Reaction Steps
A yellow suspension of 8-bromo-6-methoxy-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide (Reference Example 27b) (3.092 g, 6.75 mmol) in 40 mL N-methylpyrrolidinone was treated with sodium hydride (60% dispersion in oil, 0.410 g, 10.24 mmol). Gas evolution and warming were observed and the suspension became light brown and almost clear. The reaction was stirred for 10 minutes at room temperature under nitrogen. Addition of the 2-(trimethylsilyl)ethoxymethyl chloride (1.6 mL, 9.1 mmol) resulted in a slightly cloudy, lighter brown solution. After 4.5 hours at room temperature, the reaction mixture was poured into 300 mL water, stirred for 15 minutes and then stored at 0° C. overnight. The solids were isolated by filtration, suspended in methanol, filtered again, and dried under high vacuum to afford the product as a yellow solid (3.190 g, 80%). 1H NMR (300 MHz, DMSO, d6) δ 10.18 (s, 1 H, C(O)NH), 7.95 (d, 1 H, Jm=2.4 Hz, ArH7), 7.83 (s, 1 H, ArH3), 7.69 (d, 2 H, Jo=9.0 Hz, ArH2′ & H6′), 7.51 (d, 1 H, Jm=2.7 Hz, ArH5), 7.00 (d, 2 H, Jo=9.0 Hz, ArH3′ & H5′), 5.69 (s, 2 H, OCH2O), 3.95 (s, 3 H, OCH3), 3.85 (t, 2 H, J=8.0 Hz, OCH2CH2Si), 3.75 (t, 4 H, J=4.7 Hz, OCH2CH2N), 3.10 (t, 4 H, J=4.7 Hz, OCH2CH2N), 0.94 (t, 2 H, J=8.0 Hz, OCH2CH2Si), −0.04 (s, 9 H, Si(C H3)3; Mass Spec.: calc. for [C27H34BrN3O5Si+H]+ Theor. m/z=588, 590; Obs.=588, 590.
