CN114790212B - 恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法 - Google Patents
恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法 Download PDFInfo
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- CN114790212B CN114790212B CN202110092326.1A CN202110092326A CN114790212B CN 114790212 B CN114790212 B CN 114790212B CN 202110092326 A CN202110092326 A CN 202110092326A CN 114790212 B CN114790212 B CN 114790212B
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- JAZPBKNVJABVRA-UHFFFAOYSA-N pyrrolo[3,4-f][2,1]benzoxazine Chemical compound c1ncc2c1ccc1noccc21 JAZPBKNVJABVRA-UHFFFAOYSA-N 0.000 title claims abstract description 16
- RXINFAULMRJDAU-UHFFFAOYSA-N 7h-pyrido[3,4-f][2,1]benzoxazine Chemical class C1=CC2=CC=NC=C2C2=C1NOC=C2 RXINFAULMRJDAU-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Chemical group 0.000 claims description 3
- 239000000460 chlorine Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229940126214 compound 3 Drugs 0.000 claims description 3
- 229940125898 compound 5 Drugs 0.000 claims description 3
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 25
- 238000011160 research Methods 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 229930014626 natural product Natural products 0.000 abstract description 2
- 230000001766 physiological effect Effects 0.000 abstract description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 abstract 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical class N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000000904 isoindolyl group Chemical class C=1(NC=C2C=CC=CC12)* 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 96
- 238000005160 1H NMR spectroscopy Methods 0.000 description 48
- 239000007787 solid Substances 0.000 description 28
- 239000006260 foam Substances 0.000 description 13
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 9
- 239000003921 oil Substances 0.000 description 6
- 239000002841 Lewis acid Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- -1 Nitrogen-containing heterocyclic compounds Chemical class 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 2
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- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
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- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
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- KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
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- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- JRVWIILYWSBUMC-PRUVNFMMSA-N tubulosine Chemical compound N1C2=CC=C(O)C=C2C(CCN2)=C1[C@H]2C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC JRVWIILYWSBUMC-PRUVNFMMSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于化学合成技术领域，具体涉及恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法。本发明通过建立的方法制备了下式恶嗪并异吲哚(1)和恶嗪并异喹啉(2)化合物。本发明制备的化合物作为包含有关异吲哚、异喹啉和恶嗪的杂环骨架的新结构可用于多个具有重要生理活性天然产物的多样性合成研究，具有潜在的应用价值。本发明方法的技术路线，操作简单，路线简洁，收率较高，所用的试剂均为常用试剂，而且，适合大规模制备。
Description
技术领域
本发明属于化学合成技术领域，具体涉及恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法。
背景技术
化学合成技术的研究实践中，发现有效的方法学获取用于药物用途的骨架是合成化学中最重要的研究领域之一1。含氮杂环化合物由于在自然界中广泛存在，是一个非常重要结构单元2。例如，取代异吲哚啉A和四氢异喹啉(THIQ)B是近年来研究的热点分子和临床药物的关键骨架3,4。Emetine(C)具有抗原生动物活性5，用于治疗淋巴性白血病6。此外，其结构类似物tubulosine具有很强的抗肿瘤活性7。到目前为止，已有研究报道构建功能化异吲哚啉骨架A或四氢异喹啉骨架B，并建立了几种重要的方法，然而，恶嗪并异吲哚D和恶嗪并四氢异喹啉E等药物类似结构尚少有研究报道，因此，含恶嗪并异吲哚和恶嗪并异喹啉骨架结构的快速、高效合成方法学及普适的多样性合成研究具有重要意义，构建新的合成方法实现恶嗪并异吲哚和恶嗪并异喹啉骨架的多样性大量合成，可以为新药研究提供物质基础。基于现有技术的研究基础和现状，本申请的发明人拟提供新的恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法。
与本发明相关的参考文献：
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发明内容
本发明的目的是基于现有技术的研究基础和现状，提供新的恶嗪并异吲哚和恶嗪并异喹啉化合物及其制备方法。本发明方法的路线的特点是：反应条件温和、简单，可以进行大量制备。
本发明合成的恶嗪并异吲哚和恶嗪并异喹啉化合物具有式(I)的化学结构：
其中，取代基R1代表氢、氯、溴；R2代表烷基，芳香基；R3代表Ts，Ms，4-ClC6H4SO2；R4代表烷基、芳基、苄基；或者R3和R4作为一个整体，与N一起代表恶唑烷酮，详见结构。
进一步地，所述恶嗪并异吲哚和恶嗪并异喹啉化合物具体化学结构如下：
本发明提供了合成具有式(1，2)结构的恶嗪并异吲哚和恶嗪并异喹啉化合物的方法，其具体技术路线如下，在下文的陈述实施例中，中间体通式是根据结构式中的编号，用阿拉伯数字表示。
其中，取代基R1代表氢、氯、溴；R2代表烷基，芳香基；R3代表Ts，Ms，4-ClC6H4SO2；R4代表烷基、芳基、苄基；或者R3和R4作为一个整体，与N一起代表恶唑烷酮，如具体结构所示。
上述合成路线包括以下合成步骤：
步骤：将化合物3或4与化合物5溶于一种干燥的有机溶剂中，室温下加入一种路易斯酸，反应2-6小时，加入碳酸氢钠饱和溶液淬灭，经后处理得化合物1或2。其中一种路易斯酸是指三氟化硼乙醚、三氟甲磺酸三甲基硅酯、四氯化钛、氯化金、三氟甲磺酸铜、氯化铜、溴化铜，特别是指三氟甲磺酸酮；一种有机溶剂是指四氢呋喃、1,2-二氯乙烷、二氯甲烷或甲苯等，特别是指二氯甲烷和1,2-二氯乙烷。
本发明所述制备恶嗪并异吲哚和恶嗪并异喹啉化合物的技术路线，操作简单，路线简洁，收率较高，所用的试剂均为常用试剂，而且，可适合大规模制备，所得目标产物可用于多个具有重要生理活性天然产物的多样性合成研究。
具体实施方式
实施例1
室温下将N,O-缩醛化合物3或4(0.5mmol)、炔酰胺化合物5(1.2当量，0.6mmol)和三氟甲磺酸铜(0.2当量，0.1mmol，33mg)溶于干燥的二氯甲烷(3mL)中，室温下搅拌2-6小时，用饱和碳酸氢钠水溶液淬灭，用二氯甲烷(20mL×3)萃取。用饱和食盐水洗涤，用无水硫酸镁干燥，过滤并浓缩。残渣用硅胶柱(PE/EA＝3:1～5:1)纯化，得到目标产物1或2。
化合物1a
White solid(185mg,73％)；1H NMR(400MHz,CDCl3)δ7.80-7.70(m,2H),7.40-7.26(m,6H),7.24-7.17(m,2H),7.16-7.11(m,2H),6.98-6.80(m,5H),5.87(d,J＝8.0Hz,1H),5.75(s,1H),5.05(d,J＝14.8Hz,1H),4.60(d,J＝14.8Hz,1H),4.20-4.10(m,2H),2.45(s,3H)ppm.
化合物1b
White solid(172mg,64％)；1H NMR(400MHz,CDCl3)δ7.82-7.70(m,2H),7.35-7.29(m,2H),7.27-7.06(m,8H),6.97-6.74(m,5H),5.95(d,J＝7.2Hz,1H),5.72(s,1H),5.04(d,J＝14.8Hz,1H),4.58(d,J＝14.8Hz,1H),4.15(s,2H),2.44(s,3H),2.42(s,3H)ppm.
化合物1c
White solid(170mg,63％)；1H NMR(400MHz,CDCl3)δ7.85-7.74(m,2H),7.38-7.33(m,2H),7.30-7.27(m,1H),7.26-7.20(m,2H),7.18-7.14(m,2H),6.98-6.89(m,5H),6.88-6.59(m,2H),5.88(d,J＝8.0Hz,1H),5.71(s,1H),5.05(d,J＝14.8Hz,1H),4.61(d,J＝14.8Hz,1H),4.26-4.03(m,2H),2.46(s,3H)ppm.
化合物1d
White solid(188mg,68％)；1H NMR(400MHz,CDCl3)δ7.83-7.75(m,2H),7.36-7.32(m,2H),7.27-7.25(m,1H),7.23-7.19(m,2H),7.18-7.10(m,3H),6.99-6.86(m,4H),6.84-6.78(m,3H),5.96(d,J＝8.0Hz,1H),5.70(s,1H),5.05(d,J＝14.8Hz,1H),4.59(d,J＝14.8Hz,1H),4.24-4.15(m,1H),3.88(s,3H),2.45(s,3H)ppm；.
化合物1e
White solid(187mg,67％)；1H NMR(400MHz,CDCl3)δ7.82-7.73(m,2H),7.36-7.32(m,2H),7.28-7.19(m,6H),7.17-7.13(m,2H),6.97-6.94(m,2H),6.93-6.87(m,1H),6.78-6.71(m,1H),5.93(d,J＝8.0Hz,1H),5.71(s,1H),5.04(d,J＝14.8Hz,1H),4.60(d,J＝14.4Hz,1H),4.26-4.04(m,2H),2.45(s,3H)ppm.
化合物1f
White solid(244mg,81％)；1H NMR(400MHz,CDCl3)δ7.83-7.71(m,2H),7.40-7.33(m,4H),7.30-7.13(m,6H),6.98-6.90(m,3H),6.75-6.62(m,1H),5.94(d,J＝7.6Hz,1H),5.72(s,1H),5.05(d,J＝14.8Hz,1H),4.61(d,J＝14.8Hz,1H),4.36-3.93(m,2H),2.46(s,3H)ppm.
