CN116730897A - 基于n-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法 - Google Patents
基于n-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- -1 indole compound Chemical class 0.000 title claims abstract description 12
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims abstract description 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims abstract description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000004440 column chromatography Methods 0.000 claims abstract description 41
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical group CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000000654 additive Substances 0.000 claims abstract description 20
- 230000000996 additive effect Effects 0.000 claims abstract description 18
- 150000002475 indoles Chemical class 0.000 claims abstract description 17
- 239000003513 alkali Substances 0.000 claims abstract description 11
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 150000003990 18-crown-6 derivatives Chemical group 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 120
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 85
- 238000006243 chemical reaction Methods 0.000 claims description 49
- 238000001914 filtration Methods 0.000 claims description 42
- 238000010791 quenching Methods 0.000 claims description 42
- 238000005406 washing Methods 0.000 claims description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 40
- 238000001704 evaporation Methods 0.000 claims description 40
- 239000000843 powder Substances 0.000 claims description 40
- 230000000171 quenching effect Effects 0.000 claims description 40
- 239000000741 silica gel Substances 0.000 claims description 40
- 229910002027 silica gel Inorganic materials 0.000 claims description 40
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 22
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 239000002585 base Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 41
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 235000019270 ammonium chloride Nutrition 0.000 abstract 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract 1
- 125000001624 naphthyl group Chemical group 0.000 abstract 1
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 74
- 238000012512 characterization method Methods 0.000 description 38
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 38
- 229910052757 nitrogen Inorganic materials 0.000 description 37
- 238000003756 stirring Methods 0.000 description 37
- 238000005481 NMR spectroscopy Methods 0.000 description 26
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 3
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005935 nucleophilic addition reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
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Abstract
