反应详情

温度

120 °C

A mixture of 4-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-1-isopropylpiperazin-2-one (51 mg, 0.12 mmol), 2-ethylbenzimidazole (20 mg, 0.13 mmol), Pd2(dba)3 (2.8 mg, 2.5 mol %), Xphos (5.8 mg, 10 mol %) and Cs2CO3 (59 mg, 0.18 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 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-98%) to give 493 (28 mg, 44%) as an off white solid. LCMS: (Method I): RT 2.75 min; [M+H]+ 532.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1H), 7.80-7.76 (m, 1 H), 7.28 (m, 2 H), 4.91-4.82 (m, 1 H), 4.5-4.21 (m, 4 H), 3.87 (t, J=4.7 Hz, 4 H), 3.77 (s, 3 H), 3.37 (q, J=7.5 Hz, 2 H), 3.29 (s, 2 H), 3.26 (t, J=5.4 Hz, 2 H), 3.08-3.01 (m, 2 H), 3.00-2.93 (m, 2 H), 2.81 (t, J=5.4 Hz, 2 H), 1.45 (t, J=7.5 Hz, 3 H), 1.14 (d, J=6.9 Hz, 6 H)

1. customwas purged with argon gas
2. washwashed with MeOH
3. washthe desired product eluted with 2 M NH3 in MeOH
4. customThe resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM)