Sodium triacetoxyborohydride → 1-((9-methyl-6-morpholino-8-((4-(oxetan-3-yl)piperidin-1-yl)methyl)-9H-purin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanol

Participants

Reaction Steps

A solution of 2-[2-(2-hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.49 mmol), 4-oxetan-3-ylpiperidine (83 mg, 0.59 mmol) and molecular sieves (4 Å, powdered, 1 g) in DCE (5 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (156 mg, 0.74 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 97:3 to 95:5) to afford 512 as a white solid (51 mg, 20%). LCMS (Method I): RT=2.39 min, M+H+=533. 1H NMR (CDCl3, 400 MHz) δ 8.04 (m, 1 H); 7.75 (m, 1 H); 7.33 (m, 2 H); 4.76 (dd, J=7.8, 6.0 Hz, 2 H); 4.45 (t, J=6.0 Hz, 2 H); 4.35 (m, 4 H); 4.19 (t, J=5.5 Hz, 2 H); 3.94-3.80 (m, 9 H); 3.54 (t, J=5.5 Hz, 2 H); 3.02 (m, 2 H); 2.81-2.72 (m, 1H); 2.29 (m, 2 H); 1.71 (m, 5 H) and 1.28 (m, 1 H)

Provenance & Evidence