Dimethylformamide → 5-(3-Isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazole

Participants

Reaction Conditions

Reaction Steps

A 50-mL round bottom flask was charged with 5-iodo-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazole (0.65 g, 1.8 mmol) and THF (4.5 mL) to give a white suspension. The mixture was cooled to about −65° C. followed by the addition of a 2.0 M solution of i-PrMgCl (1.1 mL, 2.1 mmol). The resulting suspension was stirred at about −55° C. for about 30 min and at about −30° C. for about 1.75 h. To the reaction mixture was added dropwise a prepared solution of zinc chloride (0.32 g, 2.3 mmol) in THF (3.0 mL) and the resulting suspension was stirred at about −30° C. for about 30 min. In a separate flask were mixed 6-iodo-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.49 g, 1.7 mmol, Preparation #H.1), Pd(PPh3)4 (Strem, 0.073 g, 0.071 mmol), and DMF (5.0 mL). This solution was added to the reaction flask, which was immediately heated to about 80° C. in order to solubilize the resulting mixture. The mixture was heated at about 80° C. for about 1 h. The cooled reaction mixture was concentrated to dryness under reduced pressure and the residue was dissolved in DCM and washed with 1 N HCl, 5 N HCl, water, and brine. The solution was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure. The crude product was recrystallized from ACN to give a light yellow powder, followed by RP-HPLC (Table 1, Method l) purification to give the title compound as an off-white powder (0.025 g, 3.5%): LC/MS (Table 1, Method a) Rt=2.47 min; MS m/z 399.1 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, 1 H), 8.26 (d, 1 H), 8.22 (d, 1 H), 7.85-7.71 (m, 2 H), 7.07 (dd, 1 H), 3.73-3.66 (m, 1 H), 1.44 (d, 6 H).

Provenance & Evidence