反应详情

温度

110 °C

A mixture of 4-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl)-3-isopropylpiperazin-2-one (198 mg, 0.49 mmol), 2-ethylbenzimidazole (78 mg, 0.53 mmol), Pd2(dba)3 (11.1 mg, 2.5 mol %), Xphos (23.1 mg, 10 mol %) and Cs2CO3 (237 mg, 0.16 mmol) in dioxane (4 mL) was purged with argon gas then heated at 110° C., for 17 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 column chromatography (Si—PCC, 0-10% MeOH in EtOAc) to give 648 (196 mg, 78%) as a white solid. LCMS: (Method I): RT 3.37 min, [M+H]+ 518.2 1H NMR (400 MHz, CDCl3d): δ 8.05-8.00 (m, 1 H), 7.79-7.75 (m, 1 H), 7.30-7.23 (m, 2 H), 6.02 (s, 1 H), 4.50-3.96 (m, 4 H), 4.09 (d, J=13.6 Hz, 1 H), 3.94 (d, J=13.6 Hz, 1 H), 3.89 (s, 3 H), 3.87 (t, J=4.80 Hz, 4 H), 3.63-3.54 (m, 1 H), 3.37 (q, J=7.5 Hz, 2 H), 3.34-3.28 (m, 1 H), 3.13-3.04 (m, 1 H), 3.03 (d, J=5.5 Hz, 1 H), 2.74-2.66 (m, 1 H), 2.25-2.14 (m, 1 H), 1.46 (t, J=7.5 Hz, 3 H), 1.11 (d, J=6.8 Hz, 3 H), 1.03 (d, J=6.8 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 column chromatography (Si—PCC, 0-10% MeOH in EtOAc)