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

Participants

Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (112 mg, 0.29 mmol), 4-azetidin-3-yl-2,2-dimethylmorpholine (58 mg, 0.34 mmol) and 4 Å powdered molecular sieves (200 mg) in DCE (5 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (121 mg, 0.57 mmol). The reaction mixture was stirred for 40 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%). 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 331 as a yellow solid (121 mg, 76%). LCMS (Method G): RT 6.85 min [M+H]+ 546.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.77-7.73 (m, 1 H); 7.29-7.22 (m, 2 H); 4.35 (m, 4 H); 3.91-3.82 (m, 9 H); 3.73 (m, 2 H); 3.57 (t, J=6.6 Hz, 2 H); 3.35 (q, J=7.5 Hz, 2 H); 3.10 (t, J=6.6 Hz, 2 H); 2.98 (p, J=6.6 Hz, 1 H); 2.24 (m, 2 H); 2.04 (s, 2 H); 1.44 (t, J=7.5 Hz, 3 H) and 1.25 (s, 6 H)

Provenance & Evidence