Hydrochloric Acid → 2-Chloro-[1,3]thiazolo[5,4-b]pyridine

Temperature

130 °C

3-Amino-2-bromopyridine (1.14 g, 6.59 mmol) and ethyl potassium xanthate (2.324 g, 14.50 mmol) were dissolved in dry dimethylformamide (4 mL) and heated at 130° C. for 15 hours. The reaction was cooled and diluted with water (150 mL). 5 N Hydrochloric acid (4 mL) was added and the mixture stirred. The intermediate precipitated as a light yellow solid and was filtered off. The solids were suspended in warm ethyl acetate (200 mL) and dried with magnesium sulfate. The filter cake was washed with additional warm ethyl acetate (200 mL). The organic was evaporated to dryness under reduced pressure and suspended in dichloromethane (50 mL). Sulfuryl chloride (20 ml, 247 mmol) was added and the mixture stirred at room temperature. After 1 hour, the mixture was evaporated to dryness under reduced pressure and the residue partitioned between ethyl acetate (200 mL), ice (˜50 mL), water (100 mL) and saturated sodium bicarbonate (60 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired 2-chlorothiazolo[5,4-b]pyridine (0.120 g, 0.703 mmol, 10.7% yield).

1. temperatureThe reaction was cooled
2. customThe intermediate precipitated as a light yellow solid
3. filtrationwas filtered off
4. dry with materialdried with magnesium sulfate
5. washThe filter cake was washed
6. temperaturewith additional warm ethyl acetate (200 mL)
7. customThe organic was evaporated to dryness under reduced pressure
8. stirringthe mixture stirred at room temperature
9. customthe mixture was evaporated to dryness under reduced pressure
10. customthe residue partitioned between ethyl acetate (200 mL), ice (˜50 mL), water (100 mL) and saturated sodium bicarbonate (60 mL)
11. dry with materialThe organic phase was dried with magnesium sulfate
12. customevaporated to dryness under reduced pressure
13. customPurification

ORD record

ord-d437da1d70b94beeb9f83879ff83397a

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174992B2