Pramipexole impurity 7

Chemical Properties

Pale Beige Solid

Uses

(S)-N-Despropyl Pramipexole is a (S)-Pramipexole (P700745) intermediate as dopamine autoreceptor agonist.

Uses

(S)-N-Despropyl Pramipexole (Pramipexole EP Impurity A; Pramipexole BP Impurity A; Pramipexole USP Related Compound A) is a (S)-Pramipexole (P700755) intermediate as dopamine autoreceptor agonist.

Uses

(S)-Pramipexole intermediate as dopamine autoreceptor agonist.

Synthesis

General procedure for the synthesis of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole from 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole: First, 33.8 g of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole was mixed with 500 mL of water, followed by the addition of 30.0 g of L-(+)-tartaric acid. The reaction mixture was heated to 75°C and stirred for 1 hour. Thereafter, it was cooled to room temperature and stirring was continued for 24 hours. After completion of the reaction, filtration was carried out, the precipitate was washed with water and dried under vacuum at 55°C to 65°C and -0.01 MPa to -0.1 MPa for 8-12 hours to afford 35.1 g of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazolium di-L-(+)-tartrate as crude product with an enantiomeric content of 2.53% (by chiral-HPLC determination). The entire crude product was redissolved in 500 mL of water, heated to 75°C and held for 1 hour, then cooled to room temperature and stirred for 24 hours. It was filtered again, washed with water and dried under the same vacuum conditions for 8-12 hours to give 26.9 g of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazolyl di-L-(+)-tartrate with enantiomeric content reduced to 0.08%. Finally, the entire product was dissolved in a mixture of 200 mL of water and 40 mL of hydrochloric acid and stirred until completely dissolved. Subsequently, 35 drops of aqueous potassium hydroxide solution (mass percent is the ratio of potassium hydroxide to the total mass of the solution) were added to neutralize. The reaction mixture was cooled to room temperature and stirred for 1 h. The reaction mixture was filtered, the precipitate was washed with water and dried under vacuum at 55°C to 65°C and -0.01 MPa to -0.1 MPa for 8-12 h. The final product was 9.43 g of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole in a yield of 27.9% and enantiomeric content of 0.08%.

References

[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5501 - 5521
[2] Patent: CN108084115, 2018, A. Location in patent: Paragraph 0086; 0089
[3] Journal of Medicinal Chemistry, 1987, vol. 30, # 3, p. 494 - 498
[4] Patent: WO2011/21214, 2011, A2
[5] Investigational New Drugs, 2010, vol. 28, # 4, p. 454 - 465