Trifluoromethanesulfonic acid → 6-(2-(6-Methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-2-methylpyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

A solution of N,N-bis(4-methoxybenzyl)-6-(2-(6-methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-2-methylpyrimidin-4-amine (137.7 mg, 0.190 mmol) and trifluoromethanesulfonic acid (50 μL, 0.563 mmol) in TFA (2.5 mL) was stirred at 80° C. for 2.5 h. The mixture was subsequently cooled to 25° C. and concentrated in vacuo. Sat. aq. NaHCO3 (25 mL) was carefully added to the residue (final pH about 8). The resulting suspension was sonicated for 2 min, and the precipitated solid was collected by vacuum filtration, washed with water (30 mL), and air-dried. The residue was taken up in MeOH, concentrated onto silica gel, and chromatographically purified (ISCO, 12 g, 0 to 10% MeOH/DCM) to yield 6-(2-(6-methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-2-methylpyrimidin-4-amine (55.6 mg, 0.115 mmol, 60.4% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.80 (br. s., 1H); 8.37 (d, J=2.74 Hz, 1H); 8.14 (d, J=1.96 Hz, 1H); 8.10 (dd, J=8.90, 2.84 Hz, 1H); 7.86 (br. s., 1H); 6.76 (d, J=8.80 Hz, 1H); 6.70 (br. s., 1H); 4.95 (br. s., 2H); 3.93 (s, 3H); 3.43-3.56 (m, 2H); 3.26 (br. s., 4H); 2.78 (s, 3H); 2.63 (s, 3H); 2.58 (br. s., 4H). m/z (ESI, +ve ion) 485.1 (M+H)+.

Provenance & Evidence