反应详情

温度

100 °C

A vial was charged with 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.09 g, 0.429 mmol, Preparation #A.1), 4-(methylsulfonyl)aniline (0.077 g, 0.451 mmol, Oakwood), X-Phos (0.020 g, 0.043 mmol), Pd2dba3 (0.020 g, 0.021 mmol), K2CO3 (0.062 g, 0.451 mmol) and t-BuOH (3.5 mL). The vial was purged with argon and heated at about 100° C. overnight. The mixture was diluted with CHCl3 (about 10 mL) passed through a SiCO3 SPE cartridge and concentrated. The crude product was purified by preparative reverse phase HPLC (Table 2, Method a) to provide N4-allyl-N2-(4-(methylsulfonyl)phenyl)furo[3,2-d]pyrimidine-2,4-diamine (0.041 g, 27%): 1H NMR (DMSO-d6) δ 9.53 (s, 1H), 8.11 (d, J=2.1 Hz, 1H), 8.02 (m, 3H), 7.72 (d, J=8.9 Hz, 2H), 6.80 (d, J=2.1 Hz, 1H), 6.00 (ddd, J=17.1, 10.2, 5.1 Hz, 1H), 5.22 (dd, J=17.1, 1.6 Hz, 1H), 5.11 (dd, J=10.5, 1.6 Hz, 1H), 4.14 (dd, J=5.1 Hz, 2H), 3.11 (s, 3H). Syk IC50=B.

1. customThe vial was purged with argon
2. additionThe mixture was diluted with CHCl3 (about 10 mL)
3. concentrationconcentrated
4. customThe crude product was purified by preparative reverse phase HPLC (Table 2, Method a)