化合物1g
Brown solid(215mg,78％)；1H NMR(400MHz,CDCl3)δ7.82-7.77(m,2H),7.39-7.36(m,1H),7.33-7.26(m,4H),7.22-7.12(m,3H),7.10-7.05(m,2H),6.97-6.87(m,4H),6.84-6.73(m,1H),6.14(d,J＝5.2Hz,1H),5.98(s,1H),5.03(d,J＝14.4Hz,1H),4.62(d,J＝14.8Hz,1H),4.19-4.10(m,2H),3.68-3.57(m,2H),2.44(s,3H)ppm.
化合物1h
Brown solid(164mg,62％)；1H NMR(400MHz,CDCl3)δ7.82-7.77(m,2H),7.40-7.37(m,1H),7.36-7.33(m,2H),7.29-7.26(m,1H),7.25-7.18(m,2H),7.17-7.11(m,3H),7.04-7.02(m,1H),7.01-6.95(m,2H),6.13(d,J＝7.6Hz,1H),5.64(s,1H),5.06(d,J＝14.8Hz,1H),4.56(d,J＝14.8Hz,1H),4.31(d,J＝13.2Hz,1H),4.17(d,J＝13.2Hz,1H),2.45(s,3H)ppm.
化合物1i
White solid(134mg,60％)；1H NMR(400MHz,CDCl3)δ7.68-7.63(m,2H),7.48-7.44(m,3H),7.42-7.38(m,2H),7.32-7.26(m,3H),7.25-7.20(m,1H),6.97-6.92(m,1H),6.05(d,J＝8.0Hz,1H),5.99(s,1H),5.12(d,J＝15.2Hz,1H),4.63(dd,J＝14.8,2.0Hz,1H),2.80(s,3H),2.42(s,3H)ppm.
化合物1j
White solid(154mg,63％)；1H NMR(400MHz,CDCl3)δ7.78-7.68(m,2H),7.48-7.43(m,5H),7.33-7.27(m,3H),7.26-7.21(m,1H),6.98-6.92(m,1H),6.05-5.96(m,2H),5.12(d,J＝15.2Hz,1H),4.65(d,J＝14.0Hz,1H),3.05-2.95(m,2H),2.42(s,3H),1.31-1.22(m,2H),1.05-0.92(m,2H),0.75-0.66(m,3H)ppm.
化合物1k
White solid(122mg,48％)；1H NMR(400MHz,CDCl3)δ7.58-7.54(m,2H),7.47-7.42(m,3H),7.31-7.27(m,3H),7.25-7.18(m,4H),7.14-7.08(m,2H),6.95-6.90(m,1H),6.84-6.77(m,2H),6.05(d,J＝7.6Hz,1H),5.87(s,1H),5.13(d,J＝14.8Hz,1H),4.64(dd,J＝15.2,2.4Hz,1H),2.39(s,3H)ppm.
化合物1l
White solid(161mg,68％)；1H NMR(400MHz,CDCl3)δ7.85-7.66(m,2H),7.50-7.40(m,5H),7.33-7.28(m,3H),7.25-7.21(m,1H),6.98-6.92(m,1H),6.05-5.96(m,2H),5.43(s,1H),5.13-5.04(m,3H),4.63(d,J＝12.0Hz,1H),3.72-3.63(m,1H),3.62-3.55(m,1H),2.43(s,3H)ppm.
化合物1m
White solid(189mg,68％)；1H NMR(400MHz,CDCl3)δ7.80-7.68(m,2H),7.40-7.26(m,6H),7.25-7.20(m,2H),7.17-7.12(m,2H),6.93-6.89(m,2H),6.86-6.81(m,2H),5.75(d,J＝8.4Hz,1H),5.70(s,1H),5.02(d,J＝15.2Hz,1H),4.57(d,J＝15.2Hz,1H),4.21-4.12(m,2H),2.45(s,3H)ppm.
化合物1n
Brown solid(211mg,74％)；1H NMR(400MHz,CDCl3)δ7.81-7.68(m,2H),7.35-7.31(m,2H),7.26-7.20(m,3H),7.17-7.07(m,4H),6.95-6.89(m,2H),6.88-6.84(m,1H),6.80-6.71(m,1H),5.83(d,J＝7.6Hz,1H),5.67(s,1H),5.02(d,J＝14.8Hz,1H),4.56(d,J＝14.8Hz,1H),4.14(s,2H),2.45(s,3H),2.42(s,3H)ppm.
