3H-1,2,4-Triazole-3-thione, 5-amino-4-(4-cyclopropyl-1-naphthalenyl)-2,4-dihydro Chemical Properties

Boiling point:

475.2±38.0 °C(Predicted)

Density 

1.52±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

pka

8.22±0.20(Predicted)

3H-1,2,4-Triazole-3-thione, 5-amino-4-(4-cyclopropyl-1-naphthalenyl)-2,4-dihydro Usage And Synthesis

Uses

5-Amino-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole-3-thiol is a derivative of 5-Amino-4-(4-cyclopropyl-1-naphthalenyl)-2,4-dihydro-3H-1,2,4-Triazol-3-one (A602165), which is an impurity of the drug Lesinuard (L329700), which is used to synthesize febuxostat, a non-purine analog inhibitor of xanthine oxidase. Febuxostat is approved by the European Medicines Agency and the US Food and Drug Administration for treating gout.

Synthesis

1-Cyclopropyl-4-isothiocyanato naphthalene (13.3 mmol, 3.0 g) and aminoguanidine hydrochloride (26.6 mmol, 2.9 g) were mixed in 50 mL of N,N-dimethylformamide. N,N-diisopropylethylamine (39.9 mmol, 5.1 g) was slowly added under stirring conditions. The reaction mixture was stirred at room temperature for 50±12 hrs. After completion of the reaction, the solvent was removed to dryness by rotary evaporator. To the residue, 20 mL of 2 M sodium hydroxide solution was added and the reaction was continued for 50 ± 12 hours. After termination of the reaction, the reaction mixture was filtered and the filtrate was adjusted to pH=4 with dilute hydrochloric acid, at which time a large amount of white precipitate was observed to be generated. The precipitate was collected, washed with deionized water and subsequently dried under vacuum at 45-50 °C to afford the intermediate compound 5-amino-4-(4-cyclopropyl-1-naphthalene)-2,4-dihydro-3H-1,2,4-triazole-3-thiol (VI) in 2.85 g yield and 76% yield.

References

[1] Patent: CN105566237, 2016, A. Location in patent: Paragraph 0066; 0067; 0068
[2] Patent: WO2009/70740, 2009, A2. Location in patent: Page/Page column 89-90
[3] Patent: WO2006/26356, 2006, A2. Location in patent: Page/Page column 21
[4] Patent: WO2011/85009, 2011, A2. Location in patent: Page/Page column 37

3H-1,2,4-Triazole-3-thione, 5-amino-4-(4-cyclopropyl-1-naphthalenyl)-2,4-dihydro(878671-96-6)Related Product Information

• Lesinurad Impurity J
• 4-(4-cyclopropylnaphthalen-1-yl)-1H-1,2,4-triazole-5(4H)-thione
• lesinurad int
• RDEA 594
• Lesinurad Impurity 38
• Lesinurad Impurity 32 (Mixture of Isomers)
• Lesinurad Impurity H
• Lesinurad Impurity 24
• Lesinurad Impurity N
• Lesinurad Impurity 27
• Lesinurad Impurity 22
• Lesinurad Impurity 10
• 1-cyclopropylnaphthalene
• Lesinurad Impurity 4
• N-(4-Cyclopropyl-1-naphthalenyl)-2-formylhydrazinecarbothioamide
• 3-bromo-4-(4-cyclopropylnaphthalen-1-yl)-1H-1,2,4-triazole-5(4H)-thione
• Lesinurad Impurity 5 Sodium Salt
• Lesinurad Impurity 23