CN110627717B - 一种枝型1,4-二烯酰胺衍生物及其合成方法 - Google Patents
一种枝型1,4-二烯酰胺衍生物及其合成方法 Download PDFInfo
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- -1 alkenyl quinoline amide compound Chemical class 0.000 claims abstract description 77
- 238000006243 chemical reaction Methods 0.000 claims abstract description 73
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- 238000000034 method Methods 0.000 claims abstract description 10
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 9
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- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
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- 238000011068 loading method Methods 0.000 claims description 2
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- 230000035484 reaction time Effects 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
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- 238000006772 olefination reaction Methods 0.000 abstract description 3
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 116
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- IWWBBUVEYAVHKB-UHFFFAOYSA-N hept-6-enamide Chemical compound NC(=O)CCCCC=C IWWBBUVEYAVHKB-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- DWQIWPFDFXWSSP-ARJAWSKDSA-N (Z)-N-quinolin-8-ylhept-4-enamide Chemical compound C(CC\C=C/CC)(=O)NC=1C=CC=C2C=CC=NC12 DWQIWPFDFXWSSP-ARJAWSKDSA-N 0.000 description 5
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
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- 150000001993 dienes Chemical group 0.000 description 3
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- QYXANQICWIJLMS-IHWYPQMZSA-N (Z)-N-quinolin-8-ylhex-4-enamide Chemical compound C(CC\C=C/C)(=O)NC=1C=CC=C2C=CC=NC12 QYXANQICWIJLMS-IHWYPQMZSA-N 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- KURPPWHPIYBYBS-UHFFFAOYSA-N 2-ethenylaniline Chemical compound NC1=CC=CC=C1C=C KURPPWHPIYBYBS-UHFFFAOYSA-N 0.000 description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
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- BGWUOMVXFDCEQU-UHFFFAOYSA-N 4-methylidene-N-quinolin-8-ylhept-6-enamide Chemical compound C=C(CCC(=O)NC=1C=CC=C2C=CC=NC12)CC=C BGWUOMVXFDCEQU-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
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- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 description 2
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- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 238000005712 Baylis-Hillman reaction Methods 0.000 description 1
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- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
本发明公开了一种如式(1)所示的枝型1,4‑二烯酰胺衍生物及其合成方法，具体的合成方法为：将烯基喹啉酰胺化合物、烯丙基碳酸甲酯衍生物、过渡金属盐催化剂和添加剂置于有机溶剂中，于氩气氛围下加热反应，反应结束后，反应液经后处理得到所述的枝型1,4‑二烯酰胺衍生物。本发明在温和的条件下，利用8‑氨基喹啉酰胺作为N,N‑双配位的导向基团，以烯丙基碳酸甲酯作为烯基化试剂，高效实现烯基同碳位的碳氢烯基化反应，所得到的产物均为全新化合物，反应底物适用范围广泛，原料经济易得，无需外源氧化剂，操作简单，最高收率可达93％，具有广泛的应用前景和经济价值。
Description
技术领域
本发明涉及非共轭二烯类化合物合成技术领域，具体涉及一种枝型1,4-二烯酰胺衍生物及其合成方法。
背景技术
众所周知，双烯结构是一类普遍的化学结构，广泛存在于天然产物和医药生物活性分子中，如利司他汀，比塞林比洛利德等。1,4-二烯也常作为配体广泛用于过渡金属催化的反应中。目前报导了多种制备1,4二烯化合物的方法，包括：催化偶联反应，烯反应，烯基化反应以及Morita–Baylis–Hillman(森田-贝里斯-希尔曼)反应等。随着能源的枯竭和环境问题的日益严峻，发展高效、高选择性的1,4二烯化合物的合成方法显得尤为迫切。
基于碳氢活化策略实现烯烃的直接碳氢烯丙基化反应，不仅原料便宜、来源广泛，且合成方法具有较高的原子经济性和步骤经济性，符合现代有机合成化学的发展趋势。目前，基于官能团导向下的碳氢键活化策略引起了化学家们足够的重视，一系列关于导向基作用下的烯烃碳氢键的选择性烯丙基化反应被相继报道。
罗德平课题组报导了一种铑催化下的丙烯酰胺与醋酸烯丙酯的碳氢烯丙基化反应(Feng C,Feng D,Loh T P.Rhodium(III)-catalyzed C–H allylation of electron-deficient alkenes with allyl acetates[J].Chemical Communications,2015,51(2):342-345.)，该反应使用弱配位的导向基团可实现较高的反应效率，具有广泛的底物选择范围，多种官能团都可反应，且反应具有优异的选择性，从而为1,4二烯骨架的进入开辟了一条新的合成途径。
