Preparation method of 3-[4-(3-pyridyl)-1H-imidazolyl-2-sulfo]-1-propylanmine

Abstract

The invention discloses a preparation method of 3-[4-(3-pyridyl)-1H-imidazolyl-2-sulfo]-1-propylanmine which is represented in the description. The preparation method adopts a converge type synthesis route, and comprises the following steps: taking 3-acetylpyridine as the raw material, subjecting 3-acetylpyridine to bromination reactions so as to obtain 3-bromoacetylpyridine hydrobromide; taking N-(3-bromopropyl)phthalimide as the raw material, making N-(3-bromopropyl)phthalimide carry out condensation reactions with thiourea, then making the reaction product carry out ring-closing reactions with 3-bromoacetylpyridine hydrobromide, and finally subjecting the reaction product to hydrazinolysis reactions so as to obtain the target product. The synthesis method has the advantages of easily-available and cheap raw material, fewer reaction steps, stability, simple operation, high yield, and suitability for industrial massive production.

Description

Technical field: [0001] The invention belongs to the field of medicinal chemistry, and relates to a method for preparing 3-[4-(3-pyridyl)-1H-imidazolyl-2-thio]-1-propanamine, which can be used in the field of medicine to synthesize new anti- Synthesis of important intermediates such as drug-resistant ketolide derivatives such as telithromycin analogs. Background technique: [0002] Chen Xiaozhuo et al reported the synthetic route of 3-[4-(3-pyridyl)-1H-imidazolyl-2-thio]-1-propylamine in Eur J Med Chem,46(2011):208-217: [0003] [0004] The method uses 3-acetylpyridine as a raw material, reacts with potassium ethoxide to obtain 3-(2-aminoacetyl)pyridine hydrochloride through oximation, sulfonylation, and cyclization with potassium thiocyanate, and then reacts with N- (3-Bromopropyl) phthalimide is condensed, and finally the target product is obtained by hydrazinolysis. In this method, triethylamine is used in the oximation step, and the recovery process needs to be adde...

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Problems solved by technology

[0004] The method uses 3-acetylpyridine as a raw material, reacts with potassium ethoxide to obtain 3-(2-aminoacetyl)pyridine hydrochloride through oximation, sulfonylation, and cyclization with potassium thiocyanate, and then reacts with N- (3-Bromopropyl) phthalimide is condensed, and finally the target product is obtained by hydrazinolysis. In this method, triethylamine is used in the oximation step, and the recovery process needs to be added when the reproduction is enlarged; the amine formation step uses Potassium ethylate is relatively expensive, and the operation requires strict conditions such as anhydrous; the synthetic route is long, the operation is complicated, and the total yield is low

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