Pramipexole Impurity 16 Chemical Properties

storage temp. 

-20°C

solubility 

H2O: >15mg/mL

form 

powder

color 

white to beige

optical activity

[α]/D 60 to 70°, c = 1 in methanol

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

HS Code 

2934200000

Pramipexole Impurity 16 Usage And Synthesis

Description

Pramipexole (Item No. 11981) is an agonist of dopamine receptors that has applications in Parkinson’s disease and other disorders. Pramipexole is usually available as a mixture of enantiomers, with the majority of the dopamine receptor-dependent activity resulting from the (S) form. (R)-Pramipexole is an enantiomer of pramipexole that is ~100-fold less active than the (S) form as a dopamine receptor agonist. For this reason, it can be used as a negative control for the (S) form in the study of dopamine receptors. Both isoforms are antioxidants that target mitochondria to prevent apoptosis. This cytoprotective effect of (R)-pramipexole, without dopaminergic side effects, suggests utility in amyotrophic lateral sclerosis.

Uses

(R)-Pramipexole Dihydrochloride (Pramipexole EP Impurity D; Pramipexole BP Impurity D; Pramipexole USP Related Compound D) is the opposite enantiomer of Pramipexole (P700755), a dopamine-D2-receptor agonist. Dexpramipexole is a low-molecular-weight, water-soluble, orally bioavailable, renally excreted compound with linear pharmacokinetics.

Uses

These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements. Pramipexole may be used as a secondary pharma standard for the determination of the analyte in pharmaceutical formulations using reversed-phase high-performance liquid chromatography and ultraviolet spectrophotometry technique.

General Description

Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Pramipexole Related Compound D is a pharmaceutical impurity of pramipexole. Pramipexole is a non-ergot dopamine receptor agonist, widely used in the treatment of Parkinson′s disease.

Biochem/physiol Actions

R-(+)-Pramipexole is a neuroprotective agent; weak non-ergoline dopamine agonist. R-(+)-Pramipexole has been found to have neuroprotective effects and is being investigated for treatment of ALS. It reduces mitochondrial reactive oxygen species (ROS) production, inhibits the activation of apoptotic pathways, and increase cell survival in response to a variety of neurotoxins and β-amyloid neurotoxicity. Compared to the S-(-) isomer, R-(+)-Pramipexole has much lower dopamine agonist activity.

Synthesis

The general procedure for the synthesis of (R)-N6-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride using (R)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazol-6-yl)-propanamide as starting material was as follows: under nitrogen protection, (R)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazol-6-yl)-propanamide (10 g, 33.43 mmol) with dichloromethane (100 mL) was added to a round bottom flask, stirred for 10-15 min and then cooled to 0-5 °C. Subsequently, trimethylsilyl chloride (5.1 mL, 40.12 mmol) was slowly added over 10-15 minutes and stirring was continued at the same temperature for 10-15 minutes. A tetrahydrofuran solution of lithium aluminum hydride (19.5 mL, 46.81 mmol) was added dropwise at -10°C to 0°C. After dropwise addition, the reaction mixture was kept at 0-10 °C and stirring was continued for 1-2 hours. Upon completion of the reaction (monitored by thin layer chromatography), 2M sodium hydroxide solution (30 mL) was slowly added dropwise to quench the reaction and stirred for 10-15 minutes. After separating the aqueous and organic layers, the target compound was extracted from the aqueous layer with dichloromethane (50.0 mL). The organic layers were combined and washed with 20% NaCl solution. Finally, the dichloromethane layer was concentrated to give a crude product which was dissolved in isopropanol (50.0 mL).

References

[1] Tetrahedron Letters, 2013, vol. 54, # 36, p. 4908 - 4913

Pramipexole Impurity 16(104632-27-1)Related Product Information

• Aripiprazole
• Ethyl Pramipexole
• (S)-4,5,6,7-Tetrahydro-N2,N6-propionyl-2,6-benzothiazolediaMine
• (R)-Pramipexole
• 2-AMino-6-broMo-5,6-dihydro-7(4H)-benzothiazolone
• Pramipexole Impurity 18
• BENZOOXAZOL-2-YLAMINE
• rac-trans-7-Hydroxy Pramipexole
• Pramipexole EP Impurity B DiHCl
• N6-propyl-3a,4,5,6,7,7a-hexahydrobenzo[d]thiazole-2,6-diamine
• 2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazol-7-ol
• Pramipexole impurity 7
• Pramipexole
• (6S)-N6-[3-[[(6S)-2-Amino-4,5,6,7-tetrahydro-6-benzothiazolyl]amino]-1-ethyl-2-methylpropyl]-4,5,6,7-tetrahydro-2,6-benzothiazolediamine
• Pramipexole
• rac N-Propyl-2-cyanimidopyrrolidine-5-acetic Acid
• 2-N-Propyl Pramipexole
• (R)-N-(2-AMINO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-6-YL)-PROPIONAMIDE