游书立课题组报导了一种铱催化下的邻胺基苯乙烯与碳酸烯丙酯的偶联反应，用于高效、高选择性地制备1,4-二烯化合物(He H,Liu W B,Dai L X,et al.Ir-CatalyzedCross-Coupling of Styrene Derivatives with Allylic Carbonates:Free AmineAssisted Vinyl C-H Bond Activation[J].Journal of the American ChemicalSociety,2009,131(24):8346-8347.)，发现[Ir(COD)Cl]2/Feringa的配体可有效催化邻氨基苯乙烯衍生物与烯丙基碳酸酯的交叉偶联反应。该反应产物具有独特的顺式双键形成，是对传统Heck反应的补充。
这些文献合成了一系列立体专一的1,3-和1,4-二烯化合物，但是仅仅局限于共轭型烯基酰胺与缺电子烯烃为底物，且只能活化酰胺基邻位的烯基碳氢键，得到的是线型偶联产物。非共轭型烯基酰胺的烯基化偶联反应，合成酰胺取代的枝型共轭二烯衍生物的方法没有报道。
发明内容
本发明提供枝型1,4-二烯酰胺衍生物及其合成方法，利用钯催化下，以8-氨基喹啉酰胺作为N,N-双配位的导向基团，高效实现烯基同碳位的碳氢烯基化反应，得到枝型1,4-二烯酰胺衍生物。
为实现上述目的，本发明采用的技术方案是：
一种枝型1,4-二烯酰胺衍生物，结构如式(1)所示：
式中，R1为氢、C1～8烷基、C5～8的环烷烃基、取代苯基、萘基或杂环基；所述的取代苯基的取代基为C1～6的烷基、C1～6的烷氧基、卤素或卤素取代的C1～6的烷基；R2为氢、C1～6烷基、苯基、苄基或杂环基。
优选地，所述的R1为氢、C1～6烷基、C5～8的环烷烃基、取代苯基、萘基、呋喃基、噻吩基或N-甲基吡咯基；R2为氢、C1～6烷基、苯基或苄基。
进一步优选地，所述的R1为氢、甲基、乙基、正戊基、环己烷基、苯基、4-甲基苯基、4-甲氧基苯基、4-氟苯基、4-溴苯基、4-氯苯基、4-三氟甲基苯基、2-氟苯基、3-氟苯基、3-甲氧基苯基、2-甲基苯基、3-呋喃基、2-噻吩基、2-N-甲基吡咯基、萘基或叔丁基；R2为氢、苯基、正戊基或苄基。
更为具体的，所述的枝型1,4-二烯酰胺衍生物为下列化合物之一：(E)-4-苯亚甲基-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(4-氟苯亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(4-甲氧基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(4-溴亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(4-甲基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(4-氯亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-N-(喹啉-8-基)-4-(4-(三氟甲基)亚苄基)庚-6-烯酰胺、(E)-4-(2-氟苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(3-氟苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(3-甲氧基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(2-甲基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(呋喃-3-基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-N-(喹啉-8-基)-4-(噻吩-2-基亚甲基)庚-6-烯酰胺、(E)-4-((1-甲基-1H-吡咯-2-基)亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(Z)-4-((1-甲基-1H-吡咯-2-基)亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-(萘-1-基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-烯丙基-N-(喹啉-8-基)庚-4-烯酰胺、(E)-4-亚乙基-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-亚乙基-N-(喹啉-8-基)癸-6-烯酰胺、(E)-4-(环己基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺、(E)-4-烯丙基-6,6-二甲基-N-(喹啉-8-基)庚-4-烯酰胺、4-亚甲基-N-(喹啉-8-基)-庚-6-烯酰胺、(E)-4-((Z)-3-苯基烯丙基)-N-(喹啉-8-基)庚-4-烯酰胺、(E)-4-肉桂基-N-(喹啉-8-基)庚-4-烯酰胺、4-((E)-亚苄基)-7-苯基-N-(喹啉-8-基)庚-6-烯酰胺、(4E)-4-亚丙基-N-(喹啉-8-基)十三碳-6-烯酰胺、4-((E)-亚苄基)-N-(喹啉-8-基)十三碳-6-烯酰胺、(4E)-8-苯基-4-丙基-N-(喹啉-8-基)辛-6-烯酰胺、4-((E)-亚苄基)-8-苯基-N-(喹啉-8-基)辛-6-烯酰胺。
本发明提供的枝型1,4-二烯酰胺衍生物的合成方法为：将烯基喹啉酰胺化合物、烯丙基碳酸甲酯衍生物、过渡金属盐催化剂和添加剂置于有机溶剂中，于氩气氛围下加热反应，反应结束后，反应液经后处理得到所述的枝型1,4-二烯酰胺衍生物；
所述的烯基喹啉酰胺化合物结构如式(2)所示：
式中R1为氢、C1～8烷基、C5～8的环烷烃基、取代苯基、萘基或杂环基；所述的取代苯基的取代基为C1～6的烷基、C1～6的烷氧基、卤素、卤素取代的C1～6的烷基；
所述的烯丙基碳酸甲酯衍生物结构如式(3)所示：
式中R2为氢、C1～6烷基、苯基、苄基或杂环基；
所述的枝型1,4-二烯酰胺衍生物的合成方法中的反应式如下所示：
进一步优选地，所述的烯基喹啉酰胺化合物为：(Z)-5-苯基-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-甲氧基苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-溴苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-氯苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(4-三氟甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(2-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(3-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(2-甲氧基苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(2-甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(呋喃-3-基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(噻吩-2-基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(1-甲基-1H-吡咯-2-基)-N-(喹啉-8-基)戊-4-烯酰胺、(E)-5-(1-甲基-1H-吡咯-2-基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-5-(萘-1-基)-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-N-(喹啉-8-基)庚-4-烯酰胺、(Z)-N-(喹啉-8-基)己-4-烯酰胺、(Z)-N-(喹啉-8-基)癸-4-烯酰胺、(Z)-5-环己基-N-(喹啉-8-基)戊-4-烯酰胺、(Z)-6,6-二甲基-N-(喹啉-8-基)庚-4-烯酰胺、N-(喹啉-8-基)戊-4-烯酰胺。
进一步优选地，所述的烯丙基碳酸甲酯衍生物为烯丙基碳酸甲酯、1-苯基烯丙基碳酸甲酯或1-乙烯基己基碳酸甲酯。
所述的烯基喹啉酰胺化合物、烯丙基碳酸甲酯衍生物、过渡金属盐催化剂和添加剂的物质的量之比为1：2-6：0.1-0.4：1-4；所述有机溶剂的体积用量以烯基喹啉酰胺化合物的物质的量计为5～10L/mol。
所述的有机溶剂为甲醇、二甲基亚砜、乙腈、1,3-二氯乙烷、1,4-二氧六环中任一种或任几种。
所述的过渡金属盐催化剂为钯盐。
进一步地，所述的过渡金属盐催化剂为醋酸钯或氯化钯。
所述的加热反应温度为25～80℃，反应时间16～24h。