本发明公开了一种基于N‑芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,在惰性气体保护下,非质子溶剂中,将化合物(Ⅰ)、碱、添加剂混合反应后,加入饱和氯化铵溶液淬灭,滤过,洗涤后减压蒸干,柱层析分离得到吲哚类化合物;添加剂为18‑冠‑6时,化合物(Ⅰ)、碱和添加剂的混合比例为1:3:6,得到的吲哚类化合物为产物(Ⅱ);当添加剂为N,N‑二乙基乙二胺时,混合比例为1:4:12,得到的吲哚类化合物为产物(Ⅲ);其中,Ar1和Ar2分别为苯基、取代苯基、萘基、芳杂环基团中的任意一种,R为甲基、芳基、甲氧基、卤素中的任意一种。本发明以简单易得的N‑芳香磺酰基邻炔基苯胺为原料,在碱和不同添加剂条件下,实现两种吲哚类化合物的选择性合成。
Description
技术领域
本发明涉及有机合成领域,具体为一种基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法。
背景技术
2-二芳基甲烷基或苄基取代的吲哚是存在于多种具有抗癌、抗菌、抗疟疾等生物活性物质中的母核结构,在药物化学领域有着广泛的应用。2-二芳基甲烷吲哚类化合物可以通过芳基格氏试剂与吲哚酯类化合物的亲核反应(Nucleophilic addition,如下反应式a)所示)制备,也可以通过傅-克烷基化的策略(Friedel-Crafts alkylation,如下反应式b)所示)制备,但是两类方法因为反应条件的局限性导致底物普适性普遍偏低。2-苄基-3-芳基吲哚类化合物的传统合成方法是Fischer吲哚合成法(Fischer indole synthesis,如下反应式c)所示),但该方法使用的1,3-二芳基丙酮的芳基必须是对称结构,否则产物将会是两种产物组成的混合物,这也大大限制了2-苄基-3-芳基吲哚类化合物的多样性。
a)Nucleophilic addition
b)Friedel-Crafts alkylation
c)Fischer indole synthesis
综上,2-二芳基甲烷吲哚和2-苄基-3-芳基吲哚类化合物是具有重要生理活性的骨架结构,有关该类化合物的合成方法存在操作繁琐、复杂底物的预先制备、底物普适性差以及产物种类单一等诸多问题。
发明内容
针对现有技术的不足,本发明的是提供了一种以N-芳香磺酰基邻炔基苯胺为起始原料,高选择性的制备2-二芳基甲烷吲哚和2-苄基-3-芳基吲哚的方法,该方法原子经济性高、无过渡金属催化、操作简便。
本发明所采用的技术方案如下:
一种基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,在惰性气体保护下,在非质子溶剂中,将式(Ⅰ)所示的化合物、碱和添加剂混合进行反应,反应完成后加入饱和氯化铵溶液淬灭,滤过,洗涤后减压蒸干,柱层析分离得到吲哚类化合物;
当添加剂为18-冠-6时,式(Ⅰ)所示的化合物、碱和添加剂的混合比例为1:3:6,得到的吲哚类化合物为产物(Ⅱ);
当添加剂为N,N-二乙基乙二胺时,式(Ⅰ)所示的化合物、碱和添加剂的混合比例为1:4:12,得到的吲哚类化合物为产物(Ⅲ);
其中,Ar1和Ar2分别为苯基、取代苯基、萘基、芳杂环基团中的任意一种,R选自甲基、芳基、甲氧基、卤素中的任意一种。
进一步的,所述的非质子溶剂选自乙二醇二甲醚、四氢呋喃、环戊基甲醚、二氧六环中的任意一种,有助于提高产率。
进一步的,所述碱为六甲基二硅基氨基钾,有助于提高产率。
进一步的,淬灭后加入硅胶粉进行滤过。
进一步的,用乙酸乙酯进行洗涤。
进一步的,柱层析分离中PE:EA=30:1~5:1,在该洗脱剂条件下分离效果最佳。
进一步的,制备产物(Ⅱ)的添加剂为6个当量的18-冠-6,制备产物(Ⅲ)的添加剂为12个当量的N,N-二乙基乙二胺。
进一步的,制备产物(Ⅱ)的反应温度为室温,反应时间为12~18小时;制备产物(Ⅲ)的反应温度为80~100℃,反应时间为12~18小时,使反应完全、充分,并提高产物(Ⅱ)和产物(Ⅲ)的制备效率。
相对于现有技术,本发明的有益效果如下:
本发明在无金属催化的条件下,以简单易得的N-芳香磺酰基邻炔基苯胺为原料,在碱和不同添加剂条件下,实现2-二芳基甲烷吲哚和2-苄基-3-芳基吲哚类化合物的选择性合成,使这两类吲哚类化合物的合成更为简洁高效。
具体实施方式
下面根据优选实施例详细描述本发明,本发明的目的和效果将变得更加明白,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用以解释本发明,并不用于限定本发明。
实施例1
化合物II-1的制备与表征:
氮气保护下,将I-1所示的化合物(34.7mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭,加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用硅胶柱层析分离(PE:EA=30:1),得到产物II-1,产率为78%;1H NMR(500MHz,CDCl3):δ7.68(s,1H),7.48(d,J=7.7Hz,1H),7.32–7.26(m,4H),7.25–7.21(m,2H),7.21–7.15(m,5H),7.11–7.07(m,1H),7.06–7.02(m,1H),6.07(s,1H),5.54(s,1H).
实施例2
化合物II-2的制备与表征:
氮气保护下,将I-2(41.5mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-2,产率为48%;1H NMR(500MHz,DMSO–d6):δ11.07(s,1H),7.64(d,J=7.8Hz,1H),7.60–7.56(m,2H),7.53(d,J=7.6Hz,1H),7.43(d,J=7.9Hz,1H),7.38–7.33(m,2H),7.31–7.26(m,2H),7.25–7.22(m,2H),7.05–7.00(m,1H),6.96–6.92(m,1H),5.93–5.88(m,1H),5.84(s,1H).
实施例3
化合物II-3的制备与表征:
氮气保护下,将I-3(43.1mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-3,产率为75%;1H NMR(500MHz,CDCl3):δ7.74(s,1H),7.50(d,J=7.8Hz,1H),7.34–7.26(m,3H),7.24–7.17(m,5H),7.17–7.10(m,3H),7.08–7.04(m,1H),6.12–6.04(m,1H),5.57(s,1H).
实施例4
化合物II-4的制备与表征:
氮气保护下,将I-4(38.2mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-4,产率为72%;1H NMR(500MHz,CDCl3):δ7.71(s,1H),7.49(d,J=7.8Hz,1H),7.35–7.23(m,5H),7.22–7.15(m,3H),7.14–7.10(m,3H),7.08–7.04(m,1H),6.08–6.02(m,1H),5.52(s,1H).
实施例5
化合物II-5的制备与表征:
氮气保护下,将I-5(42.4mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-5,产率为70%;1H NMR(500MHz,CDCl3):δ7.74(s,1H),7.57–7.49(m,5H),7.43–7.38(m,2H),7.34–7.29(m,3H),7.28–7.22(m,5H),7.22–7.19(m,1H),7.13–7.09(m,1H),7.06(td,J=7.5,1.1Hz,1H),6.15–6.09(m,1H),5.59(s,1H).
实施例6
化合物II-6的制备与表征:
氮气保护下,将I-6(39.8mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-6,产率为94%;1H NMR(500MHz,CDCl3):δ7.84–7.74(m,3H),7.73–7.69(m,1H),7.59(s,1H),7.51(d,J=7.8Hz,1H),7.47–7.41(m,2H),7.36(dd,J=8.5,1.8Hz,1H),7.34–7.29(m,2H),7.29–7.23(m,3H),7.22–7.19(m,1H),7.14–7.10(m,1H),7.08–7.04(m,1H),6.18–6.09(m,1H),5.73(s,1H).
实施例7
化合物II-7的制备与表征:
氮气保护下,将I-7(39.8mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-7,产率为78%;1H NMR(500MHz,CDCl3):δ7.99(d,J=8.4Hz,1H),7.84(d,J=7.7Hz,1H),7.76(d,J=8.2Hz,1H),7.67(s,1H),7.46(d,J=7.7Hz,1H),7.43–7.40(m,1H),7.39–7.35(m,1H),7.34–7.31(m,1H),7.29–7.21(m,3H),7.20–7.17(m,2H),7.13(d,J=7.9Hz,1H),7.10–7.01(m,3H),6.28(s,1H),6.06(s,1H).
实施例8
化合物II-8的制备与表征:
氮气保护下,将I-8(34.8mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=5:1),得到产物II-8,产率为67%;1H NMR(500MHz,CDCl3):δ8.47(d,J=3.3Hz,2H),8.33(s,1H),7.56–7.48(m,2H),7.36–7.31(m,2H),7.30–7.27(m,1H),7.26–7.23(m,2H),7.22–7.18(m,2H),7.15–7.11(m,1H),7.09–7.05(m,1H),6.07–6.05(m,1H),5.59(s,1H).
实施例9
化合物II-9的制备与表征:
氮气保护下,将I-9(35.4mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-9,产率为41%;1H NMR(500MHz,DMSO–d6):δ11.06(s,1H),7.45–7.41(m,2H),7.37–7.32(m,4H),7.30–7.26(m,2H),7.04–6.98(m,2H),6.95–6.92(m,1H),6.88–6.84(m,1H),6.11–6.06(m,1H),5.88(s,1H).
实施例10
化合物II-10的制备与表征:
氮气保护下,将I-10(36.5mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-10,产率为32%;1H NMR(500MHz,CDCl3):δ7.76(s,1H),7.34–7.30(m,4H),7.28–7.24(m,2H),7.22–7.18(m,4H),7.12(td,J=9.3,3.4Hz,2H),6.88–6.83(m,1H),6.08–6.03(m,1H),5.57(s,1H).
实施例11
化合物II-11的制备与表征:
氮气保护下,将I-11(36.2mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-11,产率为74%;1H NMR(500MHz,CDCl3):δ7.54(s,1H),7.23–7.18(m,5H),7.18–7.14(m,2H),7.12–7.09(m,4H),7.00(d,J=8.2Hz,1H),6.85(dd,J=8.3,1.3Hz,1H),5.92(s,1H),5.46(s,1H),2.32(s,3H).
