反应详情

温度

100 °C

4-Chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 51; (2.102 g, 5.462 mmol), 5-(1,3-dioxolan-2-yl)-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Example 234; 1.901 g, 6.442 mmol), Am-Phos (200.6 mg, 0.2833 mmol), and potassium acetate (1.51 g, 15.4 mmol) were suspended in water (4 mL) and 1,4-dioxane (20 mL) and nitrogen was bubbled through the suspension for 30 s. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.) and stirred under nitrogen for 4 h. Then, the reaction was cooled to room temperature, treated with water (40 mL), and extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered through a Celite® (diatomaceous earth) pad, and concentrated. The crude material was purified on a silica gel filter (600 mL fritted funnel with about 3 inches of silica gel; DCM to 100:1 DCM/MeOH to 50:1 DCM/MeOH) to give 4-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.175 g). 1H NMR (CDCl3, 400 MHz) δ 8.65 (dd, J=8.90 Hz, 2.45 Hz, 1H), 8.42 (d, J=1.37 Hz, 1H), 7.23 (dd, J=8.41 Hz, 5.87 Hz, 4H), 6.87 (dd, J=10.27 Hz, 8.71 Hz, 4H), 5.93 (s, 1H), 4.83 (s, 2H), 4.81 (s, 2H), 4.17-4.04 (m, 4H), 3.82 (s, 3H), 3.80 (s, 3H), 2.55 (s, 3H). m/z (ESI, +ve ion) 518 (M+H)+.

1. custom1,4-dioxane (20 mL) and nitrogen was bubbled through the suspension for 30 s
2. customThen, the flask was fitted with a reflux condenser
3. customplaced in a preheated oil bath
4. temperatureThen, the reaction was cooled to room temperature
5. additiontreated with water (40 mL)
6. extractionextracted with EtOAc
7. dry with materialdried over sodium sulfate
8. filtrationfiltered through a Celite® (diatomaceous earth) pad
9. concentrationconcentrated
10. customThe crude material was purified on a silica gel
11. filtrationfilter (600 mL fritted funnel with about 3 inches of silica gel; DCM to 100:1 DCM/MeOH to 50:1 DCM/MeOH)