所述的后处理为将反应液装柱，剩余反应液用二氯甲烷溶解转移，用硅胶进行柱层析分离，洗脱剂乙酸乙酯与石油醚混合液，收集含目标化合物的洗脱液，浓缩干燥得到所述的枝型1,4-二烯酰胺衍生物。
与现有技术相比，本发明具有以下有益效果：
(1)本发明提供1,4-二烯酰胺衍生物的合成方法，利用8-氨基喹啉酰胺作为N,N-双配位的导向基团，以烯丙基碳酸甲酯作为烯基化试剂，高效实现烯基同碳位的碳氢烯基化反应，所得到的产物均为全新化合物，在此之前未见报道，合成方法也是对现有方法的一种有效补充。
(2)本发明提供的1,4-二烯酰胺衍生物的合成方法反应条件温和，无需外源氧化剂，操作简单，副产物仅为甲醇和二氧化碳，反应收率高，最高可达93％。
(3)本发明提供的1,4-二烯酰胺衍生物的合成方法反应底物适用范围广泛，原料经济易得，具有广泛的应用前景和经济价值。
附图说明
图1为实施例18制备的(E)-4-亚乙基-N-(喹啉-8-基)庚-6-烯酰胺的核磁共振氢谱图。
图2为实施例20制备的(E)-4-(环己基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的核磁共振氢谱图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。本领域技术人员在理解本发明的技术方案基础上进行修改或等同替换，而未脱离本发明技术方案的精神和范围，均应涵盖在本发明的保护范围内。
以下实施例所使用药品均为市场所购，其中过渡金属催化剂均采用醋酸钯；添加剂均采用新戊酸。
实施例中反应液后处理步骤为：将反应液装柱，剩余反应液用二氯甲烷溶解转移，用300目硅胶进行柱层析分离，洗脱剂为体积比1：4的乙酸乙酯与石油醚混合液，收集含目标化合物的洗脱液，浓缩干燥得到所述的戊二烯酰胺类化合物。
实施例1
(E)-4-苯亚甲基-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-苯基-N-(喹啉-8-基)戊-4-烯酰胺(30.2mg，0.1mmol)和烯丙基碳酸甲酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)，反应液经直接柱层析分离后得到目标产物白色液体(25.3mg，收率74％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)：δ9.77(s,1H),8.77–8.74(m,2H),8.11(dd,J＝8.5,2.0Hz,1H),7.52–7.45(m,2H),7.41(dd,J＝8.5,4.0Hz,1H),7.30–7.24(m,4H),7.18–7.15(m,1H),6.39(s,1H),5.96–5.88(m,1H),5.20–5.12(m,2H),3.00(dd,J＝7.0,1.0Hz,2H),2.81–2.78(m,2H),2.71–2.68(m,2H)；13C NMR(125MHz,CDCl3)：δ169.81,147.00,138.36,137.21,136.74,135.26,135.12,133.39,127.47,127.23,126.83,126.57,126.33,125.29,120.51,120.34,115.84,115.31,40.79,35.43,25.85；HRMS(ESI)：m/z for C23H23N2O[M+H]+:343.1805,found:343.1809；
该反应产物的红外谱图表征结果如下：FTIR(KBr,cm-1):3564.60,3473.24,3416.72,1684.11,1633.64,1616.82,1525.01,1482.24。
实施例2
(E)-4-(4-氟苯亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺(32.0mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1),反应液经直接柱层析分离后得到目标产物黄色液体(33.4mg，收率93％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.76(s,1H),8.77–8.74(m,2H),8.13(dd,J＝8.0,1.5Hz,1H),7.53–7.47(m,2H),7.43(dd,J＝8.0,4.0Hz,1H),7.20(q,J＝5.5Hz,2H),6.96(t,J＝9.0Hz,2H),6.33(s,1H),5.95–5.87(m,1H),5.20–5.13(m,2H),2.99(d,J＝8.0Hz,2H),2.77–2.73(m,2H),2.70–2.66(m,2H)；13C NMR(125MHz,CDCl3)δ169.70,160.30(d,JC-F＝243.8Hz),147.03,138.43,137.17,135.31,134.99,133.32,132.74,132.71,129.03(d,JC-F＝7.8Hz),126.84,126.33,125.48,120.48(d,JC-F＝18.5Hz),115.95,115.32,114.06(d,JC-F＝21.1Hz),40.61,35.33,25.77；19F NMR(470MHz,CDCl3)δ–116.00；HRMS(ESI):m/z for C23H22N2OF[M+H]+:361.1711,found:361.1722。
实施例3
(E)-4-(4-甲氧基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-甲氧基苯基)-N-(喹啉-8-基)戊-4-烯酰胺(33.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(28.0mg，收率76％)，反应式如下：
该反应产物的核磁谱图表征结果如下：。1H NMR(500MHz,CDCl3)δ9.79(s,1H),8.79–8.75(m,2H),8.15(dd,J＝8.5,1.5Hz,1H),7.54–7.48(m,2H),7.44(dd,J＝8.5,4.5Hz,1H),7.20(d,J＝9.0Hz,2H),6.84–6.82(m,2H),6.33(s,1H),5.96–5.88(m,1H),5.20–5.12(m,2H),3.76(s,3H),2.98(d,J＝8.0Hz,2H),2.81–2.78(m,2H),2.72–2.69(m,2H)；13C NMR(125MHz,CDCl3)δ169.97,156.99,147.04,137.24,136.95,135.33,135.29,133.42,129.29,128.62,126.86,126.37,126.04,120.54,120.36,115.70,115.34,112.67,54.15,40.96,35.45,25.86；HRMS(ESI):m/z for C24H25N2O2[M+H]+:373.1911,found:373.1918。
实施例4
(E)-4-(4-溴亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后，依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-溴苯基)-N-(喹啉-8-基)戊-4-烯酰胺(36.6mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色固体(27.0mg，收率64％)。m.p.＝74.6℃，反应结构式如下：
该反应产物的核磁谱图表征结果如下：。1H NMR(500MHz,CDCl3)δ9.76(s,1H),8.79(dd,J＝4.0,1.5Hz,1H),8.74(dd,J＝7.0,1.5Hz,1H),8.16(dd,J＝8.0,1.5Hz,1H),7.55–7.48(m,2H),7.46(dd,J＝8.0,4.0Hz,1H),7.41–7.36(m,2H),7.11(d,J＝8.0Hz,2H),6.30(s,1H),5.95–5.88(m,1H),5.25–5.07(m,2H),3.04–2.95(m,2H),2.79–2.72(m,2H),2.72–2.64(m,2H)；13C NMR(125MHz,CDCl3)δ169.63,147.06,139.32,137.13,135.65,135.40,134.83,133.29,130.31,129.17,126.88,126.39,125.42,120.59,120.45,119.15,116.10,115.41,40.67,35.30,25.87；HRMS(ESI):m/z for C23H22N2OBr[M+H]+:421.091,found:421.0917。
实施例5