化合物1o
Brown solid(239mg,83％)；1H NMR(400MHz,CDCl3)δ7.79-7.75(m,2H),7.37-7.33(m,2H),7.30-7.28(m,1H),7.27-7.23(m,3H),7.20-7.16(m,2H),6.97-6.93(m,3H),6.90-6.85(m,1H),6.74(s,1H),5.77(d,J＝7.2Hz,1H),5.67(s,1H),5.02(d,J＝15.2Hz,1H),4.58(d,J＝14.8Hz,1H),4.21-4.10(m,2H),2.46(s,3H)ppm.
化合物1p
Brown solid(255mg,87％)；1H NMR(400MHz,CDCl3)δ7.87-7.70(m,2H),7.37-7.31(m,2H),7.26-7.21(m,2H),7.18-7.12(m,2H),6.97-6.92(m,2H),6.90-6.86(m,1H),6.85-6.68(m,4H),5.85(d,J＝8.0Hz,1H),5.64(s,1H),5.02(d,J＝15.2Hz,1H),4.56(d,J＝15.2Hz,1H),4.22-4.05(m,2H),3.88(s,3H),2.45(s,3H)ppm.
化合物1q
Brown solid(245mg,83％)；1H NMR(400MHz,CDCl3)δ7.82-7.72(m,2H),7.37-7.33(m,2H),7.27-7.20(m,5H),7.18-7.14(m,2H),6.98-6.93(m,2H),6.92-6.88(m,1H),6.75-6.67(m,1H),5.83(d,J＝8.4Hz,1H),5.67(s,1H),5.03(dd,J＝16.4,15.6Hz,1H),4.57(d,J＝14.4Hz,1H),4.28-4.05(m,2H),2.46(s,3H)ppm.
化合物1r
Brown solid(159mg,66％)；1H NMR(400MHz,CDCl3)δ7.68-7.63(m,2H),7.49-7.45(m,3H),7.41-7.37(m,2H),7.30-7.26(m,3H),6.95-6.89(m,1H),5.96-5.91(m,2H),5.09(d,J＝15.2Hz,1H),4.60(d,J＝15.6Hz,1H),2.79(s,3H),2.42(s,3H)ppm.
化合物1s
Brown solid(156mg,70％)；1H NMR(400MHz,CDCl3)δ7.77-7.68(m,2H),7.48-7.42(m,5H),7.32-7.27(m,3H),6.95-6.90(m,1H),5.96-5.88(m,2H),5.10(d,J＝14.8Hz,1H),5.62(d,J＝14.8Hz,1H),3.02-2.94(m,2H),2.43(s,3H),1.30-1.22(m,2H),1.06-0.92(m,2H),0.73-0.66(m,3H)ppm.
化合物1t
Brown solid(209mg,77％)；1H NMR(400MHz,CDCl3)δ7.57-7.53(m,2H),7.48-7.42(m,3H),7.32-7.25(m,3H),7.23-7.18(m,3H),7.14-7.08(m,2H),6.94-6.86(m,1H),6.84-6.74(m,2H),5.94(d,J＝8.4Hz,1H),5.82(s,1H),5.10(d,J＝15.2Hz,1H),4.61(d,J＝15.2Hz,1H),2.39(s,3H)ppm.
化合物1u
White solid(213mg,84％)；1H NMR(400MHz,CDCl3)δ7.76-7.69(m,2H),7.48-7.39(m,5H),7.33-7.28(m,3H),6.92-6.90(m,1H),5.92-5.88(m,2H),5.50-5.36(m,1H),5.11-5.04(m,3H),4.61(d,J＝15.2Hz,1H),3.71-3.64(m,1H),3.61-3.54(m,1H),2.43(s,3H)ppm.
化合物1v
White solid(192mg,64％)；1H NMR(400MHz,CDCl3)δ7.78-7.70(m,2H),7.43-7.38(m,1H),7.35-7.30(m,5H),7.25-7.21(m,1H),7.17-7.14(m,2H),7.13-7.11(m,1H),6.96-6.80(m,4H),5.88(s,1H),5.71(s,1H),5.00(d,J＝14.8Hz,1H),4.53(dd,J＝15.2,2.0Hz,1H),4.21-4.11(m,2H),2.45(s,3H)ppm.
化合物1w
White solid(259mg,86％)；1H NMR(400MHz,CDCl3)δ7.80-7.69(m,2H),7.40-7.33(m,3H),7.32-7.31(m,1H),7.30-7.26(m,2H),7.24-7.20(m,1H),7.17-7.12(m,2H),6.98-6.79(m,4H),6.78-6.73(m,1H),5.85-5.75(m,2H),5.07(d,J＝15.6Hz,1H),4.54(dd,J＝15.6,2.4Hz,1H),4.20-4.10(m,2H),2.45(s,3H)ppm.
化合物1x
White solid(172mg,64％)；1H NMR(400MHz,CDCl3)δ7.58-7.54(m,2H),7.45-7.40(m,3H),7.28-7.25(m,2H),7.22-7.17(m,3H),7.13-7.08(m,2H),6.93-6.89(m,1H),6.82-6.78(m,2H),6.71-6.68(m,1H),5.87(s,1H),5.63(d,J＝8.0Hz,1H),5.11(dd,J＝15.2,1.6Hz,1H),4.55(dd,J＝15.2,2.4Hz,1H),3.82(s,3H),2.39(s,3H)ppm.
化合物1y
Brown solid(147mg,61％)；1H NMR(400MHz,CDCl3)δ7.38-7.17(m,8H),7.16-7.08(m,2H),6.88-6.83(m,2H),5.79-5.70(m,2H),5.04(d,J＝15.2Hz,1H),4.54(d,J＝15.6Hz,1H),4.48-4.29(m,2H),2.99(s,3H)ppm.
化合物2a
White foam(231mg,86％)；1H NMR(400MHz,CDCl3)δ7.77-7.74(m,2H),7.31-7.27(m,4H),7.26-7.20(m,3H),7.19-7.08(m,5H),7.02-6.93(m,3H),5.12(s,1H),4.40-4.32(m,1H),4.25-4.05(m,2H),3.50(ddd,J＝13.6,7.2,6.4Hz,1H),3.13(ddd,J＝16.4,7.2,6.4Hz,1H),2.83(ddd,J＝15.6,7.6,6.8Hz,1H),2.41(s,3H)ppm.
化合物2b
Light-yellow foam(147mg,64％)；1HNMR(400MHz,CDCl3)δ7.59-7.55(m,2H),7.54-7.51(m,2H),7.36-7.32(m,2H),7.28-7.24(m,1H),7.17-7.15(m,3H),7.12-7.08(m,2H),7.06-7.02(m,1H),5.33(s,1H),4.12(ddd,J＝13.6,7.2,6.4Hz,1H),3.46(ddd,J＝14.0,7.2,6.4Hz,1H),3.14(ddd,J＝15.6,7.2,6.4Hz,1H),2.86(s,3H),2.84-2.75(m,1H),2.30(s,3H)ppm.
化合物2c
Light-yellow foam(234mg,93％)；1HNMR(400MHz,CDCl3)δ7.77-7.71(m,4H),7.45-7.40(m,2H),7.36-7.32(m,1H),7.27-7.20(m,4H),7.18-7.16(m,1H),7.14-7.10(m,1H),5.43(s,1H),4.19(ddd,J＝14.0,7.6,6.8Hz,1H),3.57(ddd,J＝14.0,7.6,6.8Hz,1H),3.25-3.12(m,2H),3.10-3.01(m,1H),2.91(ddd,J＝14.4,7.2,6.4Hz,1H),2.38(s,3H),1.33-1.25(m,2H),1.08-0.95(m,2H),0.72-0.66(m,3H)ppm.
化合物2d
Colorless oil(226mg,98％)；1H NMR(400MHz,CDCl3)δ7.23-7.15(m,6H),7.12-7.03(m,4H),7.02-6.95(m,2H),6.94-6.60(m,2H),5.12(s,1H),4.47-4.41(m,1H),4.35-4.25(m,1H),4.09(ddd,J＝13.6,7.2,6.4Hz,1H),3.44(ddd,J＝13.6,7.2,6.4Hz,1H),3.09(ddd,J＝16.4,7.2,6.4Hz,1H),2.95(s,3H),2.77(ddd,J＝14.,7.2,6.4Hz,1H)ppm.
化合物2e
White solid(138mg,76％)；1H NMR(400MHz,CDCl3)δ7.47-7.43(m,2H),7.42-7.38(m,2H),7.36-7.32(m,1H),7.23-7.15(m,2H),7.10-7.03(m,2H),5.49(s,1H),4.41-4.30(m,2H),4.29-4.20(m,1H),3.90(dd,J＝16.0,8.4Hz,1H),3.71(dd,J＝15.2,8.4Hz,1H),3.53(ddd,J＝14.0,7.6,6.8Hz,1H),3.24(ddd,J＝16.4,7.6,6.8Hz,1H),2.90(ddd,J＝16.0,12.8,6.4Hz,1H)ppm.
化合物2f
White solid(242mg,87％)；1H NMR(400MHz,CDCl3)δ7.75-7.69(m,2H),7.40-7.36(m,2H),7.24-7.03(m,11H),6.97-6.85(m,3H),7.04-6.85(m,3H),5.07(s,1H),4.34-4.28(m,1H),4.26-3.96(m,2H),3.44(ddd,J＝13.6,7.2,6.4Hz,1H),3.08(ddd,J＝16.4,7.2,6.4Hz,1H),2.78(ddd,J＝15.6,7.6,6.8Hz,1H)ppm.
化合物2g
White solid(264mg,96％)；1H NMR(400MHz,CDCl3)δ7.78-7.73(m,2H),7.34-7.20(m,4H),7.19-7.10(m,6H),7.08-7.05(m,2H),7.04-6.86(m,3H),5.11(s,1H),4.40-4.33(m,1H),4.32-3.95(m,2H),3.49(ddd,J＝13.2,7.2,6.4Hz,1H),3.13(ddd,J＝16.4,7.2,6.4Hz,1H),2.83(ddd,J＝15.6,7.6,6.8Hz,1H),2.40(s,3H),2.34(s,3H)ppm.
化合物2h
Light-yellow oil(167mg,76％)；1H NMR(400MHz,CDCl3)δ7.41-7.35(m,4H),7.33-7.28(m,2H),7.24-7.19(m,2H),7.15-7.09(m,4H),6.87-6.82(m,1H),6.39-6.21(m,1H),5.22(s,1H),4.85(s,1H),4.56(dd,J＝9.2,8.4Hz,1H),4.22(dd,J＝9.6,8.8Hz,1H),4.11(ddd,J＝13.6,7.2,6.4Hz,1H),3.41(ddd,J＝14.0,7.2,6.4Hz,1H),3.09(ddd,J＝15.6,13.6,6.8Hz,1H),2.81(ddd,J＝15.6,13.2,6.8Hz,1H)ppm.
化合物2i
Light-yellow oil(176mg,68％)；1H NMR(400MHz,CDCl3)δ7.47-7.38(m,3H),7.35-7.30(m,2H),7.17-7.10(m,4H),7.04-6.98(m,2H),6.89-6.83(m,1H),6.27-6.12(m,1H),5.18(s,1H),5.01(dd,J＝8.4,7.6Hz,1H),4.62(dd,J＝8.8,2.0Hz,1H),4.28(dd,J＝9.2,8.4Hz,1H),4.10(ddd,J＝13.2,12.4,6.8Hz,1H),3.42(ddd,J＝13.6,7.2,6.4Hz,1H),3.06(ddd,J＝15.6,13.2,6.8Hz,1H),2.82(ddd,J＝14.4,7.2,6.4Hz,1H)ppm.
化合物2j
Light-yellow oil(189mg,80％)；1H NMR(400MHz,CDCl3)δ7.41-7.38(m,1H),7.34-7.28(m,4H),7.16-7.11(m,4H),7.10-7.05(m,2H),6.88-6.83(m,1H),6.25-6.13(m,1H),5.18(s,1H),5.01(dd,J＝8.0,7.2Hz,1H),4.62(dd,J＝9.2,8.4Hz,1H),4.27(dd,J＝9.6,8.8Hz,1H),4.13-4.06(m,1H),3.42(ddd,J＝13.6,6.8,6.0Hz,1H),3.05(ddd,J＝15.6,13.2,6.4Hz,1H),2.81(ddd,J＝14.4,7.2,6.4Hz,1H)ppm.
化合物2k
Yellow foam(190mg,75％)；1H NMR(400MHz,CDCl3)δ7.42-7.39(m,1H),7.38-7.34(m,3H),7.33-7.29(m,2H),7.18-7.15(m,2H),7.08-7.02(m,3H),6.38(s,1H),5.16(s,1H),5.03-4.96(m,1H),4.62(dd,J＝9.2,8.4Hz,1H),4.31(dd,J＝9.2,8.4Hz,1H),4.09(ddd,J＝13.6,7.2,6.4Hz,1H),3.40(ddd,J＝13.6,7.2,6.4Hz,1H),3.04(ddd,J＝16.0,13.6,6.8Hz,1H),2.77(ddd,J＝15.6,13.6,6.8Hz,1H)ppm.
化合物2l
Light-Yellow foam(201mg,73％)；1HNMR(400MHz,CDCl3)δ7.49-7.45(m,2H),7.42-7.34(m,4H),7.18-7.13(m,3H),7.08-7.05(m,1H),6.96-6.93(m,1H),6.38(s,1H),5.15(s,1H),5.00(dd,J＝8.4,7.6Hz,1H),4.64(dd,J＝9.2,8.4Hz,1H),4.32(dd,J＝9.2,8.4Hz,1H),4.10(ddd,J＝13.6,7.2,6.4Hz,1H),3.41(ddd,J＝13.6,7.2,6.4Hz,1H),3.05(ddd,J＝15.6,13.6,6.8Hz,1H),2.77(ddd,J＝15.6,13.6,7.2Hz,1H)ppm.
