Novel process for preparing rotigotine

Abstract

The invention discloses a novel process for preparing rotigotine based on 2-amino-5-methoxynaphthalene as a material. The process comprises the steps of splitting to obtain (S)-2-amino-5-methoxynaphthalene (II) by L-tartaric acid, reacting (S)-2-amino-5-methoxynaphthalene (II) with bromopropane to obtain (S)-2-(N-n-propyl)amido-5-methoxynaphthalene (III); reacting (S)-2-(N-n-propyl)amido-5-methoxynaphthalene (III) with 2-(2-bromethyl) thiophene to obtain (S)-2-[N-propyl-N-[2-(2-thiophene)ethyl]amino]-5-methoxyl-1,2,3,4-tetrahydronaphthalene (IV), and removing methyl of the (IV) under the effect of hydrobromic acid to obtain a target product rotigotine (-)-(S)-2-[N-propyl group-N-[2-(2-thiophene)ethyl]amino]-5-hydroxy-1,2,3,4-tetrahydronaphthalene (I), wherein the purity is higher than 99%. The novel process is simple in synthetic route, simple and convenient to operate and high in yield, and large-scale industrial production is easy to carry out.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a new preparation process of rotigotine. Background technique [0002] Parkinson's disease (PD), also known as Parkinson's paralysis, is a chronic neurodegenerative disease of the central nervous system caused by extrapyramidal dysfunction. After pathological changes, the synthesis of dopamine decreases, the function of inhibiting acetylcholine decreases, and the excitatory effect of acetylcholine is relatively enhanced. The result of the imbalance between the two results in "paralysis agitans". The typical symptoms of the disease are resting tremor, muscle rigidity, slowness of movement and impaired postural reflexes, and severe patients are accompanied by symptoms such as memory impairment and dementia. At present, there are nearly 2 million cases of PD patients in my country, 1.7% of males and 1.6% of females are older than 65 years old. The chemical nam...

AI Technical Summary

Problems solved by technology

The purpose of the present invention is to provide a new preparation process of rotigotine, which solves the problems of high preparation cost, high pressure reaction danger, and difficulty in industrial production in the prior art.

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