反应详情

温度

80 °C

A solution of 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.200 g, 0.264 mmol) in TFA (2 mL) at RT was treated with a few drops of triflic acid. The solution was heated to 80° C. for 90 minutes. The reaction mixture was allowed to cool to RT and was then concentrated. A few ice cubes were added and then saturated NaHCO3 (aq.) was added followed by CH2Cl2. The mixture was filtered and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column (12 g), eluting with a gradient of 0% to 3% MeOH in CH2Cl2, to provide 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-2-methyl-4-pyrimidinamine (0.110 g, 0.213 mmol, 81% yield) as a yellow solid. m/z (ESI, +ve) 517.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.17 (br. s, 1H); 8.35 (dd, J=13.01, 2.25 Hz, 1H); 8.22 (d, J=2.15 Hz, 1H); 8.17 (d, J=2.35 Hz, 1H); 7.95-7.98 (m, 1H); 7.04 (s, 2H); 6.80 (s, 1H); 3.94 (s, 3H); 3.61 (q, J=6.78 Hz, 1H); 3.11 (t, J=4.99 Hz, 4H); 2.87 (s, 3H); 2.53-2.58 (m, 5H); 2.43-2.50 (m, 2H); 1.38 (d, J=6.85 Hz, 3H).

1. temperatureto cool to RT
2. concentrationwas then concentrated
3. additionA few ice cubes were added
4. additionsaturated NaHCO3 (aq.) was added
5. filtrationThe mixture was filtered
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with CH2Cl2 (2×)
8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified by chromatography through a silica gel column (12 g)
12. washeluting with a gradient of 0% to 3% MeOH in CH2Cl2