反应详情

To a solution consisting of (±)-2-phenyl-5-(2-(piperidin-3-yl)-1H-imidazol-4-yl)pyrimidine (Example 22, 40 mg, 0.13 mmol) in dimethylformamide (2 mL) was added cesium carbonate (85 mg, 0.26 mmol) followed by benzyl bromide (27 mg, 0.16 mmol). The reaction mixture was stirred at room temperature for one hour and diluted with water and the organic material was extracted twice with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane/ethyl acetate and chromatographed on silica (4 g) eluted with 1:9 v/v ethanol-ethyl acetate. The purified material was diluted with toluene and concentrated. Solidification of the product was promoted with scratching under dichloromethane and hexane to afford the title compound (20 mg) as a colorless solid; melting point 179° C.; Rf 0.19 with 1:9 v/v ethanol-ethyl acetate; 1H-NMR (400 MHz; DMSO-d6) δ 12.1 (s, 1H), 9.18 (s, 2H), 8.2-8.4 (m, 2H), 7.8 (s, 1H), 7.4-7.6 (m, 4H), 7.22-7.35 (m, 4H), 7.18-7.22 (m, 4H), 3.4-3.6 (m, 2H), 2.9-3.0 (m, 2H), 2.7-2.9 (m, 1H), 2.02-2.1 (M, 1H), 1.9-2.1 (m, 2H), 1.62-1.8 (m, 1H), 1.5-1.62 (m, 2H); MS (ESI+) m/z 396 (M+1); H-PGDS FPBA IC50: 0.6 μM.

1. extractionthe organic material was extracted twice with ethyl acetate
2. dry with materialThe combined organic phase was dried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in dichloromethane/ethyl acetate
6. customchromatographed on silica (4 g)
7. washeluted with 1:9 v/v ethanol-ethyl acetate
8. additionThe purified material was diluted with toluene
9. concentrationconcentrated