反应详情

温度

120 °C

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-[2-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)ethyl]-9H-purine (75 mg, 0.19 mmol), 2-ethylbenzimidazole (31 mg, 0.21 mmol), Pd2(dba)3 (4.4 mg, 2.5 mol %), Xphos (9.1 mg, 10 mol %) and Cs2CO3 (93 mg, 0.29 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 18 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 511 (50 mg, 52%) as an off white solid. LCMS: (Method I): RT 2.49 min; [M+H]+ 503.2. 1H NMR (400 MHz, CHCl3-d): δ 8.02-7.97 (m, 1 H), 7.77-7.73 (m, 1 H), 7.29-7.22 (m, 2 H), 4.52-4.20 (m, 4 H), 3.86 (t, J=4.7 Hz, 4 H), 3.82 (s, 3 H), 3.79-3.65 (m, 2 H), 3.58-3.50 (m, 2 H), 3.35 (q, J=7.5 Hz, 2 H), 3.18-3.09 (m, 2 H), 3.09-2.99 (m, 2 H), 2.90-2.76 (m, 2 H), 2.07-1.88 (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%)