Cesium carbonate → HCID 59605502, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-8-{2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)azetidin-1-yl]-ethyl}-9-methyl-6-morpholin-4-yl-9H-purine (93 mg, 0.20 mmol), 2-ethylbenzimidazole (32 mg, 0.22 mmol), Pd2(dba)3 (4.5 mg, 2.5 mol %), Xphos (9.4 mg, 10 mol %) and Cs2CO3 (97 mg, 0.30 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 20 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 reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-90%) to give 537 (79 mg, 69%) as a beige solid. LCMS: (Method I): RT 2.42 min; [M+H]+ 580.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.22 (m, 2 H), 4.57-4.09 (m, 4 H), 3.86 (t, J=4.8 Hz, 4 H), 3.77 (s, 3 H), 3.71-3.57 (m, 2 H), 3.34 (q, J=7.5 Hz, 2 H), 3.33-3.22 (m, 1 H), 3.07 (m, 8 H), 3.00-2.89 (m, 2 H), 2.85 (t, J=4.8 Hz, 4 H), 1.44 (t, J=7.5 Hz, 3 H)

Provenance & Evidence