[go: up one dir, main page]

CN101423503A - 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof - Google Patents

2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof Download PDF

Info

Publication number
CN101423503A
CN101423503A CNA2008102039941A CN200810203994A CN101423503A CN 101423503 A CN101423503 A CN 101423503A CN A2008102039941 A CNA2008102039941 A CN A2008102039941A CN 200810203994 A CN200810203994 A CN 200810203994A CN 101423503 A CN101423503 A CN 101423503A
Authority
CN
China
Prior art keywords
benzothiazole
cyano
trans
dihydro
aryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CNA2008102039941A
Other languages
Chinese (zh)
Inventor
刘颖
任仲皎
曹卫国
童玮琦
陈杰
陆叶营
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Shanghai for Science and Technology
Original Assignee
University of Shanghai for Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Shanghai for Science and Technology filed Critical University of Shanghai for Science and Technology
Priority to CNA2008102039941A priority Critical patent/CN101423503A/en
Publication of CN101423503A publication Critical patent/CN101423503A/en
Pending legal-status Critical Current

Links

Landscapes

  • Thiazole And Isothizaole Compounds (AREA)

Abstract

本发明涉及一种2－(反式－2，3－二氢－2－芳基－1－氰基－3－甲氧羰基环丙烷)－1，3－苯并噻唑及其合成方法。该化合物的结构式如右所示。本发明方法是以易得的2－氰基芳基取代乙烯－1，3－苯并噻唑、三苯胂、溴乙酸甲酯为原料，一锅法合成目标产物，具有操作简便，产率较高等优点，为天然产物的合成提供一种有效的途径。

The invention relates to 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole and its synthesis method. The structural formula of this compound is shown on the right. The method of the invention uses easily available 2-cyanoaryl substituted vinyl-1,3-benzothiazole, triphenylarsine and methyl bromoacetate as raw materials to synthesize the target product in one pot, and has the advantages of simple operation and relatively high yield. High advantages provide an effective way for the synthesis of natural products.

Description

2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑及其合成方法 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole and its synthetic method

技术领域 technical field

本发明涉及一种2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑及其合成方法。The invention relates to 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole and a synthesis method thereof.

背景技术 Background technique

环丙烷类化合物的研究在生物有机合成及药物和农药的研究制备中占据了极其重要的地位。近来，研究越来越多地发现环丙烷基团修饰分子可以大大改善分子的药理活性，而且很多天然化合物中都存在环丙烷结构单元，因此将环丙烷引入有生物或药理活性的化合物上的研究引起了大家的广泛关注。The research on cyclopropane compounds occupies an extremely important position in the research and preparation of bioorganic synthesis and drugs and pesticides. Recently, more and more studies have found that cyclopropane group modification molecules can greatly improve the pharmacological activity of molecules, and cyclopropane structural units exist in many natural compounds, so the introduction of cyclopropane into biologically or pharmacologically active compounds. aroused widespread attention.

杂环体系在有生物和药理活性的化合物分子中具有重要的意义，在新药的研发中已经发现有许多具有临床价值。因此人们现在大量的研究含环丙烷的杂环体系，虽然已发现了许多成功的合成方法，但高立体选择性高效的合成它们仍是研究的重点。Heterocyclic systems are of great significance in compounds with biological and pharmacological activities, and many of them have been found to have clinical value in the development of new drugs. Therefore, people are now doing a lot of research on cyclopropane-containing heterocyclic ring systems. Although many successful synthesis methods have been found, their synthesis with high stereoselectivity and high efficiency is still the focus of research.

发明内容： Invention content:

本发明的目的之一在于提供一种2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑。One of the objectives of the present invention is to provide a 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole.

本发明的目的之二在于提供该化合物的制备方法。The second object of the present invention is to provide a preparation method of the compound.

为达到上述目的，本发明方法采用的反应机理为：For achieving the above object, the reaction mechanism that the inventive method adopts is:

Figure A200810203994D00031
Figure A200810203994D00031

其中，Ar为4-CH3OC6H4、4-CH3C6H4、C6H5、4-FC6H4，、4-ClC6H4，、3-ClC6H4、2-ClC6H4，、3-NO2C6H4、2，4-CH3OC6H3或3，4-CH3OC6H3。Among them, Ar is 4-CH 3 OC 6 H 4 , 4-CH 3 C 6 H 4 , C 6 H 5 , 4-FC 6 H 4 , 4-ClC 6 H 4 , 3-ClC 6 H 4 , 2-ClC 6 H 4 , 3-NO 2 C 6 H 4 , 2,4-CH 3 OC 6 H 3 or 3,4-CH 3 OC 6 H 3 .

