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A kind of preparation method of tetrahydro-1,8-naphthyridine compound and the chiral product thereof

A compound and naphthyridine technology are applied in the preparation of tetrahydro 1,8-naphthyridine compounds and the field of the prepared chiral products, and can solve problems such as catalyst poisoning

Active Publication Date: 2018-02-09
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the asymmetric hydrogenation of polyaromatic heterocyclic compounds containing multiple heteroatoms still faces great challenges, mainly because polyaromatic heterocyclic compounds not only have very stable conjugated structures, but also have multiple Heteroatoms that can coordinate with transition metals have stronger coordination ability than simple aromatic heterocycles and are more likely to cause catalyst poisoning
Therefore, there are only a few reports on the asymmetric catalytic hydrogenation of polyaromatic heterocyclic compounds.

Method used

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  • A kind of preparation method of tetrahydro-1,8-naphthyridine compound and the chiral product thereof
  • A kind of preparation method of tetrahydro-1,8-naphthyridine compound and the chiral product thereof
  • A kind of preparation method of tetrahydro-1,8-naphthyridine compound and the chiral product thereof

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Experimental program
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preparation example Construction

[0021] The present invention provides a method for preparing tetrahydro 1,8-naphthyridine compounds, wherein the method includes: in the presence of a chiral catalyst, the compound of the structure represented by formula (1) is subjected to an addition reaction with hydrogen, wherein , The chiral catalyst is a complex with the structure represented by formula (2);

[0022]

[0023] Where R 1 , R 2 And R 3 Each is independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted arylbenzyl Base, or R 2 And R 3 Linked to form a C5-C8-membered alkane ring, wherein the substituents in the substituted alkyl, substituted cycloalkyl, substituted aryl and substituted arylbenzyl are each independently selected from fluorine, chlorine, bromine, and nitro One or more of group, methyl group, methoxy group, trifluoromethyl group, hydroxyl group and acetamido group; and, R 1 Not ...

preparation example 1

[0137] (1) Dissolve (R,R)-1,2-diphenyl-ethylenediamine (20mmol, 24694 brand from Bailingwei Technology Co., Ltd.) in dichloromethane (30mL), and dissolve in dichloromethane (30mL) at 0℃ The p-methylphenylsulfonyl chloride (20mmol, purchased from Bailingwei Technology Co., Ltd. 283322 brand) in dichloroethane (30mL) was added dropwise to it (dropped within 30min), and the reaction was continued at 0°C for 1h, and then reduced pressure Rotary evaporation, the solid was separated and purified by column chromatography (the eluent was dichloromethane / methanol with a volume ratio of 10:1) to obtain 15 mmol of the formula (R, R)-(3-1-1-1) The chiral diamine shown has a yield of 75%. The identification data of the chiral diamine is: 1 H NMR(300MHz, CDCl 3 ):δ7.31(d,J=8.3Hz,2H), 7.18-7.09(m,10H), 6.97(d,J=8.3Hz,2H), 4.37(d,J=5.2Hz,1H), 4.12 (d,J=5.2Hz,1H),2.32(s,3H),1.49(br,3H); 13 C NMR(75MHz, CDCl 3 ): δ142.5, 139.2, 137.2, 129.1, 128.4, 128.2, 127.5, 127.4, 127.0, 126.9, 126.6, 63.2,...

preparation example 2

[0141] (1) According to the method of step (1) in Preparation Example 1, the difference is that methanesulfonyl chloride (20mmol, purchased from Alfa Aesar Chemical Co., Ltd. A13383 brand) is used instead of p-methylphenylsulfonyl chloride, and Reacted at 0°C for 1 hour to obtain 14.6mmol of the chiral diamine represented by the formula (R,R)-(3-1-1-2) with a yield of 73%. Identification data of the chiral diamine for: 1 H NMR(300MHz, CDCl 3 ): δ7.34-7.26 (m, 10H), 4.56 (d, J = 5.1 Hz, 2H), 4.21 (d, J = 5.1 Hz, 2H), 2.26 (s, 3H); 13 C NMR(75MHz, CDCl 3 ): δ141.9, 139.7, 128.7, 128.6, 127.9, 127.8, 126.9, 126.7, 63.4, 60.2, 40.7.

[0142] (2) According to the method of step (2) in Preparation Example 1, the difference is that the chiral diamine used is the chiral diamine represented by the above formula (R,R)-(3-1-1-2) (145mg, 0.5mmol), recrystallized to obtain 275mg of a red solid (ie the complex represented by formula (R, R)-4j);

[0143] (3) According to the method of step (3) i...

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Abstract

The invention discloses a preparation method of a tetrahydro 1, 8-naphthyridine compound. The preparation method comprises the following steps: under the existence of a chiral catalyst, enabling a compound with the structure shown in the formula (1) (in the description) and hydrogen to be subjected to addition reaction, wherein the chiral catalyst is a coordination compound with the structure shown in the formula (2) (in the description). The invention further provides a chiral product of the tetrahydro 1, 8-naphthyridine compound, prepared through the preparation method. According to the invention, the proper compound with the structure shown in the formula (1) (in the description) is used as a substrate, and the proper coordination compound with the structure shown in the formula (2) (in the description) is used as the chiral catalyst to perform selective hydrogenation reduction on 1, 8-naphthyridine compound with the structure shown in the formula (1) by adopting hydrogen, so that the chiral product of the tetrahydro 1, 8-naphthyridine compound is prepared with low cost. The chiral product of the tetrahydro 1, 8-naphthyridine compound can be used as a biologically active compound and a structural building block of a chiral drug.

Description

Technical field [0001] The invention relates to a preparation method of 1,8-naphthyridine tetrahydrogen compounds and chiral products prepared therefrom. Background technique [0002] At present, the development, production and sales of chiral drugs have become the mainstream of the development of the global pharmaceutical industry (A.M. Rouhi, "Chiral Chemistry", Chem. Eng. News 2004, 82, 47). Chiral heterocyclic compounds are the skeleton structure of many biologically active compounds and chiral drugs, and have high research value and application prospects. The high-efficiency asymmetric synthesis of chiral heterocyclic compounds has attracted great attention from the pharmaceutical circles and synthetic organic chemists. There have been many reports of asymmetric synthesis methods. Among them, the preparation of chiral heterocyclic compounds by asymmetric catalytic hydrogenation Sexual heterocyclic compounds are one of the most atomically economical and efficient synthetic m...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 范青华马文鹏陈飞何艳梅
Owner INST OF CHEM CHINESE ACAD OF SCI
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