Hydrochloric Acid → 3-Chloropyrazine-2,6-diamine

Temperature

90 °C

Lithium hydroxide (12.4 g, 0.30 mol) was added to a stirred suspension of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 90° C. for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1,4-dioxane (350 ml) and 2M aqueous HCl solution (200 ml) was added. The mixture was heated at 100° C. for 2 hours and then allowed to cool before removing the 1,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3×300 ml). The combined organic layers were washed with brine (300 ml), dried (Na2SO4) and concentrated in vacuo to afford a yellow solid (11.7 g, 82%).

1. temperatureto cool to room temperature
2. concentrationThe reaction was concentrated in vacuo
3. customto afford a yellow slurry
4. temperatureThe mixture was heated at 100° C. for 2 hours
5. temperatureto cool
6. custombefore removing the 1,4-dioxane in vacuo
7. extractionextracted into ethyl acetate (3×300 ml)
8. washThe combined organic layers were washed with brine (300 ml)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo

ORD record

ord-6b7cb45a7d6d4b66bc161e41e641665a

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572797B2