Ethanol → (R)-N-{4-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-phenyl}-acetamide

Participants

Reaction Conditions

Reaction Steps

The product of Example 9A (182 mg, 0.76 mmol), N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide (Aldrich, 500 mg, 1.9 mmol), dichlorobis(triphenylphosphine)palladium (II) (Aldrich, 53 mg, 0.076 mmol) and 2-(dicyclohexylphosphino)biphenyl (Strem Chemicals, 6.5 mg, 0.019 mmol) were combined with 1 mL each of ethanol, p-dioxane, and 1 M aq. sodium carbonate. The mixture was heated in a sealed tube to 150° C. at 330 watts for 10 min in an Emry™ Creator microwave. The mixture was cooled to room temperature, filtered through Celite®, and concentrated onto silica. The product was purified by column chromatography (SiO2, 5% methanol containing 1% NH4OH—CH2Cl2) to provide the title compound (203 mg, 79%). 1H NMR (300 MHz, CD3OD) δ 1.96 (m, 1H), 2.09 (m, 1H), 2.16 (m, 1H), 2.16 (s, 3H), 2.38 (m, 1H), 2.64 (td, J=6.5, 3.6 Hz, 1H), 3.33-3.53 (m, 6H), 3.97 (dd, J=13.9, 8.1 Hz, 1H), 5.54 (m, 1H), 7.32 (d, J=9.4 Hz, 1H), 7.69-7.78 (m, 2H), 7.91-7.98 (m, 2H), 8.11 (d, J=9.3 Hz, 1H) ppm; MS (DCI/NH3): m/z 339 (M+H)+.

Provenance & Evidence