Preparation method of oxazepine compound

A compound and alkoxy technology, which is applied in the field of preparation of oxazepine compounds, can solve the problems of poor curative effect of HBsAg and achieve the effect of high yield

Active Publication Date: 2021-02-23
푸지엔에이키링크바이오테크놀로지컴퍼니리미티드
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing clinical therapies are not effective in reducing HBsAg. Therefore, the development of small-molecule oral inhibitors that can effectively reduce HBsAg is urgently needed in clinical medicine.

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 oxazepine compound
  • Preparation method of oxazepine compound
  • Preparation method of oxazepine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Embodiment 1: the preparation of compound 4

[0079]

[0080] Step 1: Compound 2

[0081] In a 50L reactor, add ethanol (6.0L) and water (6.0L) at room temperature, and then add compound 1 (3000.00g, 22.871mol), stir evenly, and insoluble. Sodium hydroxide (1006.20 g, 25.155 moles) was dissolved in water (6.0 liters), and the temperature was controlled at 20-30° C., and slowly added dropwise to the reaction kettle, and the dripping was completed in about 0.5 hours. Will Boc 2 O (5989.80 g, 27.445 mol) was dissolved in ethanol (3.0 liters), and the temperature was controlled at 20-30°C, and slowly added dropwise to the reaction kettle, and the drop was completed in about 1 hour. Stir and react at a temperature of 25-30°C for 16 hours. TLC central control detects that the reaction is complete. The reaction solution is depressurized at -0.095Mpa and rotated at 50°C to evaporate a mixture of ethanol and water (9.2 liters). Add ethyl acetate to the concentrate Esters (...

Embodiment 2

[0089] Embodiment 2: the preparation of compound 6

[0090]

[0091] In a 50L reaction kettle, add water (20.0 liters) at room temperature, add compound 5 (4025.94 g, 21.634 moles), and control the temperature at 26-35 ° C to stir and react for 4 hours. The HPLC central control detects that the reaction is complete, and the reaction solution is allowed to stand , separate the lower organic phase, extract the upper aqueous phase with methyl tert-butyl ether (4.0 liters * 2), separate the layers, combine the organic phases, wash with saturated brine (4.0 liters), and wash the organic phase with anhydrous sodium sulfate ( 1500.00 g) was dried, filtered, and the mother liquor was collected, and decompressed at -0.095Mpa. Rotary evaporation was performed at 45°C, the solvent was removed, and the mixture was concentrated to obtain light yellow liquid compound 6 (3230.13 g, yield 93.89%, purity 99.397%).

[0092] 1H NMR (400MHz, CHLOROFORM-d) δ=9.21(d, J=6.0Hz, 1H), 4.27(q, J=7.2...

Embodiment 3

[0093] Embodiment 3: the preparation of compound 13

[0094]

[0095] Step 1: Compound 8

[0096] In a 50L reactor, add absolute ethanol (20.0 liters) and water (10.0 liters) at room temperature, then add compound 7 (5000.00 grams, 32.226 moles), potassium carbonate (4946.65 grams, 35.450 moles) and 1-bromo- 3-Methoxypropane (5601.50 g, 35.450 mol), stirred well. The temperature was raised to 75-85°C for reflux reaction for 16 hours, and the reaction was completed by the HPLC control detection. The reaction liquid was depressurized at -0.095Mpa, and 50°C was rotary evaporated to distill off the mixture of ethanol and water (22.0 L). Add water (15.0 L) to the concentrated solution to dilute, extract with ethyl acetate (15.0 L), separate the layers, wash the ethyl acetate layer with saturated brine (10.0 L), separate the layers, and use anhydrous sodium sulfate for the organic phase (2.0 kg) was dried, filtered, and the mother liquor was collected, decompressed at -0.095Mp...

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 an oxazepine compound, and particularly discloses a preparation method and an intermediate of a compound shown as a formula (I) in the specification.

Description

technical field [0001] The invention relates to a preparation method of oxazepine compounds. Background technique [0002] Hepatitis B virus, referred to as hepatitis B, is a disease caused by hepatitis B virus (Hepatitis B Virus, HBV) infection after the body. Hepatitis B virus is a hepatotropic virus that mainly exists in liver cells and damages liver cells, causing inflammation, necrosis, and fibrosis of liver cells. There are two types of hepatitis B: acute and chronic. Most acute hepatitis B can be cured by its own immune mechanism in adults. However, chronic hepatitis B (CHB) has become a great challenge to global health care, and it is also the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). It is estimated that 2 billion people in the world are infected with chronic hepatitis B virus, more than 350 million people have developed into hepatitis B, and nearly 600,000 people die of complications of chronic hepatitis B every year. my...

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): C07D498/04
CPCC07D498/04A61K31/553A61P1/16
Inventor 胡彦宾孙飞丁照中
Owner 푸지엔에이키링크바이오테크놀로지컴퍼니리미티드
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap