Preparation method for 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine succinate

Abstract

The invention discloses a preparation method for 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine succinate (I), which belongs to the field of preparation of medicament intermediates. The preparation method comprises the following steps of: undergoing a condensation reaction on 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide (III) and a methanol aqueous solution in the presence of ammonium carbonate and methanol, and directly reducing an intermediate product by performing palladium / carbon catalytic hydrogen without separating to obtain 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine (II); at the end of the reaction, recovering a solvent, performing post-treatment to obtain a crude product (II); and recrystallizing to obtain refined 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine (II), undergoing a salt-forming reaction on the refined product and succinic acid in purified water, clarifying the reaction liquid, and adding activecarbon for decolorizing to obtain 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine succinate (I). The preparation method has the characteristics of stable process and easiness for controlling.

Description

Technical field [0001] The invention relates to a preparation method of 3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide succinate compound, which belongs to the field of pharmaceutical intermediate preparation. Background technique [0002] There are several methods for preparing 3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide succinate in the existing literature: [0003] 1. Patent Publication No. CN101092387A provides a method for preparing sodium 4-chlorobutane-1,1-disulfonate by reacting 4-chlorobutanal and sodium metabisulfite, which is heated and reacted in the presence of inorganic acid or organic acid catalyst. Organic solvent extraction to obtain 3-(2-chloroethyl)-N-1H-indole-5-methanesulfonamide addition phase transfer catalyst, which reacts with dimethylamine, extracts, decolorizes, and refines sumatriptan. Prepared after heating with solvent to dissolve into salt. The total yield of this method is 29%. [0004] 2. Patent WO2004099141 repor...

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Problems solved by technology

There are many shortcomings in the above several methods, wherein method 2 prepares compound 4-(N, N-dimethylamino) butyraldehyde diethyl acetal, needs strict anhydrous Grignard reaction, and the compound has a high boiling point and is difficult to purify The total yield of this route is less than 15%

Though method 1 total yield is higher than method 2, the starting material 4-chlorobutyraldehyde unstable that this method uses is difficult to buy, and prepares 4-chlorobutane-1, and the process of 1-sodium disulfonate produces relatively A lot of waste water, in the process of preparing 3-(2-chloroethyl)-N-1H-indole-5-methanesulfonamide, a large amount of dilute hydrochloric acid, ammonia water, sodium chloride aqueous solution and sodium sulfate, etc. are used, and there are many steps. And produce a large amount of three wastes, the 3-(2-chloroethyl)-N-1H-indole-5-methanesulfonamide content and yield of its preparation are lower

In its preparation of 3-[2-(dimethylamino)ethyl[-N-methylindole-5-methanesulfonamide, a large amount of dimethylamine aqueous solution and precious potassium iodide are used, and the resulting 3-[2-(di Methylamino) ethyl]-N-methylindole-5-methanesulfonamide crude product content and yield are also lower

And 3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide reacts with succinic acid using an organic solvent, and the residual solvent in the final product is difficult to remove, seriously affecting the safety of product use , the method has a long route, complex operation, a large amount of three wastes, high total cost, poor product safety, and low yield, making it difficult to realize industrial production

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