 mmol), 벤즈옥사졸 (35.7 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60 ℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-(페닐에티닐)벤즈옥사졸 (51.3 mg, 78%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), and phenylpropiolic acid (65.8 mg, 0.45 mmol) Oxazole (35.7 mg, 0.3 mmol) was added, benzene (1.8 mL) was added, and the mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the resultant was purified by column chromatography to obtain the title compound, 2- (phenylethynyl) benzoxazole (51.3 mg, 78%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.78-7.76 (m, 1H), 7.68-7.66 (m, 2H), 7.56-7.54 (m, 1H), 7.49-7.37 (m, 5H)
1 H NMR (400 MHz, CDCl 3, 25 ℃, TMS): d = 7.78-7.76 (m, 1H), 7.68-7.66 (m, 2H), 7.56-7.54 (m, 1H), 7.49-7.37 (m , 5H)
[[ 실시예Example 2] 2-( 2] 2- ( 헵트Hept -1--One- 이닐Isil )) 벤즈옥사졸Benzoxazole [2-( [2-( hepthept -1--One- ynylynyl )) benzoxazolebenzoxazole ]의 제조]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 옥타이노익산 (63.1 mg, 0.45 mmol), 벤즈옥사졸 (35.7 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-(헵트-1-이닐)벤즈옥사졸 (39 mg, 61%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2Benzene (1.8 mL) was added thereto, and the mixture was stirred at 60 ° C for 12 hrs. After stirring, the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. The solvent was removed and the resultant was purified by column chromatography to obtain the title compound, 2- (hept-1-ynyl) benzoxazole (39 mg, 61%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.72-7.70 (m, 1H), 7.51-7.49 (m, 1H), 7.40-7.33 (m, 2H), 2.51 (t, J = 7.1 Hz, 2H), 1.68 (quint, J = 7.3 Hz, 2H), 1.51-1.32 (m, 4H), 0.93 (t, J = 7.2 Hz, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.72-7.70 (m, 1H), 7.51-7.49 (m, 1H), 7.40-7.33 (m, 2H), 2.51J = 7.1 Hz, 2H), 1.68 (quint,J = 7.3 Hz, 2H), 1.51-1.32 (m, 4H), 0.93 (t,J = 7.2 Hz, 3 H)
[[ 실시예Example 3] 2-((4- 3] 2 - ((4- 메톡시페닐Methoxyphenyl )) 에티닐Ethynyl )) 벤즈옥사졸Benzoxazole [2-((4-methoxyphenyl)ethynyl)benzoxazole]의 제조 Preparation of [2 - ((4-methoxyphenyl) ethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(4-메톡시페닐)프로피올릭산 (79.3 mg, 0.45 mmol), 벤즈옥사졸 (35.7 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-((4-메톡시페닐)에티닐)벤즈옥사졸 (47 mg, 63%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag23- (4-methoxyphenyl) propiolic acid (79.3 mg, 0.45 mmol) and benzoxazole (35.7 mg, 0.3 mmol) were added thereto and benzene (1.8 mL ) Was added and stirred at 60 ° C for 12 hours, and then the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the resultant was purified by column chromatography to obtain the title compound, 2 - ((4-methoxyphenyl) ethynyl) benzoxazole (47 mg, 63%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.75 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 7.2 Hz, 1H), 7.42-7.37 (m, 2H), 6.93 (d, J = 8.2 Hz, 2H), 3.85 (d, J = 4.8 Hz, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.75 (d,J = 7.5 Hz, 1 H), 7.61 (d,J = 8.2 Hz, 2H), 7.54 (d,J = 7.2 Hz, IH), 7.42-7.37 (m, 2H), 6.93 (d,J = 8.2 Hz, 2H), 3.85 (d,J = 4.8 Hz, 3H)
