反应详情

温度

120 °C

A microwave vial (80 mL) was charged with 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (2.496 g, 6.49 mmol), 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (2.000 g, 5.90 mmol), potassium acetate (1.777 g, 18.10 mmol), Am-Phos (0.403 g, 0.649 mmol), dioxane (20 mL) and water (3.00 mL, 167 mmol). The vial was heated in a CEM Voyager Microwave (Large-Scale Unit) for 25 minutes at 120° C. while 100 Watts of energy was supplied via Powermax (Simultaneous heating while cooling technology). The reaction mixture was diluted with water (15 mL) and extracted with Chloroform (3×50 mL). The organic extracts were combined and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude product as a yellow oil. The crude product was adsorbed onto a plug of silica gel and purified by chromatography through a SiliCycle SiliaSep pre-packed silica gel column (220 g) with a gradient of 10% to 100% ethyl acetate/hexanes over 45 min to give tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (3.000 g, 4.66 mmol, 79% yield) as a yellow oil. 1H NMR (400 MHz, d6-DMSO) δ 8.50 (dd, J=9.39, 2.35 Hz, 1H); 8.28 (d, J=1.37 Hz, 1H); 7.25 (d, J=8.61 Hz, 4H); 6.89 (dd, J=11.15, 8.61 Hz, 4H); 6.70-6.81 (m, 1H); 4.77 (d, J=4.69 Hz, 4H); 3.65-3.82 (m, 6H); 3.58 (s, 2H); 3.24-3.37 (m, 4H); 2.47 (s, 3H); 2.28-2.38 (m, 4H); 1.33-1.50 (m, 9H). m/z (ESI, +ve ion) 644.2 (M+H)+.

1. temperaturewas supplied via Powermax (Simultaneous heating while cooling technology)
2. extractionextracted with Chloroform (3×50 mL)
3. dry with materialdried over Na2SO4
4. filtrationThe solution was filtered
5. concentrationconcentrated in vacuo
6. customto give the crude product as a yellow oil
7. custompurified by chromatography through a SiliCycle SiliaSep pre-packed silica gel column (220 g) with a gradient of 10% to 100% ethyl acetate/hexanes over 45 min