2-Chloro-6-fluorobenzothiazole

Chemical Properties

White solid

Biological Activity

2-Chloro-6-fluorobenzothiazole is a potent inhibitor of diacylglycerol acyltransferase, an enzyme involved in the biosynthesis of triglycerides. It has been shown to inhibit the enzymatic activity of this enzyme and decrease triglyceride levels by inhibiting the production of fatty acids.

Synthesis

General procedure for the synthesis of 2-chloro-6-fluorobenzothiazole from 2-amino-6-fluorobenzothiazole: In a round-bottomed flask, 2-amino-6-fluorobenzothiazole (1.0017 g, 5.96 mmol, Sigma-Aldrich Chemical Company, Inc.), copper(II) chloride (1.201 g, 8.93 mmol, Sigma-Aldrich Chemical Company, Inc.) and tert-butyl nitrite (1.063 mL, 8.93 mmol, Acros Organics) in acetonitrile (ACN). The reaction mixture was heated to 65 °C and kept at this temperature for 2 hours. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate (EtOAc). The organic phase was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to afford the target product 2-chloro-6-fluorobenzothiazole (0.9249 g, 4.93 mmol, 83% yield). The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 7.45 (td, J = 9.10, 2.74 Hz, 1H), 7.97-8.07 (m, 2H).

References

[1] Patent: US2013/225552, 2013, A1. Location in patent: Paragraph 0976
[2] Patent: WO2012/69503, 2012, A1. Location in patent: Page/Page column 18-19
[3] Patent: US2013/172326, 2013, A1. Location in patent: Paragraph 0081; 0082
[4] Journal of the Indian Chemical Society, 1933, vol. 10, p. 465,469
[5] Farmaco, Edizione Scientifica, 1977, vol. 32, p. 348 - 354