Cesium carbonate → 4-(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-8-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)-9H-purin-6-yl)morpholine

Participants

Reaction Steps

A mixture of 2-chloro-8-[3-(1,1-dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-9-methyl-6-morpholin-4-yl-9H-purine (0.162 g, 0.36 mmol), 2-isopropyl-1H-benzoimidazole (0.068 g, 0.43 mmol), Xphos (0.034 g, 0.071 mmol), Pd2(dba)3 (0.017 g, 0.018 mmol) and Cs2CO3 (0.231 g, 0.71 mmol) in dioxane (2 mL) was subjected to microwave irradiation at 145° C. for 45 min. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM gradient 0:100 to 7.5:92.5) to give 449 as a yellow solid (0.1 g, 49%). LCMS (Method I): RT=2.56 min, [M+H]+ 580.2. 1H NMR (400 MHz, DMSO-d6): δ 7.91-7.86 (m, 1 H); 7.66-7.61 (m, 1 H); 7.26-7.21 (m, 2 H); 4.30-4.23 (m, 4 H); 3.97-3.86 (m, 1 H); 3.87 (s, 2 H); 3.82-3.71 (m, 7 H); 3.46 (t, J=6.6 Hz, 2 H); 3.26-3.18 (m, 1 H); 3.12-3.08 (m, 4 H); 3.00 (t, J=6.8 Hz, 2 H); 2.74 (m, 4 H); 1.35 (d, J=6.8 Hz, 6 H)

Provenance & Evidence