反应详情

温度

120 °C

A mixture of 2-chloro-8-[2-(3,3-dimethylmorpholin-4-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine (44 mg, 0.11 mmol), 2-ethylbenzimidazole (18 mg, 0.12 mmol), Pd2(dba)3 (5.2 mg, 5 mol %), Xphos (5.3 mg, 10 mol %) and Cs2CO3 (54 mg, 0.17 mmol) in dioxane (1.5 mL) was purged with argon gas then heated at 120° C., for 24 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 30-90%) to give 535 (33 mg, 59%) as a pale beige solid. LCMS: (Method I): RT 2.52 min; [M+H]+ 505.2. 1H NMR (400 MHz, CHCl3-d): δ 8.02-7.97 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.22 (m, 2 H), 4.52-4.14 (m, 4 H), 3.86 (t, J=4.8 Hz, 4 H), 3.80 (s, 3 H), 3.79-3.67 (m, 2 H), 3.35 (q, J=7.5 Hz, 2 H), 3.34-3.23 (m, 2 H), 3.05-2.92 (m, 2 H), 2.92-2.80 (m, 2 H), 2.77-2.54 (m, 2 H), 1.44 (t, J=7.5 Hz, 3 H), 0.99 (s, 6 H)

1. customwas purged with argon gas
2. washwashed with MeOH
3. washthe desired product eluted with 2 M NH3/MeOH in DCM
4. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 30-90%)