To a vial charged with N-(4-methoxybenzyl)pyrimidin-4-amine (Intermediate OO; 28.7 mg, 0.134 mmol) was added THF (509 μl) and the resulting clear solution cooled in an ice water bath prior to the drop wise addition of lithium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (26.0 μl, 0.134 mmol). The mixture was stirred for 20 min at 0° C. prior to the addition, faster than drop wise, of a solution of perfluorophenyl 8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine-3-sulfonate (see EXAMPLE 322, STEP 3) (70 mg, 0.127 mmol) in THF (0.5 ml, 0.1 ml rinse). The resulting mixture was allowed to stir and warm slowly to room temp (ice melt) for 1 hr. To the mixture was added acetic acid (about 10 drops) and the resulting solution dried under reduced pressure. The crude residue was purified with a 25 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada) (0-100% EtOAc in heptane). The crude oil obtained (52 mg) was dissolved in DCM (3 ml) and TFA (0.5 ml) was added and the mixture stirred overnight at room temperature. The material was purified with a 25 g HP spherical silica column (15 μm spherical, Interchim, Mouintlucon, France) ramping DCM:MeOH (90:10) in DCM (0 to 50%) providing product, obtained as a film which was lyophilized from MeOH/H2O to afford 8-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-1,7-naphthyridine-3-sulfonamide (3 mg, 6.50 mmol, 5.11% yield) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.69 (s, 3H) 6.77 (d, J=6.41 Hz, 1H) 7.39-7.47 (m, 2H) 7.54 (d, J=7.91 Hz, 1H) 8.08 (d, J=6.30 Hz, 1H) 8.16 (d, J=5.56 Hz, 1H) 8.44 (s, 1H) 8.75 (d, J=5.56 Hz, 1H) 8.97 (s, 1H) 9.23 (d, J=1.82 Hz, 1H). m/z (ESI) 462.2 (M+H)+.
