Acetic Acid → HCID 59605323, compound

Participants

Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.079 g, 0.20 mmol), 3-fluoro-[1,3′]biazetidinyl (0.029 g, 0.22 mmol) in DCE (3 mL), trimethoxymethane (0.22 mL, 2 mmol) and acetic acid (0.012 mL, 0.2 mmol) was stirred for 5 h at room temperature. Sodium triacetoxyborohydride (0.065 g, 0.30 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was partitioned between DCM and water. The organic layer was separated, washed with brine, dried over sodium sulphate and concentrated. The residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc, gradient 0:100 to 16:84) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 5:95) to give 345 as an off-white solid (0.054 g, 53%). LCMS (Method G): RT=5.78 min, [M+H]+ 506.2. 1H NMR (CDCl3, 400 MHz) δ 8.02-7.98 (m, 1 H); 7.77-7.73 (m, 1 H); 7.28-7.24 (m, 2 H); 5.15 (dt, J=57.3, 5.4 Hz, 1 H); 4.38-4.33 (m, 4 H); 3.90-3.85 (m, 6 H); 3.83 (s, 2 H); 3.72-3.62 (m, 3 H); 3.48-3.39 (m, 3 H); 3.35 (q, J=7.5 Hz, 2 H); 3.35-3.19 (m, 2 H); 3.17-3.15 (m, 2 H); 1.44 (t, J=7.5 Hz, 3 H)

Provenance & Evidence