化合物2m
Light-Yellow foam(220mg,85％)；1HNMR(400MHz,CDCl3)δ7.42-7.36(m,4H),7.33-7.27(m,3H),7.21-7.16(m,2H),7.13-7.07(m,2H),7.00-6.93(m,1H),6.20-6.06(m,1H),5.15(s,1H),4.86(s,1H),4.56(dd,J＝9.2,8.4Hz,1H),4.22(dd,J＝9.6,8.8Hz,1H),4.13(ddd,J＝13.6,7.2,6.4Hz,1H),3.38(ddd,J＝13.6,7.2,6.4Hz,1H),3.07(ddd,J＝16.4,7.2,6.4Hz,1H),2.78(ddd,J＝15.6,12.8,6.4Hz,1H)ppm.
化合物2n
Yellow oil(265mg,96％)；1H NMR(400MHz,CDCl3)δ7.44-7.39(m,1H),7.36-7.31(m,3H),7.30-7.28(m,2H),7.15-7.11(m,2H),7.07-7.02(m,2H),7.01-6.95(m,1H),6.10-5.95(m,1H),5.11(s,1H),5.08-4.93(m,1H),4.63(dd,J＝9.2,8.4Hz,1H),4.28(dd,J＝9.2,8.4Hz,1H),4.12(ddd,J＝13.6,7.2,6.4Hz,1H),3.40(ddd,J＝14.0,7.2,6.4Hz,1H),3.05(ddd,J＝16.4,7.2,6.4Hz,1H),2.80(ddd,J＝15.6,13.2,6.8Hz,1H)ppm.
化合物2o
Yellow foam(280mg,94％)；1H NMR(400MHz,CDCl3)δ7.48-7.44(m,2H),7.42-7.40(m,1H),7.35-7.31(m,2H),7.29-7.27(m,1H),7.15-7.11(m,2H),7.02-6.95(m,3H),6.10-5.96(m,1H),5.11(s,1H),5.07-4.95(m,1H),4.63(dd,J＝9.2,8.4Hz,1H),4.28(dd,J＝9.6,8.8Hz,1H),4.11(ddd,J＝13.6,7.2,6.4Hz,1H),3.40(ddd,J＝13.6,7.2,6.4Hz,1H),3.04(ddd,J＝16.8,7.6,6.8Hz,1H),2.79(ddd,J＝15.6,13.2,6.8Hz,1H)ppm.
化合物2p
Light-Yellow oil(265mg,97％)；1H NMR(400MHz,CDCl3)δ7.42-7.38(m,1H),7.34-7.30(m,2H),7.29-7.27(m,1H),7.15-7.08(m,4H),7.00-6.94(m,1H),6.92-6.86(m,2H),6.10(s,1H),5.10(s,1H),4.88(s,1H),4.59(dd,J＝9.2,8.4Hz,1H),4.23(dd,J＝9.6,8.8Hz,1H),4.13(ddd,J＝13.6,7.2,6.4Hz,1H),3.86(s,3H),3.38(ddd,J＝13.6,7.2,6.4Hz,1H),3.07(ddd,J＝16.4,7.2,6.4Hz,1H),2.78(ddd,J＝16.0,13.2,6.8Hz,1H)ppm.
化合物2q
Light-yellow oil(188mg,93％)；1H NMR(400MHz,CDCl3)δ7.47-7.42(m,3H),7.41-7.39(m,1H),7.37-7.34(m,1H),7.17-7.12(m,2H),7.00-6.95(m,1H),6.93-6.88(m,1H),5.59(s,1H),4.27(ddd,J＝13.2,6.4,5.6Hz,1H),4.11(dd,J＝9.2,8.4Hz,1H),4.00(dd,J＝8.8,6.4Hz,1H),3.52-3.43(m,2H),3.22(ddd,J＝16.4,7.6,6.8Hz,1H),2.86(ddd,J＝15.6,10.8,5.6Hz,1H),1.95(ddd,J＝18.4,11.6,6.8Hz,1H),0.88(s,3H),0.86(s,3H)ppm.
化合物2r
White foam(227mg,94％)；1H NMR(400MHz,CDCl3)δ7.45-7.40(m,4H),7.40-7.36(m,1H),7.32-7.28(m,1H),7.14-7.07(m,1H),6.78-6.72(m,1H),5.53(s,1H),4.30(ddd,J＝12.8,6.4,4.8Hz,1H),4.13(dd,J＝9.2,8.4Hz,1H),4.02(dd,J＝8.8,6.4Hz,1H),3.55-3.40(m,2H),3.21(ddd,J＝16.4,7.6,6.8Hz,1H),2.84(ddd,J＝16.0,10.4,5.2Hz,1H),1.95(ddd,J＝18.4,11.6,6.8Hz,1H),0.91-0.85(m,6H)ppm.
