Trifluoroacetic acid → 3-(Trifluoromethyl)-1,2,4-triazolo(4,3-a)pyrazine

Temperature

140 °C

A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140° C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3×), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid (861 mg). 1H NMR (500 MHz, CDCl3) δ 8.17˜8.20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189.

1. extraction1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane
2. filtrationfiltered
3. concentrationthe filtrate was concentrated
4. custompurified by flash chromatography on silica gel
5. washeluting with 100% ethyl acetate
6. additionThe solution was added to ice
7. extractionThe aqueous solution was extracted with ethyl acetate (3×)
8. washwashed with brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationConcentration

ORD record

ord-511fc44fcf5c421caf98b4aee3cbb929

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08440668B2