Monovalent silver-catalyzed synthesis method for azaindole seven-membered ring

A synthesis method and seven-membered ring technology are applied in the field of synthesis of indoloazepine seven-membered rings, can solve the problems of poor atom economy, expensive reagents, complicated substrate preparation and the like, and achieve low price and reaction time. Short, simple post-processing effects

Active Publication Date: 2019-02-26
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the substrate preparation of this method is cumbersome, the reaction conditions are relatively severe, and the atom economy is not good, resulting in more by-products
[0012] In summary, in the known synthetic methods of indoloazepine seve

Method used

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  • Monovalent silver-catalyzed synthesis method for azaindole seven-membered ring
  • Monovalent silver-catalyzed synthesis method for azaindole seven-membered ring
  • Monovalent silver-catalyzed synthesis method for azaindole seven-membered ring

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Add substrate a1 (0.1mmol, 43mg) into a 25mL eggplant-shaped flask, add 5mL of toluene solution, then add 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol, 2.6mg), stir at room temperature, and stir for 6h , after the completion of the reaction, the target product b1 was separated by flash column chromatography (n-hexane:ethyl acetate=10:1) with a yield of 80%.

[0043] The reaction formula of Example 1 is:

[0044]

[0045] The spectral data of product b1 is: ESI-MS (m / z): 451[M+Na] + ; 1 H-NMR (600MHz, DMSO) δ7.74 (d, J = 8.2Hz, 2H), 7.51 (d, J = 7.9Hz, 1H), 7.34–7.44 (m, 5H), 7.24–7.28 (m, 3H ),7.12(t,J=7.5Hz,1H),7.03(t,J=7.5Hz,1H),7.00(s,1H),3.85–3.88(m,2H),2.93–2.95(m,5H) ,2.35(s,3H).

Embodiment 2

[0047] Add substrate a2 (0.1mmol, 45mg) into a 25mL eggplant-shaped flask, add 5mL of toluene solution, then add 1mL of silver trifluoromethanesulfonate (0.01mmol, 2.6mg) in toluene mixed solution, stir at room temperature, and stir the reaction 5h, after the reaction was completed, the target product b2 was separated by flash column chromatography (n-hexane:ethyl acetate=10:1) with a yield of 85%.

[0048] The reaction formula of Example 2 is:

[0049]

[0050] The spectral data of product b2 is: ESI-MS (m / z): 469[M+Na] + ; 1 H-NMR (600MHz, DMSO) δ7.74 (d, J = 8.2Hz, 2H), 7.51 (d, J = 7.9Hz, 1H), 7.39 (d, J = 8.2Hz, 2H), 7.23–7.30 ( m,5H),7.11–7.15(m,1H),7.01–7.05(m,1H),6.98(s,1H),3.85–3.87(m,2H),2.96(s,3H),2.92–2.94( m,2H), 2.36(s,3H).

Embodiment 3

[0052]Add substrate a3 (0.1mmol, 44mg) into a 25mL eggplant-shaped flask, add 5mL of toluene solution, then add 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol, 2.6mg), stir at room temperature, and stir for 4h , after the reaction was completed, the target product b3 was separated by flash column chromatography (n-hexane:ethyl acetate=5:1) with a yield of 81%.

[0053] The reaction formula of example 3 is:

[0054]

[0055] The spectral data of product b3 is: ESI-MS (m / z): 457[M+Na] + ; 1 H-NMR (600MHz, DMSO) δ7.72 (d, J = 8.2Hz, 2H), 7.56 (dd, J = 5.2, 1.1Hz, 1H), 7.51 (d, J = 8.0Hz, 1H), 7.40 ( d,J=8.2Hz,2H),7.32(d,J=8.0Hz,1H),7.13–7.16(m,2H),7.10(dd,J=5.2,3.5Hz,1H),7.01–7.06(m ,2H), 3.86–3.89(m,2H), 3.12(s,3H), 2.88–2.92(m,2H), 2.36(s,3H).

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Abstract

The invention provides a monovalent silver-catalyzed synthesis method for an azaindole seven-membered ring, belonging to the field of organic synthesis. In a general reaction formula as described in the specification, R1, R2 and R3 are as defined in the claims and the specification. A silver catalyst needed in a reaction is one selected from a group consisting of silver trifluoromethanesulfonate,silver hexafluoroantimonate, silver tetrafluoroborate and silver bis(trifluoromethanesulfonimide). A medium needed in the reaction is toluene. The reaction is carried out at room temperature under thecondition of stirring. The method has the advantages of easy availability of raw materials, simple operation, a wide application scope, good atomic economy, green reaction, and low price.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and relates to a synthesis method of indole-containing tryptamine alkyne amide substrate at room temperature under the catalysis of monovalent silver to form an indoloaza seven-membered ring. Background technique [0002] The seven-membered indoloazepine ring is a very important structure, which exists in some natural products and active molecules of indole alkaloids. (J.Org.Chem., 2010, 75, 7026., Org.Biomol.Chem., 2009, 7, 1388.) However, due to the particularity of the indoloazepine seven-membered ring structure, it is also difficult to synthesize , Therefore, finding simple and effective synthetic methods has always been the focus of attention of organic chemists. The currently reported methods for the synthesis of indoloazepine seven-membered rings are: [0003] 1. Synthesize a six-membered ring first, and then form a seven-membered ring by ring expansion. (J. Or...

Claims

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Application Information

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IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 刘永祥程卯生庞亚东李阳明刘成军肖建勇
Owner SHENYANG PHARMA UNIVERSITY
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