反应详情

温度

75 °C

N,N-Bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (499.0 mg, 0.6744 mmol) was dissolved in trifluoroacetic acid (10.4 mL, 140 mmol) and the flask was fitted with a reflux condenser, placed in a preheated oil bath (75° C.) and stirred overnight. Then, the reaction was cooled to room temperature, concentrated, diluted with DCM (40 mL) and treated with saturated sodium bicarbonate, water, and 5N NaOH until the pH of the aqueous phase was about 7. Then, the layers were separated, and the aqueous phase was extracted with DCM and 10:1 DCM/MeOH. During these extractions, 5N NaOH was added to the aqueous phase to raise the pH from about 5 to about 11. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; 75:1 DCM/MeOH to 50:1 DCM/MeOH to 35:1 DCM/2N ammonia in MeOH to 20:1 DCM/2N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH) to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (241.9 mg, 72% yield) as a yellow powder. 1H NMR (CDCl3, 400 MHz) δ 11.68 (s, 1H), 8.71 (s, 1H), 8.36 (d, J=2.74 Hz, 1H), 8.27 (d, J=2.35 Hz, 1H), 8.13 (dd, J=8.80 Hz, 2.74 Hz, 1H), 6.79 (d, J=8.80 Hz, 1H), 5.42 (br s, 2H), 3.95 (s, 3H), 3.60-3.52 (m, 1H), 3.30-3.20 (m, 4H), 2.77 (s, 3H), 2.70-2.53 (m, 7H), 1.45 (d, J=6.06 Hz, 3H). m/z (ESI, +ve ion) 500 (M+H)+.

1. customthe flask was fitted with a reflux condenser
2. customplaced in a preheated oil bath
3. temperatureThen, the reaction was cooled to room temperature
4. concentrationconcentrated
5. additiondiluted with DCM (40 mL)
6. additiontreated with saturated sodium bicarbonate, water, and 5N NaOH until the pH of the aqueous phase
7. customThen, the layers were separated
8. extractionthe aqueous phase was extracted with DCM and 10:1 DCM/MeOH
9. extractionDuring these extractions, 5N NaOH
10. additionwas added to the aqueous phase
11. temperatureto raise the pH from about 5 to about 11
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. custompurified on a silica gel
16. filtrationfilter (150 mL fritted filter with about 2 inches of silica gel; 75:1 DCM/MeOH to 50:1 DCM/MeOH to 35:1 DCM/2N ammonia in MeOH to 20:1 DCM/2N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH)