Dichloromethane → Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

Participants

Reaction Steps

Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.200 g, 0.5 mmol) was dissolved in dioxane (3 mL) and 2-chlorophenylboronic acid (0.156 g, 1.0 mmol). K2CO3 (0.207 g, 1.5 mmol) was dissolved in H2O (0.2 mL) and added to the dioxane. The solution was degassed by bubbling argon through the mixture for five minutes. {1,1′-Bis(diphenylphosphino)-ferrocene}dichloropalladium(II) complex with dichloromethane (1:1) (0.012 g, 0.015 mmol) was added and the mixture heated under argon to 70° C. for 3 hours (followed by TLC 15:1 hexane:EtOAc). The solvents were removed and the mixture partitioned between EtOAc and H2O. The EtOAc layer was dried (MgSO4) and absorbed onto silica gel. The product was purified by flash chromatography (20:1 hexane:EtOAc) to yield methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.169 g) as a white solid. mp 57-59° C.; 1H NMR (500 MHz, DMSO-d6) δ: 0.87 (t, 6H, J=7.3 Hz), 1.50 (m, 2H), 1.55 (m, 2H), 3.35 (s, 3H), 3.53 (s, 2H), 3.75 (m, 1H), 7.31 (d, 1H, J=7.2 Hz), 7.43 (m, 3H), 7.59 (m, 3H), 7.96 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8.7 Hz). MS (ES) m/z456.1 ([M+H]+). MS (ES) m/z488.1 ([M+CH3OH+H]+). MS (ES) m/z 911.2 ([2M+H]+). Anal. Calcd for C25H26ClNO3S: C, 65.85; H, 5.75; N, 3.07. Found: C, 65.92; H, 5.96; N, 3.27.

Provenance & Evidence