Pivalic acid → 3-(5-Tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

Temperature

80 °C

2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (47.7 g, 148.69 mmol) was added portionwise over 15 minutes to a stirred suspension of N-ethyl-N-isopropylpropan-2-amine (70.6 mL, 405.51 mmol), pivalic acid (17.08 mL, 148.69 mmol) and 3-aminopyrazine-2-carbohydrazide (20.7 g, 135.17 mmol) in acetonitrile (350 mL) and the reaction mixture was stirred at 80° C. for 20 minutes (a solution was obtained). The reaction mixture was cooled to 0° C. and N-ethyl-N-isopropylpropan-2-amine (70.6 mL, 405.51 mmol), followed by 4-methylbenzene-1-sulfonyl chloride (77 g, 405.51 mmol) were added over a period of 15 minutes. The reaction mixture (yellow suspension) was brought to reflux (solubilisation) and then allowed to stir at room temperature for 14 hours affording a dark orange solution. The solution was concentrated. The residue was diluted with dichloromethane, washed with water, brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in dichloromethane. The solvent was evaporated to dryness. The resulting mixture was triturated with ether (100 mL), filtered, washed with the minimum of ether and dried to afford 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (20.8 g, 70.2%) as a pale yellow soild: 1H NMR Spectrum; (CDCl3) 1.53 (9H, s), 1.58-1.68 (2H, m), 6.67 (2H, s), 8.13 (2H, dt); Mass Spectrum [M+H]+=220.

1. customwas obtained)
2. temperatureThe reaction mixture was cooled to 0° C.
3. additionwere added over a period of 15 minutes
4. temperatureto reflux (solubilisation)
5. stirringto stir at room temperature for 14 hours
6. customaffording a dark orange solution
7. concentrationThe solution was concentrated
8. additionThe residue was diluted with dichloromethane
9. washwashed with water, brine
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated
12. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in dichloromethane
13. customThe solvent was evaporated to dryness
14. customThe resulting mixture was triturated with ether (100 mL)
15. filtrationfiltered
16. washwashed with the minimum of ether
17. customdried

ORD record

ord-62b255729e2d4647b6bce8b4ed5929e4

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156831B2