Pyrazine-2-Carboxylic Acid Hydrazide → (6S)-7-[2-Chloro-3-(trifluoromethyl)benzyl]-6-ethyl-3-pyrazin-2-yl-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

Participants

Reaction Steps

A solution of Intermediate 6 (100 mg, 0.29 mmol) and pyrazine-2-carbohydrazide (39 mg, 0.29 mmol) in 1-butanol (3 mL) was heated to 130° C. for 16 h. After cooling to rt, the reaction was concentrated to give a brown oil. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a white solid (94 mg, 75%). MS (ESI): mass calcd. for C19H16ClF3N6O, 436.1; m/z found, 437.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 9.62 (d, J=1.5 Hz, 1H), 8.69 (d, J=2.5 Hz, 1H), 8.62 (dd, J=2.5, 1.6 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.69 (dd, J=7.8, 1.1 Hz, 1H), 7.42 (t, J=7.8 Hz, 1H), 5.56-5.42 (m, 2H), 4.54 (d, J=15.5 Hz, 1H), 4.46 (dd, J=14.1, 4.4 Hz, 1H), 3.77 (ddd, J=9.4, 4.6, 3.5 Hz, 1H), 1.87-1.78 (m, 1H), 1.63-1.53 (m, 1H), 0.97 (t, J=7.4 Hz, 3H).

Provenance & Evidence