(E)-4-(4-甲基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后，依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺(31.6mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(25.7mg，收率70％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.77(s,1H),8.78(dd,J＝4.0,1.5Hz,1H),8.76(dd,J＝7.5,1.5Hz,1H),8.15(dd,J＝8.0,1.5Hz,1H),7.54–7.47(m,2H),7.44(dd,J＝8.0,4.0Hz,1H),7.16(d,J＝8.0Hz,2H),7.10(d,J＝8.0Hz,2H),6.36(s,1H),5.96–5.88(m,1H),5.20–5.12(m,2H),2.99(dd,J＝7.0,1.0Hz,2H),2.81–2.78(m,2H),2.71–2.68(m,2H),2.29(s,3H)；13C NMR(125MHz,CDCl3)δ169.94,147.01,137.71,137.26,135.30,135.27,134.91,133.84,133.44,127.95,127.38,126.87,126.47,126.38,120.52,120.34,115.74,115.36,40.92,35.48,25.88,20.09；HRMS(ESI):m/z for C24H25N2O[M+H]+:357.1961,found:357.1969。
实施例6
(E)-4-(4-氯亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-氯苯基)-N-(喹啉-8-基)戊-4-烯酰胺(33.7mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色固体(23.4mg，收率62％)，m.p.＝107.0℃，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.75(s,1H),8.78(dd,J＝5.5,1.0Hz,1H),8.74(dd,J＝7.5,1.5Hz,1H),8.15(dd,J＝8.0,1.5Hz,1H),7.54–7.48(m,2H),7.45(dd,J＝8.0,4.0Hz,1H),7.24–7.22(m,2H),7.17(d,J＝8.5Hz,2H),6.33(s,1H),5.95–5.87(m,1H),5.21–5.13(m,2H),3.01–2.99(m,2H),2.77–2.74(m,2H),2.71–2.67(m,2H)；13C NMR(125MHz,CDCl3)δ169.63,147.09,139.23,137.21,135.33,135.20,134.88,133.34,131.01,128.82,127.37,126.88,126.36,125.42,120.59,120.44,116.07,115.35,40.68,35.33,25.87；HRMS(ESI):m/z for C23H22N2OCl[M+H]+:377.1415,found:377.1422。
实施例7
(E)-N-(喹啉-8-基)-4-(4-(三氟甲基)亚苄基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(4-三氟甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺(37.0mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)，反应液经直接柱层析分离后得到白色液体(29.2mg，收率71％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.76(s,1H),8.77(dd,J＝4.0,2.0Hz,1H),8.74(dd,J＝7.0,1.5Hz,1H),8.15(dd,J＝8.0,1.5Hz,1H),7.54–7.49(m,4H),7.45(dd,J＝8.0,4.0Hz,1H),7.34(d,J＝8.0Hz,2H),6.40(s,1H),5.96–5.88(m,1H),5.23–5.16(m,2H),3.04–3.02(m,2H),2.80–2.76(m,2H),2.72–2.69(m,2H)；13C NMR(125MHz,CDCl3)δ169.49,147.08,140.65,140.43(d,JC-F＝1.1Hz),137.20,135.35,134.64,133.29,127.77,127.26(q,JC-F＝32.3Hz),126.89,126.36,125.37,124.15(q,JC-F＝3.6Hz),123.203(q,JC-F＝270.3Hz),120.55(d,JC-F＝13.6Hz),116.29,115.38,40.59,35.27,25.94；19F NMR(470MHz,CDCl3)δ-62.38；HRMS(ESI):m/z for C24H22N2OF3[M+H]+:327.1382,found:327.1387。
实施例8
(E)-4-(2-氟苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(2-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺(32.0mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(22.8mg，收率63％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.77(s,1H),8.78(dd,J＝4.0,1.5Hz,1H),8.76–8.70(d,J＝8.5Hz,1H),8.15(dd,J＝8.5,1.5Hz,1H),7.53–7.47(m,2H),7.44(dd,J＝8.0,4.0Hz,1H),7.28–7.25(m,1H),7.16(q,J＝5.5Hz,1H),7.06–6.99(m,2H),6.33(s,1H),5.98–5.90(m,1H),5.23–5.15(m,2H),3.04(d,J＝6.5Hz,2H),2.69(s,4H)；13C NMR(125MHz,CDCl3)δ169.82,158.99(d,JC-F＝244.1Hz),147.03,140.81,137.26,135.30,134.86,133.41,129.48(d,JC-F＝3.4Hz),127.22(d,JC-F＝8.1Hz),126.87,126.37,124.38(d,JC-F＝15.0Hz),122.76(d,JC-F＝3.5Hz),120.53,120.36,119.22,116.06,115.35,114.36(d,JC-F＝22.3Hz),40.23,35.23,26.25；19F NMR(470MHz,CDCl3)δ-114.84；HRMS(ESI):m/z for C23H22N2OF[M+H]+:361.1711,found:361.1719。
实施例9
(E)-4-(3-氟苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后，依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(3-氟苯基)-N-(喹啉-8-基)戊-4-烯酰胺(32.0mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(23.0mg，收率64％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.77(s,1H),8.78(dd,J＝4.5,2.0Hz,1H),8.74(dd,J＝7.5,1.5Hz,1H),8.15(dd,J＝8.5,1.5Hz,1H),7.54–7.48(m,2H),7.45(dd,J＝8.5,4.5Hz,1H),7.25–7.21(m,1H),7.03(d,J＝7.5Hz,1H),6.95(d,J＝10.5Hz,1H),6.86(td,J＝8.5,2.0Hz,1H),6.34(s,1H),5.95–5.87(m,1H),5.21–5.14(m,2H),3.00–3.00(dd,J＝6.5,0.5Hz,2H),2.80–2.77(m,2H),2.71–2.68(m,2H)；13CNMR(125MHz,CDCl3)δ169.61,161.71(d,JC-F＝243.9Hz),147.06,139.03(d,JC-F＝7.6Hz),137.24,135.31,134.82,133.36,128.64(d,JC-F＝8.5Hz),126.88,126.37,125.53,123.22,120.48(d,JC-F＝17.6Hz),116.11,115.37,114.33(d,J＝21.1Hz),112.18(d,JC-F＝20.9Hz),40.64,35.31,25.84；19F NMR(470MHz,CDCl3)δ-113.50；HRMS(ESI):m/z forC23H22N2OF[M+H]+:361.1711,found:361.1718。
实施例10
(E)-4-(3-甲氧基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(2-甲氧基苯基)-N-(喹啉-8-基)戊-4-烯酰胺(33.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(25.0mg，收率67％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.77(s,1H),8.77(dd,J＝4.5,2.0Hz,1H),8.75(dd,J＝7.0,1.0Hz,1H),8.14(dd,J＝8.0,1.5Hz,1H),7.53–7.47(m,2H),7.44(dd,J＝8.5,4.5Hz,1H),7.20(t,J＝8.0Hz,1H),6.86(d,J＝7.5Hz,1H),6.79(s,1H),6.73(dd,J＝8.0,2.0Hz,1H),6.37(s,1H),5.96–5.88(m,1H),5.20–5.13(m,2H),3.76(s,3H),3.00(dd,J＝7.0,1.5Hz,2H),2.82–2.78(m,2H),2.72–2.68(m,2H).13CNMR(125MHz,CDCl3)δ169.82,158.49,147.04,138.67,138.22,137.29,135.29,135.12,133.45,128.21,126.89,126.55,126.38,120.53,120.36,119.98,115.87,115.39,112.82,111.23,54.13,40.80,35.53,26.00；HRMS(ESI):m/z for C24H25N2O2[M+H]+:373.1911,found:373.1918。
实施例11
(E)-4-(2-甲基亚苄基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(2-甲基苯基)-N-(喹啉-8-基)戊-4-烯酰胺(31.6mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(28.9mg，收率81％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.70(s,1H),8.76(dd,J＝4.0,1.5Hz,1H),8.72(d,J＝7.0Hz,1H),8.14(dd,J＝8.0,1.0Hz,1H),7.52–7.46(m,2H),7.43(dd,J＝8.0,4.0Hz,1H),7.16(d,J＝6.5Hz,1H),7.12–7.08(m,3H),6.35(s,1H),5.99–5.90(m,1H),5.21–5.13(m,2H),3.03(d,J＝6.5Hz,2H),2.62(s,4H),2.19(s,3H)；13C NMR(125MHz,CDCl3)δ169.91,147.00,138.00,137.24,136.11,135.33,135.27,135.21,133.42,128.67,127.84,126.85,126.36,125.99,125.65,124.51,120.50,120.30,115.69,115.32,39.99,35.56,25.82,18.90；HRMS(ESI):m/z for C24H25N2O[M+H]+:357.1961,found:357.1969。
实施例12
(E)-4-(呋喃-3-基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(呋喃-3-基)-N-(喹啉-8-基)戊-4-烯酰胺(29.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色固体(22.1mg，收率66％)，m.p.＝51.3℃，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.91(s,1H),8.81–8.79(m,2H),8.16(dd,J＝8.0,1.5Hz,1H),7.56–7.49(m,2H),7.46–7.44(m,2H),6.39(dd,J＝3.0,1.5Hz,1H),6.31(d,J＝3.5Hz,1H),6.14(s,1H),5.91–5.83(m,1H),5.17–5.11(m,2H),2.98–2.33(m,4H),2.77–2.74(m,2H)；13C NMR(125MHz,CDCl3)δ170.32,151.91,147.03,140.52,137.55,137.32,135.35,134.70,133.54,126.92,126.42,120.55,120.38,116.14,115.44,114.65,110.09,107.49,41.70,36.01,27.60；HRMS(ESI):m/z forC21H21N2O2[M+H]+:333.1598,found:333.1606。
实施例13
(E)-N-(喹啉-8-基)-4-(噻吩-2-基亚甲基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(噻吩-2-基)-N-(喹啉-8-基)戊-4-烯酰胺(30.8mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色固体(22.9mg，收率66％)，m.p.＝74.4℃，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.90(s,1H),8.81–8.78(m,2H),8.16(dd,J＝8.5,1.5Hz,1H),7.56–7.49(m,2H),7.45(dd,J＝8.0,4.0Hz,1H),7.23–7.21(m,1H),7.00(d,J＝3.5Hz,2H),6.49(s,1H),5.93–5.84(m,1H),5.19–5.12(m,2H),3.00(dd,J＝7.0,1.0Hz,2H),2.95–2.92(m,2H),2.78–2.75(m,2H)；13C NMR(125MHz,CDCl3)δ169.83,147.06,139.23,137.47,137.31,135.31,134.77,133.48,126.90,126.40,125.90,125.73,123.44,120.56,120.40,119.37,116.14,115.41,41.66,35.03,26.95；HRMS(ESI):m/z for C21H21N2OS[M+H]+:349.1369,found:349.1374。
实施例14
(E)-4-((1-甲基-1H-吡咯-2-基)亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(1-甲基-1H-吡咯-2-基)-N-(喹啉-8-基)戊-4-烯酰胺(30.5mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到橙红色固体(6.7mg，收率20％)，m.p.＝87.0℃，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.83(s,1H),8.80–8.78(m,2H),8.15(dd,J＝8.0,1.5Hz,1H),7.55–7.48(m,2H),7.45(dd,J＝8.0,4.0Hz,1H),6.58–6.57(m,1H),6.32(d,J＝3.5Hz,1H),6.14–6.13(m,2H),5.93–5.85(m,1H),5.18–5.11(m,2H),3.56(s,3H),3.00(dd,J＝7.0,1.0Hz,2H),2.88–2.85(m,2H),2.76–2.72(m,2H)；13CNMR(125MHz,CDCl3)δ170.10,147.06,137.31,136.75,135.29,135.23,133.50,128.73,126.89,126.40,120.96,120.53,120.34,115.77,115.39,114.98,107.29,106.61,41.46,35.02,33.06,26.65；HRMS(ESI):m/z for C22H24N3O[M+H]+:346.1914,found:346.1923。
实施例15
(Z)-4-((1-甲基-1H-吡咯-2-基)亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(E)-5-(1-甲基-1H-吡咯-2-基)-N-(喹啉-8-基)戊-4-烯酰胺(29.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到棕红色固体(13.5mg，收率40％)，m.p.＝100.5℃，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.85(s,1H),8.79(dd,J＝7.5,1.5Hz,1H),8.77(dd,J＝4.0,1.5Hz,1H),8.16(dd,J＝8.0,1.5Hz,1H),7.55–7.49(m,2H),7.45(dd,J＝8.5,4.5Hz,1H),6.55–6.54(m,1H),6.26(s,1H),6.18–6.17(m,1H),6.09–6.08(m,1H),5.96–5.88(m,1H),5.20–5.12(m,2H),3.45(s,3H),3.17(d,J＝4.0Hz,2H),2.80–2.76(m,2H),2.73–2.70(m,2H)；13C NMR(125MHz,CDCl3)δ170.02,147.09,137.29,136.09,135.33,134.47,133.45,128.80,126.90,126.38,120.94,120.57,120.40,115.41,115.25,115.16,107.39,106.21,35.95,35.23,32.94,32.31；HRMS(ESI):m/z forC22H24N3O[M+H]+:346.1914,found:346.1923。
实施例16
(E)-4-(萘-1-基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-(萘-1-基)-N-(喹啉-8-基)戊-4-烯酰胺(35.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(21.0mg，收率54％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.61(s,1H),8.70(dd,J＝4.0,1.5Hz,1H),8.66(dd,J＝7.0,1.0Hz,1H),8.11(dd,J＝8.0,1.5Hz,1H),7.93–7.91(m,1H),7.76(dd,J＝6.0,2.5Hz,1H),7.68(d,J＝8.0Hz,1H),7.49–7.32(m,7H),6.77(s,1H),6.09–6.01(m,1H),5.29–5.19(m,2H),3.14(d,J＝7.0Hz,2H),2.67–2.64(m,2H),2.61–2.58(m,2H)；13C NMR(125MHz,CDCl3)δ169.81,146.92,139.91,137.15,135.21,134.18,133.33,132.45,130.99,127.17,126.79,126.32,126.03,125.24,124.79,124.65,124.60,124.36,123.95,120.45,120.25,115.97,115.26,40.03,35.69,26.22；HRMS(ESI):m/z for C27H25N2O[M+H]+:393.1961,found:393.1969。
实施例17
(E)-4-烯丙基-N-(喹啉-8-基)庚-4-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后，依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)庚-4-烯酰胺(25.4mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(23.5mg，收率80％)，反应式如下：
该反应产物的核磁谱图表征结果如图1所示：1H NMR(500MHz,CDCl3)δ9.80(s,1H),8.80–8.77(m,2H),8.14(dd,J＝8.0,1.5Hz,1H),7.54–7.47(m,2H),7.44(dd,J＝8.0,4.0Hz,1H),5.87–5.79(m,1H),5.26(t,J＝7.0Hz,1H),5.11–5.04(m,2H),2.81(d,J＝8.0Hz,2H),2.63–2.60(m,2H),2.57–2.53(m,2H),2.12–2.06(m,2H),0.95(t,J＝8.0Hz,3H)；13C NMR(125MHz,CDCl3)δ170.24,147.05,137.28,135.98,135.30,133.99,133.50,128.69,126.88,126.39,120.53,120.31,115.35,115.02,76.28,76.02,75.77,40.42,35.89,25.05,20.13,13.47；HRMS(ESI):m/z for C19H23N2O[M+H]+:295.1805,found:295.1813。
实施例18
(E)-4-亚乙基-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)己-4-烯酰胺(24.0mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到无色液体(23.7mg，收率85％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.80(s,1H),8.81–8.77(m,2H),8.15(dd,J＝8.0,1.5Hz,1H),7.55–7.48(m,2H),7.45(dd,J＝8.0,4.0Hz,1H),5.86–5.78(m,1H),5.35(q,J＝6.5Hz,1H),5.11–5.04(m,2H),2.82(d,J＝7.0Hz,2H),2.64–2.61(m,2H),2.58–2.55(m,2H),1.66(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3)δ170.33,147.06,137.30,135.92,135.49,135.33,133.50,126.90,126.42,120.71,120.54,120.34,115.40,115.03,40.50,35.51,24.78,12.37；HRMS(ESI):m/z for C18H21N2O[M+H]+:281.1648,found:281.1652。
实施例19
(E)-4-亚乙基-N-(喹啉-8-基)癸-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)癸-4-烯酰胺(29.6mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到无色液体(26.1mg，收率78％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.80(s,1H),8.80–8.77(m,2H),8.15(d,J＝8.0Hz,1H),7.55–7.48(m,2H),7.45(dd,J＝8.5,5.0Hz,1H),5.87–5.79(m,1H),5.26(t,J＝7.0Hz,1H),5.07(dd,J＝19.5,14.0Hz,2H),2.82(d,J＝6.5Hz,2H),2.63–2.54(m,4H),2.06(q,J＝7.0Hz,2H),1.35–1.29(m,6H),0.85(t,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3)δ170.27,147.03,137.29,136.02,135.29,134.37,133.51,127.19,126.88,126.40,120.52,120.29,115.34,114.98,40.45,35.90,30.54,28.59,26.86,25.17,21.55,13.03；HRMS(ESI):m/z for C22H29N2O[M+H]+:337.2274,found:337.2284。
实施例20
(E)-4-(环己基亚甲基)-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-环己基-N-(喹啉-8-基)戊-4-烯酰胺(30.8mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色液体(25.9mg，收率74％)，反应式如下：
