106006-84-2

Usage

Chemical Properties

Off-White Solid

Uses

A pramipexole intermediate.

InChI:InChI=1/C10H15N3OS/c1-2-9(14)12-6-3-4-7-8(5-6)15-10(11)13-7/h6H,2-5H2,1H3,(H2,11,13)(H,12,14)/t6-/m0/s1

Upstream product

• 375824-96-7 2-amino-6-(propionylamino)-4,5,6,7-tetrahydrobenzothiazole 
• 123-62-6 propionic acid anhydride 
• 27514-08-5 N-(4-oxocyclohexyl)acetamide 
• 104617-50-7 N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)acetamide hydrobromide 
• 106006-83-1 2,6-diamino-4,5,6,7-tetrahydro-benzthiazole 
• 106092-09-5 (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine 

Downstream Products

• 104632-25-9 pramipexole dihydrochloride 
• 191217-81-9 pramipexole dihydrochloride monohydrate 
• 104632-26-0 pramipexole 

Relevant academic research and scientific papers

Preparation method of high-purity pramipexole

The invention relates to the technical field of pharmacy, and provides a preparation method of high-purity pramipexole. According to the invention, raceme 2, 6-diamino 4, 5, 6, 7-tetrahydrobenzothiazole is used as an initial raw material, and pramipexole is obtained through a three-step chemical reaction, so the introduction of uncontrollable factors of drug quality is reduced, and the requirements of drug application are better met; the market price of the initial raw materials is low, so that the preparation cost of pramipexole can be greatly reduced; the solvent used in the method is green, environmentally friendly, cheap, easy to obtain and suitable for industrial production, the HPLC purity of the obtained pramipexole can reach 99.86%, and the isomer purity can reach 99.89%.

Method for synthesizing pramipexole dihydrochloride key intermediate by one-pot method

The invention provides a method for synthesizing a pramipexole dihydrochloride key intermediate by a one-pot method, which comprises the following steps: dissociating (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole tartrate, discharging, and carrying out amidation on the free alkali and propionic anhydride to obtain (S)-2-amino-6-propionamido-4,5,6,7-tetrahydrobenzothiazole. The free alkali has high water solubility, and the dissociating step can cause 10% or above of loss. In the amidation step, tetrahydrofuran is used as a solvent and triethylamine is used as an acid-binding agent, so that the pollution is serious, the cost is high, and the post-treatment is tedious. Based on the problems, the dissociation and amidation processes are completed in one step in the same system by taking water and ethyl acetate as solvents and inorganic base as an acid-binding agent under the condition of relatively low temperature, so that the method is simple to operate, high in yield and low in cost.

A preparation method of pramipexole hydrochloride (by machine translation)

The invention discloses a method for preparation of pramipexole hydrochloride, comprises the following steps: 1) in the organic solvent, in order to 2, 6 - diamino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole as the raw material, to join the resolving agent, heating to reflux, cooling, filtering, basified, make the (-) - (6 s) - 2, 6 - diamino 4, 5, 6, 7 - tetrahydrobenzo and thiazole; 2) in ethanol solution, the (-) - (6 s) - 2, 6 - diamino 4, 5, 6, 7 - tetrahydrobenzo and thiazole, and c anhydride reaction, by heating to reflux, to obtain (-) - (6 s) - 2 - amino - 6 - propionyl amino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole; 3) (-) - (6 s) - 2 - amino - 6 - propionyl amino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole in toluene solution in red aluminum reduction reaction, by heating to reflux, stirring, after devitrifying, make the use of pramipexole; the pramipexole into the isopropyl alcohol solution, by stirring, after devitrifying, react with hydrochloric acid, by decompression, drying, hydrochloride pramipexole. The preparation method is reaction low requirements on the equipment, the pramipexole prepared hydrochloric acid content is high, high purity, high solubility, the output is high, there is little impurity. (by machine translation)

Synthesis method of high-purity pramipexole

The invention discloses a synthesis method of high-purity pramipexole, which includes the steps of: 1) an acylation reaction; 2) crystallization; 3) preparation of an intermediate; 4) a reduction reaction; 5) extraction and purification; 6) reflux decolorization; and 7) recrystallization. In the method, through the acylation reaction then the reduction reaction, reaction efficiency of a raw material, S-(-)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole, is increased, thereby increasing the yield of the pramipexole; and through operations of decolorization, extraction, recrystallization and the like, purity and quality of the pramipexole are increased effectively. The method has gentle and controllable reaction conditions, is simple in operations in crystallization, recrystallization and purification steps and has high practicability. The pramipexole is high in yield and purity, is low in impurity content and has great market prospect.

A compound and its preparation method

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.

IMPROVED PROCESS FOR THE PREPARATION OF (S)-2-AMINO-4,5,6,7-TETRAHYDRO-6 - (PROPYLAMINO) BENZOTHIAZOLE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

The present invention relates to an improved process for the preparation of of (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and its pharmaceutically acceptable salts. Specifically relates to the compound represented by the following structural formula- Ia.

PROCESS FOR PREPARING CHIRALLY PURE 2-AMINO-6-(ALKYL)AMINO-4,5,6,7-TETRAHYDROBENZOTHIAZOLES BY LIQUID CHROMATOGRAPHIC RESOLUTION

Processes for obtaining single enantiomers of 2-amino-6-(alkyl)amino-4,5,6,7-tetrahydrobenzothiazoles by liquid chromatography are disclosed.

INTERMEDIATES FOR THE PREPARATION OF PRAMIPEXOLE

Intermediates useful for the preparation of pramipexole and the use thereof in such synthesis.

Dopamine autoreceptor agonists: Resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine

The enantiomers of the aminothiazole analogues of the known dopaminergic agonists apomorphine (1) and 2-aminohydroxytetralin (2) have been prepared. The absolute configurations of the enantiomers of 2,6-diaminotetrahydrobenzothiazole have been established by X-ray crystallographic analysis. Dopamine (DA) autoreceptor agonist activities of the compounds were evaluated. Testing revealed (-)-5, the S enantiomer, to be the most active compound tested (inhibition of GBL accelerated dopamine synthesis and inhibition of α-methyltyrosine-induced decline of DA). In addition (-)-5 does not exhibit stereotyped behavior, suggesting a pronounced selectivity for DA autoreceptors.