反应详情

温度

70 °C

To a 50-mL round-bottomed flask was added 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((R)-1-((R)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.130 g, 0.168 mmol), 2,2,2-trifluoroacetic acid (5 mL, 0.842 mmol), and trifluoromethanesulfonic acid (0.2 mL, 0.168 mmol).The solution was stirred at 70° C. for 30 minutes. The volatiles were removed under a vacuum and the residue was cooled in ice bath and neutralized with 1 N NaOH. The mixture was stirred at room temperature overnight and the precipitate was filtered and washed with water. The precipitate was purified with preparative TLC using 5% (MeOH in DCM). The sample dried overnight under high vacuum to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((R)-1-((R)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.047 g, 0.088 mmol, 52.5% yield). m/z (ESI, positive ion) 532.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (d, J=6.26 Hz, 3H) 1.38 (d, J=6.65Hz, 3H) 2.45 (m, 4H) −2.55 (m, 1H) 2.84 (s, 5H) 3.01-3.18 (m, 3H) 3.94 (s, 3H) 4.00 (d, J=6.85 Hz, 1H) 7.74-7.78 (m, 1H) 7.88-7.92 (m, 1H) 8.31-8.34 (m, 1H) 8.37-8.43 (m, 2H) 8.70-8.74 (m, 1H) 11.93 (s, 1H).

1. customThe volatiles were removed under a vacuum
2. temperaturethe residue was cooled in ice bath
3. stirringThe mixture was stirred at room temperature overnight
4. filtrationthe precipitate was filtered
5. washwashed with water
6. customThe precipitate was purified with preparative TLC
7. customThe sample dried overnight under high vacuum