Reaction Steps
To a solution of 5-hydroxy-1-(2-hydroxyethoxy)-6-oxo-3,7-diazatricyclo[7.2.2.02,7]trideca-2,4-diene-4-carboxylic acid ethyl ester (203 mg, 0.600 mmol) in DMF (1 mL) was added K2CO3 (249 mg, 1.80 mmol) and (bromomethyl)benzene (103 mg, 0.600 mmol) and the mixture stirred at room temperature overnight under N2. Additional (bromomethyl)benzene (206 mg, 1.2 mmol, 2 eq.) and K2CO3 (166 mg, 1.2 mmol, 2 eq.) were added and the mixture stirred overnight. The mixture was concentrated in vacuo to remove most of DMF, and the residue was diluted with ethyl acetate (15 mL),washed with water followed by brine, then dried (Na2SO4) and concentrated to provide an amber oil which was purified by silica gel column chromatography (18 g SiO2, 45% ethyl acetate/CH2Cl2) to gave the title compound (141 mg, 0.329 mmol, 55% yield) as an amber oil; HPLC: retention time=2.18 min (area percent=92%); LCMS: m/z 429 (M+H); 1H NMR (500 MHz, CDCl3) δ ppm 1.28 (3H, t, J=7.2 Hz), 1.63 (2H, ddd, J=14.3, 7.5, 7.2 Hz), 1.83-1.94 (2H, m), 2.06 (4H, t, J=7.6 Hz), 2.42 (1H, brs), 3.59 (2H, t, J=4 Hz), 3.70 (2H, d, J=4 Hz), 4.05 (2H, d, J=4.0 Hz), 4.31 (2H, q, J=7.2 Hz), 5.22 (2H, s), 7.27 (1H, t, J=7.4 Hz), 7.32 (2H, t, J=7.2 Hz), 7.46 (2H, d, J=6.7 Hz); 13C NMR (126 MHz, CDCl3) δ ppm 14.1, 23.2, 27.6, 30.5, 53.6, 62.1, 62.2, 65.3, 74.5, 76.7, 128.3, 128.5, 128.6, 136.8, 140.0, 142.4, 159.2, 161.3, 163.9.
