Acetic Acid → 7-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-2-oxa-7-azaspiro[3.5]nonane

Participants

Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.075 g, 0.19 mmol), 2-oxa-7-azaspiro[3.5]nonane trifluoroacetate (0.05 g, 0.20 mmol) in DCE (2 mL), trimethoxymethane (0.204 mL, 1.9 mmol) and acetic acid (0.011 mL, 0.2 mmol) was stirred for 2 h at room temperature. Sodium triacetoxyborohydride (0.061 g, 0.29 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:DCM gradient 0:100 to 10:90) to give 324 as a white solid (0.066 g, 70%). LCMS (Method G): RT=5.88 min, [M+H]+ 503.2. 1H NMR (CDCl3, 400 MHz) δ 8.03-7.99 (m, 1 H); 7.83-7.79 (m, 1 H); 7.33-7.29 (m, 2 H); 4.48-4.37 (m, 4 H); 4.34-4.30 (m, 4 H); 3.90-3.84 (m, 7 H); 3.76-3.72 (m, 2 H); 3.40 (d, J=8.3 Hz, 2 H); 2.49-2.44 (m, 4 H); 1.95-1.91 (m, 4 H); 1.48 (t, J=7.5 Hz, 3 H)

Provenance & Evidence