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]azetidin-3-yl}propan-2-ol (84 mg, 0.21 mmol), 2-ethylbenzimidazole (34 mg, 0.23 mmol), Pd2(dba)3 (4.9 mg, 2.5 mol %), Xphos (10.1 mg, 10 mol %) and Cs2CO3 (104 mg, 0.32 mmol) in dioxane (1.5 mL) was purged with argon gas then heated at 120° C., for 23 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, 0-20% 2 M NH3/MeOH in DCM) to give 451 (38 mg, 35%) as a yellow solid. LCMS: (Method I): RT 2.53 min; [M+H]+ 505.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.77-7.73 (m, 1 H), 7.27-7.22 (m, 2 H), 4.49-4.24 (m, 4 H), 3.88-3.83 (m, 4 H), 3.76 (s, 3 H), 3.48-3.40 (m, 2 H), 3.38-3.27 (m, 4 H), 3.15-2.95 (m, 2 H), 2.95-2.90 (m, 2 H), 2.55-2.47 (m, 1 H), 1.43 (t, J=7.48 Hz, 3 H), 1.17 (s, 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, 0-20% 2 M NH3/MeOH in DCM)