Reaction Steps
A brown solution of (R)-N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)quinolin-7-amine (170.8 mg, 0.225 mmol) and trifluoromethanesulfonic acid (0.2 mL, 2.252 mmol) (10% v/v with TFA) in TFA (2.0 mL) was stirred at 75° C. for 1.5 h. The reaction mixture was subsequently cooled to 25° C. and concentrated in vacuo. The residue was taken up in CH2Cl2 (50 mL), and the resulting solution was washed with saturated aqueous sodium bicarbonate (40 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). All organic layers were then combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in DMSO (2.0 mL) and purified by rpHPLC (Phenomenex Luna 5 μm C18, 30×150 mm, 45 mL/min, 10 to 100% CH3CN/H2O (plus 0.1% TFA, both solvents)) to provide (R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)quinolin-7-amine 2,2,2-trifluoroacetate (52.0 mg, 0.082 mmol, 36.5% yield) as a yellow-orange solid. 1H NMR (400 MHz, d4-MeOH) δ 9.52 (d, J=1.8 Hz, 1H), 9.18 (d, J=2.5 Hz, 1H), 8.99 (d, J=8.2 Hz, 1H), 8.96 (dd, J=5.6, 1.3 Hz, 1H), 8.68 (d, J=2.5 Hz, 1H), 8.25 (d, J=9.2 Hz, 1H), 8.04 (dd, J=9.0, 2.0 Hz, 1H), 7.83 (dd, J=8.0, 5.7 Hz, 1H), 4.70 (q, J=7.0 Hz, 1H), 3.55 (br. s., 4H), 2.94 (s, 3H), 2.65 (s, 4H), 2.58 (s, 3H), 1.89 (d, J=6.8 Hz, 3H). 19F NMR (376 MHz, d4-MeOH) δ −77.36 (s, 3F). m/z (ESI, +ve) 520.2 (M+H)+.
