Potassium Carbonate → 4-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholine

Participants

Reaction Steps

To a solution of 8-chloromethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (107 mg, 0.26 mmol) and 4-azetidin-3-ylmorpholine (44 mg, 0.31 mmol) in DMF (3 mL) was added K2CO3 (106 mg, 0.77 mmol). The resulting mixture was allowed to stir at room temperature for 16 h. The reaction mixture was dissolved in EtOAc, washed with H2O (×4) then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%). The resulting residue was further purified by Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH, followed by reverse phase HPLC (Phenomenex Luna C18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 309 as a white solid (14 mg, 11%). LCMS (Method G): RT 5.74 min, [M+H]+ 518.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.98 (m, 1 H); 7.77-7.73 (m, 1 H); 7.27-7.23 (m, 2 H); 4.35 (m, 4 H); 3.89-3.82 (m, 6 H); 3.83 (s, 3 H); 3.72 (m, 4 H); 3.56 (m, 2 H); 3.34 (q, J=7.5 Hz, 2 H); 3.15-3.03 (m, 3 H); 2.34 (m, 4 H) and 1.44 (t, J=7.5 Hz, 3 H)

Provenance & Evidence