反应详情

温度

20 °C

To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) was added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture was stirred at room temp. (20° C.) for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) was then added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3 h at reflux, the mixture was allowed to cool and filtered to collect the precipitated solid. Further product were collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids were washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford the triazolopyridine derivative (3) as a solid. The compound was used as such for the next step without any purification. 1H (400 MHz, DMSO-d6) δ 7.43-7.34 (2H, m, 2×aromatic-H), 7.24 (1H, dd, J 6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).

1. temperaturethe mixture slowly heated
2. temperatureto reflux
3. custom(Note: bleach scrubber is required to quench H2S evolved)
4. temperatureAfter 3 h at reflux
5. temperatureto cool
6. filtrationfiltered
7. customto collect the precipitated solid
8. filtrationFurther product were collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration
9. washThe combined solids were washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL)
10. customthen dried in vacuo