[[ 실시예Example 4] 2-( 4] 2- ( 메타Meta -- 톨릴에티닐Tolyl ethynyl )) 벤즈옥사졸Benzoxazole [2-(m- [2- (m- tolylethynyltolylethynyl )) benzoxazolebenzoxazole ]의 제조]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-메타-톨릴프로피올릭산 (72.1 mg, 0.45 mmol), 벤즈옥사졸 (35.7 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-(메타-톨릴에티닐)벤즈옥사졸 (49 mg, 70%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag23-meta-tolylpropiolic acid (72.1 mg, 0.45 mmol) and benzoxazole (35.7 mg, 0.3 mmol) were added thereto, followed by addition of benzene (1.8 mL) After stirring at 60 DEG C for 12 hours, the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the resultant was purified by column chromatography to obtain the title compound, 2- (meta-tolylethynyl) benzoxazole (49 mg, 70%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.77-7.75 (m, 1H), 7.54 (dd, J = 7.0 Hz, 1.8 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.43-7.36 (m, 2H), 7.32-7.28 (m, 2H), 2.38 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.77-7.75 (m, 1 H), 7.54 (dd,J = 7.0 Hz, 1.8 Hz, 1 H), 7.47 (d,J 2H), 7.33-7.36 (m, 2H), 7.32-7.28 (m, 2H), 2.38 (s, 3H)
[[ 실시예Example 5] 2-(나프탈렌-1- 5] 2- (Naphthalene-1- 일에티닐Ylethynyl )) 벤즈옥사졸Benzoxazole [2-( [2-( naphthalennaphthalen -1-ylethynyl)benzoxazole]의 제조-1-ylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(나프탈렌-1-일)프로피올릭산 (88.3 mg, 0.45 mmol), 벤즈옥사졸 (35.7 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-(나프탈렌-1-일에티닐)벤즈옥사졸 (33.1 mg, 41%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2(88.3 mg, 0.45 mmol) and benzoxazole (35.7 mg, 0.3 mmol) were added thereto, followed by the addition of benzene (1.8 mL, ) Was added and stirred at 60 ° C for 12 hours, and then the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the product was separated by column chromatography to obtain the title compound, 2- (naphthalen-1-ylethynyl) benzoxazole (33.1 mg, 41%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 8.47 (d, J = 8.4 Hz, 1H), 7.99-7.91 (m, 3H), 7.82-7.80 (m, 1H), 7.69-7.65 (m, 1H), 7.61-7.57 (m, 2H), 7.54-7.50 (m, 1H), 7.47-7.39 (m, 2H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 8.47 (d,J 1H), 7.61-7.57 (m, 2H), 7.54-7.50 (m, 1H), 7.69-7. ), 7.47-7.39 (m, 2H)
[[ 실시예Example 6] 5- 6] 5- 메틸methyl -2-(-2-( 페닐에티닐Phenylethynyl )) 벤즈옥사졸Benzoxazole [5- [5- methylmethyl -2-(phenylethynyl)benzoxazole]의 제조-2- (phenylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 페닐프로피올릭산 (65.8 mg, 0.45 mmol), 5-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-메틸-2-(페닐에티닐)벤즈옥사졸 (49.7 mg, 71%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2Phenylpropiolic acid (65.8 mg, 0.45 mmol) and 5-methylbenzoxazole (39.9 mg, 0.3 mmol) were added to the mixture, followed by addition of benzene (1.8 mL) The reaction mixture was stirred for 12 hours at < RTI ID = 0.0 > 0 C < / RTI > After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the title compound was separated by column chromatography to obtain 5-methyl-2- (phenylethynyl) benzoxazole (49.7 mg, 71%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.68-7.65 (m, 2H), 7.54 (t, J = 0.7 Hz, 1H), 7.49-7.39 (m, 4H), 7.22 (dd, J = 8.4 Hz, 1.3 Hz, 1H), 2.49 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.68-7.65 (m, 2H), 7.54 (t,J = 0.7 Hz, 1 H), 7.49-7.39 (m, 4H), 7.22 (dd,J = 8.4 Hz, 1.3 Hz, 1 H), 2.49 (s, 3 H)
