Tetrahydrofuranoindole compound as well as preparation method and application thereof

A technology of tetrahydrofuran and compounds, applied in the field of medicinal chemistry, to achieve good inhibitory activity, high yield and high efficiency

Active Publication Date: 2021-04-16
INST OF NEW MATERIALS & IND TECH WENZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite these achievements, these 1,1-carbon alkoxylations are limited to endocyclizations, which eventually lead to the formation of endocyclic metallocarbenes after internal migration

Method used

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  • Tetrahydrofuranoindole compound as well as preparation method and application thereof
  • Tetrahydrofuranoindole compound as well as preparation method and application thereof
  • Tetrahydrofuranoindole compound as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The synthesis of embodiment 1 compound 4a

[0029]

[0030] wxya 2 (0.01mmol, 8.7mg) was added to the dichloromethane solution (4mL, 0.05M) of the propargyl amine compound (0.2mmol) shown in formula 3a, and the reaction was protected with nitrogen, and the reaction mixture was stirred at room temperature. Reaction 1 Hours, the raw material of formula 3a was completely consumed through TLC monitoring, then the reaction mixture was concentrated to obtain a residue, and the residue was separated by silica gel column chromatography with n-hexane / ethyl acetate as the eluting solvent to obtain tetrahydrofuran shown in formula 4a and Indole compounds. Yield 99% yield (70.4mg) colorless oily liquid. 1 H NMR (400MHz, CDCl 3 )δ7.92(d, J=8.4Hz, 2H), 7.54(d, J=8.0Hz, 1H), 7.24–7.15(m, 3H), 7.09(d, J=7.2Hz, 1H), 7.00– 6.92(m,1H),6.06–5.82(m,2H),3.92(t,J=7.6Hz,1H),3.67(d,J=8.8Hz,1H),3.06–2.96(m,1H),2.35 (s,3H),2.31–2.22(m,1H),1.90–1.82(m,1H),1.77(dd,J=6.4,1.2Hz,3H); 13 C NMR...

Embodiment 2

[0031] The synthesis of embodiment 2 compound 4b

[0032]

[0033] wxya 2 24 Hours, the raw material of formula 3b was completely consumed through TLC monitoring, then the reaction mixture was concentrated to obtain a residue, and the residue was separated by silica gel column chromatography with n-hexane / ethyl acetate as the eluting solvent to obtain tetrahydrofuran shown in formula 4b and Indole compounds. Yield 64% (55.6 mg); white solid (mp 122–123°C). 1 H NMR (400MHz, CDCl 3 )δ7.88(d, J=8.4Hz, 2H), 7.43(d, J=8.8Hz, 1H), 7.32–7.28(m, 1H), 7.25–7.17(m, 3H), 6.02–5.86(m ,2H),3.92(t,J=8.0Hz,1H),3.64(d,J=8.8Hz,1H),3.02–2.93(m,1H),2.37(s,3H),2.33–2.21(m, 1H), 1.88–1.81(m, 1H), 1.77(d, J=5.2Hz, 3H); 13 C NMR (100MHz, CDCl 3 )δ143.7, 141.2, 137.1, 132.1, 132.0, 131.2, 129.1, 127.9, 127.7, 126.6, 115.4, 114.2, 107.0, 67.9, 53.4, 33.5, 21.5, 17.5; HRESIMS Calcd for [C 20 h 20 BrNNaO 3 S] + (M+Na + ) 456.0239, found 456.0238.

Embodiment 3

[0034] The synthesis of embodiment 3 compound 4c

[0035]

[0036] wxya 2 (0.01mmol, 8.7mg) was added to the dichloromethane solution (4mL, 0.05M) of the propargyl amine compound (0.2mmol) shown in formula 3c, and the reaction was protected with nitrogen, and the reaction mixture was stirred at room temperature. Reaction 1 Hours, the raw material of formula 3c monitored by TLC has been completely consumed, then the reaction mixture is concentrated to obtain a residue, and the residue is separated by silica gel column chromatography with n-hexane / ethyl acetate as the eluting solvent to obtain tetrahydrofuran shown in formula 4c and Indole compounds. Yield 99% (73.2 mg); white solid (mp 155–156°C). 1 H NMR (400MHz, CDCl 3 )δ7.90(d, J=8.4Hz, 2H), 7.43(d, J=8.0Hz, 1H), 7.20(d, J=8.4Hz, 2H), 7.03–6.95(m, 1H), 6.90( s,1H),6.03–5.84(m,2H),3.89(t,J=7.6Hz,1H),3.62(d,J=8.4Hz,1H),2.03–2.93(m,1H),2.34(s ,3H),2.31–2.19(m,4H),1.88–1.80(m,1H),1.76(dd,J=6.0,1.2Hz,3H); 13 C NMR (100MH...

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Abstract

The invention firstly reports a novel synthesis method for obtaining various tetrahydrofuranoindole compounds by performing 1, 1-carbon alkoxylation on gold-catalyzed propynylamine compounds, performing external cyclization at room temperature to obtain external-ring gold carbene, migrating the external-ring gold carbene to gold carbene through 1, 2-H, and constructing and obtaining various tetrahydrofuranoindole compounds by a high-atom economy and diversity strategy. According to the method, the ternary nitrogen-containing heterocyclic compound is obtained only through one-step reaction construction, the reaction only needs to be carried out at room temperature, no additional auxiliary agent is needed, the reaction can be completed in only one hour, the reaction conditions are mild and simple, the efficiency is high, the yield of a target product is high, and the adaptability of a reaction substrate group is good.

Description

technical field [0001] The application belongs to the technical field of medicinal chemistry, and in particular relates to a tetrahydrofuroindole compound and its preparation method and application. Background technique [0002] Transition-metal-catalyzed intramolecular carbon alkoxylation has received extensive attention from chemists over the past few decades because of its high bond-forming efficiency and atom economy in the rapid construction of functionalized cyclic compounds. The reaction typically involves an alkyne difunctionalized product via exo- or endo-cycloalkoxylation followed by internal or external migration. However, compared with the 1,2-carbon alkoxylation of alkynes established by Fürstner, Yamamoto, Toste et al. ((1) Angew. Chem. Int. Ed. 2020, 59, 8522; (2) J.Am. Chem.Soc.2001, 123, 11863; (3) Adv.Synth.Catal.2009, 351, 1089; (4) J.Am.Chem.Soc.2013, 135, 12600, etc.), related 1,1- The development of carbon alkoxylation is still very little ((5) Angew....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/048A61P35/00A61P35/02
CPCC07D491/04Y02P20/55
Inventor 钱鹏程杨晓乐姚智礼叶龙武夏威
Owner INST OF NEW MATERIALS & IND TECH WENZHOU UNIV
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