化合物2s
White foam(129mg,57％)；1H NMR(400MHz,CDCl3)δ7.45-7.41(m,2H),7.41-7.37(m,3H),7.31-7.25(m,3H),7.17-7.12(m,2H),7.10-7.07(m,2H),6.98-6.92(m,1H),6.82-6.80(m,1H),5.38(s,1H),4.25-4.14(m,2H),4.01-3.86(m,2H),3.40(ddd,J＝14.4,8.4,6.0,1H),3.20(ddd,J＝16.4,7.6,6.8,1H),3.11(dd,J＝13.6,6.4,1H),2.87-2.75(m,2H)ppm.
化合物2t
White foam(183mg,69％)；1H NMR(400MHz,CDCl3)δ7.48-7.42(m,2H),7.41-7.38(m,1H),7.37-7.34(m,2H),7.30-7.26(m,3H),7.12-7.02(m,3H),6.69-6.59(m,1H),5.30(s,1H),4.26-4.14(m,2H),4.03-3.83(m,2H),3.34(ddd,J＝14.8,8.8,6.0Hz,1H),3.22-3.05(m,2H),2.85-2.75(m,2H)ppm.
化合物2u
White foam(187mg,77％)；1H NMR(400MHz,CDCl3)δ7.50-7.45(m,2H),7.44-7.40(m,1H),7.39-7.36(m,2H),7.32-7.27(m,2H),7.26-7.20(m,1H),7.11-7.09(m,2H),7.08-7.02(m,1H),6.75-6.72(m,1H),5.34(s,1H),4.26(ddd,J＝12.8,6.4,4.8Hz,1H),4.18(dd,J＝8.8,8.0Hz,1H),4.02-3.87(m,2H),3.33(ddd,J＝14.8,8.8,5.6Hz,1H),3.22-3.07(m,2H),2.85-2.73(m,2H)ppm.
化合物2v
White foam(174mg,77％)；1H NMR(400MHz,CDCl3)δ7.45-7.40(m,5H),7.36-7.32(m,3H),7.17-7.13(m,2H),7.08-7.02(m,2H),6.98-6.93(m,1H),6.87-6.84(m,1H),5.85(s,1H),5.48(d,J＝8.0Hz,1H),4.37-4.23(m,2H),0.91-0.86(m,3H)ppm.
化合物2w
White foam(205mg,84％)；1H NMR(400MHz,CDCl3)δ7.41-7.35(m,4H),7.35-7.31(m,3H),7.19-7.14(m,2H),7.06-7.00(m,2H),6.99-6.95(m,1H),6.83-6.77(m,1H),5.62(s,1H),5.52(d,J＝8.0Hz,1H),4.43(dd,J＝6.4,5.6Hz,1H),4.27(ddd,J＝13.2,6.8,6.0Hz,1H),3.48(ddd,J＝14.4,8.8,6.0Hz,1H),3.22(ddd,J＝16.4,8.0,7.2Hz,1H),2.88(ddd,J＝16.0,10.8,5.6Hz,1H),0.90-0.84(m,3H)ppm.。
实施例2
化合物1b-y，2a-2w的制备同和施例1。
合成化合物1a
室温下将N,O-缩醛化合物3a(0.5mmol)、炔酰胺化合物5a(1.2当量，0.6mmol)和三氟甲磺酸钪(0.2当量，0.1mmol)溶于干燥的二氯甲烷(3mL)中，室温下搅拌2-6小时，用饱和碳酸氢钠水溶液淬灭，用二氯甲烷(20mL×3)萃取。用饱和食盐水洗涤，用无水硫酸镁干燥，过滤并浓缩。残渣用硅胶柱(PE/EA＝3:1～5:1)纯化，得到目标产物1a(139mg,55％)。
Claims (3)
1.一种恶嗪并异吲哚和恶嗪并异喹啉化合物的制备方法，其特征在于，采用下述反应路线：
；
其中，取代基 R1 代表氢、氯、溴； R2 代表烷基，芳香基； R3 代表 Ts，Ms，
4-ClC6H4SO2；R4 代表烷基、芳基、苄基；或者 R3 和 R4 作为一个整体，与 N 一起代表恶唑烷酮，
步骤：将化合物 3 或 4 与化合物 5 溶于一种有机溶剂中，室温下加入三氟 甲磺酸铜 Cu(OTf)2 或 三氟甲磺酸钪， 反应 2-6 小时， 加入碳酸氢钠饱和溶液淬灭， 经后处理得化合物 1 或 2。
2.按权利要求 1 所述的制备方法， 其特征在于， 所述的一种有机溶剂是指四氢呋喃、1,2-二氯乙烷或二氯甲烷或甲苯。
3.按权利要求 2 所述的制备方法，其特征在于，所述的一种有机溶剂是二氯甲烷或1,2-二氯乙烷。
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