Dichloromethane → HCID 117993526, compound

Participants

Reaction Conditions

Reaction Steps

An oven-dried 20 mL vial was charged with 6-bromo-1-ethyl-4-methyl-1H-indazole (345 mg, 1.4 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi(1,3,2-dioxaborinane) (591 mg, 1.7 mmol), oven dried KOAc (566 mg, 5.8 mmol), anhydrous dioxane (5 mL) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropaladium(II) complex with dichloromethane (56.8 mg, 0.072 mmol). The mixture was bubbled with nitrogen gas for 5 minutes, and the reaction vial was sealed and heated at 110° C. for 1 h. After being cooled to r.t., to the reaction mixture was added (R)-3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (294 mg, 1.2 mmol), an aqueous solution of sodium carbonate (2M, 1.8 mL, 3.6 mmol) and additional [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (56.8 mg, 0.072 mmol). The reaction mixture was degassed with nitrogen, and heated at 100° C. for 75 min. The reaction mixture was cooled to r.t., diluted with EtOAc, filtered over Celite®, and the filtrate was concentrated. The crude residue was purified by silica gel column chromatography (0-10% EtOH/DCM, 40 g column) to afford (R)-3-(6-(1-ethyl-4-methyl-1H-indazol-6-yl)-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (429 mg, 79%) as an off-white solid. 1H NMR (600 MHz, CDCl3) δ 1.56 (t, 3H), 1.64-1.91 (m, 2H), 1.74 (s, 3H), 1.97-2.08 (m, 1H), 2.35-2.44 (m, 1H), 2.66 (s, 3H), 3.39-3.50 (m, 1H), 3.51-3.62 (m, 1H), 4.13 (s, 3H), 4.51 (q, 2H), 6.07 (brs, 1H), 7.43 (d, 1H), 7.55 (s, 1H), 7.68 (d, 1H), 7.89 (s, 1H), 8.01 (s, 1H). MS (AP+)(M+H) 379.

Provenance & Evidence