Methanol → Ethyl 4-ethyl-1-(5-(2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl trifluoromethanesulfonate (Intermediate 13) (0.25 g, 0.587 mmol) in 1,4-dioxane:MeOH (21 mL: 14 mL) were added ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate (0.46 g, 1.17 mmol) and potassium phosphate (0.19 g, 0.88 mmol) at rt under N2 atmosphere. The reaction mixture was degassed by N2 for 15 min followed by addition of tetrakis (triphenylphosphine)palladium(0) (0.068 g, 0.058 mmol). The reaction mixture was further degassed by N2 for 15 min then stirred for 2 h at 80° C. After the completion of reaction (by TLC), water (50 mL) was added, extracted with EtOAc (3×50 mL) and the combined organic layers washed with water, brine, dried over anhydrous Na2SO4, filtered then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 100-200 M, 70% EtOAc-hexane) to afford the desired product as an off-white solid (0.110 g, 35%). 1H NMR (DMSO-d6): δ 10.70 (br s, 1H), 8.87 (s, 2H), 8.23 (s, 1H), 8.14 (s, 1H), 6.80 (br s, 1H), 4.47 (m, 2H), 4.17 (q, J=7.20 Hz, 2H), 3.33 (m, 2H), 3.12-3.22 (m, 4H), 2.09 (m, 2H), 1.56 (q, J=7.60 Hz, 2H), 1.39 (m, 2H), 1.22 (t, J=7.20 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H), 1.10 (t, J=7.2 Hz, 3H) and 0.75 (t, J=7.2 Hz, 3H). MS: 539.52 [M+H]+

Provenance & Evidence