反应详情

温度

100 °C

6-Chloro-N,N-bis(4-methoxybenzyl)-2-methylpyrimidin-4-amine (214.0 mg, 0.557 mmol), 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (Example 34, Step 3)(189 mg, 0.557 mmol), PdCl2 (AmPhos)2 (Aldrich, St. Louis, Mo.) (19.74 mg, 0.028 mmol), and potassium acetate (164 mg, 1.672 mmol) in a mixture of ethanol (3.0 mL) and water (0.300 mL) was sparged with argon and then heated (microwave) at 100° C. in a 20 mL microwave vial for 20 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (ISCO, 24 g, 0 to 100% EtOAc/Hexanes) to provide tert-butyl 4-((5-(6-(bis(4-methoxybenzyl)amino)-2-methylpyrimidin-4-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (152.0 mg, 0.236 mmol, 42.4% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=9.39, 2.15 Hz, 1H); 8.14 (s, 1H); 7.17 (d, J=7.82 Hz, 4H); 6.86 (d, J=8.61 Hz, 5H); 4.74 (br. s., 4H); 3.79 (s, 6H); 3.55 (s, 2H); 3.42 (t, J=4.69 Hz, 4H); 2.62 (s, 3H); 2.37-2.43 (m, 4H); 1.45 (s, 9H). 19F NMR (377 MHz, CDCl3) 6-71.01 (d, J=9.16 Hz, 1F). m/z (ESI, +ve ion) 643.2 (M+H)+.

1. customwas sparged with argon
2. concentrationThe reaction mixture was then concentrated onto silica gel
3. customchromatographically purified (ISCO, 24 g, 0 to 100% EtOAc/Hexanes)