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(1R)-phenylamino-(2S)-2-aryl-2-azaaryl cyclopentane as well as preparation method and application thereof

A technology based on cyclopentane and aniline, applied in the field of synthesis of chiral quaternary carbocyclopentane, can solve the problems of limited application, and achieve the effects of no metal involved, mild reaction conditions, and environmental friendliness

Active Publication Date: 2021-05-04
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, there are few reports on the synthesis of quaternary carbon-rich electron-deficient azaarenes, which undoubtedly greatly limits its practical application.

Method used

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  • (1R)-phenylamino-(2S)-2-aryl-2-azaaryl cyclopentane as well as preparation method and application thereof
  • (1R)-phenylamino-(2S)-2-aryl-2-azaaryl cyclopentane as well as preparation method and application thereof
  • (1R)-phenylamino-(2S)-2-aryl-2-azaaryl cyclopentane as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] (1 R )-anilino-(2 S )-2-(4'-methylphenyl)-2-(2'-pyridyl)cyclopentane III-1 The specific preparation steps are as follows:

[0036]

[0037]Preparation process: Take a dry 25 mL schlenk tube, add 53.2 mg (0.4 mmol) N-phenylcyclopropane, 39.0 mg (0.2 mmol) 2-(1-(4´-methylphenyl) vinyl) pyridine, DPZ (0.35 mg, 0.001 mmol), BA (33.3 mg, 0.04 mmol), and then add 5 mL of cyclopentyl methyl ether (CPME), cover the bottle, and remove it with a vacuum pump at no higher than -78 °C. Gas 2-3 times, 5-10 min each time, pass through argon gas for protection, then place it at 25°C, and irradiate with a 3 W blue light with a wavelength of 410-510 nm at a distance of about 3 cm from the schlenk tube, and react 8 hours, after the reaction was completed, separated by column chromatography (petroleum ether / ethyl acetate = 20 ~ 4:1, volume ratio), concentrated by rotary evaporation, and dried in vacuum (dried at 25°C for 1 hour) to obtain 60.4 mg of yellow oil (1 R )-anilino-(2 S )...

Embodiment 2

[0039] (1 R )-anilino-(2 S )-2-(4'-fluorophenyl)-2-(2'-pyridyl)cyclopentane III-2 The specific preparation steps are as follows:

[0040]

[0041] In this example, the 2-(1-(4´-methylphenyl)vinyl)pyridine in Example 1 is replaced with 2-(1-phenylvinyl)-3-picoline, other steps Same as Example 1, obtain 59.8 mg yellow oil (1 R )-anilino-(2 S )-2-(4´-fluorophenyl)-2-(2´-pyridyl)cyclopentane III-2 in 90% yield and 82% enantiomeric excess. NMR and mass spectrometry data are: 1 HNMR (300 MHz, CDCl 3 ) δ 8.57 (d, J = 4.1 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H),7.26 (t, J = 6.8 Hz, 3H), 7.12 (m, 3H), 6.98 (t, J = 8.7 Hz, 2H), 6.66 (m,3H), 4.95 (t, J = 5.1 Hz, 1H), 3.30 (br, 1H), 2.62 (t, J = 7.3 Hz, 2H), 2.17(m, 1H), 1.92 (dt, J = 15.6, 9.7 Hz, 1H), 1.69 (m, 2H); 13 C NMR (75 MHz, CDCl 3 ) Δ 165.4, 163.1, 159.8, 148.7, 147.5, 139.1, 139.0, 136.4, 130.4,130.3, 129.1, 121.6, 117.0, 115.2, 113.3, 60.9, 36.0,30.6, 20.5; m / z 333.1762 (M+H + ), calc. for C 22 h 22 FN ...

Embodiment 3

[0043] (1 R )-anilino-(2 S )-2-phenyl-2-(2'-(3'-methyl)pyridyl)cyclopentane III-3 The specific preparation steps are as follows:

[0044]

[0045] In this example, the 2-(1-(4´-methylphenyl)vinyl)pyridine in Example 1 is replaced with 2-(1-phenylvinyl)-3-picoline, other steps Same as Example 1, obtain 57.1 mg yellow oil (1 R )-anilino-(2 S )-2-phenyl-2-(2´-(3´-methyl)pyridyl)cyclopentane III-3 in 87% yield and 71% enantiomeric excess. NMR and mass spectrometry data are: 1 HNMR (300 MHz, CD 2 Cl 2 ) δ 8.37 (d, J = 4.0 Hz, 1H), 7.42 – 7.18 (m, 4H), 7.07(dd, J = 14.9, 7.4 Hz, 5H), 6.58 (dd, J = 13.8, 7.4 Hz, 3H), 5.26 – 5.12 (m,1H), 3.23 (br, 1H), 3.04 – 2.73 (m, 1H), 2.25 (dt, J = 12.8, 6.6 Hz, 1H),2.18 – 2.03 (m, 1H), 1.96 (d, J = 6.6 Hz, 1H), 1.76 (s, 3H), 1.71 – 1.59 (m,1H), 1.49 (td, J = 18.9, 9.4 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 163.7, 144.8,143.1, 139.7, 132.0, 128.8, 128.2, 128.1, 126.5, 121.4, 114.0, 60.6, 34.5,30.6, 26.9, 21.0, 20.1; HRMS (ES...

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Abstract

The invention discloses (1R)-phenylamino-(2S)-2-aryl-2-aza-aryl cyclopentane and a preparation method and application thereof. During preparation, N-phenylcyclopropane, 2-(1-aryl vinyl) aza-aromatic hydrocarbon, a photosensitizer DPZ and a chiral catalyst BA are dispersed in an organic solvent, after degassing treatment is conducted under the condition that the temperature is not higher than-78 DEG C, the mixture is placed at the temperature of 20-30 DEG C under the protective atmosphere, irradiation is conducted with a 3-10W blue lamp, the reaction is conducted for 8-12 h, and the (1R)-phenylamino-(2S)-2-aryl-2-aza-aryl cyclopentane is obtainedby separating and purifyingafter the reaction is finished. The enantiomeric excess of the target product is more than 70%, the yield is more than 80%, the reaction conditions are mild, and no pollution is caused.

Description

technical field [0001] The invention belongs to the technical field of chiral quaternary carbocyclopentane synthesis, and specifically relates to a (1 R )-anilino-(2 S )-2-aryl-2-azarylcyclopentane, its preparation method and application. Background technique [0002] Pyridine, isoquinoline, benzimidazole and other azaaryl structural units widely exist in molecular structures such as pharmaceuticals, pesticides, natural and non-natural products with biological activity ( Nat. Chem. 2013, 5 , 54–60; science 1963, 142 ,24−33; Nature 1964, 201 , 639−640; Nature 1968, 217 , 562−563; Nature 1969, 223 , 785−788). According to statistics, nearly half of the top 200 commercially available chemical drugs in the world contain azaaryl structural units. It can be said that "there is no medicine without nitrogen". Amino structural units are also widely found in nature. The combination of these two types of structural units has potential application value in drug developm...

Claims

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Application Information

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IPC IPC(8): C07D213/38C07D215/12C07D235/14A61P35/00
CPCC07D213/38C07D215/12C07D235/14A61P35/00
Inventor 乔保坤江智勇赵筱薇
Owner HENAN UNIVERSITY