Dichloromethane → ethyl ((1S)-5-{3-[[5-cyano-3-fluoro-6-(4-methoxyphenyl)-2-pyridinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl ((1S)-5-{3-[(6-chloro-5-cyano-3-fluoro-2-pyridinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 312, 0.10 g, 0.22 mmol) in a mixture of toluene (1.5 mL), 1,4-dioxane (0.5 mL), and water (0.6 mL) were added sodium carbonate (0.24 g, 2.24 mmol), 4-methoxyphenyl boronic acid (0.14 g, 0.90 mmol) and PdCl2(dppf).CH2Cl2 (0.04 g, 0.04 mmol). The mixture was heated at 80° C. for 4 h, and then concentrated under reduced pressure. The product (0.10 g, 88%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD2Cl2) δ 7.87 (d, 2H), 7.37 (d, 1H), 7.04 (d, 1H), 6.98 (d, 2H), 6.72 (d, 1H), 6.65 (dd, 1H), 4.16 (q, 2H), 4.00 (t, 2H), 3.90-3.85 (m, 5H), 3.49 (qt, 1H), 3.30 (d, 3H), 2.94-2.76 (m, 2H), 2.70 (dd, 1H), 2.45-2.32 (m, 2H), 2.16 (qt, 2H), 1.80-1.70 (m, 1H), 1.29 (t, 3H).

Provenance & Evidence