Synthesis method of deuterated albendazole

A technology of albendazole and a synthetic method, applied in the field of pharmaceutical preparation, can solve problems such as no literature reports, and achieve the effects of reducing production cost, improving atom economy, good reproducibility and stability

Pending Publication Date: 2022-04-22
天津阿尔塔科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] At present, the synthesis methods of albendazole with natural abundance are many and relatively mature, and the literatures such as US2013303782A1 and CN105585333 have reported their synthesis methods, but there is no literature for the synthesis of stable isotope-labeled albendazole Report, in view of this, the present invention has designed a comparatively reasonable preparation route, and has optimi

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  • Synthesis method of deuterated albendazole
  • Synthesis method of deuterated albendazole
  • Synthesis method of deuterated albendazole

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0046] Example 1: Preparation of Compound 1:

[0047] In a 500 ml round bottom bottle, albendazole (8.0 g, 30.2 mmol), sodium hydroxide (1.8 g, 45.0 mmol), methanol (250 ml) and water (50 ml) were added, and then the reaction system was heated and refluxed for 16 h, and the albendazole raw material disappeared. Cooled to room temperature, concentrated under reduced pressure to remove most of the methanol, a large amount of solids precipitated, filtered, washed with water and dichloromethane in turn, the solids were dried to compound 1,5.5g, yield 88%, MS(m / z): 208.1 [M+H] + 。

Example Embodiment

[0048] Example 2-1:

[0049] In a 50 ml round bottom bottle, compounds 1 (207 mg, 1.0 mmol), sodium bicarbonate (256 mg, 3.0 mmol) and acetone 6 ml were added. Under stirring, methyl deuterium chloroformate (100 mg, 1.1 mmol) is added slowly. Gabi stirred the reaction mixture at room temperature, TLC and LC-MS tracked the reaction, and the reaction was complete within 2.5 hours. Filtered, washed sequentially with water, dichloromethane and methanol, the solids were dried to an intermediate of 2,220 mg, yield 83.0%, MS(m / z): 269.0 [M+H] + 。

Example Embodiment

[0050] Example 2-2:

[0051] In a 100 ml round bottom bottle, compounds 1 (2.1 g, 10.1 mmol), sodium bicarbonate (2.5 g, 30.0 mmol) and acetone 50 ml were added. Methyl deuterium chloroformate (1.1 g, 11.2 mmol) is added slowly and added in 5 minutes. The reaction mixture was stirred at room temperature, TLC and LC-MS tracked the reaction, and the reaction was complete in 2.5 hours. Then heated reflux reaction for 16 hours, LC-MS tracking reaction, intermediate 2 disappeared, such reaction cooled to room temperature, filtered, washed with water, dichloromethane and methanol successively, the solid was dried to deuterium albendazole, 2.3g. Yield 85%, Chemical Purity 99.0%, Isotope Abundance 99.5%, MS(m / z): 269.0[M+H] + 。

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Abstract

The invention relates to a method for synthesizing deuterated albendazole, which comprises the following steps of: hydrolyzing albendazole which is industrially produced on a large scale and is used as a raw material under an alkaline condition to remove a methyl formate group on an amino group at the 2-position of the albendazole, and then connecting the deuterated methyl formate group to the amino group at the 2-position of the albendazole. According to the deuterated albendazole synthesis method, albendazole is taken as a raw material, deuterated albendazole is synthesized through two-step reaction, the raw material is low in price and easy to obtain, the synthesis route is simple, conditions are easy to control, the yield is high, and the obtained product is high in purity.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, in particular to a method for synthesizing deuterated albendazole. Background technique [0002] Albendazole (albendazole), the chemical name is 5-propylthiobenzimidazole-2-methyl carbamate, is a broad-spectrum, high-efficiency, low-toxic anthelmintic drug listed by Smith Kline Company of the United States in 1977. It has significant efficacy against Fasciola hepatica, tapeworm, lung and gastrointestinal nematodes. It is the most effective one among benzimidazoles, and it is the drug of choice for the prevention and treatment of parasitic diseases in livestock and poultry. In recent years, it has been found that this product also has a strong effect on bovine cysticercosis. After treatment, the cysticercosis decreases and the lesions disappear. In addition, this product can also be used to prevent parasitic infection, so it can have good effects on promoting sheep growth and increa...

Claims

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Application Information

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IPC IPC(8): C07D235/32C07B59/00
CPCC07D235/32C07B59/002C07B2200/05
Inventor 张磊龙正宇韩世磊
Owner 天津阿尔塔科技有限公司
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