实施例12
化合物II-12的制备与表征:
氮气保护下,将I-12(42.4mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-12,产率为67%;1H NMR(500MHz,DMSO–d6):δ11.05(s,1H),7.67–7.64(m,1H),7.60–7.56(m,2H),7.40–7.35(m,2H),7.34–7.27(m,6H),7.25–7.19(m,7H),5.96–5.90(m,1H),5.64(s,1H).
实施例13
化合物II-13的制备与表征:
氮气保护下,将I-13(37.7mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-13,产率为52%;1H NMR(500MHz,CDCl3):δ7.67(s,1H),7.32–7.28(m,4H),7.26–7.22(m,2H),7.21–7.18(m,4H),7.08(d,J=8.8Hz,1H),6.97(d,J=2.4Hz,1H),6.77(dd,J=8.8,2.5Hz,1H),6.02(s,1H),5.54(s,1H),3.79(s,3H).
实施例14
化合物II-14的制备与表征:
氮气保护下,将I-14(41.2mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-14,产率为92%;1H NMR(500MHz,CDCl3):δ7.78–7.73(m,1H),7.74(d,J=8.5Hz,1H),7.70–7.65(m,2H),7.56(s,1H),7.48(d,J=7.7Hz,1H),7.43–7.38(m,2H),7.33(dd,J=8.5,1.8Hz,1H),7.15–7.02(m,7H),6.10(s,1H),5.62(s,1H),2.31(s,3H).
实施例15
化合物II-15的制备与表征:
氮气保护下,将I-15(47.4mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-15,产率为80%;1H NMR(500MHz,CDCl3):δ7.83–7.74(m,3H),7.73–7.69(m,1H),7.62(s,1H),7.57–7.50(m,5H),7.46–7.37(m,5H),7.33–7.28(m,3H),7.19(d,J=8.1Hz,1H),7.14–7.10(m,1H),7.09–7.05(m,1H),6.17(s,1H),5.73(s,1H).
实施例16
化合物II-16的制备与表征:
氮气保护下,将I-16(42.8mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=20:1),得到产物II-16,产率为93%;1H NMR(500MHz,CDCl3):δ7.82–7.72(m,3H),7.71–7.67(m,1H),7.56(s,1H),7.49(d,J=7.7Hz,1H),7.45–7.40(m,2H),7.34(dd,J=8.5,1.8Hz,1H),7.19–7.08(m,4H),7.07–7.03(m,1H),6.85–6.81(m,2H),6.11(s,1H),5.65(s,1H),3.75(s,3H).
实施例17
化合物II-17的制备与表征:
氮气保护下,将I-17(41.6mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-17,产率为87%;1H NMR(500MHz,CDCl3):δ7.81–7.73(m,2H),7.70–7.62(m,2H),7.53(s,1H),7.49(d,J=7.7Hz,1H),7.45–7.39(m,2H),7.30(dd,J=8.5,1.8Hz,1H),7.18–7.12(m,3H),7.12–7.08(m,1H),7.07–7.03(m,1H),6.99–6.93(m,2H),6.08(s,1H),5.63(s,1H).
实施例18
化合物II-18的制备与表征:
氮气保护下,将I-18(45.8mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=10:1),得到产物II-18,产率为95%;1H NMR(500MHz,CDCl3):δ7.79(s,1H),7.77–7.70(m,2H),7.68–7.63(m,1H),7.57(s,1H),7.48(d,J=7.6Hz,1H),7.41–7.36(m,2H),7.33(dd,J=8.5,1.7Hz,1H),7.12–7.01(m,3H),6.41(d,J=2.2Hz,2H),6.36(t,J=2.2Hz,1H),6.15(s,1H),5.58(s,1H),3.63(s,6H).
实施例19
化合物II-19的制备与表征:
氮气保护下,将I-19(41.5mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-19,产率为84%;1H NMR(500MHz,CDCl3):δ7.82–7.73(m,3H),7.71–7.66(m,1H),7.58(s,1H),7.50(d,J=7.8Hz,1H),7.46–7.40(m,2H),7.35(dd,J=8.5,1.8Hz,1H),7.27–7.21(m,1H),7.19–7.16(m,1H),7.13–7.02(m,5H),6.16–6.10(m,1H),6.02(s,1H).
