反应详情

In a 500 ml, 3-neck flask equipped with a mechanical stirrer, dropping funnel and thermometer, acetic acid (100 mL) was added and cooled in an ice bath. Potassium thiocyanate (40 g, 412 mmol) and 6-methoxypyridin-3-amine (6.2 g, 49.9 mmol) were added to the reaction mixture. The reaction was cooled in an ice-salt bath until the reaction temperature reached <0° C. A solution of bromine (8 mL, 156 mmol) in acetic acid (30.0 mL) was added dropwise over 2 hours at a rate that maintained the reaction temperature <0° C. Mechanical stirring was required. After the addition was complete, the mixture was left to stir and allowed to slowly warm to room temperature overnight. Water (30 mL) was then added and the mixture was heated to 85° C. in an oil bath. This mixture was then filtered while still hot. The orange filter cake was returned to the reaction flask, and an additional 50 ml acetic acid was added. The mixture was heated again to 85° C., and then filtered while still hot once more. The combined filtrates were cooled in an ice bath and neutralized to pH 8 with conc. ammonium hydroxide. A purple precipitate formed which was then collected by filtration to afford 5 g of crude material. This crude material was recrystallized from methanol (40 mL) to yield 5-methoxythiazolo[5,4-b]pyridin-2-amine (3 g, 16.55 mmol, 33.1% yield) as purple crystals. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.60 (1 H, d, J=8.42 Hz), 7.41 (2 H, s), 6.67 (1 H, d, J=8.78 Hz), 3.81 (3 H, s).

1. customIn a 500 ml, 3-neck flask equipped with a mechanical stirrer
2. temperaturecooled in an ice bath
3. temperatureThe reaction was cooled in an ice-salt bath until the reaction temperature
4. customreached <0° C
5. temperaturemaintained the reaction temperature <0° C
6. additionAfter the addition
7. waitthe mixture was left
8. stirringto stir
9. temperaturethe mixture was heated to 85° C. in an oil bath
10. filtrationThis mixture was then filtered while still hot
11. additionan additional 50 ml acetic acid was added
12. temperatureThe mixture was heated again to 85° C.
13. filtrationfiltered while still hot once more
14. temperatureThe combined filtrates were cooled in an ice bath
15. customA purple precipitate formed which
16. filtrationwas then collected by filtration
17. customto afford 5 g of crude material
18. customThis crude material was recrystallized from methanol (40 mL)