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

Preparation method of antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate

A kind of technology of chloromethyl isopropyl carbonate and tenofovir disoproxil, applied in the field of preparation of intermediates, can solve the complex steps, high cost, rarely reported chloromethyl chloroformate or chloromethyl isopropyl Carbonate synthesis and other problems, to achieve the effects of high reactivity, improved yield and low cost

Inactive Publication Date: 2012-04-04
扬州三友合成化工有限公司
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its methyl chloroformate is still prepared by the reaction of phosgene and methanol, the steps are cumbersome and the cost is high
[0010] Foreign relevant patent literature is seldom reporting the synthesis of chloromethyl chloroformate or chloromethyl isopropyl carbonate

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 antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate
  • Preparation method of antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate
  • Preparation method of antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 1. Synthesis of methyl chloroformate and chloromethyl formate mixture:

[0041] Under nitrogen protection, with magnetic stirring, add 500 g methyl formate and 4 g AIBN into a 1000 mL four-neck flask, connect with condensed water, heat directly to reflux state, pass Cl 2 , the tail gas uses 20% NaOH solution to absorb the discharged HCl gas. It takes about 8-10h to complete the first step of chlorination of methyl formate. On gas chromatography (GC), it was completely converted into methyl chloroformate and chloromethyl formate with a ratio close to 1:1. The mixed product is reserved for later use.

[0042] 2. Synthesis of chloromethyl chloroformate:

[0043] Add the entire mixture of methyl chloroformate and chloromethyl formate obtained above, add 4g of AIBN again, and feed chlorine gas again under reflux (60-80°C), when the main peak of chloromethyl chloroformate reaches 75-80% content At this time, the dichloromethyl chloroformate has reached about 2%, and ...

Embodiment 2

[0047] 1. Synthesis of methyl chloroformate and chloromethyl formate mixture:

[0048] Under nitrogen protection, with magnetic stirring, add 500 g methyl formate and 4 g BPO into a 1000 mL four-necked flask, connect with condensed water, heat directly to reflux state, pass Cl 2 , the tail gas uses 20% NaOH solution to absorb the discharged HCl gas. It takes about 8-10h to complete the first step of chlorination of methyl formate. On GC, it is completely converted to methyl chloroformate and chloromethyl formate, the ratio of which is close to 1:1. The mixed product is reserved for later use.

[0049] 2. Synthesis of chloromethyl chloroformate:

[0050]Add the entire mixture of methyl chloroformate and chloromethyl formate obtained above, add 4g of BPO again, and feed chlorine gas again under reflux (60-80°C), when the main peak of chloromethyl chloroformate reaches 75-80% content At this time, the dichloromethyl chloroformate has reached about 2%, and the reaction is...

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 antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate, and belongs to the field of antiviral chemical drugs. The preparation method is characterized in that methyl formate as a raw material is synthesized into chloromethyl chloroformate by an one-kettle method and the chloromethyl chloroformate undergoes an esterification reaction to form chloromethyl isopropyl carbonate. The preparation method is easy for operation, has a low cost and a high yield, realizes high purity of products, and is very suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of antiviral chemical drugs, and in particular relates to a preparation method of an intermediate of tenofovir disoproxil, an anti-hepatitis B and HIV virus drug. Background technique [0002] Tenofovir disoproxil fumarate, tenofovir disoproxil fumarate, chemical name (R)-[[2-(6-amino-9H-purine-9- Base]-l-methylethoxy]methyl]phosphonic acid bis(isopropionyloxymethyl)fumarate is a nucleotide reverse transcriptase inhibitor developed by Gilead Sciences in the United States. The prodrug of the oral open ring nucleotide monophosphonate has the following structural formula: [0003] [0004] Tenofovir disoproxil is rapidly converted to tenofovir (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA) after oral absorption. PMPA has been confirmed to have broad-spectrum antiviral activity against human immunodeficiency virus HIV and other retroviruses, and has been approved by the US FDA in 2001 as a drug for clinical treatme...

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): C07C69/96C07C68/00
Inventor 魏开举李明成张扬张众笑李辉宁张才山
Owner 扬州三友合成化工有限公司
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