反应详情

温度

80 °C

4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.363 g, 0.522 mmol) in TFA (3 mL) was treated with trifluoromethanesulfonic acid (0.232 mL, 2.61 mmol). The reaction was sealed and heated at 80° C. for 30 min, cooled, and poured onto ice. The mixture was basified with 10 N NaOH and the reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO and purified by prep HPLC (10-55% MeCN/H2O with 0.1% TFA). Product-containing fractions were treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×) and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.069 g, 0.152 mmol, 29.1% yield). m/z (ESI, +ve ion) 455 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.91 (s, 1H); 8.90 (d, J=2.5 Hz, 1H); 8.48 (d, J=2.5 Hz, 1H); 8.33-8.44 (m, 2H); 7.88 (br. s., 1H); 7.73 (br. s., 1H); 3.93 (s, 3H); 3.57 (br. s., 4H); 2.44 (s, 3H); 2.36-2.43 (m, 4H); 1.35 (s, 6H).

1. customThe reaction was sealed
2. temperaturecooled
3. additionpoured onto ice
4. customthe reaction was partitioned between water and DCM
5. extractionThe aqueous layer was extracted with DCM (3×)
6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThis material was dissolved in DMSO
10. custompurified by prep HPLC (10-55% MeCN/H2O with 0.1% TFA)
11. additionProduct-containing fractions were treated with sat'd aq. NaHCO3 and DCM
12. extractionThe aq. layer was extracted with DCM (3×)
13. dry with materialthe combined organic extracts were dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo