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Method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by chiral phosphoric acid

A technology of phosphoric acid-catalyzed quinoline and chiral exocyclic amines, applied in the direction of organic chemistry, etc., to achieve the effects of complete conversion of raw materials, mild reaction conditions, and easy availability of raw materials

Active Publication Date: 2015-10-28
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the aromatic stability of aromatic amines and the special coordination of amine groups, there are few reports on the asymmetric reduction of aromatic amines.
In 2014, our group used a homogeneous iridium catalyst to successfully realize the asymmetric hydrogenation of quinolin-3-amine with an alkyl group at the 2-position, with a maximum ee value of 94%. However, for the phenyl group at the 2-position substrate, the reaction only achieved moderate enantioselectivity (Reference 1: Cai, X.-F.; Guo, R.-N.; Chen, M.-W.; Shi, L.; Zhou, Y. -G.Chem.Eur.J.2014, DOI: 10.1002 / chem.201402592)

Method used

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  • Method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by chiral phosphoric acid
  • Method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by chiral phosphoric acid
  • Method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by chiral phosphoric acid

Examples

Experimental program
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Effect test

Embodiment

[0026] Example: Chiral phosphoric acid catalyzed asymmetric transfer hydrogenation of quinoline-3-amine to synthesize various chiral exocyclic amine compounds

[0027] Under nitrogen protection, add quinoline-3-amine (1), Hantzsch ester (2.4eq.) and chiral phosphoric acid ((S)-TRIP, 5mol%) into the Schlenk tube with a volume ratio of 2:1 3 milliliters of mixed solvents of 1,4-dioxane and dichloromethane, stirred and reacted at 25 ℃ for 24 hours afterwards, column chromatography (eluent: sherwood oil and ethyl acetate) after removing solvent with rotary evaporator The volume ratio is 10:1-5:1) to obtain pure product, and the reaction formula is as follows.

[0028]

[0029] 4-Methyl-N-((2S,3S)-2-phenyl-1,2,3,4-tetrahydroquinolin-3-yl)benzonesulfonamide(2a):94%yield,95%ee,white solid,mp175- 177℃,[α] 20 D =+73.2(c0.88,CH 2 Cl 2 ), R f =0.40(petroleum ether / EtOAc5:1). 1 H NMR (400MHz, CDCl 3 )δ=7.35(d,J=8.2,2H),7.25-7.17(m,5H),7.04(t,J=8.8,3H),6.93(d,J=7.4,1H),6.72(t,J ...

Embodiment 2

[0043] Embodiment 2: the synthesis of a kind of substance P antagonist 4

[0044] Under the protection of nitrogen, under the condition of vigorous stirring, add naphthalene (2.00 mmol) to the 4 mL tetrahydrofuran solution added with Na (2.00 mmol), after 1 hour, transfer it to a constant pressure dropping funnel, Under the condition of ℃, drop it into 4mL tetrahydrofuran solution dissolved with 2a (0.10 mmol), after the reaction is complete (about 1 hour), stop the reaction, add 10mL water to quench the reaction, separate the layers, and extract the aqueous phase with dichloromethane, The organic phases were combined, dried with anhydrous sodium sulfate, filtered, and spin-dried, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and then the solvent was removed by rotary evaporation, and the pure product 3 was obtained by column chromatography.

[0045] Under nitrogen protection, compound 3 (0.10 mmol) and NaBH (OAc) 3 (0.30 mmol) was dissolved i...

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Abstract

A catalysis system used in a method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by chiral phosphoric acid adopts chiral phosphoric acid as a catalyst and substituted 1,4-dihydropyridine (HEH ester) as a hydrogen source. Transfer hydrogenation of simple and easily available substituted quinolin-3-amine is carried out in the system to obtain the cyclic amine compound containing two continuous chiral centers, and the enantiomer excess value can reach 99%. The method has the advantages of simple operation, good diastereoselectivity / enantioselectivity, high yield, and green, atom-economic and environmentally-friendly reaction.

Description

technical field [0001] The invention relates to a method for synthesizing chiral exocyclic amine compounds containing two continuous chiral centers through the asymmetric transfer hydrogenation of quinoline-3-amine catalyzed by chiral phosphoric acid. Background technique [0002] Chiral exocyclic amine compounds are widely used as a class of very useful reaction intermediates in organic synthetic chemistry. In addition, many compounds with physiological and pharmacological activities contain such structures. Therefore, the synthesis of chiral exocyclic amine compounds has high research value and application prospects. [0003] In view of the simple and easy-to-obtain characteristics of aromatic amine compounds, asymmetric reduction of such compounds will provide a direct and effective way to prepare the corresponding chiral exocyclic amine compounds. However, due to the aromatic stability of aromatic amines and the special coordination of amine groups, there are few report...

Claims

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Application Information

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IPC IPC(8): C07D215/38
CPCC07D215/38
Inventor 周永贵蔡先锋郭冉柠陈木旺
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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