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

A kind of synthetic technique of dexmedetomidine hydrochloride intermediate

A technology of dexmedetomidine hydrochloride and synthesis process, which is applied in the field of drug synthesis, can solve the problems of low reaction yield, long reaction time, large amount of strong acid waste liquid, etc., and achieves simplified purification operation, reduced dosage and production process. Environmentally friendly effect

Active Publication Date: 2019-03-22
石药银湖制药有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The technical problem to be solved by the present invention is to overcome the defects such as the long reaction time, the large amount of strong acid waste liquid produced and the low reaction yield in the synthesis process of the existing dexmedetomidine hydrochloride intermediate medetomidine , and then provide a short reaction time, low output of strong acidic waste liquid and high yield of dexmedetomidine hydrochloride intermediate synthesis process

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 synthetic technique of dexmedetomidine hydrochloride intermediate
  • A kind of synthetic technique of dexmedetomidine hydrochloride intermediate
  • A kind of synthetic technique of dexmedetomidine hydrochloride intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The preparation method of the medetomidine provided by the present embodiment comprises the steps:

[0043] Put 9.58g (0.0505mol) of titanium tetrachloride into a reaction flask filled with 16ml of dichloromethane, add dropwise 14.03g of N-trimethylsilylimidazole dissolved in 16mL of dichloromethane under an ice bath, and the dropping process is controlled The internal temperature is lower than 10°C. After the dropwise addition, keep stirring for 30 minutes, then add 8.4g of 1-(1-chloroethyl)-2,3-xylene dropwise. 16mL of water was used to stop the reaction, and the internal temperature was controlled to be lower than 20°C during the dropwise addition process. After standing for 15 minutes, the solution was divided into three layers. Discard the bottom water layer, separate the medetomidine middle layer, extract the upper organic layer with 15mL of water, collect the water layer and add 10mL water to the water layer, then merge with the medetomidine middle layer, and sti...

Embodiment 2

[0047] Put 4.10Kg (21.6mol) of titanium tetrachloride into a 50L reactor containing about 10L of dichloromethane, and start dropping 6.00Kg (42.8mol) of N-trimethylsilane diluted with 2L of dichloromethane below -5°C For imidazole, keep within 10°C during the titration process, and stir for 30 minutes below 10°C. Add 3.60Kg (21.3mol) of 1-(1-chloroethyl)-2,3-xylene dropwise into the reaction kettle, raise the temperature to reflux, keep it warm for 3 hours, control the internal temperature below 30°C and slowly add water dropwise 7L was used to stop the reaction, the dropwise addition was completed, stirred for 30 minutes, and stood to separate into three layers.

[0048] Let go of the lower titanium hydrochloric acid water layer, separate the middle material layer, add 2L water to the upper layer for washing, separate the liquid, keep the water layer, add 2L of water, add the material layer, stir for 10 minutes, separate the liquid, and discard the strong acidic upper layer ...

Embodiment 3

[0052] The preparation method of the medetomidine provided by the present embodiment comprises the steps:

[0053] Put 9.58g (0.0505mol) of titanium tetrachloride into a reaction flask filled with 16ml of dichloromethane, add dropwise 14.026g of N-trimethylsilyl imidazole dissolved in 16mL of dichloromethane under an ice bath, and the dropping process is controlled The internal temperature is lower than 10°C. After the dropwise addition, keep stirring for 30 minutes, then add 8.433g of 1-(1-chloroethyl)-2,3-xylene dropwise. 16mL of water was used to stop the reaction, and the internal temperature was controlled to be lower than 20°C during the dropwise addition process. After standing for 15 minutes, the solution was divided into three layers. Discard the bottom water layer, separate the medetomidine middle layer, extract the upper organic layer with 15mL of water, collect the water layer and add 10mL water to the water layer, then merge with the medetomidine middle layer, and...

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 provides a synthesis process of a dexmedetomidine hydrochloride midbody. The process comprises the following steps: in the presence of titanium tetrachloride, carrying out reaction on 1-(1-chloroethyl)-2,3-dimethylbenzene and N-(trimethylsilyl)imidazole in a non-protonic solvent, so as to prepare medetomidine, wherein the mole ratio of 1-(1-chloroethyl)-2,3-dimethylbenzene to N-(trimethylsilyl)imidazole to titanium tetrachloride is (0.8-1.0): 2: (1.005-1.05). According to the process provided by the invention, the charge rates of the raw materials are initiatively adjusted, and the use amount of titanium tetrachloride is decreased while the use amount of N-(trimethylsilyl)imidazole is increased, so that the yield of the target product can be remarkably improved, the yield is 72.4% when an optimum raw material ratio is achieved, and the yield is much higher than the yield of 39.3% in the prior art.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis process of a dexmedetomidine hydrochloride intermediate. technical background [0002] Dexmedetomidine hydrochloride is the hydrochloride salt of the active dextrorotatory body of medetomidine, is the α-2 adrenoceptor agonist that Orion Pharma / Abott company cooperates research and development, in March, 2000 listed in the U.S. ( trade name Precedex). The chemical name of dexmedetomidine hydrochloride is (R)-4-[1-(2,3-dimethylphenyl)ethyl]-1H imidazole monohydrochloride, and its structural formula is as follows: [0003] [0004] The affinity of dexmedetomidine hydrochloride to adrenergic receptors is 8 times higher than that of clonidine. Its half-life is short and the effective dose is small. It is suitable for sedation of patients who start intubation and use ventilators during intensive care treatment. In addition, dexmedetomidine hydroc...

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): C07D233/58
CPCC07D233/58
Inventor 狄彩霞盖来兵张爱萍郑勇郭良姚春虎黄晋渊孙文超
Owner 石药银湖制药有限公司