Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Chiral bridge ring skeleton oxindole piperidine compound and synthesis method of compound

A technology of oxindole spiropiperidine and its synthesis method, which is applied in the field of chiral nitroxide-bridged ring skeleton and spiro-ring oxindole compound and its synthesis, which can solve the problems of few reports on the synthesis method and achieve enantioselectivity And the effects of excellent diastereoselectivity, good yield, and good chemoselectivity

Inactive Publication Date: 2018-01-19
SUZHOU UNIV
View PDF0 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the prior art, the synthesis methods of spiro-oxindole derivatives are relatively common, but the synthesis methods of oxindole spiroheterocyclic compounds, especially oxindole spiropiperidine ring compounds, are rarely reported.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Chiral bridge ring skeleton oxindole piperidine compound and synthesis method of compound
  • Chiral bridge ring skeleton oxindole piperidine compound and synthesis method of compound
  • Chiral bridge ring skeleton oxindole piperidine compound and synthesis method of compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039]

[0040] 1a (38.1 mg, 0.15 mmol, 1.5 equiv), 2a (21.2 mg, 0.1 mmol) and catalyst Cat. (4.1 mg, 0.01 mmol, 10 mol%) were placed in a test tube containing methyl tert-butyl ether (1.0 mL) , reacted at room temperature for 12 hours until the substrate 2a disappeared, and removed the solvent under reduced pressure. The resulting residue was separated by petroleum ether / ethyl acetate (2 / 1) column chromatography, and the obtained product was dissolved in toluene (1.0 ml) , and then added bistrifluoromethanesulfonimide (5.6 mg, 0.02mmol, 20 mol%) to the solution, and continued to react at room temperature for 12 hours, and the system was directly chromatographed with petroleum ether / ethyl acetate (3 / 1) Isolated to give 29.1 mg of 3aa as a white solid, 65% yield, 160–161 °C.

[0041] The product 3aa was analyzed and the results were as follows: >20:1 dr , 97% ee [Daicel Chiralcel AD-H, hexanes / i -PrOH = 80 / 20, flow rate: 1.0 mL·min –1 , λ = 254.4 nm, t (major)=5.857,...

Embodiment 2

[0044]

[0045] 1b (33.0 mg, 0.15 mmol, 1.5 equiv), 2a (21.2 mg, 0.1 mmol) and catalyst Cat. (4.1 mg, 0.01 mmol, 10 mol%) were placed in a test tube containing methyl tert-butyl ether (1.0 mL) , reacted at room temperature for 12 hours until the substrate 2a disappeared, and removed the solvent under reduced pressure. The resulting residue was separated by petroleum ether / ethyl acetate (2 / 1) column chromatography, and the obtained product was dissolved in toluene (1.0 ml) , and then add bistrifluoromethanesulfonimide (5.6 mg, 0.02mmol, 20 mol%) to the solution, continue the reaction at room temperature for 4 hours, and directly use petroleum ether / ethyl acetate (3 / 1) column chromatography Isolated to give 21.5 mg of 3ab as a white solid, 62% yield, 245–246 °C.

[0046] The product 3ab was analyzed and the results were as follows: >20:1 dr , 87% ee [Daicel Chiralcel AD-H, hexanes / i-PrOH = 80 / 20, flow rate: 1.0 mL min–1, λ = 254.4 nm, t (major) =9.448, t (minor) = 13.286...

Embodiment 3

[0049]

[0050] 1c (35.1 mg, 0.15 mmol, 1.5 equiv), 2a (21.2 mg, 0.1 mmol) and catalyst Cat. (4.1 mg, 0.01 mmol, 10 mol%) were placed in a test tube containing methyl tert-butyl ether (1.0 mL) , reacted at room temperature for 12 hours until the substrate 2a disappeared, and removed the solvent under reduced pressure. The resulting residue was separated by petroleum ether / ethyl acetate (2 / 1) column chromatography, and the obtained product was dissolved in toluene (1.0 ml) , and then add bistrifluoromethanesulfonimide (5.6 mg, 0.02mmol, 20 mol%) to the solution, continue to react at room temperature for 6 hours, and directly use petroleum ether / ethyl acetate (3 / 1) column chromatography Isolated to give 22.6 mg of 3ac as a white solid, 63% yield, 210–211 °C.

[0051] The product 3ac was analyzed and the results were as follows: >20:1 dr , 73% ee [Daicel Chiralcel AD-H, hexanes / i-PrOH = 80 / 20, flow rate: 1.0 mL min–1, λ = 254.4 nm, t (major) =10.739, t (minor) = 12.835]; [...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a chiral nitrogen oxygen bridge ring skeleton and spiro oxindole compound and a synthesis method of the compound. The method specifically comprises the following steps: takinga 3-pyrrolyl oxindole and beta,gamma-unsaturated alpha-keto ester derived from salicylaldehyde as a reactant, and in the presence of a chiral thiourea compound and bis(trifluoromethanesulfonyl)imide,performing an asymmetric tandem cyclization reaction in a methyl tert-butyl ether and toluene solvent to obtain a product. The method disclosed by the invention has simple and easily available raw materials, mild reaction conditions, simple and convenient post-treatment, wide application range, good yield, and high enantioselectivity and non-enantioselectivity; and therefore, the synthesized product has a potential medicinal value.

Description

technical field [0001] The invention relates to the synthesis of oxindole-spiropiperidine compounds with bridging ring skeleton, in particular to a chiral nitroxide bridging ring skeleton and spiro-ring oxindole compound and a synthesis method thereof. Background technique [0002] Nitroxide heterocyclic skeletons widely exist in natural products and synthetic drug molecules, and have a broad spectrum of physiological and pharmacological activities, so they have attracted extensive attention from many chemical and pharmaceutical researchers. Among them, spiro heterocyclic compounds containing five or six members often also have important physiological and pharmacological activities, such as spiro oxindole pyrrole heterocycle or spiro oxindole piperidine heterocycle. It is of great significance to be able to synthesize chiral oxindole-spiropiperidine compounds with complex structures containing multiple important structural units such as quaternary carbon chiral centers, hete...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D491/22B01J31/02
Inventor 王兴旺范巍泰
Owner SUZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com