Sodium triacetoxyborohydride → 4-(8-((4-(3,3-difluoroazetidin-1-yl)piperidin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-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 (0.139 g, 0.36 mmol), 4-(3,3-difluoroazetidin-1-yl)piperidine (0.075 g, 0.43 mmol) and 4 Å molecular sieves (0.4 g) in DCE (5 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.15 g, 0.71 mmol) was added and the reaction mixture was stirred for 72 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 12:88) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 576 as an off-white solid (0.104 g, 53%). LCMS (Method I): RT=2.61 min, [M+H]+ 552.2 1H NMR (400 MHz, DMSO-d6): δ 8.03-7.99 (m, 1 H), 7.65-7.61 (m, 1 H), 7.27-7.20 (m, 2 H), 4.60-3.95 (s, 4 H), 3.81 (s, 3 H), 3.80-3.74 (m, 6 H), 3.52 (t, J=12.3 Hz, 4 H), 3.27 (q, J=7.4 Hz, 2 H), 2.79-2.70 (m, 2 H), 2.20-2.10 (m, 3 H), 1.68-1.59 (m, 2 H), 1.34 (t, J=7.4 Hz, 3 H), 1.30-1.17 (m, 2 H)

Provenance & Evidence