反应详情

温度

120 °C

A mixture of 1-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-4-methylpiperidin-4-ol (45 mg, 0.11 mmol), 2-ethylbenzimidazole (18 mg, 0.13 mmol), Pd2(dba)3 (2.6 mg, 2.5 mol %), Xphos (5.4 mg, 10 mol %) and Cs2CO3 (56 mg, 0.17 mmol) in dioxane (1 0 mL) was purged with argon gas then heated at 120° 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 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) to give 452 (46 mg, 80%) as a pale orange solid. LCMS: (Method I): RT 2.46 min; [M+H]+ 505.2. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.77-7.73 (m, 1 H), 7.28-7.22 (m, 2 H), 4.47-4.19 (m, 4 H), 3.88-3.83 (m, 4 H), 3.78 (s, 3 H), 3.34 (q, J=7.5 Hz, 2 H), 3.15-3.05 (m, 2H), 2.98-2.80 (m, 2 H), 2.78-2.73 (m, 2 H), 2.65-2.57 (m, 2 H), 1.69-1.65 (m, 4 H), 1.44 (t, J=7.5 Hz, 3 H), 1.33-1.27 (s, 3 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)