Cesium carbonate → HCID 59606048, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-3-isopropyl-azetidin-3-ol (33 mg, 0.08 mmol), 2-ethylbenzimidazole (14 mg, 0.09 mmol), Pd2(dba)3 (1.9 mg, 2.5 mol %), Xphos (4.0 mg, 10 mol %) and Cs2CO3 (41 mg, 0.13 mmol) in dioxane (1.0 mL) was purged with argon gas then heated at 120° C., for 18 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) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-98%) to give 466 (18 mg, 42%) as an off white solid. LCMS: (Method I): RT 2.62 min; [M+H]+ 505.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1H), 7.76-7.72 (m, 1 H), 7.28-7.22 (m, 2 H), 4.45-4.33 (m, 4 H), 3.86 (t, J=4.7 Hz, 4 H), 3.77 (s, 3 H), 3.41 (d, J=8.1 Hz, 2 H), 3.34 (q, J=7.5 Hz, 2 H), 3.18 (d, J=8.1 Hz, 2 H), 3.04 (t, J=7.2 Hz, 2 H), 2.93 (t, J=7.2 Hz, 2 H), 2.01-1.89 (m, 1 H), 1.44 (t, J=7.5 Hz, 3 H), 0.94 (d, J=6.8 Hz, 6 H)

Provenance & Evidence