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

Synthesis method of stable deuterium-labeled melitracen hydrochloride

A technology of melitracen hydrochloride and synthesis method, which is applied in the field of synthesis of melitracen hydrochloride, and achieves the effects of large application research value, reasonable process design and strong operability

Active Publication Date: 2021-07-13
TLC NANJING PHARMA RANDD CO LTD
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

What existing bibliography reports is all the synthetic method of unmarked melitracen hydrochloride, and the method used in the present invention is different; There is no synthetic method of the isotope-labeled melitracen hydrochloride of bibliographical report at present

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
  • Synthesis method of stable deuterium-labeled melitracen hydrochloride
  • Synthesis method of stable deuterium-labeled melitracen hydrochloride
  • Synthesis method of stable deuterium-labeled melitracen hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Such as figure 1 Shown, a kind of synthetic method of the melitracen hydrochloride of stable deuterium label comprises the following steps:

[0031] (1) Take 20.0 g of commercially available 10,10-dimethylanthrone I, add it to a 500 mL round bottom flask, dissolve it with 100 mL of dry ether, add commercially available cyclopropylmagnesium bromide (1M in THF) , After the dropwise addition, react at 35°C for 12 hours; TLC board monitors the complete reaction of the raw materials, process and purify, and obtain 21.2g of intermediate II, MS: 265.2[M+1] + , yield 89.25%;

[0032]

[0033] (2) Dissolve 20.0g of intermediate II in 80mL of formic acid, slowly add 48% hydrobromic acid under ice bath conditions, and then react at 60°C for 8 hours. TLC board monitors the complete reaction of the raw materials, process them out, and purify by column chromatography , to obtain 22.0g of intermediate III, the yield is 88.86% (X=Br); 1H NMR (400MHz, CDCl3) of intermediate III: δ7...

Embodiment 2

[0040] Such as figure 1 Shown, a kind of synthetic method of the melitracen hydrochloride of stable deuterium label comprises the following steps:

[0041] (1) Take 20.0 g of commercially available 10,10-dimethylanthrone I, add it to a 500 mL round bottom flask, dissolve it in 100 mL of dry tetrahydrofuran, add dropwise 130 mL of commercially available cyclopropylmagnesium chloride (1M in THF) , after the dropwise addition was completed, the oil bath was reacted at 60 degrees for 6 hours; the TLC board monitored the reaction of the raw materials, quenched the reaction, and purified by column chromatography to obtain 18.0 g of intermediate II, which was a light brown oil with a yield of 75.78%; the intermediate The structure of II is as follows, MS: 265.2[M+1] + .

[0042]

[0043] (2) Dissolve 10.0 g of intermediate II in 40 mL of acetic acid, slowly add 15 mL of commercially available concentrated hydrochloric acid with a concentration of 36% under ice bath conditions, a...

Embodiment 3

[0050] Such as figure 1 Shown, a kind of synthetic method of the melitracen hydrochloride of stable deuterium label comprises the following steps:

[0051] (1) Take 20.0g of commercially available 10,10-dimethylanthrone I, put it into a 500mL round bottom flask, dissolve it with 100mL of dry tetrahydrofuran, add dropwise commercially available cyclopropylmagnesium bromide (1M in THF ) 120mL, after the dropwise addition, put the oil bath at 50 degrees to react for 8 hours; the TLC board monitors the reaction of the raw materials completely, quenches the reaction, and purifies by column chromatography to obtain 19.2g of intermediate II, which is a light brown oil, with a yield of 80.83% ; The structure of intermediate II is as in Example 1, MS: 265.2[M+1] + .

[0052]

[0053] (2) Dissolve 15.0g of intermediate II in 75mL of ethanol, slowly add 15mL of commercially available hydriodic acid with a concentration of 55% under ice bath conditions, and then react at 60°C for 24 ...

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 synthesis method of stable deuterium-labeled melitracen hydrochloride, belongs to the field of stable isotope labeling of drugs, and provides a synthesis method which is reasonable in process design, high in operability and high in yield, can efficiently convert isotope-labeled raw materials into labeled target products and can realize industrial production of the isotope-labeled melitracen hydrochloride. According to the method, methylamine hydrochloride labeled by deuterium 6 is used as a starting raw material, the methylamine hydrochloride marked by deuterium 6 is synthesized through four-step reaction, optimal preparation steps and reaction conditions are screened out through a large number of experiments, the whole process is reasonable in design and high in operability, the marked raw material can be efficiently converted into a marked target product, and the marked melitracen hydrochloride prepared by the method is suitable for industrial production; and the chemical purity can reach 98.5% or above, and the abundance of the labelled isotope is larger than 98.5%.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a method for synthesizing stable deuterium-labeled melitracen hydrochloride. Background technique [0002] Melitracen hydrochloride, also known as melitracene hydrochloride, is an antipsychotic drug whose chemical name is 3-[10,10-dimethyl-9(10H)-anthracene]-N,N-dimethyl propylamine hydrochloride; 3-[10,10-dimethyl-9(10H)-anthracenyl]-N,N-dimethylpropylamine hydrochloride; has strong antipsychotic effect, clinically compared with Chlorprothixene is 4 to 8 times stronger, but its sedative effect is weaker. It also has anti-anxiety and anti-depressant effects. It is suitable for acute and chronic schizophrenia, depression and depressive neurosis. This product is easy to absorb, has a first-pass effect, and is metabolized by the liver and kidney. Tablets are not produced by domestic manufacturers, but have been imported. Capsules are not yet available. The raw material medicine 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
IPC IPC(8): C07C209/00C07C209/08C07C211/31
CPCC07C209/00C07C209/08C07C17/00C07C29/40C07B2200/05C07C2603/24C07C211/31C07C22/04C07C35/40
Inventor 张帅胡永铸刘春樊高骏
Owner TLC NANJING PHARMA RANDD CO LTD
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