反应详情

温度

120 °C

A glass microwave reaction vessel was charged with 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (2.140 g, 5.56 mmol) and 5-(1-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (4.12 g, 11.68 mmol) in dioxane (25 mL). Then A-Phos (0.394 g, 0.556 mmol), potassium acetate (1.637 g, 16.68 mmol) and water (3 mL) were added into the reaction mixture. The reaction mixture was stirred and heated in a CEM Voyager Microwave (Large Scale Unit) at 120° C. for 20 min (160 watts, Powermax feature on). The mixture was diluted with dichloromethane (20 mL), water (20 mL) and brine solution (10 mL). The organic layer was collected by extracting with dichloromethane (3×15 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. This gave the crude product as a tan oil. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through silica-gel column (220 g), eluting with 100% ethyl acetate to give tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)piperazine-1-carboxylate (3.65 g, 5.55 mmol, 99% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO) δ 8.47 (dd, J=9.39, 2.35 Hz, 1H) 8.31 (d, J=1.57 Hz, 1H) 7.26 (dd, J=8.61, 3.33 Hz, 4H) 6.90 (dd, J=12.42, 8.71 Hz, 4H) 4.78 (d, J=12.91 Hz, 4H) 3.74 (d, J=8.02 Hz, 6H) 3.70 (d, J=6.85Hz, 1H) 3.28 (d, J=6.06 Hz, 4H) 2.50-2.53 (m, 3H) 2.21-2.39 (m, 4H) 1.37 (d, J=1.76 Hz, H). m/z (ESI, +ve ion) 658.3 (M+H)+.

1. customA glass microwave reaction vessel
2. customThe organic layer was collected
3. extractionby extracting with dichloromethane (3×15 mL)
4. dry with materialThe combined organic extracts were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThis gave the crude product as a tan oil
8. custompurified by chromatography through silica-gel column (220 g)
9. washeluting with 100% ethyl acetate