1-(2-(Methylsulfonyl)ethyl)piperazine → 4-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-8-((4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine

Participants

Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (65 mg, 0.17 mmol) and 1-(2-methanesulfonylethyl)piperazine (38 mg, 0.20 mmol) in DCE (4 mL) was stirred at room temperature for 1.5 h before the addition of sodium triacetoxyborohydride (70 mg, 0.33 mmol). The reaction mixture was stirred for 16 h then partitioned between brine and DCM. 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 312 as a cream solid (29 mg, 30%). LCMS (Method G): RT 5.97 min [M+H]+ 568.3. 1H NMR (CDCl3, 400 MHz): δ 8.03-7.99 (m, 1 H); 7.78-7.73 (m, 1 H); 7.30-7.24 (m, 2 H); 4.35 (m, 4 H); 3.90-3.83 (m, 7 H); 3.77 (s, 2 H); 3.36 (q, J=7.5 Hz, 2 H); 3.22-3.11 (m, 2 H); 3.04 (s, 3 H); 2.91 (t, J=6.4 Hz, 2 H); 2.59 (m, 8 H) and 1.45 (t, J=7.5 Hz, 3 H)

Provenance & Evidence