Synthetic method for nicergoline

A kind of synthetic method, the technology of nicergoline, are applied in the synthetic field of nicergoline

Inactive Publication Date: 2018-04-20
广州普星药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These two processes are more reasonable, but both use methyl iodide with low boiling point and high toxicity as the methylation reagent. In addition, in the post-treatment process of the methoxylation step, the reaction solution containing concentrated sulfuric acid is directly poured It is dangerous to enter the ice water

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  • Synthetic method for nicergoline

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preparation example Construction

[0030] A kind of synthetic method of Nicergoline, comprising:

[0031] The preparation steps of intermediate product 1: methoxylation reaction occurs between ergot alcohol and methanol, and after purification, 10α-methoxyl-dihydroergot alcohol is obtained, namely intermediate product 1;

[0032] The preparation steps of intermediate product 2: 10α-methoxy-dihydroergool and trimethylsulfoxide iodide undergo methylation reaction, after purification, 1-methyl-10α-methoxy-dihydroergool is obtained , the intermediate product 2;

[0033] The preparation steps of Nicergoline: 1-methyl-10α-methoxy-dihydroergoline is subjected to acylation reaction with 5-bromonicotinoyl chloride, and after refining, Nicergoline is obtained.

[0034] As a preferred embodiment,

[0035] The preparation steps of intermediate product 1: under the protection of nitrogen, add ergot alcohol into the mixed solution of methanol and concentrated sulfuric acid, turn on the ultraviolet lamp to irradiate, contro...

Embodiment 1

[0048] A kind of synthetic method of Nicergoline, comprising:

[0049] The preparation steps of intermediate product 1: under the protection of nitrogen, add 20 g of ergot alcohol into the mixed solution of 500 ml of methanol and 100 ml of concentrated sulfuric acid, turn on the ultraviolet light, control the temperature at 20-40 ° C, react for 6 hours, and detect the reaction process by TLC (UV. 254, the volume ratio of methanol, chloroform, and ammonia water is 1:8:0.1), after the reaction is completed, add 400ml of chloroform, add dropwise ammonia water to adjust the pH value to 7, extract with chloroform, and then use chloroform Methane (400ml*2) was extracted twice, the chloroform layer was washed with purified water, the organic solvent was removed by distillation under reduced pressure, and the residue was recrystallized with 1000ml of acetonitrile to obtain 10α-methoxy-dihydroergool (intermediate product 1) 17.2 g, yield 82%.

[0050] The preparation steps of intermed...

Embodiment 2

[0053] A kind of synthetic method of Nicergoline, comprising:

[0054] Preparation steps of intermediate product 1: under nitrogen protection, add 100 g of ergot alcohol into a mixture of 2000 ml of methanol and 600 ml of concentrated sulfuric acid, turn on the ultraviolet light, control the temperature at 20-40 ° C, react for 6 hours, and detect the reaction progress by TLC (UV. 254, the volume ratio of methanol, chloroform, and ammonia water is 1:8:0.1), after the reaction is completed, add 2000ml of chloroform, drop ammonia to adjust the pH value to 7, extract with chloroform, and then use chloroform Methane (2000ml*2) was extracted twice, the chloroform layer was washed with purified water, the organic solvent was removed by distillation under reduced pressure, and the residue was recrystallized with 5000ml of acetonitrile to obtain 10α-methoxy-dihydroergool (intermediate product 1) 85.3 g, yield 85.3%.

[0055] The preparation steps of intermediate product 2: add powdery...

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Abstract

The invention discloses a synthetic method for nicergoline. The synthetic method comprises the following steps: allowing lysergol and methanol to generate a methoxylation reaction, and carrying out purifying so as to obtain 10alpha-methoxyl-dihydrolysergol; allowing the 10alpha-methoxyl-dihydrolysergol and trimethylsulphoxonium iodide to generate a methylation reaction, and carrying out purifyingso as to obtain 1-methyl-10alpha-methoxyl-dihydrolysergol; and allowing the 1-methyl-10alpha-methoxyl-dihydrolysergol and 5-bromonicotinoyl chloride to generate an acylation reaction, and carrying outrefining so as to obtain the nicergoline. The synthetic method provided by the invention has the advantages of simple process, mild reaction conditions, easy operation, low toxicity of raw materials,high quality of a finished product, and facilitation of industrial popularization and application.

Description

technical field [0001] The invention relates to a synthetic method of nicergoline, which belongs to the technical field of chemical synthesis. Background technique [0002] Nicergoline, its chemical name is 10α-methoxy-1,6-dimethylergoline-8β-methanyl-5′-bromonicotinate, molecular formula C24H26BrN3O3, molecular weight 484.39, white to slightly yellow crystalline powder, Soluble in ethanol, hardly soluble in water, its structural formula is as structural formula 1: [0003] [0004] Nicergoline is mainly used clinically for the treatment of cognitive, emotional and behavioral disorders in the elderly, especially for vascular senile dementia. The pharmacological action of Nicergoline mainly acts on the α-receptor to cause vasodilation and is regarded as a vasoactive drug. In vitro studies, animal experiments and clinical trials in recent years have revealed its wide range of pharmacological effects and clinical application indications. [0005] The technique of existing...

Claims

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Application Information

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IPC IPC(8): C07D457/02
Inventor 何演安陈秀秀邓团飞
Owner 广州普星药业有限公司
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