Method for preparing Zolmitriptan

Abstract

The invention relates to a method for preparing Zolmitriptan, which comprises the following steps: (1) obtaining a mixed solution containing (S)-4-(4-hydrazinobenzyl)-2-oxazolidinone by sequentially conducting diazotization reaction, reduction reaction and hydrolysis reaction on (S)-4-(4- aminobenzyl)-2-oxazolidinone; and (2) leading the (S)-4-(4-hydrazinobenzyl)-2-oxazolidinone in the mixed solution obtained in the step (1) and the dimethylamine butyral to carry out fisher-indole reaction so as to generate the Zolmitriptan, wherein in the step (2), the fisher-indole reaction is kept under the condition with the pH of 3-5. Compared with the prior art, the preparation method has the advantages that the molar yield is improved to 55%, the production cost of the Zolmitriptan is low and the preparation method is more applicable to industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry and medicinal chemistry, in particular to a preparation method of zolmitriptan. Background technique [0002] Zolmitriptan (zolmitriptan), chemical name (S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxa Oxazolidinone has the following structural formula: [0003] [0004] Zolmitriptan is a highly selective and potent 5-HTIB / ID receptor agonist. It is used for the treatment of migraine. It can not only relieve headache quickly, but also relieve photophobia, sound fear, nausea, etc. complication. It is of great significance to study the synthesis of zolmitriptan. [0005] Zolmitriptan is mainly prepared by the following route in the prior art: [0006] [0007] There are following deficiencies in the above-mentioned route: [0008] 1. In the production process, highly toxic phosgene is used, which increases the danger of production; [0009] 2. In the reduction step of anili...

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Problems solved by technology

[0008] 1. In the production process, highly toxic phosgene is used, which increases the danger of production;

[0009] 2. In the reduction step of aniline, stannous chloride or sodium sulfate is used as a reducing agent, the former is not easy to filter, and has great environmental pollution; the latter has a poor reduction effect, takes a lot of time and has an incomplete reaction;

[0010] 3. The overall molar yield is low, especially the fisher-indole reaction in the last step, the molar yield is low (only about 10-20%), resulting in high cost of zolmitriptan

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