Acetone → 3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-isopropylazetidin-3-ol

Participants

Reaction Steps

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-azetidin-3-ol (100 mg, 0.23 mmol), propan-2-one (34 μL, 27 mg, 0.46 mmol) and 4 Å powdered molecular sieves (150 mg) in DCE (3 mL) was stirred for 3 h before sodium triacetoxyborohydride (96 mg, 0.46 mmol) was added. The resulting mixture was stirred for 16 h at r.t., then filtered through Celite®, washing with DCM. The filtrate was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-20%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 50-70%) affording 738 as a white solid (15 mg, 13%). LCMS (method I): RT 2.43 min, [M+H]+ 477.2. 1H NMR (MeOD, 400 MHz): δ 8.01-8.01 (1 H, m), 7.64-7.61 (1 H, m), 7.29-7.28 (2 H, m), 4.39 (5 H, s), 4.19-4.17 (2 H, m), 3.85 (4 H, s), 3.46 (2 H, d, J=8.87 Hz), 3.31-3.30 (5 H, m), 2.56-2.54 (1 H, m), 1.39 (3 H, t, J=7.50 Hz), 1.01 (6 H, d, J=6.25 Hz)

Provenance & Evidence