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Oxazepine [3, 2-b] indole compound and synthetic method thereof

A kind of technology of indole compound and synthesis method, applied in the field of organic synthesis

Inactive Publication Date: 2020-10-27
GUIZHOU MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0022] In summary, although many have been developed for the synthesis of aza seven-membered fused ring compounds, benzofuran-structured aza-7-membered rings and benzothiophene-structured oxa-7-membered rings, the direct use of crotonic acid The synthesis of ester-derived sulfur ylide reagents as C3 synthons for the construction of oxazo[3,2-b]indoles has rarely been reported

Method used

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  • Oxazepine [3, 2-b] indole compound and synthetic method thereof
  • Oxazepine [3, 2-b] indole compound and synthetic method thereof
  • Oxazepine [3, 2-b] indole compound and synthetic method thereof

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preparation example Construction

[0054] The present invention provides a kind of synthetic method of oxazo[3,2-b]indole compound, comprising the following steps:

[0055] Dissolve the sulfur ylide reagent derived from crotonate ester of formula (2) and base in an organic solvent, then add the 3-oxindolinone substrate of formula (1), and carry out [4+3] at 0-100°C The cycloaddition reaction takes 8 to 10 minutes to obtain the oxazo[3,2-b]indole compound of formula (3); its synthetic route is as follows:

[0056]

[0057] In formula (1), formula (2), formula (3),

[0058] R is selected from one of hydrogen atom, methyl group, methoxy group and halogen;

[0059] R1 is selected from one of substituted or unsubstituted aryl, naphthyl, O or S five-membered heterocycles;

[0060] EWG is carboethoxylate.

[0061] For the first time, the present invention uses 3-oxindolinone compounds and crotonate-derived sulfur ylide reagents as raw materials, and under the promotion of alkali, through an intermolecular [4+3] ...

Embodiment 1

[0065] A kind of synthetic method of oxazolo [3,2-b] indole compound (3a), comprises the steps:

[0066] With 0.15mmol formula (2a) crotonate derived sulfur ylide reagent and 0.15mmol, 48.9mg of the base Cs 2 CO 3 Dissolve in 1.0ml of organic solvent dichloromethane to prepare the mixture, then quickly add 0.1mmol, 36.1 mg of the compound of formula (1a) into the above mixture, continue to stir and react at room temperature for 8min, monitor the reaction by TLC, after the reaction is complete, directly spin dry Organic solvent, petroleum ether: ethyl acetate (20:1) column chromatography, to obtain a white solid, that is, the formula (3a) oxazo [3,2-b] indole compound; confirmed by NMR, GC-MS It is an oxazo[3,2-b]indole derivative; Yield: 85%; Reaction time: 8min; White solid; m.p.: 118 -120°C;

[0067] Its synthetic route is as follows:

[0068]

[0069] 1 H NMR (400MHz, CDCl 3 ):δ8.23(d,J=8.0Hz,1H),7.57(d,J=7.6Hz,2H), 7.51–7.40(m,4H),7.39–7.31(m,1H),7.29–7.20( m,6H),...

Embodiment 2

[0071] A synthetic method of oxazo[3,2-b]indole compound (3b), which is the same as Example 1, except that the formula (1a) in Example 1 is replaced by the compound of formula (1b) compound; the reaction temperature is 50°C, and the base used is K 2 CO 3 , the organic solvent is N,N-dimethylformamide;

[0072] Synthesized oxazo[3,2-b]indole compound of formula (3b), yield: 75%; reaction time: 8 min; white solid; m.p.: 136-137°C;

[0073] Wherein, the molar ratio of formula (1b) to formula (2a) is 1:1

[0074] Formula (1b) and base K 2 CO 3 The molar ratio is 1:1

[0075] Formula (1b) and organic solvent consumption ratio are 0.1mol:0.5L;

[0076] Its synthetic route is as follows:

[0077]

[0078] 1 H NMR (400MHz, CDCl 3 ):δ8.23(dd,J=8.4,0.8Hz,1H),7.56(d,J=8.0Hz,2H),7.50–7.39(m,4H),7.35(t,J=7.8Hz,1H) ,7.29(s,1H),7.26–7.24(m,1H),7.21–7.15(m,2H),7.08(t,J=5.8Hz,1H),6.50(s,1H),4.84(dd,J =16.0, 6.0Hz, 1H), 4.49(dd, J=16.4, 4.4Hz, 1H), 4.33–4.23(m, 2H), 1.33(t, J=7.2 ...

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Abstract

The invention discloses a synthetic method of an oxazepine [3, 2-b] indole compound, and belongs to the technical field of organic synthesis. The synthetic method comprises the following steps: performing [4 + 3] cycloaddition reaction on a crotonate-derived sulfur ylide reagent shown as a formula (2) and a 3-oxindolone substrate shown as a formula (1) under an alkaline condition to obtain the oxazepine [3, 2-b] indole compound shown as a formula (3), the invention also provides the oxazepine [3, 2-b] indole compound. The synthetic method is simple, convenient and efficient, large instrumentsand expensive raw materials are not needed, the reaction conditions are mild, the derivatization range of the substrate is wide, and a foundation is laid for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and specifically relates to an oxazo[3,2-b]indole compound and a synthesis method thereof. Background technique [0002] The rapid construction of indole polycyclic frameworks with complex structures is one of the most important frontiers in the field of natural product and drug synthesis, and has attracted the attention of organic chemistry and drug synthesis workers. The heterozo[3,2-b]indole skeleton is the core skeleton of many biologically active natural products and drug molecules. For example, Arboflorine is isolated from malayan pistil; Paullone shows anti-tumor activity; Ibogamine (Ibogamine) is an alkaloid with anti-cancer activity isolated from Apocynaceae vinblastine vinca; Exotine, isolated, shows inhibitory effect of lipopolysaccharide-induced nitric oxide in BV-2 microglia. Among them, the structural formulas of Arboflorine, Paullone, Ibogamine and Exotine are as follow...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/044
CPCC07D491/044
Inventor 赵永龙费兴海何彬杨芬芬管香
Owner GUIZHOU MEDICAL UNIV
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