6-Bromo-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine

Synthesis

A mixture of 2-hydrazino-5-bromopyridine (4.34 g, 23.1 mmol) and isobutyryl chloride (21.8 mL, 0.208 mol) was refluxed under mild conditions for 3 hours. After the reaction was completed, the mixture was cooled to room temperature. Hexane (22.0 mL) was added and the resulting slurry was stirred at room temperature for 15 minutes, followed by filtration. The filter cake was washed three times (3×) with hexane and dried in a vacuum oven at 30-35 °C for 48 h to give an off-white powdery product (5.90 g, 92.3% yield). The resulting product (5.87 g, 21.2 mmol) was cooled to 5-10 °C with a two-phase mixture formed with water (12.0 mL) and dichloromethane (18.0 mL). An aqueous NaOH solution (21.5 mL) was added dropwise over 10 min. The reaction mixture was stirred in an ice-water bath for 15 min, followed by separation of the organic layer. The aqueous layer was extracted twice (2×) with dichloromethane. The combined organic extracts were washed with 1:1 brine and dried with anhydrous magnesium sulfate (MgSO). After removing most of the dichloromethane under reduced pressure, ethyl acetate (8.0 mL) was added. When about half of the solvent was evaporated, hexane (32.0 mL) was added. The slurry was stirred in an ice-water bath for 2 hours and subsequently filtered. The filter cake was washed three times (3×) with a 9:1 hexane-ethyl acetate mixture and dried in a vacuum oven at 30-35 °C for 18 h. The final product was 6-bromo-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine as a tan powder (4.72 g, 92.5% yield).

References

[1] Patent: WO2004/20440, 2004, A1. Location in patent: Page 46
[2] Patent: WO2004/20440, 2004, A1. Location in patent: Page 55