反应详情

温度

75 °C

N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (459.4 mg, 0.6277 mmol) was dissolved in trifluoroacetic acid (Aldrich, redistilled, 99+%, 7.5 mL) and the flask was fitted with a reflux condenser and put in a preheated oil bath (75° C.) and stirred overnight. Then, the reaction was cooled to room temperature, concentrated, diluted with DCM, and treated with saturated sodium bicarbonate and 5 N NaOH to raise the pH of the aqueous phase to about 6. The layers were separated, and the aqueous phase was extracted with DCM. The organic phases were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel column (25:1 DCM/MeOH to 20:1 DCM/MeOH). The fractions with product were collected, concentrated, treated with MeOH, and filtered. The solid was washed with MeOH, but was still not 95% pure by HPLC. So, the filtrate and solid were combined, concentrated, treated with EtOAc and acetone (which in combination dissolved the compound), concentrated, and purified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min; total flow rate of 100 mL/min) to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (192.4 mg). 1H NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.48 (s, 1H), 8.16 (d, J=1.57 Hz, 1H), 8.07 (d, J=8.02 Hz, 1H), 7.91 (d, J=8.22 Hz, 2H), 7.45 (d, J=8.22 Hz, 2H), 6.93 (d, J=9.00 Hz, 1H), 4.28 (q, J=7.56 Hz, 1H), 4.03 (s, 3H), 3.06 (s, 3H), 2.63 (s, 3H), 1.74 (d, J=7.04 Hz, 3H). m/z (ESI, pos. ion) 492 (M+H)+.

1. customthe flask was fitted with a reflux condenser
2. customput in a preheated oil bath
3. temperatureThen, the reaction was cooled to room temperature
4. concentrationconcentrated
5. additiondiluted with DCM
6. additiontreated with saturated sodium bicarbonate and 5 N NaOH
7. temperatureto raise the pH of the aqueous phase to about 6
8. customThe layers were separated
9. extractionthe aqueous phase was extracted with DCM
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. custompurified on a silica gel column (25:1 DCM/MeOH to 20:1 DCM/MeOH)
14. customThe fractions with product were collected
15. concentrationconcentrated
16. additiontreated with MeOH
17. filtrationfiltered
18. washThe solid was washed with MeOH
19. concentrationconcentrated
20. additiontreated with EtOAc and acetone (which in combination
21. dissolutiondissolved the compound),
22. concentrationconcentrated
23. custompurified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min; total flow rate of 100 mL/min)