[[ 실시예Example 7] 2-( 7] 2- ( 헵트Hept -1--One- 이닐Isil )-5-) -5- 메틸벤즈옥사졸Methyl benzoxazole [2-( [2-( hepthept -1--One- ynylynyl )-5-methylbenzoxazole] 의 제조) -5-methylbenzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 옥타이노익산 (63.1 mg, 0.45 mmol), 5-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-(헵트-1-이닐)-5-메틸벤즈옥사졸 (34.8 mg, 51%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2Octaneoxy acid (63.1 mg, 0.45 mmol) and 5-methylbenzoxazole (39.9 mg, 0.3 mmol) were added thereto, benzene (1.8 mL) was added thereto, And the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the resultant was purified by column chromatography to obtain the title compound, 2- (hept-1-ynyl) -5-methylbenzoxazole (34.8 mg, 51%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.48 (t, J = 0.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.19-7.16 (m, 1H), 2.50 (t, J = 7.1 Hz, 3H), 2.46 (s, 2H), 1.68 (quint, J = 5.5 Hz, 2H), 1.50-1.32 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.48 (t,J = 0.8 Hz, 1 H), 7.36 (d,J = 8.4 Hz, 1 H), 7.19-7.16 (m, 1 H), 2.50 (t,J = 7.1 Hz, 3H), 2.46 (s, 2H), 1.68 (quint,J = 5.5 Hz, 2H), 1.50-1.32 (m, 4H), 0.92 (t,J = 7.2 Hz, 3 H)
[[ 실시예Example 8] 2-((4- 8] 2 - ((4- 메톡시페닐Methoxyphenyl )) 에티닐Ethynyl )-5-) -5- 메틸벤즈옥사졸Methyl benzoxazole [2-((4-methoxyphenyl)ethynyl)-5-methylbenzoxazole]의 제조 Preparation of [2 - ((4-methoxyphenyl) ethynyl) -5-methylbenzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(4-메톡시페닐)프로피올릭산 (79.3 mg, 0.45 mmol), 5-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-((4-메톡시페닐)에티닐)-5-메틸벤즈옥사졸 (56.9 mg, 72%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag23- (4-methoxyphenyl) propiolic acid (79.3 mg, 0.45 mmol) and 5-methylbenzoxazole (39.9 mg, 0.3 mmol) were added thereto, (1.8 mL), and the mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. The solvent was removed and the residue was purified by column chromatography to obtain the title compound, 2 - ((4-methoxyphenyl) ethynyl) -5-methylbenzoxazole (56.9 mg, 72%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.61-7.59 (m, 2H), 7.52 (d, J = 0.8 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.21 (dd, J = 8.3 Hz, 1.0 Hz, 1H), 6.94-6.92 (m, 2H), 3.86 (s, 3H), 2.48 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.61-7.59 (m, 2H), 7.52 (d,J = 0.8 Hz, 1 H), 7.40 (d,J = 8.4 Hz, 1 H), 7.21 (dd,J 2H), 3.86 (s, 3H), 2.48 (s, 3H)
[[ 실시예Example 9] 5- 9] 5- 메틸methyl -2-(-2-( 메타Meta -- 톨릴에티닐Tolyl ethynyl )) 벤즈옥사졸Benzoxazole [5- [5- methylmethyl -2-(m-tolylethynyl)benzoxazole]의 제조-2- (m-tolylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-메타-톨릴프로피올릭산 (72.1 mg, 0.45 mmol), 5-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-메틸-2-(메타-톨릴에티닐)벤즈옥사졸 (57.1 mg, 77%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), followed by addition of 3-meta-tolylpropiolic acid 5-methylbenzoxazole (39.9 mg, 0.3 mmol), benzene (1.8 mL) was added, and the mixture was stirred at 60 ° C for 12 hours. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the reaction mixture was separated by column chromatography to obtain the title compound, 5-methyl-2- (meta-tolylethynyl) benzoxazole (57.1 mg, 77%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.54 (t, J = 0.8 Hz, 1H), 7.48-7.46 (m, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.32-7.28 (m, 2H), 7.23-7.21 (m, 1H), 2.49 (s, 3H), 2.38 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.54 (t,J = 0.8 Hz, 1H), 7.48-7.46 (m, 2H), 7.41 (d,J 2H), 7.23-7.21 (m, 1H), 2.49 (s, 3H), 2.38 (s, 3H)
[[ 실시예Example 10] 5- 10] 5- 클로로Chloro -2-(-2-( 페닐에티닐Phenylethynyl )) 벤즈옥사졸Benzoxazole [5- [5- chlorochloro -2-(phenylethynyl)benzoxazole]의 제조-2- (phenylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 페닐프로피올릭산 (65.8 mg, 0.45 mmol), 5-클로로벤즈옥사졸 (46.1 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60 ℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-클로로-2-(페닐에티닐)벤즈옥사졸 (45.7 mg, 60%)을 얻었다. To the V-vial was added PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2Phenylpropionic acid (65.8 mg, 0.45 mmol) and 5-chlorobenzoxazole (46.1 mg, 0.3 mmol) were added to the mixture, followed by benzene (1.8 mL) The reaction mixture was stirred for 12 hours at < RTI ID = 0.0 > 0 C < / RTI > After lowering the temperature of the V-vial to room temperature, Et2O (20 mL x 3) and extracted with saturated NH4Cl < / RTI > solution (20 mL). The extracted organic layer was dried over anhydrous MgSO 44Lt; / RTI > and filtered. After removal of the solvent, the product was separated by column chromatography to obtain the title compound, 5-chloro-2- (phenylethynyl) benzoxazole (45.7 mg, 60%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.75 (d, J = 1.7 Hz, 1H), 7.69-7.66 (m, 2H), 7.51-7.38 (m, 5H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.75 (d,J = 1.7 Hz, 1 H), 7.69-7.66 (m, 2H), 7.51-7.38 (m, 5H)
[[ 실시예Example 11] 5- 11] 5- 클로로Chloro -2-(-2-( 헵트Hept -1--One- 이닐Isil )-) - 벤즈옥사졸Benzoxazole [5- [5- chlorochloro -2-(-2-( hepthept -1-ynyl)benzoxazole]의 제조-1-ynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 옥타이노익산 (63.1 mg, 0.45 mmol), 5-클로로벤즈옥사졸 (46.1 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-클로로-2-(헵트-1-이닐)-벤즈옥사졸 (37.9 mg, 51%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), followed by addition of octanoin acid (63.1 mg, After adding chlorobenzoxazole (46.1 mg, 0.3 mmol), benzene (1.8 mL) was added, and the mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the product was separated by column chromatography to obtain the title compound, 5-chloro-2- (hept-1-ynyl) -benzoxazole (37.9 mg, 51%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.69 (d, J = 1.7 Hz, 1H), 7.41 (dd, J = 8.7 Hz, 0.3 Hz, 1H), 7.34 (dd, J = 8.7 Hz, 2.0 Hz, 1H), 2.51 (t, J = 7.1 Hz, 2H), 1.68 (quint, J = 7.3 Hz, 2H), 1.40-1.32 (m, 4H), 0.96 (t, J = 7.2 Hz, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.69 (d,J = 1.7 Hz, 1 H), 7.41 (dd,J = 8.7 Hz, 0.3 Hz, 1 H), 7.34 (dd,J = 8.7 Hz, 2.0 Hz, 1 H), 2.51 (t,J = 7.1 Hz, 2H), 1.68 (quint,J = 7.3 Hz, 2H), 1.40-1.32 (m, 4H), 0.96 (t,J = 7.2 Hz, 3 H)
