Pyridine → HCID 86727125, compound

Participants

Reaction Steps

A flask was charged with (S)-2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoic acid hydrochloride (Intermediate 8) (8.96 g, 31.0 mmol), (S)-6-(2-(2-methylpyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amine (7.23 g, 28.2 mmol), HOAt (3.84 g, 28.2 mmol), nitrogen, DCM (141 ml) and stirred at room temperature. The suspension was cooled to 0° C. followed by addition of pyridine (4.60 ml, 56.4 mmol), then DIC (6.59 ml, 42.3 mmol). The reaction was removed from ice bath immediately after addition of DIC was complete. The reaction was complete after 7.5 hours. The reaction mixture was diluted with 100 mL DCM. The organic layer was washed with 0.5 M HCl aq. (2×20 mL). The resulting organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated. The resulting DCM filtrate was slowly added dropwise to 300 mL of stirred hexanes at room temperature. The resulting solids were collected via vacuum filtration with aide of hexanes and dried on on frit filter overnight to afford off-white solids (6.5 g, 13.25 mmol, 47.0% yield, 93% ee). ESI-MS (EI+, m/z): 491.33, 1H NMR (DMSO-d6) δ: 11.35 (s, 1H), 9.10 (s, 1H), 9.05 (s, 2H), 8.91 (s, 1H), 8.36 (s, 1H), 5.85 (d, J=7.2 Hz, 1H), 4.30 (s, 1H), 3.59 (d, J=27.6 Hz, 2H), 3.46 (s, 3H), 3.19 (s, 3H), 2.08 (s, 3H), 1.95 (s, 1H), 1.88 (d, J=7.3 Hz, 3H), 1.72 (s, 1H), 1.24 (d, J=6.3 Hz, 3H)

Provenance & Evidence