根据上述反应机理，本发明采用如下技术方案：According to above-mentioned reaction mechanism, the present invention adopts following technical scheme:

一种2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑，其特征在于该化合物的结构式为：A kind of 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole is characterized in that the structural formula of the compound is :

Figure A200810203994D00032
Figure A200810203994D00032

其中，Ar为4-CH3OC6H4、4-CH3C6H4、C6H5、4-FC6H4，、4-ClC6H4，、3-ClC6H4、2-ClC6H4，、3-NO2C6H4、2，4-CH3OC6H3或3，4-CH3OC6H3。Among them, Ar is 4-CH 3 OC 6 H 4 , 4-CH 3 C 6 H 4 , C 6 H 5 , 4-FC 6 H 4 , 4-ClC 6 H 4 , 3-ClC 6 H 4 , 2-ClC 6 H 4 , 3-NO 2 C 6 H 4 , 2,4-CH 3 OC 6 H 3 or 3,4-CH 3 OC 6 H 3 .

一种制备上述的2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑的方法，其特征在于该方法的具体步骤为：将2-氰基芳基取代乙烯-1，3-苯并噻唑、三苯胂、溴乙酸甲酯和碳酸氢钠按1：(0.09～0.11)：(1.1～1.3)：(2.9～3.1)的摩尔比溶于乙氰中，搅拌回流反应至2-氰基芳基取代乙烯-1，3-苯并噻唑反应完全，除去溶剂，柱层析分离得到2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑；所述的2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：A method for preparing the above-mentioned 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole, characterized in that The specific steps of the method are as follows: 2-cyanoaryl substituted vinyl-1,3-benzothiazole, triphenylarsine, methyl bromoacetate and sodium bicarbonate according to 1:(0.09～0.11):(1.1～1.3 ): (2.9 ~ 3.1) molar ratio is dissolved in acetocyanide, stirred and refluxed until 2-cyanoaryl substituted vinyl-1,3-benzothiazole reacts completely, removes solvent, and separates by column chromatography to obtain 2-( trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole; the 2-cyanoaryl substituted vinyl-1 , the structural formula of 3-benzothiazole is:

Figure A200810203994D00041
Figure A200810203994D00041

其中，Ar为4-CH3OC6H4、4-CH3C6H4、C6H5、4-FC6H4，、4-ClC6H4、3-ClC6H4、2-ClC6H4，、3-NO2C6H4、2，4-CH3OC6H3或3，4-CH3OC6H3。Among them, Ar is 4-CH 3 OC 6 H 4 , 4-CH 3 C 6 H 4 , C 6 H 5 , 4-FC 6 H 4 , 4-ClC 6 H 4 , 3-ClC 6 H 4 , 2 -ClC 6 H 4 , 3-NO 2 C 6 H 4 , 2,4-CH 3 OC 6 H 3 or 3,4-CH 3 OC 6 H 3 .

从理论上分析认为本发明得到的反式环丙烷苯并噻唑衍生物可用于生物医药，是一种具很好生物活性的结构单元。本发明方法本发明的方法是以易得的2-氰基芳基取代乙烯-1，3-苯并噻唑、三苯胂、溴乙酸甲酯为原料，一锅法合成目标产物，具有操作简便，产率较高等优点，为天然产物的合成提供种有效的途径。According to theoretical analysis, the trans-cyclopropane benzothiazole derivative obtained in the present invention can be used in biomedicine, and is a structural unit with good biological activity. The method of the present invention The method of the present invention uses readily available 2-cyanoaryl substituted vinyl-1,3-benzothiazole, triphenylarsine, and methyl bromoacetate as raw materials to synthesize the target product in one pot, and has the advantages of simple and convenient operation. , high yield and other advantages, it provides an effective way for the synthesis of natural products.

具体实施方式 Detailed ways

反应的具体步骤为：将2-氰基芳基取代乙烯-1，3-苯并噻唑、三苯胂、溴乙酸甲酯和碳酸氢钠按1：(0.09～0.11)：(1.1～1.3)：(2.9～3.1)的摩尔比溶于乙氰中，搅拌回流反应至2-氰基芳基取代乙烯-1，3-苯并噻唑反应完全，除去溶剂，柱层析分离得到2-(反式-2，3-二氢-2-芳基-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑。The specific steps of the reaction are: 2-cyanoaryl substituted vinyl-1,3-benzothiazole, triphenylarsine, methyl bromoacetate and sodium bicarbonate according to 1:(0.09～0.11):(1.1～1.3) : (2.9 ~ 3.1) molar ratio is dissolved in acetocyanide, stirred and refluxed until 2-cyanoaryl substituted vinyl-1,3-benzothiazole reacts completely, removes solvent, and separates by column chromatography to obtain 2-(trans Formula - 2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonylcyclopropane)-1,3-benzothiazole.

