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

Preparation method of quinolizinones compound

A compound, the technology of quinozinone, applied in the field of preparation of quinozinone compounds, can solve the problems of low yield of cis structure, difficult preparation of compounds, high cost of raw materials, etc.

Active Publication Date: 2017-07-07
河南春风医药科技有限公司
View PDF4 Cites 25 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The problem that this preparation method exists comprises: (1) formula I 2 The compound is not easy to prepare, and the raw material cost is higher; (2) by formula Ⅰ 2 Reductive amination of the compound of formula I 1 When the compound, the carbonyl carbon atom becomes a chiral carbon, there are two isomers R and S, the stereoselectivity of the reductive amination process is not high, and finally leads to the target product formula Ⅰ 0 The compound stereoselectivity is not high
Due to the existence of trans isomers, the method disclosed in this patent document has a low yield of preparing cis structures

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 quinolizinones compound
  • Preparation method of quinolizinones compound
  • Preparation method of quinolizinones compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1 cis-10-methoxy-11-(3-methoxypropoxy)-3,3-dimethyl-7-oxo-3,3a,7,12b-tetrahydro-2H- Preparation of Furo[3,2-c]pyrido[2,1-a]isoquinazine-6-carboxylic acid

[0087] The synthetic route is as follows:

[0088]

[0089] Step 1: Preparation of 6-(2-Hydroxy-1,1-dimethyl-ethyl)-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7 -Ethyl dihydrobenzo[a]quinazine-3-carboxylate

[0090] 6-(2-Benzyloxy-1,1-dimethyl-ethyl)-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7- Ethyl dihydrobenzo[a]quinazine-3-carboxylate (1.65g, 3mmol, preparation reference patent US20160122344A1), and Pd / C (10%) (0.5g) were slowly added to ethanol (200mL), under a hydrogen atmosphere Press down and stir mechanically to obtain crude 6-(2-hydroxy-1,1-dimethyl-ethyl)-10-methoxy-9-(3-methoxypropoxy)-2- Ethyl oxo-6,7-dihydrobenzo[a]quinazine-3-carboxylate (1.10 g, yield about 79.7%) was directly used in the next step without purification.

[0091] 1 H NMR (400MHz, CDCl 3 )δ:8.43(s,1H),7.12(s,1H),6.89(s,1H),6....

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 method for preparing a quinolizinones compound in a formula I, which comprises: S (A), oxidizing a compound in a formula III in a solvent under the action of an oxidizing agent and under the electro-oxidation and reduction condition or under the photo-oxidation and reduction condition, and then processing the compound by acid to obtain a ringed syn-oxime compound in a formula II; and S (B), carrying out hydrolysis on the compound in the formula II to obtain the compound in the formula I. The invention further discloses another method for preparing the quinolizinones compound in the formula I on the basis of the same conception. The two methods have key points that before oxidative cyclization, a pyrazine ring is closed in a raw material compound, and due to the influence of a steric hindrance, when oxidative cyclization is carried out to form a five-membered ring, ring closing can only be carried out selectively at the same side of the pyrazine ring so as to obtain a syn-oxime structure, i.e., a syn-oxime isomer can be highly selectively generated.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of quinozinone compounds for treating and preventing hepatitis B virus infection. Background technique [0002] Formula I is disclosed in recently published PCT patent application WO 2017 / 017042A1 0 A class of quinazinone compounds with anti-HBV activity shown, [0003] [0004] Formula I disclosed in this patent document 0 In the preparation method of the compound, use formula I 2 The compound is the starting material, and the formula I is first obtained by reductive amination 1 The compound of formula Ⅰ is obtained through two steps of ring closure, dehydrogenation and hydrolysis 0 compound of. [0005] [0006] The problem that this preparation method exists comprises: (1) formula I 2 The compound is not easy to prepare, and the raw material cost is higher; (2) by formula Ⅰ 2 Reductive amination of the compound of formula I 1 When the compou...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D455/06C07D455/03C07D491/147A61P31/20
CPCC07B2200/07C07D455/03C07D455/06C07D491/147
Inventor 李定芳程森祥郭应臣
Owner 河南春风医药科技有限公司
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