[[ 실시예Example 12] 5- 12] 5- 클로로Chloro -2-((4--2 - ((4- 메톡시페닐Methoxyphenyl )) 에티닐Ethynyl )) 벤즈옥사졸Benzoxazole [5- [5- chlorochloro -2-((4-methoxyphenyl)ethynyl)benzoxazole]의 제조-2 - ((4-methoxyphenyl) ethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(4-메톡시페닐)프로피올릭산 (79.3 mg, 0.45 mmol), 5-클로로벤즈옥사졸 (46.1 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-클로로-2-((4-메톡시페닐)에티닐)벤즈옥사졸 (62.1 mg, 73%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol) and 3- (4- methoxyphenyl) propiolic acid 79.3 mg, 0.45 mmol) and 5-chlorobenzoxazole (46.1 mg, 0.3 mmol) were added. Benzene (1.8 mL) was added and the mixture was stirred at 60 ° C for 12 hours. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the reaction mixture was separated by column chromatography to obtain the title compound, 5-chloro-2 - ((4-methoxyphenyl) ethynyl) benzoxazole (62.1 mg, 73%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.72(d, J = 2.0 Hz, 1H), 7.63-7.58 (m, 2H), 7.44 (d, J = 8.6 Hz, 1H), 7.36 (dd, J = 8.7 Hz, 2.0 Hz, 1H), 6.94-6.91 (m, 2H), 3.85 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.72 (d,J = 2.0 Hz, 1H), 7.63-7.58 (m, 2H), 7.44 (d,J = 8.6 Hz, 1 H), 7.36 (dd,J = 8.7 Hz, 2.0 Hz, 1H), 6.94-6.91 (m, 2H), 3.85 (s, 3H)
[[ 실시예Example 13] 5- 13] 5- 클로로Chloro -2-(-2-( 메타Meta -- 톨릴에티닐Tolyl ethynyl )) 벤즈옥사졸Benzoxazole [5- [5- chlorochloro -2-(m-tolylethynyl)benzoxazole]의 제조-2- (m-tolylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-메틸-톨릴프로피올릭산 (72.1 mg, 0.45 mmol), 5-클로로벤즈옥사졸 (46.1 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-클로로-2-(메타-톨릴에티닐)벤즈옥사졸 (23.3 mg, 29%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), followed by 3-methyl- tolylpropiolic acid 5-chlorobenzoxazole (46.1 mg, 0.3 mmol) was added thereto, followed by benzene (1.8 mL). The mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the reaction mixture was separated by column chromatography to obtain the title compound, 5-chloro-2- (meta-tolylethynyl) benzoxazole (23.3 mg, 29%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.73 (d, J = 1.9 Hz, 1H), 7.48-7.45 (m, 3H), 7.37 (dd, J = 8.7 Hz, 2.0 Hz, 1H), 7.32-7.26 (m, 2H), 2.38 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.73 (d,J = 1.9 Hz, 1 H), 7.48-7.45 (m, 3 H), 7.37 (dd,J = 8.7 Hz, 2.0 Hz, 1 H), 7.32-7.26 (m, 2 H), 2.38 (s, 3 H)
[[ 실시예Example 14] 5- 14] 5- 클로로Chloro -2-(나프탈렌-1--2- (naphthalene-1- 일에티닐Ylethynyl )) 벤즈옥사졸Benzoxazole [5- [5- chlorochloro -2-(naphthalen-1-ylethynyl)benzoxazole]의 제조-2- (naphthalen-1-ylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(나프탈렌-1-일)프로피올릭산 (88.3 mg, 0.45 mmol), 5-클로로벤즈옥사졸 (46.1 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-클로로-2-(나프탈렌-1-일에티닐)벤즈옥사졸 (58.3 mg, 64%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), and 3- (naphthalen-1-yl) propiolic acid 88.3 mg, 0.45 mmol) and 5-chlorobenzoxazole (46.1 mg, 0.3 mmol) were added. Benzene (1.8 mL) was added and the mixture was stirred at 60 ° C for 12 hours. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the product was separated by column chromatography to obtain the title compound, 5-chloro-2- (naphthalen-1-ylethynyl) benzoxazole (58.3 mg, 64%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 8.43 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.93-7.89 (m, 2H), 7.77 (d, J = 1.9 Hz, 1H), 7.68-7.64 (m, 1H), 7.60-7.56 (m, 1H), 7.52-7.48 (m, 2H), 7.39 (dd, 8.7 Hz, 2.0 Hz, 1H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 8.43 (d,J = 8.3 Hz, 1 H), 7.97 (d,J = 8.3 Hz, 1 H), 7.93-7.89 (m, 2 H), 7.77 (d,J 2H), 7.39 (dd, 8.7 Hz, 2.0 Hz, IH), 7.60-7.66 (m,
