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Method for preparing five-membered-ring-fused seven-membered homopiperazinone derivative through catalyzed oxidative carbonylation of amino olefin amine

A technology for the catalytic oxidation of amino olefin amines, applied in the direction of organic chemistry, etc., to achieve the effects of reduced separation costs, high selectivity, and simple and easy-to-obtain reaction raw materials

Active Publication Date: 2020-12-11
LANZHOU INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The synthesis of pentaheptadic homopiperazinone derivatives has always been challenging

Method used

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  • Method for preparing five-membered-ring-fused seven-membered homopiperazinone derivative through catalyzed oxidative carbonylation of amino olefin amine
  • Method for preparing five-membered-ring-fused seven-membered homopiperazinone derivative through catalyzed oxidative carbonylation of amino olefin amine
  • Method for preparing five-membered-ring-fused seven-membered homopiperazinone derivative through catalyzed oxidative carbonylation of amino olefin amine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] The synthesis of embodiment 1, compound 2a

[0020]

[0021] In a 25ml reaction tube, sequentially add N-(2-(phenylamino)ethyl)-2-propenylbenzamide (1 mmol), benzoquinone (1.2 mmol), PdCl 2 (1mol%) and 1,4-dioxane (5 mL), then the reaction tube was replaced with CO gas 5 times, reacted at 50°C for 30 hours, cooled to room temperature after the reaction, and removed 1,4- The crude product was obtained from dioxane; further separated by silica column chromatography, the eluent was petroleum ether / ethyl acetate (volume ratio: 1 / 1), and the pure compound 2a was obtained with a yield of 96%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.89 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.5Hz, 1H), 7.53-7.50 (m, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.33-7.27 (m, 3H), 4.72(dd, J = 14.7, 4.9 Hz, 1H), 4.00 (dd, J = 15.6, 10.4 Hz, 1H), 3.82 (dd, J =15.5, 4.8 Hz, 1H), 3.45 (dd, J = 14.8, 10.4 Hz, 1H), 3.19 (d, J = 14.2 Hz,1H), 2.92 (d, J = 14.2 Hz, 1H), 1.70 (s, 3H); 13 C NMR (100 MHz, CDCl ...

Embodiment 2

[0022] Embodiment 2, the synthesis of compound 2b

[0023]

[0024] In a 25 ml reaction tube, sequentially add 2-methyl-N-(2-(phenylamino)ethyl)-2-propenylbenzamide (1 mmol), benzoquinone (1.2 mmol), PdCl 2 (1mol%) and 1,4-dioxane (5 mL), and then the reaction tube was replaced with CO gas 5 times, and reacted at 150°C for 10 hours, cooled to room temperature after the reaction, and removed 1,4- The crude product obtained from dioxane was further separated by silica column chromatography, and the eluent was petroleum ether / ethyl acetate (volume ratio: 1 / 1) to obtain pure compound 2b with a yield of 90%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.49-7.41 (m, 3H), 7.33-7.23 (m,5H), 4.69 (ddd, J = 14.9, 4.9, 1.4 Hz, 1H), 3.99 (ddd, J = 15.6, 10.5, 1.4Hz, 1H), 3.81 (ddd, J = 15.6, 5.0, 1.6 Hz, 1H), 3.41 (ddd, J = 14.8, 10.5,1.6 Hz, 1H), 3.15 (d, J = 14.2 Hz, 1H), 2.90 (d, J = 14.2 Hz, 1H), 2.75 (s, 3H), 1.67 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) Δ 170.01, 166.06, 160.45, 143....

Embodiment 3

[0025] Embodiment 3, the synthesis of compound 2c

[0026]

[0027] In a 25 ml reaction tube, sequentially add 5-fluoro-N-(2-(phenylamino)ethyl)-2-propenylbenzamide (1 mmol), benzoquinone (1.2 mmol), PdCl 2 (1mol%) and 1,4-dioxane (5 mL), then the reaction tube was replaced with CO gas 5 times, and reacted at 100°C for 20 hours. After the reaction was completed, cool to room temperature and remove 1,4- The crude product obtained from dioxane was further separated by silica column chromatography, and the eluent was petroleum ether / ethyl acetate (volume ratio: 1 / 1) to obtain pure compound 2c with a yield of 88%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.54 (dd, J = 7.5, 2.4 Hz, 1H),7.50-7.42 (m, 3H), 7.35-7.26 (m, 4H), 4.70 (ddd, J = 14.9, 5.0, 1.5 Hz, 1H),4.00 (dd, J = 15.5, 10.4 Hz, 1H), 3.83 (dd, J = 15.7, 5.0 Hz, 1H), 3.44 (ddd, J = 14.8, 10.4, 1.6 Hz, 1H), 3.17 (d, J = 14.3 Hz, 1H), 2.92 (d, J = 14.2 Hz,1H), 1.70(s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.78, 165.09 (...

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Abstract

The invention discloses a method for preparing a five-membered-ring-fused seven-membered homopiperazinone derivative through catalyzed oxidative carbonylation of an amino olefin amine, which comprisesthe following steps: stirring an amino alkene amide compound serving as a raw material in a solvent at the temperature of 50-150 DEG C for 10-30 hours in the presence of an oxidant and a palladium catalyst under the atmosphere of carbon monoxide; and after the reaction is finished, conducting cooling to room temperature, removing the reaction solvent under reduced pressure, and carrying out silica column chromatography purification on the obtained crude product to obtain the five-membered-ring-fused seven-membered homopiperazinone derivative. In the method, the carbonylation reaction has theadvantages of high activity, high selectivity, few byproducts, mild reaction conditions and simple operation process; and gas participates in the reaction, and the product is low in purification and separation cost and suitable for mass production.

Description

technical field [0001] The invention relates to a synthesis method of a five-and seven-membered nitrogen heterocyclic compound, in particular to a method for preparing five and seven-membered homopiperazinone derivatives by catalyzing the carbonylation of aminoalkene amines, and belongs to the technical field of organic chemical synthesis. Background technique [0002] Pentaheptadic homopiperazinone derivatives widely exist in drug molecules and natural products, and are an important class of active molecular skeletons with high application value. The structural formula of the five and seven yuan homopiperazinone derivatives is: [0003] [0004] In the formula, R (Directing Group) is methyl, benzyl, H, etc.; R' is H, methyl, phenyl, etc.; R" is methyl, benzyl, aromatic ring, etc. [0005] The synthesis of pentaheptadic homopiperazinone derivatives has always been challenging. Through the retrosynthetic analysis of the molecular skeleton, the Wacker cyclization of alken...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 石利军李福伟高广岳成涛孙鹏赵泽伦王嘉龙向东聂超李成阳
Owner LANZHOU INST OF CHEM PHYSICS CHINESE ACAD OF SCI