实施例20
化合物II-20的制备与表征:
氮气保护下,将I-20(42.4mg,0.1mmol,1.0equiv)和18-冠-6(158.4mg,0.6mmol,6.0equiv)溶于1mL四氢呋喃溶剂中,在搅拌下加入六甲基二硅基氨基钾(1.0mol/L inTHF,0.3mL,0.3mmol,3.0equiv),于室温搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物II-20,产率为72%;1H NMR(500MHz,CDCl3):δ7.81–7.74(m,2H),7.74–7.65(m,2H),7.57(s,1H),7.49(d,J=7.7Hz,1H),7.45–7.39(m,2H),7.36–7.31(m,3H),7.20–7.15(m,3H),7.12–7.08(m,1H),7.08–7.03(m,1H),6.68(dd,J=17.6,10.9Hz,1H),6.14–6.09(m,1H),5.71(dd,J=17.6,0.7Hz,1H),5.67(s,1H),5.22(dd,J=10.9,0.6Hz,1H).
实施例21
化合物III-1的制备与表征:
氮气保护下,将I-1(34.7mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-1,产率为80%;1H NMR(500MHz,CDCl3):δ7.71–7.65(m,1H),7.61(s,1H),7.55–7.49(m,2H),7.44–7.38(m,2H),7.32–7.22(m,3H),7.22–7.16(m,1H),7.15–7.06(m,5H),4.14(s,2H).
实施例22
化合物III-2的制备与表征:
氮气保护下,将I-2(41.5mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-2,产率为37%;1H NMR(500MHz,CDCl3):δ7.90(s,1H),7.83(s,1H),7.75–7.70(m,1H),7.66(d,J=7.8Hz,1H),7.61–7.56(m,2H),7.37–7.26(m,4H),7.23–7.15(m,4H),4.24(s,2H).
实施例23
化合物III-3的制备与表征:
氮气保护下,将I-3(43.1mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-3,产率为63%;1H NMR(500MHz,CDCl3):δ7.86(s,1H),7.68(d,J=7.9Hz,1H),7.59–7.55(m,2H),7.39–7.26(m,6H),7.24–7.19(m,3H),7.19–7.14(m,1H),4.24(s,2H).
实施例24
化合物III-5的制备与表征:
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氮气保护下,将I-5(42.4mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-5,产率为87%;1H NMR(500MHz,CDCl3):δ7.82(d,J=7.6Hz,2H),7.78–7.68(m,6H),7.55–7.50(m,2H),7.43–7.36(m,3H),7.34–7.30(m,2H),7.29–7.26(m,2H),7.26–7.19(m,2H),4.32(s,2H).
实施例25
化合物III-6的制备与表征:
氮气保护下,将I-6(39.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-6,产率为71%;1H NMR(500MHz,CDCl3):δ7.96(d,J=0.7Hz,1H),7.91(d,J=8.5Hz,1H),7.87–7.81(m,2H),7.78(s,1H),7.75–7.72(m,1H),7.70(dd,J=8.4,1.7Hz,1H),7.49–7.43(m,2H),7.32–7.27(m,2H),7.26–7.21(m,2H),7.20–7.11(m,4H),4.25(s,2H).
实施例26
化合物III-7的制备与表征:
氮气保护下,将I-7(39.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-7,产率为71%;1H NMR(500MHz,CDCl3):δ7.93–7.79(m,4H),7.54–7.50(m,2H),7.48–7.43(m,1H),7.37–7.32(m,1H),7.25–7.08(m,8H),7.02–6.98(m,1H),4.02–3.94(m,2H).
实施例27
化合物III-8的制备与表征:
氮气保护下,将I-8(34.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=5:1),得到产物Ⅲ-8,产率为78%;1H NMR(500MHz,DMSO–d6):δ11.36(s,1H),8.62(d,J=1.6Hz,1H),8.46(dd,J=4.7,1.3Hz,1H),7.85–7.77(m,1H),7.49(d,J=7.9Hz,1H),7.44(m,1H),7.37(d,J=8.0Hz,1H),7.28–7.22(m,2H),7.19–7.07(m,4H),7.04–6.99(m,1H),4.16(s,2H).
