Dimethylformamide → 5-(9-Methyl-6-oxo-2-(3,4,5-trifluorophenoxy)-6H-purin-1(9H)-yl)picolinonitrile

Participants

Reaction Conditions

Reaction Steps

1-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1,9-dihydro-6H-purin-6-one (0.3 g, 0.73 mmol), Zn(CN)2 (0.43 mg, 3.65 mmol), Pd2(dba)3 (0.07 g, 0.073 mmol) and DPPF (0.04 g, 0.073 mmol) are added to DMF (3 mL). The mixture is purged with N2 for 3 min and then heated at 120° C. for 18 h. Water (20 mL) is added and the resulting mixture is extracted with DCM (2×20 mL). The organic layer is passed through celite and Na2SO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography on silica gel (MeOH:CH2Cl2=2:98) to afford the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.71 (s, 1H), 7.90 (s, 2H), 7.68 (s, 1H), 7.25 (s, 2H), 6.85-6.89 (m, 2H), 3.65 (s, 3H, s). MS (M+1): 399.07; RT=1.41 min. The IC50 determined as described in Example 6 is 100 nanomolar or less.

Provenance & Evidence