Compound and preparation method thereof

Abstract

The invention relates to a compound and a preparation method thereof, and specifically relates to an intermediate for synthesizing pramipexole dihydrochloride and a preparation method thereof. The intermediate is easy to purify. The synthesis of the intermediate comprises the following steps: subjecting (s)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to carry out reactions with propionic anhydride, and then reducing the reaction products with a reductant so as to obtain the intermediate. The whole reaction process does not contain any intermediate treatment, and the preparation method has the advantages of simple reaction process, mild reaction conditions, high safety, high yield, and suitability for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis and relates to a compound and a preparation method thereof. Background technique [0002] Parkinson's disease is a common slowly progressive neurodegenerative disease that occurs in middle-aged and elderly people, and is characterized clinically by resting tremor, muscle rigidity, and dyskinesia. With the aging of the population, its prevalence is increasing year by year, and it has become a common neurological disease second only to cerebrovascular disease. For a long time, levodopa-based drug substitution therapy has been the first choice for the treatment of Parkinson's disease, but none of the existing treatments can effectively prevent or even slow down the progression of the disease. Pramipexole hydrochloride can be used alone in the treatment of Parkinson's disease to reduce the incidence of dyskinesia caused by levodopa treatment, and when used in combination with levodopa, it can reduce the...

AI Technical Summary

Problems solved by technology

The shortcoming of this method is: utilize (-) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole with higher purity and NaBH4 and BF3 After contacting and reacting in tetrahydrofuran, after a A series of post-treatment processes to obtain relatively pure (S)-(-)2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole, and then react with HCl to obtain (S)-( -)-2-Amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole dihydrochloride, the reaction is complicated, and the reaction conditions are harsh. If necessary, the whole reaction is carried out under the protection of an inert gas. For large-scale production, a large amount of equipment investment will be required to ensure the corresponding harsh reaction conditions

[0011] The disadvantage of this method is that the intermediate N-((S)-2-amino 4,5,6,7-tetrahydrobenzo[D]thiazol-6-yl) propionamide needs to be pure, so as to obtain relatively high yield

The shortcoming of this method is: when borane tetrahydrofuran complex is added dropwise, because borane is volatile, a large amount of bubbles will be produced in the reaction process, and the reaction solution overflows the reactor, so nitrogen protection is taken, and the method finally Product yield is as low as 50%

The disadvantage of this method is: the whole synthetic route needs to be carried out under the conditions of avoiding light and reaction temperature -5°C-0°C before the post-treatment, and the post-treatment needs to be concentrated under reduced pressure to remove the solvent methanol, the reaction conditions are harsh, and the steps are complicated. It is beneficial to large-scale industrial production. This method does not report yield data, but the purity of the obtained product is very low

[0015] The synthetic method of pramipexole hydrochloride in the above-mentioned prior art has the following disadvantages: 1) the reaction conditions are harsh, and it needs to be carried out under the protection of an inert gas. It needs to be separated and purified, the intermediate treatment process is complicated, and consumes a lot of manpower and material resources, so it is not suitable for industrial production; 3) The reaction yield is low and the purity is not high

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