该反应产物的核磁谱图表征结果如图2所示：1H NMR(500MHz,CDCl3)δ9.81(s,1H),8.81–8.77(m,2H),8.16(dd,J＝8.5,1.5Hz,1H),7.55–7.49(m,2H),7.46(dd,J＝8.0,4.0Hz,1H),5.86–5.77(m,1H),5.11–5.03(m,3H),2.79(d,J＝8.0Hz,2H),2.64–2.60(m,2H),2.56(dd,J＝10.5,7.0Hz,2H),2.30–2.23(m,1H),1.67–1.56(m,6H),1.25–1.21(m,2H),1.16–1.11(m,1H),1.06–0.98(m,2H)；13C NMR(125MHz,CDCl3)δ170.35,147.07,137.28,136.11,135.34,133.47,133.30,132.54,126.90,126.41,120.54,120.33,115.38,114.92,40.28,36.33,35.88,32.55,25.37,25.01,24.88；HRMS(ESI):m/z for C23H30N2O[M+H]+:349.2274,found:349.2283。
实施例21
(E)-4-烯丙基-6,6-二甲基-N-(喹啉-8-基)庚-4-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-6,6-二甲基-N-(喹啉-8-基)庚-4-烯酰胺(28.2mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后，将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到黄色液体(25.6mg，收率80％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.82(s,1H),8.81–8.77(m,2H),8.15(dd,J＝8.0,1.5Hz,1H),7.55–7.48(m,2H),7.45(dd,J＝8.5,4.5Hz,1H),5.86–5.77(m,1H),5.30(s,1H),5.11–5.04(m,2H),2.77(dd,J＝7.0,1.0Hz,2H),2.71–2.63(m,4H),1.16(s,9H)；13C NMR(125MHz,CDCl3)δ170.22,147.08,137.33,137.28,136.37,135.33,133.74,133.50,126.92,126.41,120.54,120.36,115.44,114.87,41.54,36.08,31.50,30.48,25.43；HRMS(ESI):m/z for C21H27N2O[M+H]+:323.2118,found:323.2125。
实施例22
4-亚甲基-N-(喹啉-8-基)-庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，N-(喹啉-8-基)戊-4-烯酰胺(22.6mg，0.1mmol)和甲基碳酸烯丙酯(46.4mg，0.4mmol)。将小瓶在氩气下密封并加热至100℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到无色液体(4.3mg，收率17％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.84(s,1H),8.81(dd,J＝4.0,1.5Hz,1H),8.78(dd,J＝7.5,1.5Hz,1H),8.17(dd,J＝8.0,1.5Hz,1H),7.56–7.48(m,2H),7.46(dd,J＝8.5,4.5Hz,1H),5.90–5.82(m,1H),5.13–5.07(m,2H),4.90(s,1H),4.86(s,1H),2.86(d,J＝7.0Hz,2H),2.75–2.72(m,2H),2.57–2.54(m,2H)；13C NMR(125MHz,CDCl3)δ170.08,147.08,145.55,137.32,135.35,135.04,133.47,126.92,126.42,120.56,120.38,115.51,115.44,109.71,40.04,35.28,30.32；HRMS(ESI):m/z forC17H19N2O[M+H]+:267.1492,found:267.1495。
实施例23
(E)-4-((Z)-3-苯基烯丙基)-N-(喹啉-8-基)庚-4-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)庚-4-烯酰胺(25.4mg，0.1mmol)和1-苯基烯丙基碳酸甲酯(76.9mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到棕色液体(16.7mg，收率45％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.80(s,1H),8.78(m,2H),8.16(dd,J＝8.5,1.5Hz,1H),7.55–7.49(m,2H),7.45(dd,J＝8.0,4.0Hz,1H),7.34(d,J＝7.5Hz,2H),7.28(d,J＝7.5Hz,2H),7.18(t,J＝7.5Hz,1H),6.43(d,J＝15.5Hz,1H),6.25–6.19(m,1H),5.31(t,J＝7.0Hz,1H),2.97(d,J＝6.5Hz,2H),2.67–2.58(m,4H),2.14–2.09(m,2H),0.96(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ170.20,147.07,137.32,136.61,135.31,134.27,133.52,130.25,128.97,127.81,127.42,126.91,126.43,125.93,125.06,120.53,120.33,115.39,39.49,36.02,25.30,20.20,13.48；HRMS(ESI):m/z forC25H27N2O[M+H]+:371.2118,found:371.2120。
实施例24
(E)-4-肉桂基-N-(喹啉-8-基)庚-4-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)庚-4-烯酰胺(25.4mg，0.1mmol)和1-苯基烯丙基碳酸甲酯(76.9mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到棕色液体(11.2mg，收率30％)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.75(s,1H),8.80(dd,J＝4.0,1.5Hz,1H),8.76(dd,J＝7.5,1.5Hz,1H),8.16(dd,J＝8.0,1.5Hz,1H),7.55–7.49(m,2H),7.47–7.44(dd,J＝8.0,4.0Hz,1H),7.30–7.27(m,4H),7.21–7.17(m,1H),6.57(d,J＝11.5Hz,1H),5.78–5.72(m,1H),5.33(t,J＝7.0Hz,1H),3.06(d,J＝7.5Hz,2H),2.60–2.53(m,4H),2.15–2.09(m,2H),0.95(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ170.16,147.04,137.32,136.35,135.31,134.34,133.51,129.32,128.26,127.57,127.13,126.91,126.42,125.62,120.54,120.32,116.32,115.41,35.75,34.51,25.69,20.15,13.49；HRMS(ESI):m/z for C25H27N2O[M+H]+:371.2118,found:371.2117。
实施例25
