Sodium triacetoxyborohydride → 2,2-dimethyl-4-(1-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholine

Participants

Reaction Steps

A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.26 mmol), 4-azetidin-3-yl-2,2-dimethylmorpholine (54 mg, 0.32 mmol) and 4A powdered molecular sieves (200 mg) in DCE (5 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (112 mg, 0.53 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 353 as a white solid (113 mg, 82%). LCMS (Method G): RT 6.47 min [M+H]+ 532.3. 1H NMR (CDCl3, 400 MHz): δ 8.10-8.05 (m, 1 H); 7.73-7.69 (m, 1 H); 7.29-7.24 (m, 2 H); 4.35 (m, 4 H); 3.89-3.83 (m, 9H); 3.73 (m, 2 H); 3.55 (t, J=6.5 Hz, 2 H); 3.08 (t, J=6.8 Hz, 2 H); 3.01-2.90 (m, 4 H); 2.24 (m, 2 H); 2.07 (s, 2 H) and 1.25 (s, 6 H)

Provenance & Evidence