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

Preparation method of tetrahydro 1, 8-naphthyridine compound and chiral product prepared by adopting preparation method

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

Active Publication Date: 2015-12-02
INST OF CHEM CHINESE ACAD OF SCI
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

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
  • Preparation method of tetrahydro 1, 8-naphthyridine compound and chiral product prepared by adopting preparation method
  • Preparation method of tetrahydro 1, 8-naphthyridine compound and chiral product prepared by adopting preparation method
  • Preparation method of tetrahydro 1, 8-naphthyridine compound and chiral product prepared by adopting preparation method

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

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

[0022]

[0023] Among them, R 1 , R 2 and R 3 each 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 Connect 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, nitro One or more of radical, methyl, methoxy, trifluoromethyl, hydroxyl and acetamido; and, R 1 not hydrogen;

[0024]

[0025] Wherein, M i...

preparation example 1

[0137] (1) Dissolve (R,R)-1,2-diphenyl-ethylenediamine (20mmol, purchased from Bailingwei Technology Co., Ltd. 24694 brand) in dichloromethane (30mL), and dissolve in P-methylphenylsulfonyl chloride (20mmol, purchased from Bailingwei Technology Co., Ltd. 283322 brand) in dichloroethane (30mL) was added dropwise (dropped within 30min), continued to react 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), so as to obtain 15 mmol of the formula (R, R)-(3-1-1-1) The chiral diamine shown has a yield of 75%, and the identification data of this chiral diamine is: 1 HNMR (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 CNMR (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, 60.5, 21.4.

...

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 Aisha Chemical Co., Ltd. A13383 brand) is used instead of p-methylphenylsulfonyl chloride, and Reaction at 0°C for 1 h, thereby obtaining 14.6 mmol of chiral diamine represented by the formula (R,R)-(3-1-1-2), with a yield of 73%. The identification data of the chiral diamine for: 1 HNMR (300MHz, CDCl 3 ): δ7.34-7.26(m, 10H), 4.56(d, J=5.1Hz, 2H), 4.21(d, J=5.1Hz, 2H), 2.26(s, 3H); 13 CNMR (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 shown in the above formula (R, R)-(3-1-1-2) (145 mg, 0.5 mmol), recrystallized to obtain 275 mg of a red solid (ie, the complex shown in formula (R, R)-4j);

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

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 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 tetrahydro-1,8-naphthyridine compounds and a chiral product thereof. Background technique [0002] At present, the R&D, 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 structures 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 community and organic synthetic chemists, and a variety of asymmetric synthetic methods have been reported. Among them, chiral heterocyclic compounds are prepared by asymmetric catalytic hydrogenation of aromatic heterocyclic compounds. Sexual heterocyclic compounds are one of the most atom-economical and efficie...

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): C07D471/04
CPCC07D471/04
Inventor 范青华马文鹏陈飞何艳梅
Owner INST OF CHEM CHINESE ACAD OF SCI
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