Method for preparing detomidine and the intermediate thereof

A technology for imidazole and imidazole carboxamide is applied in the field of preparing detomidine and intermediates thereof, and can solve the problems of difficulty in purchasing, high cost of detomidine raw materials, low yield of imidazole aldehyde, etc., and achieves low cost, cheap source, Easy-to-source effects

Inactive Publication Date: 2011-11-09
SHANGHAI DESANO PHARMA INVESTMENT +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Because the raw material dihydroxyacetone dimer of synthesizing imidazole aldehyde is difficult to buy, and the yield that obtains imidazole aldehyde is also low (26%), the synthetic detomidine raw material cost height with this method

Method used

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  • Method for preparing detomidine and the intermediate thereof
  • Method for preparing detomidine and the intermediate thereof
  • Method for preparing detomidine and the intermediate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Preparation of 4-imidazolecarboxamide:

[0030] Add ethyl 4-imidazolate (8.5g) into water (68ml), blow in ammonia gas, heat and reflux for 6 hours, concentrate to obtain a white solid, and beat with acetone (10ml) to obtain 6.7g of a white solid, which is 4- For imidazole carboxamide, the mother liquor is recovered and merged to continue ammonolysis.

Embodiment 2

[0032] Preparation of 4-(2,3-dimethylbenzoyl)-imidazole

[0033] Magnesium turnings (45.0 g, 1.88 mol) were overlaid with 150 ml tetrahydrofuran. 2,3-Dimethylbromobenzene (220.0 ml, 1.62 mol) was dissolved in 600 ml tetrahydrofuran. Add this solution dropwise to the magnesium shavings, continue to drop slowly after the reaction is initiated, and keep refluxing. After the addition, heat to reflux until the magnesium reaction is complete, and then react for 30 minutes to obtain the Grignard reagent.

[0034] Suspend 4-imidazole carboxamide (50.0 g, 0.45 mol) in 1500 ml of pyridine, heat to 70° C., add the above-mentioned Grignard reagent dropwise, and keep the reaction for 2 hours after the dropwise addition. Cool in an ice bath to 0°C, add dropwise 1500ml of saturated ammonium chloride solution to terminate the reaction, and control the internal temperature at 5°C. The obtained solid was filtered, the filtrate was separated into layers, and the aqueous layer was extracted th...

Embodiment 3

[0036] Preparation of 4-(2,3-dimethylbenzoyl)-imidazole:

[0037] Magnesium turnings (72.0 g, 3.00 mol) were overlaid with 240 ml tetrahydrofuran. 2,3-Dimethylbromobenzene (350.0 ml, 2.58 mol) was dissolved in 800 ml tetrahydrofuran. Add this solution dropwise to the magnesium shavings, continue to drop slowly after the reaction is initiated, and keep refluxing. After the addition, heat to reflux until the magnesium reaction is complete, and then react for 30 minutes to obtain the Grignard reagent.

[0038] Suspend 4-imidazole carboxamide (50.0 g, 0.45 mol) in 1500 ml of pyridine, heat to 60° C., add the above-mentioned Grignard reagent dropwise, and keep the reaction for 2 hours after the dropwise addition. Under cooling in an ice bath, 1500 ml of saturated ammonium chloride solution was added dropwise to terminate the reaction, and the internal temperature was controlled at 5°C. The obtained solid was filtered, the filtrate was separated into layers, and the aqueous layer...

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PUM

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Abstract

The invention provides a method for preparing detomidine and the intermediate thereof. The method for preparing the intermediate of the detomidine comprises the steps that: 4-imidazolecarboxamide is condensed with 2, 3-Dimethylbromobenzene to produce 4-(2, 3- dimethylbenzoyl)-imidazole. The 4-(2, 3- dimethylbenzoyl)-imidazole can be reduced to produce the detomidine. The method of the invention has cheap and easy-to-get raw materials, easy-to-control technological processes, high yield factor and low cost and is suitable for being produced in an industrialized manner.

Description

technical field [0001] The present invention relates to the method for preparing detomidine and its intermediate. Background technique [0002] The chemical name of Detomidine is 4-(2,3-dimethylbenzyl)-1H-imidazole, and its structural formula is as follows: [0003] [0004] Detomidine is a veterinary anesthetic, which has sedative and analgesic effects on various animals, especially on horses and cattle. The drug, like clonidine and xylazine (Xylazine), also belongs to the central α_2 adrenergic receptor stimulant. [0005] U.S. Patent US4443466 has reported the synthetic method of detomidine, and synthetic route is as follows: [0006] [0007] In the technology reported in the above-mentioned patent, imidazole aldehyde is used as a raw material, condensed with 2,3-dimethylbromobenzene, and then reduced to generate detomidine. Because the raw material dihydroxyacetone dimer of synthesizing imidazole aldehyde is difficult to buy, and the yield of obtaining imidazol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/58A61P25/20A61P25/04
Inventor 李金亮赵楠
Owner SHANGHAI DESANO PHARMA INVESTMENT
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