实施例28
化合物III-9的制备与表征:
氮气保护下,将I-9(35.4mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/L in THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-9,产率为47%;1H NMR(500MHz,CDCl3):δ7.92–7.78(m,2H),7.39–7.32(m,3H),7.32–7.23(m,4H),7.22–7.17(m,4H),4.35(s,2H).
实施例29
化合物III-10的制备与表征:
氮气保护下,将I-10(36.5mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-10,产率为83%;1H NMR(500MHz,CDCl3):δ7.79(s,1H),7.59–7.53(m,2H),7.52–7.48(m,2H),7.41–7.33(m,4H),7.33–7.27(m,1H),7.25–7.20(m,2H),7.17(dd,J=8.8,4.3Hz,1H),6.93(td,J=9.0,2.5Hz,1H),4.25(s,2H).
实施例30
化合物III-11的制备与表征:
氮气保护下,将I-11(36.2mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-11,产率为88%;1H NMR(500MHz,CDCl3):δ7.73(s,1H),7.64–7.58(m,2H),7.56–7.49(m,3H),7.41–7.33(m,3H),7.32–7.28(m,1H),7.24(d,J=7.0Hz,2H),7.19(d,J=8.2Hz,1H),7.05(dd,J=8.2,1.5Hz,1H),4.26(s,2H),2.49(s,3H).
实施例31
化合物III-12的制备与表征:
氮气保护下,将I-12(42.4mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-12,产率为85%;1H NMR(500MHz,CDCl3):δ7.97(d,J=1.4Hz,1H),7.83(s,1H),7.70–7.64(m,4H),7.57–7.52(m,2H),7.50–7.45(m,3H),7.43–7.30(m,6H),7.28–7.24(m,2H),4.29(s,2H).
实施例32
化合物III-13的制备与表征:
氮气保护下,将I-13(37.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-13,产率为66%;1H NMR(500MHz,CDCl3):δ7.74(s,1H),7.60–7.57(m,2H),7.53–7.49(m,2H),7.39–7.31(m,3H),7.30–7.26(m,1H),7.24–7.15(m,4H),6.86(dd,J=8.7,2.5Hz,1H),4.23(s,2H),3.84(s,3H).
实施例33
化合物III-14的制备与表征:
氮气保护下,将I-14(41.2mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-14,产率为74%;1H NMR(500MHz,CDCl3):δ8.03(d,J=0.7Hz,1H),7.98(d,J=8.5Hz,1H),7.94–7.89(m,2H),7.86(s,1H),7.82–7.79(m,1H),7.78(dd,J=8.4,1.7Hz,1H),7.56–7.50(m,2H),7.33–7.29(m,1H),7.25–7.22(m,1H),7.21–7.14(m,5H),4.29(s,2H),2.39(s,3H).
实施例34
化合物III-15的制备与表征:
氮气保护下,将I-15(47.4mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-15,产率为71%;1H NMR(500MHz,CDCl3):δ8.04(d,J=0.7Hz,1H),7.98(d,J=8.5Hz,1H),7.96–7.87(m,3H),7.83–7.77(m,2H),7.64–7.57(m,4H),7.56–7.50(m,2H),7.49–7.45(m,2H),7.40–7.36(m,1H),7.35–7.30(m,3H),7.26–7.18(m,2H),4.36(s,2H).
实施例35
化合物III-16的制备与表征:
氮气保护下,将I-16(42.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-16,产率为71%;1H NMR(500MHz,CDCl3):δ8.00(d,J=0.6Hz,1H),7.96(d,J=8.5Hz,1H),7.92–7.86(m,3H),7.77(d,J=7.8Hz,1H),7.75(dd,J=8.4,1.7Hz,1H),7.54–7.48(m,2H),7.33–7.30(m,1H),7.23–7.19(m,1H),7.19–7.15(m,3H),6.90–6.86(m,2H),4.26(s,2H),3.81(s,3H).
实施例36
化合物III-17的制备与表征:
氮气保护下,将I-17(41.6mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=30:1),得到产物Ⅲ-17,产率为56%;1H NMR(500MHz,CDCl3):δ7.99–7.95(m,2H),7.93–7.82(m,3H),7.78(d,J=7.8Hz,1H),7.73(dd,J=8.4,1.7Hz,1H),7.55–7.49(m,2H),7.35–7.32(m,1H),7.26–7.22(m,1H),7.21–7.16(m,3H),7.05–7.00(m,2H),4.28(s,2H).
实施例37
化合物III-18的制备与表征:
氮气保护下,将I-18(45.8mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=20:1),得到产物Ⅲ-18,产率为80%;1H NMR(500MHz,CDCl3):δ8.02(s,1H),8.01–7.89(m,4H),7.81–7.76(m,2H),7.56–7.50(m,2H),7.33(d,J=7.9Hz,1H),7.25–7.17(m,2H),6.47–6.37(m,3H),4.25(s,2H),3.76(s,6H).
实施例38
化合物III-19的制备与表征:
氮气保护下,将I-19(41.6mg,0.1mmol,1.0equiv)和N,N-二乙基乙二胺(139mg,1.2mmol,12.0equiv)溶于2mL干燥的环戊基甲醚在搅拌下加入六甲基二硅基氨基钾(1.0mol/Lin THF,0.4mL,0.4mmol,4.0equiv),于100℃搅拌12小时。反应结束后,加入四滴饱和氯化铵溶液淬灭。加入少量硅胶粉滤过,用乙酸乙酯洗涤后减压蒸干,混合物用柱层析分离(PE:EA=20:1),得到产物Ⅲ-19,产率为60%;1H NMR(500MHz,CDCl3):δ8.27–8.18(m,2H),8.11–8.07(m,1H),8.03–7.92(m,3H),7.57–7.54(m,1H),7.50–7.43(m,2H),7.39–7.36(m,1H),7.34–7.28(m,2H),7.24–7.16(m,3H),3.77(q,J=14.0Hz,2H).
除四氢呋喃和环戊基甲醚以外,二氧六环、乙二醇二甲醚等非质子溶剂均可作为备选溶剂,只是产率略低于四氢呋喃和环戊基甲醚。
以上所述仅为本发明的优选实施例,并非因此限制本发明的专利范围,凡是利用本发明说明书内容所作的等效结构或等效流程变换,或直接或间接运用在其他相关的技术领域,均同理包括在本发明的专利保护范围内。
Claims (8)
1.一种基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,在惰性气体保护下,在非质子溶剂中,将式(Ⅰ)所示的化合物、碱和添加剂混合进行反应,反应完成后加入饱和氯化铵溶液淬灭,滤过,洗涤后减压蒸干,柱层析分离得到吲哚类化合物;
当添加剂为18-冠-6时,式(Ⅰ)所示的化合物、碱和添加剂的混合比例为1:3:6,得到的吲哚类化合物为产物(Ⅱ);
当添加剂为N,N-二乙基乙二胺时,式(Ⅰ)所示的化合物、碱和添加剂的混合比例为1:4:12,得到的吲哚类化合物为产物(Ⅲ);
其中,Ar1和Ar2分别为苯基、取代苯基、萘基、芳杂环基团中的任意一种,R选自甲基、芳基、甲氧基、卤素中的任意一种。
2.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,所述非质子溶剂选自乙二醇二甲醚、四氢呋喃、环戊基甲醚、二氧六环中的任意一种。
3.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,所述碱为六甲基二硅基氨基钾。
4.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,淬灭后加入硅胶粉进行滤过。
5.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,用乙酸乙酯进行洗涤。
6.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,柱层析分离中PE:EA=20:1~5:1。
7.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,制备产物(Ⅱ)的添加剂为6个当量的18-冠-6,制备产物(Ⅲ)的添加剂为12个当量的N,N-二乙基乙二胺。
8.根据权利要求1所述的基于N-芳香磺酰基邻炔基苯胺的吲哚类化合物的制备方法,其特征在于,制备产物(Ⅱ)的反应温度为室温,反应时间为12~18小时;制备产物(Ⅲ)的反应温度为80~100℃,反应时间为12~18小时。
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