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

Participants

Reaction Steps

To a solution of 2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acid (70 mg, 0.289 mmol) in DMF (2.0 mL) was added 1-amino-3,6-dimethylpyrazin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (98 mg, 0.289 mmol) followed by O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (93 mg, 0.289 mmol) and triethylamine (0.040 mL, 0.289 mmol) at rt. After 2 h stirring at rt, the reaction mixture was stirred at 70° C. for 12 h. The crude was purified by prep HPLC using Phenomenex column and MeOH—H2O-TFA as eluent (20% to 100% over 12 min gradient; flow: 40 mL/min). Collected the pure fractions and removed solvent. Obtained 5,8-dimethyl-2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-[1,2,4]triazolo[1,5-a]pyrazine in 44% yield. Prepared hydrochloride salt by adding 1.0 M HCl (3 mL) and MeOH (3 mL) and removing solvent. 1H NMR (500 MHz, METHANOL-d4) δ 6.63 (s, 1H), 6.24 (s, 1H), 6.15-6.11 (m, 2H), 5.90-5.85 (m, 2H), 5.84-5.79 (m, 1H), 2.33 (s, 3H), 1.74-1.71 (m, 1H), 1.50-1.44 (m, 4H), 1.28 (s, 3H), 0.63-0.58 (m, 1H), 0.56-0.51 (m, 1H); MS (ESI) 345 (M+H); Rf=1.61 (Condition A).

Provenance & Evidence