4-((E)-亚苄基)-7-苯基-N-(喹啉-8-基)庚-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-苯基-N-(喹啉-8-基)戊-4-烯酰胺(30.2mg，0.1mmol)和1-苯基烯丙基碳酸甲酯(76.9mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色液体(34.3mg，收率82％，E/Z＝11:9)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.79(s,0.55H),9.72(s,0.45H),8.78–8.73(m,2H),8.16–8.13(m,1H),7.54–7.48(m,2H),7.46–7.42(m,1H),7.37(d,J＝7.5Hz,1H),7.32–7.25(m,7H),7.21–7.16(m,2H),6.66(d,J＝11.5Hz,0.45H),6.52(d,J＝15.5Hz,0.55H),6.47(d,J＝9.0Hz,1H),6.34–6.29(m,0.55H),5.88–5.83(m,0.45H),3.25(d,J＝7.5Hz,0.9H),3.16(d,J＝7.0Hz,1.1H),2.86–2.80(m,2H),2.75–2.72(m,1.1H),2.65–2.61(m,0.9H)；13C NMR(125MHz,CDCl3)δ169.83,169.76,147.05,147.02,138.81,138.72,137.32,136.85,136.79,136.45,136.21,135.30,133.46,131.04,130.10,128.42,127.59,127.57,127.53,127.46,127.28,127.26,127.23,126.91,126.90,126.85,126.40,126.25,126.10,125.80,125.37,125.33,125.13,120.53,120.36,115.43,39.94,35.62,35.39,35.02,30.91,30.61,30.49,30.42,29.20,29.14,28.68,28.64,28.49,28.34,28.14,27.95,26.46,26.12,21.67,13.09；HRMS(ESI):m/z forC29H27N2O[M+H]+:419.2118,found:419.2127。
实施例26
(4E)-4-亚丙基-N-(喹啉-8-基)十三碳-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-N-(喹啉-8-基)庚-4-烯酰胺(25.4mg，0.1mmol)和1-乙烯基己基碳酸甲酯(76.9mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色液体(22.0mg，收率58％，E/Z＝63:37)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.80(s,1H),8.80–8.78(m,2H),8.16(d,J＝8.0Hz,1H),7.55–7.48(m,2H),7.46–7.43(m,1H),5.51–5.46(m,1H),7.44–7.37(m,1H),5.24(q,J＝6.5Hz,1H),2.81(d,J＝7.0Hz,1.25H),2.75(d,J＝6.5Hz,0.75H),2.64–2.59(m,2H),2.56–2.49(m,2H),2.11–2.05(m,2.5H),2.04–1.99(m,1.5H),1.42–1.26(m,8H),0.96–0.92(m,3H),0.86–0.84(m,3H)；13C NMR(125MHz,CDCl3)δ170.16,147.04,137.32,136.35,135.31,134.34,133.51,129.32,128.26,127.57,127.13,126.91,126.42,125.62,120.54,120.32,116.32,115.41,35.75,34.51,25.69,20.15,13.49；HRMS(ESI):m/z for C25H35N2O[M+H]+:379.2744,found:379.2754。
实施例27
4-((E)-亚苄基)-N-(喹啉-8-基)十三碳-6-烯酰胺的制备
向螺旋盖小瓶中装入醋酸钯(4.5mg，0.02mmol)，二甲基亚砜(0.35mL)和甲醇(0.7mL)。然后依次向溶液中加入新戊酸(20.4mg，0.2mmol)，(Z)-5-苯基-N-(喹啉-8-基)戊-4-烯酰胺(30.2mg，0.1mmol)和1-乙烯基己基碳酸甲酯(74.5mg，0.4mmol)。将小瓶在氩气下密封并加热至40℃并搅拌16小时。冷却后将混合物直接应用于快速柱色谱(PE/EA＝4/1)。反应液经直接柱层析分离后得到白色液体(21.2mg，收率46％，E/Z＝50:50)，反应式如下：
该反应产物的核磁谱图表征结果如下：1H NMR(500MHz,CDCl3)δ9.78(s,1H),8.78(d,J＝4.0Hz,1H),8.76(d,J＝7.5Hz,1H),8.15(d,J＝8.0Hz,1H),7.54–7.48(m,2H),7.45(dd,J＝8.0,3.5Hz,1H),7.30–7.24(m,5H),7.16(t,J＝6.5Hz,1H),6.39(d,J＝6.5Hz,1H),5.59–5.55(m,1H),5.54–5.47(m,1H),3.00(d,J＝6.5Hz,1H),2.94(d,J＝6.5Hz,1H),2.79–2.77(m,2H),2.72–2.68(m,2H),2.13–2.09(m,1H),2.06–2.02(m,1H),1.39–1.26(m,8H),0.86–0.86(m,3H)；13C NMR(125MHz,CDCl3)δ169.90,147.03,139.38,139.12,137.31,137.02,136.99,135.30,133.49,132.25,131.29,127.51,127.23,126.90,126.40,126.28,126.05,125.82,125.54,125.20,125.19,120.53,120.34,120.33,115.38,39.72,35.68,35.56,34.12,31.54,30.53,30.42,28.31,28.12,26.27,25.91,21.55,21.49,13.03；HRMS(ESI):m/z for C29H35N2O[M+H]+:427.2744,found:427.2750。
Claims (6)
1.一种枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述枝型1,4-二烯酰胺衍生物如式(1)所示：
式中，R1为氢、C1～8烷基、C5～8的环烷烃基、取代苯基、萘基或杂环基；所述的取代苯基的取代基为C1～6的烷基、C1～6的烷氧基、卤素或卤素取代的C1～6的烷基；R2为氢、C1～6烷基、苯基、苄基或杂环基；
合成方法为：将烯基喹啉酰胺化合物、烯丙基碳酸甲酯衍生物、过渡金属盐催化剂和添加剂置于有机溶剂中，于氩气氛围下加热反应，反应结束后，反应液经后处理得到所述的枝型1,4-二烯酰胺衍生物；所述添加剂为新戊酸；所述的过渡金属盐催化剂为醋酸钯或氯化钯；所述的加热反应温度为25～80℃，反应时间16～24h；
所述的烯基喹啉酰胺化合物结构如式(2)所示：
式中R1为氢、C1～8烷基、C5～8的环烷烃基、取代苯基、萘基或杂环基；所述的取代苯基的取代基为C1～6的烷基、C1～6的烷氧基、卤素、卤素取代的C1～6的烷基；
所述的烯丙基碳酸甲酯衍生物具有结构如式(3)所示：
式中R2为氢、C1～6烷基、苯基、苄基或杂环基。
2.根据权利要求1所述的枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述的R1为氢、C1～6烷基、C5～8的环烷烃基、取代苯基、萘基、呋喃基、噻吩基或N-甲基吡咯基；R2为氢、C1～6烷基、苯基或苄基。
3.根据权利要求1所述的枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述的R1为氢、甲基、乙基、正戊基、环己烷基、4-甲基苯基、4-甲氧基苯基、4-氟苯基、4-溴苯基、4-氯苯基、4-三氟甲基苯基、2-氟苯基、3-氟苯基、3-甲氧基苯基、2-甲基苯基、3-呋喃基、2-噻吩基、2-N-甲基吡咯基、萘基或叔丁基；R2为氢、苯基、正戊基或苄基。
4.根据权利要求1所述的枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述的烯基喹啉酰胺化合物、烯丙基碳酸甲酯衍生物、过渡金属盐催化剂和添加剂的物质的量之比为1：2-6：0.1-0.4：1-4；所述有机溶剂的体积用量以烯基喹啉酰胺化合物的物质的量计为5～10L/mol。
5.根据权利要求1所述的枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述的有机溶剂为甲醇、二甲基亚砜、乙腈、1,3-二氯乙烷、1,4-二氧六环任一种或其混合物。
6.根据权利要求1所述的枝型1,4-二烯酰胺衍生物的合成方法，其特征在于，所述的后处理为将反应液装柱，剩余反应液用二氯甲烷溶解转移，用硅胶进行柱层析分离，洗脱剂乙酸乙酯与石油醚混合液，收集含目标化合物的洗脱液，浓缩干燥得到所述的枝型1,4-二烯酰胺衍生物。
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