1,1'-Carbonyldiimidazole → 2-N-Methyl-2-N-phenyl-6-(5-{6-[2-(2,2,2-trifluoroethoxy)ethoxy]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

Participants

Reaction Steps

6-[2-(2,2,2-Trifluoroethoxy)ethoxy]pyridine-3-carboxylic acid (Intermediate 242, 0.133 g, 0.50 mmol) and 1,1′-carbonyldiimidazole (0.081 g, 0.50 mmol) were combined in pyridine (3 mL) and stirred at room temperature for 3 h. 4-Amino-N-hydroxy-6-[methyl(phenyl)amino]-1,3,5-triazine-2-carboximidamide (prepared in an analogous manner to Intermediate 1, 0.100 g, 0.39 mmol) was added and the mixture stirred at room temperature for 4 h before being heated to 80 C for 16 h. Pyridine was removed under vacuum and the residue was partitioned between EtOAc (20 mL) and water (20 mL). The organic layer was dried over sodium sulfate and concentrated to yield an orange solid. This was purified by FCC, using a gradient of 30-70% EtOAc in heptane to afford the title compound as a white solid (0.116 g, 61%). Method A HPLC-MS: MH+ requires m/z=489 Found: m/z=489, Rt=4.58 min (100%). 1H NMR (500 MHZ, CDCl3) δ ppm 9.06 (1H, s), 8.41 (1H, d), 7.47 (2H, m), 7.34 (3H, m), 6.96 (1H, d), 5.34 (2H, br s), 4.64 (2H, t), 4.04 (2H, t), 3.97 (2H, q) and 3.65 (3H, s).

Provenance & Evidence