[[ 실시예Example 15] 6- 15] 6- 메틸methyl -2-(-2-( 페닐에티닐Phenylethynyl )) 벤즈옥사졸Benzoxazole [6- [6- methylmethyl -2-(phenylethynyl)benzoxazole]의 제조-2- (phenylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 페닐프로피올릭산 (65.8 mg, 0.45 mmol), 6-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 6-메틸-2-(페닐에티닐)벤즈옥사졸 (51.1 mg, 73%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), and phenylpropiolic acid (65.8 mg, -Methylbenzoxazole (39.9 mg, 0.3 mmol), benzene (1.8 mL) was added, and the mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the product was isolated by column chromatography to obtain the title compound, 6-methyl-2- (phenylethynyl) benzoxazole (51.1 mg, 73%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.68-7.62 (m, 3H), 7.48-7.39 (m, 3H), 7.35 (t, J = 0.7 Hz, 1H), 7.20 (dd, J = 8.2 Hz, 0.9 Hz, 1H), 2.51 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.68-7.62 (m, 3H), 7.48-7.39 (m, 3H), 7.35 (t,J = 0.7 Hz, 1 H), 7.20 (dd,J = 8.2 Hz, 0.9 Hz, 1 H), 2.51 (s, 3 H)
[[ 실시예Example 16] 2-((4- 16] 2 - ((4- 메톡시페닐Methoxyphenyl )) 에티닐Ethynyl )-6-) -6- 메틸벤즈옥사졸Methyl benzoxazole [2-((4-methoxyphenyl)ethynyl)-6-methylbenzoxazole]의 제조 Preparation of [2 - ((4-methoxyphenyl) ethynyl) -6-methylbenzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-(4-메톡시페닐)프로피올릭산 (79.3 mg, 0.45 mmol), 6-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 2-((4-메톡시페닐)에티닐)-6-메틸벤즈옥사졸 (49.0 mg, 62%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol) and 3- (4- methoxyphenyl) propiolic acid 79.3 mg, 0.45 mmol) and 6-methylbenzoxazole (39.9 mg, 0.3 mmol) were added. Benzene (1.8 mL) was added and the mixture was stirred at 60 ° C for 12 hours. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. The solvent was removed and the residue was purified by column chromatography to obtain the title compound, 2 - ((4-methoxyphenyl) ethynyl) -6-methylbenzoxazole (49.0 mg, 62%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.62-7.58 (m, 3H), 7.33 (t, J = 0.7 Hz, 1H), 7.19 (dd, J = 8.2 Hz, 0.9 Hz, 1H), 6.94-6.91 (m, 2H), 3.85 (s, 3H), 2.50 (s, 3H)
One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.62-7.58 (m, 3H), 7.33 (t,J = 0.7 Hz, 1 H), 7.19 (dd,J = 8.2 Hz, 0.9 Hz, 1H), 6.94-6.91 (m, 2H), 3.85 (s, 3H), 2.50
[[ 실시예Example 17] 6- 17] 6- 메틸methyl -2-(-2-( 메타Meta -- 톨릴에티닐Tolyl ethynyl )) 벤즈옥사졸Benzoxazole [6- [6- methylmethyl -2-(m-tolylethynyl)benzoxazole]의 제조-2- (m-tolylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 3-메타-톨릴프로피올릭산 (72.1 mg, 0.45 mmol), 6-메틸벤즈옥사졸 (39.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 6-메틸-2-(메타-톨릴에티닐)벤즈옥사졸 (51.2 mg, 69%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), followed by addition of 3-meta-tolylpropiolic acid mmol) and 6-methylbenzoxazole (39.9 mg, 0.3 mmol) were added. Benzene (1.8 mL) was added thereto, followed by stirring at 60 ° C for 12 hours. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removing the solvent, the reaction mixture was separated by column chromatography to obtain the title compound, 6-methyl-2- (meta-tolylethynyl) benzoxazole (51.2 mg, 69%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.62 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 8.2 Hz, 2H), 7.33-7.25 (m, 3H), 7.19 (dd, J = 8.2 Hz, 0.7 Hz, 1H), 2.50 (s, 3H), 2.37 (s, 3H)
1 H NMR (400 MHz, CDCl 3, 25 ℃, TMS): d = 7.62 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 8.2 Hz, 2H), 7.33-7.25 (m, 3H) , 7.19 (dd, J = 8.2 Hz, 0.7 Hz, IH), 2.50 (s, 3H), 2.37
[[ 실시예Example 18] 5- 18] 5- terttert -부틸-2-(-Butyl-2- ( 페닐에티닐Phenylethynyl )) 벤즈옥사졸Benzoxazole [5- [5- terttert -- butylbutyl -2-(phenylethynyl)benzoxazole]의 제조-2- (phenylethynyl) benzoxazole]
V-바이알에 PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol)를 넣고 여기에 페닐프로피올릭산 (65.8 mg, 0.45 mmol), 5-tert-부틸벤즈옥사졸 (78.9 mg, 0.3 mmol)을 첨가한 후 벤젠 (1.8 mL)을 첨가하여 60℃에서 12시간 교반 시킨 후 반응을 종결시켰다. 실온으로 V-바이알의 온도를 낮춘 후 Et2O (20 mL x 3)로 추출하고 포화 NH4Cl 수용액 (20 mL)으로 씻어 주었다. 추출한 유기층은 무수 MgSO4로 건조하고 여과하였다. 용매를 제거한 후 관 크로마토그래피로 분리하여, 표제 화합물인 5-tert-부틸-2-(페닐에티닐)벤즈옥사졸 (55.3 mg, 67%)을 얻었다.To the V-vial was added PdCl 2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol) and Ag 2 O (208.6 mg, 0.9 mmol), phenylpropiolic acid (65.8 mg, butylbenzoxazole (78.9 mg, 0.3 mmol), benzene (1.8 mL) was added, and the mixture was stirred at 60 ° C for 12 hours, and then the reaction was terminated. The temperature of the V-vial was reduced to room temperature, extracted with Et 2 O (20 mL x 3) and washed with saturated aqueous NH 4 Cl (20 mL). The extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, the reaction mixture was separated by column chromatography to obtain the title compound, 5-tert-butyl-2- (phenylethynyl) benzoxazole (55.3 mg, 67%).
1H NMR (400 MHz, CDCl3 , 25℃, TMS): d = 7.76-7.75 (m, 1H), 7.68-7.66 (m, 2H), 7.50-7.39 (m, 5H), 1.39 (s, 9H) One≪ 1 > H NMR (400 MHz, CDCl33 ,25 C, TMS):d = 7.76-7.75 (m, 1H), 7.68-7.66 (m, 2H), 7.50-7.39 (m, 5H), 1.39
Claims (8)
[화학식 1]
[화학식 2]
[화학식 3]
(Ag)nX1
[화학식 4]
[상기 화학식 1 내지 화학식 4에서
R1 내지 R4는 각각 독립적으로 수소, 할로겐 및 (C1~C7)알킬기로부터 선택되고;R은 (C1~C7)알킬기, (C6~C20)아릴기, (C1-C7)알킬기 또는 (C1-C7)알콕시로 치환된 (C6~C20)아릴기로부터 선택되고;
X1은 Cl, Br, I, NO2, OTf, CO3 또는 O이며;
n은 X1의 산화수이다.]PdCl 2 catalyst, a propiolic acid derivative represented by the following formula (2), a silver salt represented by the following formula (3) and a benzoxazole compound represented by the following formula (4) in the presence of dppp [1,3-bis (diphenylphosphino) propane] Lt; RTI ID = 0.0 > 1. ≪ / RTI >
[Chemical Formula 1]
(2)
(3)
(Ag) nX 1
[Chemical Formula 4]
[In the formulas (1) to (4)
R 1 to R 4 are each independently selected from hydrogen, halogen and (C 1 -C 7) alkyl groups; R is selected from the group consisting of a (C 1 -C 7) alkyl group, a (C 6 -C 20) C7) alkoxy (C6-C20) aryl groups;
X 1 is Cl, Br, I, NO 2 , OTf, CO 3 or O;
n is an oxidation number of X < 1 & gt ;.
