Preparation method of arbidol hydrochloride

Abstract

The invention discloses a preparation method of arbidol hydrochloride. The preparation method comprises the following steps of: (1) performing hydroxylation reaction on 3-iodo-4-nitrophenol serving as a raw material by using acetyl chloride to obtain a compound I; (2) performing substitution reaction on the compound I and ethyl acetoacetate under the action of alkali to obtain a compound II; (3) performing reduction-condensation concerted reaction on the compound II under the conditions of acetic acid and iron powder to synthesize an indole ring, and obtaining a compound III; (4) performing N-methylation reaction on the compound III by using dimethyl sulfate to obtain a compound IV; (5) performing di-bromination reaction on the compound IV in carbon tetrachloride by using bromine to obtain a compound V; (6) reacting the compound V and thiophenol under the alkali condition, and obtaining a compound VI after acidifying; (7) preparing a compound VII from the compound VI in the presence of a reaction solvent, namely aqueous solution of dimethylamine and formaldehyde; and (8) acidifying the compound VII in hot acetone to obtain the arbidol hydrochloride. The preparation method is facile in raw materials, mild in reaction conditions, high in yield, easy in separation and purification, low in cost and suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method of Arbidol hydrochloride. Background technique [0002] Arbidol hydrochloride (Arbidol hydrochloride), chemical name: 6-bromo-4-(dimethylaminomethyl)-5-hydroxy-1-methyl-2-(phenylthiomethyl)-1H- Indole-3-carboxylic acid ethyl ester hydrochloride, the structural formula is as follows: [0003] [0004] Arbidol hydrochloride is an antiviral drug developed by the Soviet Medicinal Chemistry Research Center. It was first launched in Russia in 1993. It is a monohydrate for medicinal purposes. This product not only has immune regulation and interferon induction, but also has good anti-influenza virus activity, and is clinically used to prevent and treat influenza and other acute viral respiratory infections. [0005] The preparation of Arbidol hydrochloride has many synthetic routes, Chinese patent CN1687033A and Wang blunt, Wu Xiujing, Gong Pingpin...

AI Technical Summary

Problems solved by technology

[0019] The reaction conditions of this method are relatively mild, and the raw materials are relatively easy to obtain, but the total yield is still on the low side, about 20%.

[0020] The above synthetic methods of Arbidol hydrochloride all use the Nenitzescu indole ring synthesis method to synthesize the indole ring of Arbidol hydrochloride, resulting in a low overall reaction yield, about 10% to 20%.

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