Ammonium Hydroxide → 2-(Trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrazine
Reaction equation
[F:1][C:2]([F:14])([F:13])[C:3](=[N:11]O)[NH:4][C:5]1[CH:10]=[N:9][CH:8]=[CH:7][N:6]=1.[OH-].[NH4+]>>[F:1][C:2]([F:14])([F:13])[C:3]1[N:4]=[C:5]2[CH:10]=[N:9][CH:8]=[CH:7][N:6]2[N:11]=1Participants
3
Conditions
- Temperature
- 150 °C
Procedure
A mixture of 2,2,2-trifluoro-N′-hydroxy-N-pyrazin-2-ylethanimidamide (10.5 g, 50.97 mmol, from Step B) and polyphosphoric acid (80 mL) was heated to 150° C. with stirring for 18 h. The solution was added to ice and neutralized by addition of ammonium hydroxide. The dark aqueous solution was extracted three times with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (50% then 100% ethyl acetate/hexane) afforded the title compound as a yellow solid. 1H-NMR (500 MHz, CDCl3): δ 8.42 (d, 1H, J=4.6 Hz), 8.67 (dd, 1H, J=1.4 and 4.6 Hz), 9.47 (d, 1H, J=1.4 Hz). LC/MS 189 (M+1).