191217-81-9

Basic information

• Product Name: Pramipexole
• Synonyms: Mirapex;(S)-2-Amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazol2HClH2Otetrahydrobenzothiazol;Mirapex,Sifrol,Mirapexin;Pramipexole dihydrochloride monohydrate;(6S)-N'-Propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine hydrate dihydrochloride;(S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate;Pramipexole;2,6-Benzothiazolediamine, 4,5,6,7-tetrahydro-N6-propyl-, dihydrochloride, monohydrate, (6S)-
• CAS NO: 191217-81-9
• Molecular Formula: C10H21Cl2N3OS
• Molecular Weight: 302.26
• EINECS: 1806241-263-5
• Product Categories: Pramipexole;Inhibitors
• Mol File: 191217-81-9.mol

Chemical Properties

• Melting Point: 290 °C(dec.)
• Boiling Point: 378 °C at 760 mmHg
• Flash Point: 182.4 °C
• Appearance: gray white crystalline powder
• Vapor Pressure: 9.93E-11mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Freely soluble in water, soluble in methanol, sparingly soluble or slightly soluble in ethanol (96 per cent), practically insoluble in methylene chloride.
• Merck: 14,7705
• CAS DataBase Reference: Pramipexole(CAS DataBase Reference)
• NIST Chemistry Reference: Pramipexole(191217-81-9)
• EPA Substance Registry System: Pramipexole(191217-81-9)

Safety Data

• WGK Germany: 3
• RTECS: DL3375000
• Hazardous Substances Data: 191217-81-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Pramipexole is used as a pharmaceutical secondary standard for various analytical applications. It is suitable for use in pharma release testing, pharma method development for qualitative and quantitative analyses, and other calibration requirements.
Used in Parkinson's Disease Treatment:
Pramipexole is used as an antiparkinsonian agent for the treatment of early and advanced Parkinson's disease (PD). It helps in managing the symptoms and improving the quality of life for patients with PD.
Used in Restless Legs Syndrome Treatment:
Pramipexole is used as a treatment for restless legs syndrome, a neurological disorder characterized by an uncontrollable urge to move the legs, often accompanied by uncomfortable sensations.
Used in Antidepressant Applications:
Pramipexole is used as an antidepressant, helping to alleviate symptoms of depression by modulating the levels of dopamine in the brain.
Used in Antipsychotic Applications:
Pramipexole is used as an antischizophrenic agent, assisting in the management of schizophrenia symptoms by targeting dopamine receptors in the brain.
Used in Dopamine Agonist Applications:
Pramipexole functions as a dopamine agonist, meaning it mimics the effects of dopamine in the body, which can be beneficial for various medical conditions related to dopamine imbalances.

Clinical Use

Parkinson’s disease Symptomatic treatment of restless legs

Drug interactions

Potentially hazardous interactions with other drugs Avoid concomitant use with antipsychotics.

Metabolism

Pramipexole undergoes <10% metabolism to inactive metabolites. More than 90% of a dose is excreted via renal tubular secretion unchanged into the urine.

InChI:InChI=1/C10H17N3S.2ClH.H2O/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8;;;/h7,12H,2-6H2,1H3,(H2,11,13);2*1H;1H2

Upstream product

• 104632-26-0 pramipexole 
• 943319-02-6 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole p-toluenesulfonic acid 
• 104632-25-9 pramipexole dihydrochloride 
• 106006-84-2 (S)?2?amino?6?propionamido?4,5,6,7?tetrahydrobenzothiazole 

Relevant articles and documents

Preparation method of high-purity pramipexole dihydrochloride

The invention provides a preparation method of high-purity pramipexole dihydrochloride, which comprises the following steps: (a) by using (S)-2-amino- 6-propionamido 4, 5, 6, 7-tetrahydrobenzothiazoleas a raw material and tetrahydrofuran as a solvent, reacting in the presence of a reducing agent, and adding diluted hydrochloric acid to terminate the reaction after the reaction is completed; (b) adding a sodium hydroxide solution to adjust the pH value, adding an extraction agent for extraction, adding an alcohol reagent, dropwise adding concentrated hydrochloric acid for salifying, cooling for crystallization, filtering and drying to obtain pramipexole dihydrochloride monohydrate; and (c) refining the pramipexole dihydrochloride monohydrate obtained in the step (b) through a ternary system of water, an alcohol reagent and an ester reagent, filtering and drying to obtain a pramipexole dihydrochloride finished product. The novel synthetic method of pramipexole dihydrochloride is simplein reaction steps, high in safety, high in yield, stable in water content and suitable for industrial production, and the purity of pramipexole dihydrochloride reaches 99.95% or above. The pramipexoledihydrochloride has stable water content and is suitable for industrial production.

A novel scalable synthesis of pramipexole

Pramipexole is a dopamine D2 subfamily receptor agonist that is used for the treatment of Parkinsons disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6S)-N-(2-amino-4,5,6,7- tetrahydrobenzothiazole-6-yl)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro- N-propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.

PROCESSES FOR THE PREPARATION OF PRAMIPEXOLE AND SALTS THEREOF

The invention relates to processes for the preparation of pramipexole or pharmaceutically acceptable salts thereof. More particularly, it relates to a process for the preparation of pramipexole dihydrochloride monohydrate. The invention also relates to a novel compound, 2-bromo-4-aminocyclohexanone and processes for its preparation. The 2- bromo-4-aminocyclohexanone is a useful intermediate in the preparation of pramipexole or salts thereof. The invention further relates to a single step process for the preparation of 2,6-diamino-4,5,6,7-tetrahydrobenzathiazole, an intermediate useful in the preparation of pramipexole or salts thereof.

PROCESS FOR THE PREPARATION OF PRAMIPEXOLE BASE AND/OR ITS SALTS

The process for the preparation of pramipexole base and/or its pharmaceutically accepted salts, especially hydrochloride salt, is based on the reaction of (S)-(-)2,6-diamino-4,5,6,7-tetrahydrobenzothiazole with an alkylating agent, wherein the reaction is carried out with the absence of a base, in a solvent from which the resulting N-monoalkylated product selectively precipitates out as a salt, which, after isolation from the reaction mixture: a) upon the treatment of inorganic base is converted into free pramipexole base, and then into another pharmaceutically accepted pramipexole salt, or b) is converted directly into another pharmaceutically accepted pramipexole salt or the hydrate thereof.