Eg5 Inhibitor VII synthesis

Yield:912953-25-4 85%

Reaction Conditions:

with potassium carbonate;tetrakis(triphenylphosphine) palladium⁽⁰⁾ in 1,4-dioxane;water at 90; for 20 h;

Steps:

12

6-(4-TrifluoromethylphenylV3.4-dihvdro-1 H-αuinolin-2-one A mixture of 6-bromo-3,4-dihydro-1 H-quinolin-2-one (0.226 g, 1.00 mmol), 4-(trifluoromethyl)phenylboronic acid (0.380 g, 2.0 mmol), tetrakis(triphenylphosphine)palladium (0) (0.065 g, 0.056 mmol), 2M aqueous EPO potassium carbonate (5 mL, 10 mmol) and dioxane (5 ml_) was stirred under argon at 90 ⁰C for 20 h, then cooled, poured into 0.4M aqueous HCI (50 mL) and extracted with ethyl acetate. The extracts were washed with water, brine and dried (MgSO₄), then the solvent removed under reduced pressure and the residue chromatographed (silica gel, 20-80% ethyl acetate/ hexane) to give the title compound (0.249 g, 85%) as a cream solid. ¹H NMR (400MHz, D₆-DMSO) δ 10.23 (s, 1 H), 7.86 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.60 (s, 1 H), 7.55 (dd, J = 8.2, 2.1 Hz, 1 H), 6.98 (d, J = 8.2 Hz, 1 H), 2.97 (t, J = 7.5 Hz, 2H), 2.51 (partially obscured by D₅-DMSO, 2H).

References:

WO2006/113432,2006,A2 Location in patent:Page/Page column 44-45