Process for synthesizing pramipexole

Abstract

The invention provides a process for synthesizing pramipexole. The process comprises the following steps: taking S-(-)-2-amino-6-propionamido-4,5-6,7-tetralin benzothiazole as a raw material to restore into free alkali in a reduction reaction system of sodium borohydride or potassium borohydride and fatty acid; and finally generating pramipexole together with an ethyl alcohol salt by the free alkali. The dependence on toxic compounds such as borane or boron fluoride and the like in the traditional craft is cast off by adopting the reduction reaction system of the sodium borohydride or potassium borohydride and the fatty acid, the overall craft process is simple to operate and easy to control, free of toxicity, more environment-friendly, and more beneficial to industrial production, meanwhile, the reduction process is intensively improved by the process disclosed by the invention, side reaction is avoided, and the reaction yield is greatly improved.

Description

【Technical field】 [0001] The invention relates to a synthesis process of pramipexole. 【Background technique】 [0002] Psoracac is a dopamine agonist, a new generation of non-ergot selective dopamine D2 and D3 receptor agonists, it can effectively improve the motor symptoms of patients with early and late Parkinson's disease, while alleviating associated depression Symptoms, protect nerves, delay disease progression and improve quality of life; it can also effectively relieve and reduce levodopa-related motor complications. It can be used alone (without levodopa) or in combination with levodopa, and the combination can reduce the dose of levodopa. It is easy to use and well tolerated by patients. The synthetic method of existing psolac has: [0003] Method 1: WO2006070349A2 discloses a method for preparing pramipexole by reducing sodium triacetoxyborohydride, which uses (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole As the starting material, react with n-propionaldehyde,...

AI Technical Summary

Problems solved by technology

[0005] The problem that this preparation method exists is: (1) sodium triacetoxy borohydride is expensive, and process cost is high

(2) The reaction selectivity of propionaldehyde is poor, and it is easy to imidize with 2-amino, causing side reactions and low yield

[0008] The problem that this document preparation method exists is: 1, used o-nitrobenzenesulfonyl chloride in the reaction, this material is difficult for storage, easy deliquescence, mercaptoacetic acid toxicity is big and peculiar smell is heavy, is unfavorable for suitability for industrialized production

2. The reaction yield is low and the production cost is high

[0011] This document has the following disadvantages: 1. The borane used is a colorless and highly toxic gas, flammable, explosive, easy to hydrolyze, poor in stability, difficult to store and transport, easy to cause safety accidents, and is not suitable for industrialized production

2. The homemade method of borane tetrahydrofuran solution is complex and poor in repeatability. The content of solvent borane prepared in different batches is inconsistent, and it is difficult to industrialize large-scale preparation

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