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

Participants

Reaction Conditions

Reaction Steps

A 15 mL round bottom flask is charged with 3-iodo-2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine (0.200 g, 0.000539 moles), 4-(4-chloro-thiazol-2-yl)-morpholine (0.165 g, 0.000808 moles), Cs2CO3 (0.361 g, 0.00108 moles, 2.0 equiv), Pd(dba)2 (0.0092 g, 0.0000161 moles, 0.03 equiv), PPh3 (0.00847 gram, 0.000323 moles, 0.060 equiv) and DMF (2.0 mL). Nitrogen is bubbled through the reaction mixture for 15 minutes; then, the reaction mixture is heated at 130° C. overnight. The next day, the reaction mixture is partitioned between Et2O and a saturated solution of NH4Cl. The aqueous layer is extracted twice more with Et2O. The organic extracts are combined, washed 2-3 times with H2O, washed once with brine, and dried over Na2SO4. The solvents are evaporated in vacuo and the crude reaction mixture is purified via silica gel chromatography. Yield=0.1737 g (72%). 1H-NMR (CDCl3), δ 0.87 (t, J=7 Hz, 6H), 1.14-1.37 (m, 4H), 1.74 (q, J=8 Hz, 4H), 2.54 (s, 3H), 2.50 (s, 3H), 3.48 (m, 1H), 3.53 (t, J=5 Hz, 4H), 3.83 (t, J=5 Hz, 4H), 6.71 (br s, 1H) ppm. LC/MS (m/z): calcd. for C22H30ClN5OS (M+H)+: 448; found: 448.

Provenance & Evidence