实施例一：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 1: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00042
Figure A200810203994D00042

其中Ar为4-CH3OC6H4，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-(4-甲氧苯基)环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 4-CH 3 OC 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-(4-methoxyphenyl) Cyclopropane)-1,3-benzothiazole, its structural formula is:

Figure A200810203994D00051
Figure A200810203994D00051

分子式：C20H16N2O3SMolecular formula: C 20 H 16 N 2 O 3 S

分子量：364.0882Molecular weight: 364.0882

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.27(d，J＝8.0Hz，1H，CH)，3.64(s，3H，OCH3)，3.83(s，3H，OCH3)，4.09(d，.J＝8.0Hz，1H，CH)，7.00(d，J＝8.6Hz，2H，Ar-H)，7.35(d，J＝8.5Hz，2H，Ar-H)，7.44-7.50(dt，J＝8.0，8.3Hz，2H，Ar-H)，7.89(d，J＝7.8Hz，1H，Ar-H)，8.04(d，J＝8.0Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.27 (d, J=8.0Hz, 1H, CH), 3.64 (s, 3H, OCH 3 ), 3.83 (s, 3H, OCH 3 ) , 4.09 (d, .J=8.0Hz, 1H, CH), 7.00 (d, J=8.6Hz, 2H, Ar-H), 7.35 (d, J=8.5Hz, 2H, Ar-H), 7.44- 7.50(dt, J=8.0, 8.3Hz, 2H, Ar-H), 7.89(d, J=7.8Hz, 1H, Ar-H), 8.04(d, J=8.0Hz, 1H, Ar-H)

红外吸收(KBr)cm-13036，2239，1730，1518.Infrared absorption (KBr) cm -1 3036, 2239, 1730, 1518.

质谱m/z：364(M+，16)，305(100)，306(22)，261(15)，278(10)，290(10)，290(9)，289(9)，274(8)Mass spectrum m/z: 364(M + , 16), 305(100), 306(22), 261(15), 278(10), 290(10), 290(9), 289(9), 274( 8)

元素分析：C，65.79；H，4.43；N，7.66.Elemental analysis: C, 65.79; H, 4.43; N, 7.66.

实施例二：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 2: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00052
Figure A200810203994D00052

其中Ar为4-CH3C6H4，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-(4-甲苯基)-环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 4-CH 3 C 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-(4-tolyl)-cyclo Propane)-1,3-benzothiazole, its structural formula is:

Figure A200810203994D00053
Figure A200810203994D00053

分子式：C20H16N2O2SMolecular formula: C 20 H 16 N 2 O 2 S

分子量：348.0932Molecular weight: 348.0932

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 2.37(s，3H，CH3)，3.30(d，J＝8.0Hz，1H，CH)，3.64(s，3H，OCH3)，4.10(d，J＝8.0Hz，1H，CH)，7.24(d，J＝7.6Hz，2H，Ar-H)，7.32(d，J＝7.9Hz，2H，Ar-H)，7.41-7.46(t，J＝7.5Hz，1H，Ar-H)，7.49-7.54(t，J＝7.5Hz，1H，Ar-H)，7.88(d，J＝7.6Hz，1H，Ar-H)，8.04(d，J＝7.6Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 2.37(s, 3H, CH 3 ), 3.30(d, J=8.0Hz, 1H, CH), 3.64(s, 3H, OCH 3 ) , 4.10 (d, J=8.0Hz, 1H, CH), 7.24 (d, J=7.6Hz, 2H, Ar-H), 7.32 (d, J=7.9Hz, 2H, Ar-H), 7.41-7.46 (t, J=7.5Hz, 1H, Ar-H), 7.49-7.54 (t, J=7.5Hz, 1H, Ar-H), 7.88 (d, J=7.6Hz, 1H, Ar-H), 8.04 (d, J=7.6Hz, 1H, Ar-H)

红外吸收(KBr)cm-13031，2238，1754，1516.Anal.Calcd.for C20H16N2O2S:C，68.95；H，4.63；N，8.04.Found：C，68.93；H，4.61；N，8.05.Infrared absorption (KBr) cm -1 3031, 2238, 1754, 1516. Anal. Calcd. for C 20 H 16 N 2 O 2 S: C, 68.95; H, 4.63; N, 8.04. Found: C, 68.93; H , 4.61; N, 8.05.

质谱m/z：348(M+，12)，289(100)，290(21)，262(20)，274(15)，288(6)，291(6)127(5)Mass spectrum m/z: 348(M + , 12), 289(100), 290(21), 262(20), 274(15), 288(6), 291(6)127(5)

元素分析：C，68.93；H，4.61；N，8.05.Elemental analysis: C, 68.93; H, 4.61; N, 8.05.

实施例三：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 3: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

其中Ar为C6H5，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-苯基环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is C 6 H 5 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-phenylcyclopropane)-1,3-benzo Thiazole, its structural formula is:

分子式：C19H14N2O2SMolecular formula: C 19 H 14 N 2 O 2 S

分子量：334.0776Molecular weight: 334.0776

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.33(d，J＝8.0Hz，1H，CH)，3.66(s，3H，OCH3)，4.17(d，J＝8.2Hz，1H，CH)，7.40-7.55(m，7H，Ar-H)，7.90(d，J＝7.7Hz，1H，Ar-H)；8.06(d，J＝7.8Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.33(d, J=8.0Hz, 1H, CH), 3.66(s, 3H, OCH 3 ), 4.17(d, J=8.2Hz, 1H, CH), 7.40-7.55(m, 7H, Ar-H), 7.90(d, J=7.7Hz, 1H, Ar-H); 8.06(d, J=7.8Hz, 1H, Ar-H)

红外吸收(KBr)cm-13030，2240，1746，1513.Infrared absorption (KBr) cm -1 3030, 2240, 1746, 1513.

质谱m/z：334(M+，6)，275(100)，276(21)，248(21)，40(13)，140(13)，59(11)274(10)，205(10)Mass spectrum m/z: 334(M + , 6), 275(100), 276(21), 248(21), 40(13), 140(13), 59(11), 274(10), 205(10 )

元素分析：C，68.25；H，4.22；N，8.39.Elemental analysis: C, 68.25; H, 4.22; N, 8.39.

实施例四：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 4: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00071
Figure A200810203994D00071

其中Ar为4-FC6H4，得到的产物为2-(反式-2，3-二氢-1-氰基-2-(4-氟苯基)-3-甲氧羰基环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 4-FC 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-2-(4-fluorophenyl)-3-methoxycarbonylcyclopropane) -1,3-benzothiazole, its structural formula is:

Figure A200810203994D00072
Figure A200810203994D00072

分子式：C19H13FN2O2SMolecular formula: C 19 H 13 FN 2 O 2 S

分子量：352.0682Molecular weight: 352.0682

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.28(d，J＝8.0Hz，1H，CH)，3.65(s，3H，OCH3)，4.13(d，J＝8.0Hz，1H，CH)，7.11-7.16(t，J＝7.1Hz，2H，Ar-H)，7.40-7.44(m，3H，Ar-H)，747-7.55(m，1H，Ar-H)，7.73(d，J＝7.8Hz，1H，Ar-H)，8.05(d，J＝8.0Hz，1H，Ar-H)红外吸收(KBr)cm-13023，2238，1741，1513.Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.28(d, J=8.0Hz, 1H, CH), 3.65(s, 3H, OCH 3 ), 4.13(d, J=8.0Hz, 1H, CH), 7.11-7.16(t, J=7.1Hz, 2H, Ar-H), 7.40-7.44(m, 3H, Ar-H), 747-7.55(m, 1H, Ar-H), 7.73 (d, J=7.8Hz, 1H, Ar-H), 8.05 (d, J=8.0Hz, 1H, Ar-H) infrared absorption (KBr) cm -1 3023, 2238, 1741, 1513.

质谱m/z：352(M+，7)，293(100)，294(21)，266(15)，158(11)，290(10)，292(8)，295(6)，146(5)元素分析：C，64.70；H，3.67；N，7.92.Mass spectrum m/z: 352(M + , 7), 293(100), 294(21), 266(15), 158(11), 290(10), 292(8), 295(6), 146( 5) Elemental analysis: C, 64.70; H, 3.67; N, 7.92.

