Cesium carbonate → 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

In a dry 25 mL round bottom flask, 8-(1-ethyl-propyl)-3-iodo-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine (250 mg, 0.630 mmol), 4-(4-chloro-thiazol-2-yl)-morpholine (194 mg, 0.945 mmol), and Cs2CO3 (410 mg, 1.26 mmol) are dissolved in DMF. The mixture is degassed with bubbling nitrogen for 15 minutes. Then, Pd2(dba)3 (18 mg, 0.032 mmol) and PPh3 (33 mg, 0.126 mmol) are added. The reaction mixture is heated to 130° C. overnight. The reaction is cooled to room temp., quenched with a solution of NH4Cl sat? (20 mL), and extracted with Et2O (3×50 mL). The combined organic extracts are washed with brine (30 mL), dried with Na2SO4, filtered and concentrated. The residue is purified via reverse phase HPLC with a 30-80% gradient of CH3CN in 10 mM NH4HCO3/H2O/5% CH3CN (pH 10.0) to give the title compound (11 mg, 0.023 mmol, 4%). 1H-NMR (CDCl3), δ 0.86 (t, J=7.3 Hz, 6H), 1.84 (m, 4H), 2.55 (s, 3H), 3.31 (m, 1H), 3.54 (dd, J=5.2, 4H), 3.84 (dd, J=5.2 Hz, 4H), 6.82 (s, 1H) ppm. ES-MS (m/z): calcd for C20H23ClF3N5OS (M+H)+: 473.95; found: 474.2.

Provenance & Evidence