4-Toluenesulfonyl chloride → 5-Bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

Temperature

70 °C

p-Toluenesulfonyl chloride (164 g, 861.60 mmol) was added portion wise to a suspension of 3-amino-6-bromo-N′-pivaloylpyrazine-2-carbohydrazide (227 g, 718.00 mmol) and N,N-diisopropylethylamine (297 mL, 1795.01 mmol) in acetonitrile (2200 mL). The mixture was stirred for 2 hours at 70° C. The reaction was left to cool to room temperature overnight. The reaction mixture was partitioned between ethyl acetate (2 L) and sodium bicarbonate solution (2 L). The organic layer was washed with saturated brine, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown/beige solid was triturated with hot MTBE (1000 mL) and isolated by filtration and dried to afford 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine as a yellow solid (187 g, 87%). The mother liquors were evaporated to dryness. The crude solid was triturated with MTBE (500 mL) filtered and washed with 100 mL of MTBE. The resulting solid was air dried overnight to afford a second crop of 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (36 g, 17%): 1H NMR Spectrum: (DMSO-d6) 1.43 (9H, s), 7.70 (2H, s), 8.39 (1H, s); Mass Spectrum [M+H]+=298.

1. waitThe reaction was left
2. temperatureto cool to room temperature overnight
3. customThe reaction mixture was partitioned between ethyl acetate (2 L) and sodium bicarbonate solution (2 L)
4. washThe organic layer was washed with saturated brine
5. dry with materialdried with magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe resulting brown/beige solid was triturated with hot MTBE (1000 mL)
9. customisolated by filtration
10. customdried

ORD record

ord-e24d121fd5bb45448efabb0dbd0dd691

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156831B2