6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Synthesis

General procedure for the synthesis of 6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine from ethyl N-[[(5-chloro-2-pyridinyl)amino]thiomethyl]carbamate: Hydroxylammonium chloride (4.4 g) was suspended in methanol (35 mL), and ethanol (35 mL) and Hünig's base (10.2 mL) were added sequentially at room temperature. The reaction mixture was heated to 60 °C, N-[[(5-chloro-2-pyridinyl)amino]thiomethyl]carbamic acid ethyl ester (4.4 g) was added in batches and the reaction was stirred at 60 °C for 2 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure and the solid was precipitated by addition of water (150 mL). The solid product was collected by filtration, washed with water and dried under reduced pressure to afford 6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (2.0 g). The product was characterized by 1H-NMR (300 MHz, DMSO-d6): δ[ppm] = 6.09 (2H), 7.28-7.37 (1H), 7.39-7.49 (1H), 8.84 (1H).

References

[1] Patent: WO2014/9219, 2014, A1. Location in patent: Page/Page column 111
[2] Patent: WO2014/195276, 2014, A1. Location in patent: Page/Page column 113-114
[3] Patent: WO2014/198647, 2014, A2. Location in patent: Page/Page column 79
[4] Patent: US2015/148542, 2015, A1. Location in patent: Paragraph 0531; 0532; 0533; 0534