R1 및 R4는 수소이며;
R2는 수소 및 (C1~C7)알킬기로부터 선택되고;
R3은 수소, (C1~C7)알킬기 및 할로겐으로부터 선택되는 것을 특징으로 하는 벤즈옥사졸 유도체의 제조방법.The method according to claim 1,
R 1 and R 4 are hydrogen;
R 2 is selected from hydrogen and (C 1 -C 7) alkyl groups;
R 3 is selected from hydrogen, (C 1 -C 7) alkyl, and halogen.
상기 화학식 2는 하기 화학식 5로 표시되는 것을 특징으로 하는 벤즈옥사졸 유도체의 제조방법.
[화학식 5]
[상기 화학식 5에서,
R11 내지 R15는 수소, (C1-C7)알킬 또는 (C1-C7)알콕시이거나, 서로 인접한 치환체들은 (C2-C7)알케닐렌 또는 (C2-C7)알키닐렌으로 연결되어 방향족고리를 형성할 수 있다.]The method according to claim 1,
Wherein the formula (2) is represented by the following formula (5).
[Chemical Formula 5]
[In the formula (5)
R 11 to R 15 are hydrogen, (C 1 -C 7) alkyl or (C 1 -C 7) alkoxy, or adjacent substituents are connected by (C 2 -C 7) alkenylene or (C 2 -C 7) alkynylene to form an aromatic ring Can be.]
상기 화학식 1의 벤즈옥사졸 유도체는 하기 화합물로부터 선택되는 벤즈옥사졸 유도체의 제조방법.
The method according to claim 1,
The benzoxazole derivative of Formula 1 is selected from the following compounds.
상기 PdCl2촉매 는 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 0.1 몰 내지 1.0 몰 범위로 사용되는 벤즈옥사졸 유도체의 제조방법.The method according to claim 1,
Wherein the PdCl 2 catalyst is used in a range of 0.1 mol to 1.0 mol per 1 mol of the benzoxazole compound of the formula (4).
상기 포스핀계 리간드는 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 0.2 몰 내지 2.0 몰 범위로 사용되는 벤즈옥사졸 유도체의 제조방법.6. The method of claim 5,
Wherein the phosphine-based ligand is used in an amount of 0.2 to 2.0 mol per 1 mol of the benzoxazole compound of the formula (4).
상기 화학식 2의 프로피올릭 산은 화학식 4의 벤즈옥사졸 화합물, 1몰에 대해 1.0 몰 내지 3.0 몰 범위로 사용되는 벤즈옥사졸 유도체의 제조방법.The method according to claim 1,
Wherein the propiolic acid of Formula 2 is used in a range of 1.0 to 3.0 moles per mole of the benzoxazole compound of Formula 4. [
상기 반응은 다이옥산, 테트라하이드로퓨란, 다이메틸포름아마이드, 다이클로로메탄, 다이클로로에탄, 벤젠, 톨루엔 및 이들의 혼합물로부터 선택되는 용매 하에서 수행되는 벤즈옥사졸 유도체의 제조방법.The method according to claim 1,
Wherein the reaction is carried out in a solvent selected from dioxane, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, benzene, toluene and mixtures thereof.
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