Phenolate → 1-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1H-purin-6(9H)-one

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Reaction Steps

1.0 M KOtBu in isopropanol (2 mL) is added to the solution of 3,4,5-trifluorophenol (0.29 g, 1.86 mmol) and stirred for 20 minutes at RT. To the resulting phenoxide solution is added a solution of 2-chloro-1-(6-chloropyridin-3-yl)-1,9-dihydro-6H-purin-6-one (0.5 g, 1.69 mmol) in dimethylacetamide (3 mL) and the resulting mixture is stirred overnight at 50° C. The resulting reaction mixture is cooled, quenched with saturated NH4Cl solution, extracted with DCM (2×50 mL) and dried (Na2SO4). The organic layer is filtered and concentrated under vacuum to afford the crude product as a light brown solid. The crude product is further purified by flash column chromatography using 5% MeOH/CH2Cl2 to afford the title compound as white solid. 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 7.55-7.81 (m, 2H), 7.4 (brs, 1H), 6.71-7.02 (m, 2H), 3.85 (s, 3H). MS (M+1): 408.04; RT=1.48 min. The IC50 determined as described in Example 6 is 100 nanomolar or less.

Provenance & Evidence