反应详情

温度

7.5 °C

A suspension of tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (3009.5 g, 6.05 mol) in DCM (9 L) was cooled to 5-10° C. under N2. TFA (9 L) was added portionwise to the suspension whilst maintaining the temperature <30° C. The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated, the resulting residue was dissolved in water (30 L) and added slowly to a 35% aqueous ammonia solution (12 L) at 0-5° C. The suspension was stirred for 30 min then the product was filtered off and washed with water (2×6 L). The product was dried at 50° C. in vacuo for 2 days to afford 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-ethyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine ((2496 g): 1H NMR Spectrum: (DMSO-d6) 1.4-1.52 (12H, m), 1.57-1.73 (2H, m), 1.83-1.93 (2H, nm), 2.57-2.7 (2H, m), 2.71-2.84 (1H, m), 2.96-3.09 (2H, m), 4.58 (2H, q), 8.06 (2H, s), 8.84 (1H, s): Mass Spectrum [M+H]+=398.

1. temperaturewhilst maintaining the temperature <30° C
2. concentrationThe mixture was concentrated
3. dissolutionthe resulting residue was dissolved in water (30 L)
4. additionadded slowly to a 35% aqueous ammonia solution (12 L) at 0-5° C
5. stirringThe suspension was stirred for 30 min
6. filtrationthe product was filtered off
7. washwashed with water (2×6 L)
8. customThe product was dried at 50° C. in vacuo for 2 days