3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride → 2,2-Dimethyl-1-{2-[3-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-propan-1-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-[2-(3-iodo-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.083 g, 0.16 mmol), 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (0.05 g, 0.24 mmol), Pd(PPh3)4 (0.023 g, 0.02 mmol) and sodium t-butoxide (0.046 g, 0.48 mmol) in toluene (2 mL) were heated under an argon atmosphere in a microwave oven at 90° C. for 1 h. After cooling to room temperature, the reaction mixture was directly purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min) to give 25 mg of the desired product as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 8.84 (s, 1H), 8.48 (s, 1H), 8.23 (s, 1H), 7.95 (br s, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.74 (s, 2H), 4.80 (s, 2H), 4.37 (t, J=5.3 Hz, 2H), 3.91 (t, J=5.4 Hz, 2H), 3.66 (dd, J=8.2 Hz, 2H), 1.62 (s, 9H), 0 (s, 9H); MS [M+H]+: 600.

Provenance & Evidence