实施例五：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment five: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

其中Ar为4-ClC6H4，得到的产物为2-(反式-2，3-二氢-2-(4-氯苯基)-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 4-ClC 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-2-(4-chlorophenyl)-1-cyano-3-methoxycarbonylcyclopropane) -1,3-benzothiazole, its structural formula is:

Figure A200810203994D00074
Figure A200810203994D00074

分子式：C19H13ClN2O2SMolecular formula: C 19 H 13 ClN 2 O 2 S

分子量：368.0386Molecular weight: 368.0386

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.27(d，J＝8.0Hz，1H，CH)，3.65(s，3H，OCH3)，4.13(d，J＝8.0Hz，1H，CH)，7.36-7.45(m，4H，Ar-H)，7.47-7.65(m，2H，Ar-H)，7.89(d，J＝8.0Hz，1H，Ar-H)，8.04(d，J＝8.0Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.27(d, J=8.0Hz, 1H, CH), 3.65(s, 3H, OCH 3 ), 4.13(d, J=8.0Hz, 1H, CH), 7.36-7.45(m, 4H, Ar-H), 7.47-7.65(m, 2H, Ar-H), 7.89(d, J=8.0Hz, 1H, Ar-H), 8.04(d , J=8.0Hz, 1H, Ar-H)

红外吸收(KBr)cm-13011，2240，1680，1556.Infrared absorption (KBr) cm -1 3011, 2240, 1680, 1556.

质谱m/z：368(M+，16)，309(100)，311(38)，274(37)，310(22)，273(12)，275(8)，312(7)Mass spectrum m/z: 368(M + , 16), 309(100), 311(38), 274(37), 310(22), 273(12), 275(8), 312(7)

元素分析：C，61.86；H，3.56；N，7.54.Elemental analysis: C, 61.86; H, 3.56; N, 7.54.

实施例六：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 6: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00081
Figure A200810203994D00081

其中Ar为3-ClC6H4，得到的产物为2-(反式-2，3-二氢-2-(3-氯苯基)-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑，其结构为：Where Ar is 3-ClC 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-2-(3-chlorophenyl)-1-cyano-3-methoxycarbonylcyclopropane) -1,3-Benzothiazole, the structure of which is:

Figure A200810203994D00082
Figure A200810203994D00082

分子式：C19H13ClN2O2SMolecular formula: C 19 H 13 ClN 2 O 2 S

分子量：368.0386Molecular weight: 368.0386

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.31(d，J＝8.0Hz，1H，CH)，3.65(s，3H，OCH3)，4.13(d，J＝8.0Hz，1H，CH)，7.33-7.56(m，6H，Ar-H)，7.90(d，J＝8.0Hz，1H，Ar-H)，8.05(d，J＝8.0Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.31(d, J=8.0Hz, 1H, CH), 3.65(s, 3H, OCH 3 ), 4.13(d, J=8.0Hz, 1H, CH), 7.33-7.56(m, 6H, Ar-H), 7.90(d, J=8.0Hz, 1H, Ar-H), 8.05(d, J=8.0Hz, 1H, Ar-H)

红外吸收(KBr)cm-13031，2240，1749，1569.Infrared absorption (KBr) cm -1 3031, 2240, 1749, 1569.

质谱m/z：368(M+，16)，309(100)，274(40)，311(38)，310(22)，273(17)，275(9)，247(8)元素分析：C，61.90；H，3.50；N，7.52.Mass spectrum m/z: 368(M + , 16), 309(100), 274(40), 311(38), 310(22), 273(17), 275(9), 247(8) Elemental analysis: C, 61.90; H, 3.50; N, 7.52.

实施例七：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 7: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00091
Figure A200810203994D00091

其中Ar为2-ClC6H4，得到的产物为2-(反式-2，3-二氢-2-(2-氯苯基)-1-氰基-3-甲氧羰基环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 2-ClC 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-2-(2-chlorophenyl)-1-cyano-3-methoxycarbonylcyclopropane) -1,3-benzothiazole, its structural formula is:

Figure A200810203994D00092
Figure A200810203994D00092

分子式：C19H13ClN2O2SMolecular formula: C 19 H 13 ClN 2 O 2 S

分子量：368.0386Molecular weight: 368.0386

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.34(d，J＝8.0Hz，1H，CH)，3.69(s，3H，OCH3)，4.11(d，J＝8.0Hz，1H，CH)，7.33-7.58(m，6H，Ar-H)，7.91(d，J＝8.0Hz，1H，Ar-H)，8.04(d，J＝8.0Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.34(d, J=8.0Hz, 1H, CH), 3.69(s, 3H, OCH 3 ), 4.11(d, J=8.0Hz, 1H, CH), 7.33-7.58(m, 6H, Ar-H), 7.91(d, J=8.0Hz, 1H, Ar-H), 8.04(d, J=8.0Hz, 1H, Ar-H)

红外吸收(KBr)cm-13054，2241，1731，1505.Infrared absorption (KBr) cm -1 3054, 2241, 1731, 1505.

质谱m/z：368(M+，16)，309(100)，40(44)，311(38)，274(34)，275(24)，310(21)，43(17)，59(16)Mass spectrum m/z: 368(M + , 16), 309(100), 40(44), 311(38), 274(34), 275(24), 310(21), 43(17), 59( 16)

元素分析C，61.92；H，3.55；N，7.55.Elemental analysis C, 61.92; H, 3.55; N, 7.55.

