Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of method for preparing medicinal amifostine

A technology of amifostine trihydrate and sodium thiophosphate, which is applied in the fields of chemical instruments and methods, compounds of Group 5/15 elements of the periodic table, organic chemistry, etc., and can solve complex operations, uneven standards, and non-green Environmental protection and other issues, to achieve the effect of convenient purification and low dosage

Active Publication Date: 2016-05-25
MERRO PHARMA +1
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the patent US2006042761, methanol is added as a crystallization agent under DMF as a promoter, and the crude product is purified by at least one ion exchange resin column or an activated carbon column, and the operation is complicated
[0005] It can be seen that the last step of the above methods all involves ω-(aminoalkylamino) alkyl halides to carry out phosphorus-sulfurylation to obtain amifostine, but the post-treatment methods of the key steps all need to add alcohol solvents as crystallizers, or The product is obtained by adding a large amount of polar aprotic solvent, which is not a green and environmentally friendly process
Moreover, the standards achieved by the final refined quality are uneven. Except that the patent CN200810146538.8 mentions that the requirements of USP29 version are met, there are no relevant literature and patent reports on the quality achieved by refined amifostine.

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 method for preparing medicinal amifostine
  • A kind of method for preparing medicinal amifostine
  • A kind of method for preparing medicinal amifostine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] In the present invention, the detailed preparation steps of the crude product of synthetic amifostine using DMAC as the accelerator are as follows:

[0021] Take 140g of purified water, 68.0g (0.2mol) of N-bromoethyl-1,3-propanediamine dihydrobromide, and 79.2g (0.2mol) of sodium thiophosphate as raw materials and put them into a 250mL three-necked flask. Stir and dissolve, and control the temperature not to exceed 35°C. 122.40g DMAC was added dropwise at a uniform speed, the temperature was lowered after 3.5 hours of reaction, and when the temperature was lowered to 0°C with frozen brine, the stirring was stopped, and the mixture was left to stand overnight. The next day, it was filtered under reduced pressure, dried, and weighed to obtain 43.16g of crude amifostine, with a crude yield of 80.30%. The main body content was 93.55% as measured by the USP35 method and the external standard method.

Embodiment 2

[0023] Take 140g of purified water, 68.0g (0.2mol) of N-bromoethyl-1,3-propanediamine dihydrobromide, and 75.28g (0.19mol) of sodium thiophosphate as raw materials and put them into a 250mL three-necked flask. Stir and dissolve, and control the temperature not to exceed 35°C. Add 122.40g DMAC dropwise at a uniform speed while controlling the temperature of the system not to exceed 35°C. After 3.5h, the temperature was lowered, and when the temperature was lowered to 0°C with frozen brine, the stirring was stopped, and the mixture was allowed to stand overnight. The next day, it was filtered under reduced pressure, dried, and weighed to obtain 42.22 g of crude amifostine, with a crude yield of 82.83%. According to USP35 version method, the main body content is 97.18% measured by external standard method.

Embodiment 3

[0025] Take 140g of purified water, 68.0g (0.2mol) of N-bromoethyl-1,3-propanediamine dihydrobromide, and 75.28g (0.19mol) of sodium thiophosphate as raw materials and put them into a 250mL three-necked flask. The magnet is stirred and dissolved, and the temperature is controlled not to exceed 35°C. 61.50g DMAC was added dropwise at a uniform speed while controlling the temperature of the system not to exceed 35°C. After the temperature was lowered, the stirring was stopped when the temperature was lowered to 0°C with frozen brine, and the mixture was left to stand overnight. The next day, it was filtered under reduced pressure, dried, and weighed to obtain 26.09 g of crude amifostine, with a crude yield of 51.19%. According to USP35 version method, the main body content is 95.85% measured by external standard method.

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 relates to the field of drug synthesis and discloses a method for preparing medicinal amifostine trihydrate with high efficiency and convenience. The method comprises the following steps: under the conditions that the aqueous solution concentration is 10-70%, the molecular molar ratio is in the range of 1.0 : (0.8-1.2) and the reaction temperature is in the range of 5.0-60 DEG C, reacting a N-bromoethyl-1,3-propanediamine dihydrobromide solution and a sodium thiosulfate solution in the presence of N,N-dimethylacetamide (DMAC) as a promoter to produce amifostine; filtering the reaction liquid without any treatment to obtain crude amifostine; purifying through recrystallization using a compound solvent to obtain medicinal amifostine with a content of higher than or equal to 99.7%, a thiol content of lower than 0.2%, a sodium thiosulfate content of lower than 0.1%, an other single relevant substance content of lower than 0.1% and a total impurity content of lower than 0.3%. The method is environment-friendly, highly-efficient, low in cost, convenient in operation and suitable for industrial large-scale production.

Description

Technical field [0001] The invention belongs to the field of drug synthesis, and relates to a preparation method of amifostine trihydrate. Background technique [0002] Amifostine is a broad-spectrum cytoprotective agent. It was first screened by the Walter Reed Army Medical Research Institute of the United States in the 1960s. It is a highly effective anti-radiation and safe to use radiation protection agent. It has been used until now. The code used is WR-2721. It is currently used clinically to reduce the side effects caused by radiation and drugs during radiotherapy and chemotherapy, and was approved by the FDA in 1996 as the first cytoprotective agent. The chemical structure is H 2 N-(CH 2 ) 3 -NH-(CH 2 ) 2 -SPO 3 H 2 , Is an organophosphorylated amine thio-based prodrug, which is hydrolyzed into active metabolites by alkaline phosphatase in normal tissues, code-named WR-1065, namely H 2 N-(CH 2 ) 3 -NH-(CH 2 ) 2 -SH, it can scavenge free radicals generated during radiation...

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): C07F9/165
Inventor 孟庆伟宋晓飞戴晓威刘广志李智董述祥张成海初永坤李周民毕文生贾萍梁敏王东杜博曹雪静王军宋旭阳刘维浩
Owner MERRO PHARMA