A kind of preparation method of adenosine monophosphate arabinoside

A technology for adenosine monophosphate and adenosine monophosphate wet crude product is applied in the field of preparation of adenosine monophosphate, which can solve the problems of complex process operation, affecting product yield and final product quality, etc. Simple process, low cost, high yield and high purity

Active Publication Date: 2020-04-21
HAINAN HULUWA PHARMA GRP CO LTD
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The method is complex in process operation, and mercaptolation and hydrogenation are prone to produce by-product ammonia, which affects the yield of the product and the quality of the final product.

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
  • A kind of preparation method of adenosine monophosphate arabinoside
  • A kind of preparation method of adenosine monophosphate arabinoside
  • A kind of preparation method of adenosine monophosphate arabinoside

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Synthesis of vidarabine monophosphate crude product:

[0032] 1. Prepare an aqueous sodium hydroxide solution with a mass fraction of 40%. Add 37.5 kg of purified water to a 50 L reaction kettle, add 15.0 kg of sodium hydroxide in portions under stirring, stir and dissolve for later use.

[0033] 2. Add 10.0 kg of β-D-adenosine vidarabine and 100.0 kg of triethyl phosphate into a 200L reaction tank, and cool down to -10°C.

[0034] 3. Add 10.2 kg of phosphorus oxychloride dropwise under stirring, control the temperature not higher than 0°C, and complete the dropwise addition within 3 to 5 hours; after the dropwise addition, stir and react at -5°C for 90 minutes, TLC detects that the reaction reaches the end point, stop reaction.

[0035] 4. Slowly pump the reaction solution into a 500L reaction tank (with 150kg of purified water pre-frozen to 0°C), and control the temperature not higher than 15°C.

[0036] 5. Cool down to 0°C, add dropwise NaOH aqueous solution with a...

Embodiment 2

[0049]Synthesis of vidarabine monophosphate crude product:

[0050] 1. Prepare an aqueous sodium hydroxide solution with a mass fraction of 40%. Add 37.5 kg of purified water to a 50 L reaction kettle, add 15.0 kg of sodium hydroxide in portions under stirring, stir and dissolve for later use.

[0051] 2. Add 10.0 kg of β-D-arabinoadenosine and 100.0 kg of triethyl phosphate into a 200L reaction tank, and cool down to -13°C.

[0052] 3. Add 10.2 kg of phosphorus oxychloride dropwise under stirring, control the temperature not higher than 0°C, and complete the dropwise addition within 3 to 5 hours; after the dropwise addition is completed, stir and react at -2.5°C for 120 minutes, and stop when the reaction reaches the end point by TLC. reaction.

[0053] 4. Slowly pump the reaction liquid into a 500L reaction tank (with 150kg of purified water pre-frozen to 1.5°C), and control the temperature not higher than 15°C.

[0054] 5. Cool down to 0°C, add dropwise NaOH aqueous solut...

Embodiment 3

[0067] Synthesis of vidarabine monophosphate crude product:

[0068] 1. Prepare an aqueous sodium hydroxide solution with a mass fraction of 40%. Add 37.5 kg of purified water to a 50 L reaction kettle, add 15.0 kg of sodium hydroxide in portions under stirring, stir and dissolve for later use.

[0069] 2. Add 10.0 kg of β-D-adenosine vidarabine and 100.0 kg of triethyl phosphate into a 200L reaction tank, and cool down to -15°C.

[0070] 3. Add 10.2 kg of phosphorus oxychloride dropwise under stirring, control the temperature not higher than 0°C, and complete the dropwise addition within 3 to 5 hours; after the dropwise addition, stir and react at -0°C for 150 minutes, and stop the reaction when it reaches the end point by TLC detection reaction. Add 10.2 kg of phosphorus oxychloride dropwise under stirring, and control the temperature not higher than 0°C.

[0071] 4. Slowly pump the reaction solution into a 500L reaction tank (with 150kg of purified water pre-frozen to 2°C...

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

PropertyMeasurementUnit
specific rotationaaaaaaaaaa
Login to view more

Abstract

The invention discloses a preparation method of vidarabine monophosphate. The preparation method comprises the following two steps: crude product synthesis and crude product refining. In a crude product synthesis stage, reaction conditions are controlled severely, side reaction and production of related substances are reduced effectively, and high percent conversion of a target product is ensured.Meanwhile, because most of side products of reaction are dissolved in the reaction system and the target product is not dissolved in the reaction system basically, aftertreatment is facilitated to improve the purity of the product. The method is simple in process, high in product yield, high in purity and high in reaction selectivity; any special equipment is not used during production; and the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of raw material drug preparation, in particular to a preparation method of adenosine vidarabine monophosphate. Background technique [0002] Vidarabine monophosphate, chemical name: 9-(β-D-arabinofuranosyl) adenine 5'-monophosphate, molecular formula: C 10 h 14 N 5 o 7 P·H 2 O, molecular weight: 365.26, chemical structure formula is as follows: [0003] [0004] Adenosine monophosphate is a nucleotide antiviral drug, which is the second-generation preparation of adenosine vidarabine (Ara-A), which can selectively inhibit the activity of viral polymerase and nucleotide reductase, and has a wide range of antiviral effects on DNA viruses. Inhibitory effect, and its water solubility is obviously better than Ara-A, it is an effective and safe antiviral drug for the treatment of hepatitis B, especially for chronic hepatitis B. [0005] Adenosine monophosphate is an anti-deoxyribonucleic acid (DNA) virus drug, and i...

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 Patents(China)
IPC IPC(8): C07H19/20C07H1/00
CPCC07H1/00C07H19/20
Inventor 刘景萍刘全国陈克领林文君王家李党
Owner HAINAN HULUWA PHARMA GRP CO LTD
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