实施例八：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 8: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

其中Ar为3-NO2C6H4，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-(3-硝基苯基)环丙烷)-1，3-苯并噻唑，其结构为：Where Ar is 3-NO 2 C 6 H 4 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-(3-nitrophenyl) Cyclopropane)-1,3-benzothiazole, its structure is:

Figure A200810203994D00094
Figure A200810203994D00094

分子式：C19H13N3O4SMolecular formula: C 19 H 13 N 3 O 4 S

分子量：379.0627Molecular weight: 379.0627

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.39(d，J＝8.0Hz，1H，CH)，3.67(s，3H，OCH3)，4.29(d，J＝8.0Hz，1H，CH)，7.44-7.57(m，2H，Ar-H)，7.64-7.69(t，J＝8.0Hz，1H，Ar-H)，7.79-7.82(d，J＝7.7Hz，1H，Ar-H)，7.81(d，J＝8.0Hz，1H，Ar-H)，8.06(d，J＝8.0Hz，1H，Ar-H)，8.27-8.33(t，J＝8.0Hz，2H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.39(d, J=8.0Hz, 1H, CH), 3.67(s, 3H, OCH 3 ), 4.29(d, J=8.0Hz, 1H, CH), 7.44-7.57(m, 2H, Ar-H), 7.64-7.69(t, J=8.0Hz, 1H, Ar-H), 7.79-7.82(d, J=7.7Hz, 1H, Ar -H), 7.81(d, J=8.0Hz, 1H, Ar-H), 8.06(d, J=8.0Hz, 1H, Ar-H), 8.27-8.33(t, J=8.0Hz, 2H, Ar -H)

红外吸收(KBr)cm-13069，2235，1733，1533.Infrared absorption (KBr) cm -1 3069, 2235, 1733, 1533.

质谱m/z：379(M+，9)，320(100)，274(36)，321(22)，273(22)，272(13)，59(13)198(10)Mass spectrum m/z: 379(M + , 9), 320(100), 274(36), 321(22), 273(22), 272(13), 59(13)198(10)

元素分析：C，60.11，H，3.38，N，11.07.Elemental analysis: C, 60.11, H, 3.38, N, 11.07.

实施例九：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 9: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

其中Ar为2，4-CH3OC6H3，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-(2，4-二甲氧苯基)环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 2,4-CH 3 OC 6 H 3 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-(2,4-di Methoxyphenyl) cyclopropane)-1,3-benzothiazole, its structural formula is:

Figure A200810203994D00102
Figure A200810203994D00102

分子式：C19H13N3O4SMolecular formula: C 19 H 13 N 3 O 4 S

分子量：394.0987Molecular weight: 394.0987

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.21(d，J＝7.8Hz，1H，CH)，3.67(s，3H，OCH3)，3.80(d，J＝8.0Hz，1H，CH)，3.83(s，3H，OCH3)，3.93(s，3H，OCH3)，6.50-6.55(m，2H，Ar-H)，7.09-7.12(d，J＝8.2n Hz，1H，Ar-H)，7.41-7.53(m，2H，Ar-H)，7.90(d，J＝8.0Hz，1H，Ar-H)，8.03(d，J＝8.0Hz，1H，Ar-H)Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.21(d, J=7.8Hz, 1H, CH), 3.67(s, 3H, OCH 3 ), 3.80(d, J=8.0Hz, 1H, CH), 3.83 (s, 3H, OCH 3 ), 3.93 (s, 3H, OCH3), 6.50-6.55 (m, 2H, Ar-H), 7.09-7.12 (d, J=8.2n Hz, 1H , Ar-H), 7.41-7.53 (m, 2H, Ar-H), 7.90 (d, J=8.0Hz, 1H, Ar-H), 8.03 (d, J=8.0Hz, 1H, Ar-H)

红外吸收(KBr)cm-13062，2240，1733，1585.Infrared absorption (KBr) cm -1 3062, 2240, 1733, 1585.

质谱m/z：205(100)，40(97)，335(74)，43(45)，309(27)，275(24)，41(22)，176(19)Mass spectrum m/z: 205(100), 40(97), 335(74), 43(45), 309(27), 275(24), 41(22), 176(19)

元素分析：63.71，H，4.50，N，7.09.Elemental analysis: 63.71, H, 4.50, N, 7.09.

实施例十：采用的原料2-氰基芳基取代乙烯-1，3-苯并噻唑的结构式为：Embodiment 10: The structural formula of the raw material 2-cyanoaryl substituted vinyl-1,3-benzothiazole used is:

Figure A200810203994D00111
Figure A200810203994D00111

其中Ar为3，4-CH3OC6H3，得到的产物为2-(反式-2，3-二氢-1-氰基-3-甲氧羰基-2-(3，4-二甲氧苯基)环丙烷)-1，3-苯并噻唑，其结构式为：Where Ar is 3,4-CH 3 OC 6 H 3 , the product obtained is 2-(trans-2,3-dihydro-1-cyano-3-methoxycarbonyl-2-(3,4-di Methoxyphenyl) cyclopropane)-1,3-benzothiazole, its structural formula is:

Figure A200810203994D00112
Figure A200810203994D00112

分子式：C19H13N3O4SMolecular formula: C 19 H 13 N 3 O 4 S

分子量：394.0987Molecular weight: 394.0987

外观：无色固体Appearance: colorless solid

核磁共振氢谱(300MHz，CDCl3，，内标：TMS)δ 3.29(d，J＝8.0Hz，1H，CH)，3.67(s，3H，OCH3)，3.91(s，3H，OCH3)，3.94(s，3H，OCH3)，4.10(d，J＝8.0Hz，1H，CH)，6.90-6.99(m，3H，Ar-H)，7.46-7.53(m，2H，Ar-H)，7.90(d，J＝7.8Hz，1H，Ar-H)，8.06(d，J＝8.2Hz，1H，Ar-H)红外吸收(KBr)cm-13035，2238，1738，1520.Proton NMR spectrum (300MHz, CDCl 3 , internal standard: TMS) δ 3.29 (d, J=8.0Hz, 1H, CH), 3.67 (s, 3H, OCH 3 ), 3.91 (s, 3H, OCH 3 ) , 3.94 (s, 3H, OCH 3 ), 4.10 (d, J=8.0Hz, 1H, CH), 6.90-6.99 (m, 3H, Ar-H), 7.46-7.53 (m, 2H, Ar-H) , 7.90(d, J=7.8Hz, 1H, Ar-H), 8.06(d, J=8.2Hz, 1H, Ar-H) infrared absorption (KBr) cm -1 3035, 2238, 1738, 1520.

质谱m/z：57(100)，43(93)，335(82)，71(63)，85(43)，55(43)，69(37)，41(35)Mass spectrum m/z: 57(100), 43(93), 335(82), 71(63), 85(43), 55(43), 69(37), 41(35)

元素分析：C，63.88，H，4.52，N，7.00。Elemental analysis: C, 63.88, H, 4.52, N, 7.00.

Claims (2)

1. a 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonyl cyclopropane)-1, the 3-benzothiazole is characterized in that the structural formula of this compound is:
Figure A200810203994C00021
Wherein, Ar is 4-CH 3OC 6H 4, 4-CH 3C 6H 4, C 6H 5, 4-FC 6H 4,, 4-ClC 6H 4,, 3-ClC 6H 4, 2-ClC 6H 4,, 3-NO 2C 6H 4, 2,4-CH 3OC 6H 3Or 3,4-CH 3OC 6H 3
2. one kind prepares 2-according to claim 1 (trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonyl cyclopropane)-1, the method of 3-benzothiazole, the concrete steps that it is characterized in that this method are: with 2-cyano-aryl substituted ethylene-1, the 3-benzothiazole, triphenylarsine, methyl bromoacetate and sodium bicarbonate are by 1:(0.09～0.11): (1.1～1.3): the mol ratio of (2.9～3.1) is dissolved in the second cyanogen, stirring and refluxing is reacted to 2-cyano-aryl substituted ethylene-1, the 3-benzothiazole reacts completely, remove and desolvate, column chromatography for separation obtains 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-methoxycarbonyl cyclopropane)-1, the 3-benzothiazole; Described 2-cyano-aryl substituted ethylene-1, the structural formula of 3-benzothiazole is:
Figure A200810203994C00022
Wherein, Ar is 4-CH 3OC 6H 4, 4-CH 3C 6H 4, C 6H 5, 4-FC 6H 4,, 4-ClC 6H 4,, 3-ClC 6H 4, 2-ClC 6H 4,, 3-NO 2C 6H 4, 2,4-CH 3OC 6H 3Or 3,4-CH 3OC 6H 3
CNA2008102039941A 2008-12-04 2008-12-04 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof Pending CN101423503A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNA2008102039941A CN101423503A (en) 2008-12-04 2008-12-04 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNA2008102039941A CN101423503A (en) 2008-12-04 2008-12-04 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof

Publications (1)

