反应详情

温度

120 °C

A mixture of 2-{1-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-piperidin-4-yl}propan-2-ol (71 mg, 0.17 mmol), 2-ethylbenzimidazole (27 mg, 0.19 mmol), Pd2(dba)3 (3.8 mg, 2.5 mol %), Xphos (8.0 mg, 10 mol %) and Cs2CO3 (82 mg, 0.25 mmol) in dioxane (1.0 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% MeOH in DCM) to give 367 (45 mg, 50%) as a yellow solid. LCMS: (Method G): RT 6.09 min; [M+H]+ 533.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.97 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.23 (m, 2 H), 4.49-4.15 (m, 4 H), 3.88-3.83 (m, 4 H), 3.78 (s, 3 H), 3.34 (q, J=7.5, 2 H), 3.14 (m, 4 H), 2.93-2.75 (m, 2 H), 2.20-2.08 (m, 2 H), 1.85-1.78 (m, 2 H), 1.44 (t, J=7.5 Hz, 3 H), 1.40-1.21 (m, 3 H), 1.24-1.18 (m, 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% MeOH in DCM)