Triethylamine → 2-(2-(1-Ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine

Participants

Reaction Steps

To a solution of 2-(1-ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acid (103 mg, 0.4 mmol) in DMF (3.0 mL) was added 1-amino-3,6-dimethylpyrazin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (135 mg, 0.400 mmol) followed by O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (128 mg, 0.400 mmol) and triethylamine (0.277 mL, 2.000 mmol) at rt. After 1 h stirring at rt, the reaction mixture was heated at 70° C. for 15 h. The crude was purified by prep HPLC using Phenomenex column and MeOH—H2O-TFA as eluent (25% to 100% over 12 min gradient; 40 mL/min flow). Collected the pure fractions and removed solvent. Prepared HCl salt by adding MeOH (3 mL) and 1.0 M HCl (3 mL) and removing solvent. Obtained 2-(2-(1-ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine, 1.0HCl (85 mg, 0.202 mmol, 50.6% yield) as a white solid. 1H NMR (500 MHz, METHANOL-d4) δ 8.13 (d, J=0.9 Hz, 1H), 7.99 (s, 1H), 7.80-7.78 (m, 1H), 7.77-7.75 (m, 1H), 7.58-7.50 (m, 2H), 7.40-7.22 (m, 1H), 4.38 (q, J=7.3 Hz, 2H), 3.29-3.25 (m, 1H), 3.10-3.08 (m, 1H), 2.98 (s, 3H), 2.85 (s, 3H), 2.21-2.18 (m, 2H), 1.60 (t, J=7.4 Hz, 3H); MS (ESI) 359 (M+H); Rf=1.99 (Condition A).

Provenance & Evidence