反应详情

温度

80 °C

A mixture of 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.050 g, 0.065 mmol) in TFA (1 mL) was treated with triflic acid (5.76 μL, 0.065 mmol) and heated to 80° C. for 1 h. The reaction mixture was concentrated and then ice cubes were added to the brown residue. Saturated NaHCO3 (aq.) was added followed by CH2Cl2. The layers were separated and 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 (4 g), eluting with a gradient of 0% to 5% MeOH in CH2Cl2, to provide 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-2-methyl-4-pyrimidinamine (0.010 g, 0.019 mmol, 29.1% yield) as a brown solid. m/z (ESI, +ve) 531.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.14 (s, 1H); 8.36 (dd, J=12.91, 2.35 Hz, 1H); 8.22-8.25 (m, 1H); 8.16 (d, J=2.35 Hz, 1H); 7.95 (dd, J=1.96, 0.39 Hz, 1H); 7.04 (s, 2H); 6.79 (s, 1H); 4.02 (q, J=6.65 Hz, 1H); 3.94 (s, 3H); 3.05-3.20 (m, 2H); 2.77-2.95 (m, 5H); 2.53 (br. s., 3H); 2.45 (dd, J=11.35, 5.28 Hz, 1H); 1.40 (d, J=6.65 Hz, 3H); 1.10 (d, J=6.26 Hz, 3H).

1. concentrationThe reaction mixture was concentrated
2. additionice cubes were added to the brown residue
3. additionSaturated NaHCO3 (aq.) was added
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. custompurified by chromatography through a silica gel column (4 g)
10. washeluting with a gradient of 0% to 5% MeOH in CH2Cl2