反应详情

温度

120 °C

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-{2-[4-(tetrahydropyran-4-yl)piperazin-1-yl]ethyl}-9H-purine (37 mg, 0.08 mmol), 2-ethylbenzimidazole (13 mg, 0.09 mmol), Pd2(dba)3 (1.9 mg, 2.5 mol %), Xphos (3.9 mg, 10 mol %) and Cs2CO3 (37 mg, 0.11 mmol) in dioxane (1.5 mL) was purged with argon gas then heated at 120° C., for 19 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 557 (32 mg, 70%) as a pale beige solid. LCMS: (Method I): RT 2.42 min; [M+H]+ 560.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.97 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.22 (m, 2 H), 4.56-4.21 (m, 4 H), 4.04 (dd, J=11.4, 4.2 Hz, 2 H), 3.86 (t, J=4.7 Hz, 4 H), 3.77 (s, 3 H), 3.38-3.34 (m, 2 H), 3.34 (q, J=7.5 Hz, 2 H), 3.13-3.00 (m, 2 H), 3.00-2.87 (m, 2 H), 2.82-2.58 (m, 6 H), 2.57-2.42 (m, 1 H), 1.88-1.75 (m, 2 H), 1.71-1.55 (m, 4 H), 1.44 (t, J=7.5 Hz, 3 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%)