Publication Number Publication Date
CN101423503A true CN101423503A (en) 2009-05-06

Family

ID=40614407

Family Applications (1)

Application Number Title Priority Date Filing Date
CNA2008102039941A Pending CN101423503A (en) 2008-12-04 2008-12-04 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof

Country Status (1)

Country Link
CN (1) CN101423503A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2491030A4 (en) * 2009-10-22 2013-04-17 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
US9561201B2 (en) 2006-07-05 2017-02-07 Fibrotech Therapeutics Pty Ltd Therapeutic compounds
US11014873B2 (en) 2017-02-03 2021-05-25 Certa Therapeutics Pty Ltd. Anti-fibrotic compounds

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9561201B2 (en) 2006-07-05 2017-02-07 Fibrotech Therapeutics Pty Ltd Therapeutic compounds
EP2491030A4 (en) * 2009-10-22 2013-04-17 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
US9062076B2 (en) 2009-10-22 2015-06-23 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
US9951087B2 (en) 2009-10-22 2018-04-24 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
US11014873B2 (en) 2017-02-03 2021-05-25 Certa Therapeutics Pty Ltd. Anti-fibrotic compounds
US11603349B2 (en) 2017-02-03 2023-03-14 Certa Therapeutics Pty Ltd Anti-fibrotic compounds

Similar Documents

Publication Publication Date Title
Wang et al. GAP chemistry for pyrrolyl coumarin derivatives: a highly efficient one-pot synthesis under catalyst-free conditions
Zeng et al. Enantioselective construction of polyfunctionalized spiroannulated dihydrothiophenes via a formal thio [3+ 2] cyclization
Guchhait et al. One-pot preparation of isocyanides from amines and their multicomponent reactions: crucial role of dehydrating agent and base
Shi et al. Tandem C–O and C–N Bonds Formation Through O-Arylation and [3, 3]-Rearrangement by Diaryliodonium Salts: Synthesis of N-Aryl Benzo [1, 2, 3] triazin-4 (1H)-one Derivatives
CN103113308B (en) A method for preparing dihydropyrimidinone derivatives
CN106699632B (en) Process for preparing 3-methylideneisoindol-1-one derivatives
Deng et al. A Formal [3+ 2] Annulation of β‐Oxoamides and 3‐Alkyl‐or 3‐Aryl‐Substituted Prop‐2‐Ynyl Sulfonium Salts: Substrate‐Controlled Chemoselective Synthesis of Substituted γ‐Lactams and Furans
CN101423503A (en) 2-(trans-2,3-dihydro-2-aryl-1-cyano-3-carbomethoxyl cyclopropane)-1,3-benzopyrene and synthetic method thereof
Shi et al. Three-component one-pot synthesis of 1, 6-dioxa-5-oxo-1, 4, 5, 6-tetrahydrophenanthrene derivatives in aqueous media
CN106380440B (en) A kind of indone simultaneously pyrrole derivatives and its synthetic method and application
CN105820174B (en) A kind of preparation method of polysubstituted thiophene diindyl derivative
CN102775367B (en) Synthetic method of 3,4,5-tri-substituted oxazole-2-one
Hsueh et al. ortho-Lithiation driven one-pot synthesis of quinazolines via [2+ 2+ 2] cascade annulation of halofluorobenzenes with nitriles
CN107963976A (en) A kind of preparation method of phenyl ethyl amine compounds intermediate
CN105541835A (en) Cis-tetrahydrocarboline intermediate and synthesis method thereof, and application of cis-tetrahydrocarboline intermediate in preparing tadalafil
CN110194723A (en) A kind of N- Benzoylbenzene Isoserine derivatives and its synthetic method and application
Yu et al. K 2 CO 3-accelerated amidation of carboxylic acids using α-oxo ketene-N, S-acetals as amine surrogates
CN110204554A (en) Polysubstituted 1,4- oxaza heptane class compound and synthetic method
CN102127014B (en) Azaphenanthrone compound and preparation method thereof
CN101768118B (en) Bi-imidazoline diphenylamine compound and preparation method thereof
CN105017238A (en) Method for chiral spirophosphonate catalyzed synthesis of optically active 2H-1,4-benzoxazine-2-one derivative
Boshta et al. Synthesis of 2, 2-functionalized benzo [1, 3] dioxoles
CN1263084A (en) 1-trifluoromethyl-2-alkylvinylaniline derivative and its synthesis
CN109251192B (en) The preparation method of 3-position or 4-position trifluoromethyl substituted isocoumarin
CN107056808B (en) 3- aryl replaces isoxazole and succinimide class compound and its synthetic method

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Open date: 20090506