Water → 2-Oxo-2-(2-phenylpyrimidin-5-yl)ethyl 2-phenylacetate

Temperature

40 °C

To a solution consisting of phenylacetic acid (27 mg, 0.20 mmol) and cesium carbonate (117 mg, 0.360 mmol) in tetrahydrofuran (1.5 mL) at room temperature was added 2-bromo-1-(2-phenylpyrimidin-5-yl)ethanone (Step B, 50 mg, 0.18 mmol). The reaction mixture was heated at 40° C. for one hour and cooled to room temperature. To the mixture was added water (10 mL) with vigorous stirring and the precipitate was filtered, washed with water, and dried on the suction filter to provide 2-oxo-2-(2-phenylpyrimidin-5-yl)ethyl 2-phenylacetate as a tan solid (34.5 mg, 57% yield) as an isolated intermediate. The tan solid was dissolved in toluene (4 mL) and freshly prepared ammonium acetate under toluene (300 mg wet with toluene) was added and the mixture was stirred vigorously and heated in a capped vial at 112° C. overnight. The brown reaction mixture was poured into aqueous sodium bicarbonate and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to dryness. The brown solid was dissolved in dichloromethane and chromatographed on a 4 g silica column eluted with 1:4:5 to 1:6:3 dichloromethane-ethyl acetate-hexane to afford the title compound as a tan solid; Rf 0.08 with 6:4 v/v hexanes-ethyl acetate and Rf 0.61 with 3:7 v/v hexanes-ethyl acetate; melting point 235° C.; 1H-NMR (400 MHz; DMSO-d6) δ 9.21 (s, 2H), 8.3-8.5 (m, 2H), 7.82 (d, 1H), 7.5-7.6 (m, 3H), 7.2-7.4 (m, 5H), 4.08 (s, 2H); MS (ESI+) m/z 313 (M+1); H-PGDS FPBA IC50: 0.625 μM; H-PGDS inhibitor EIA IC50: 0.059 μM.

1. temperaturecooled to room temperature
2. filtrationthe precipitate was filtered
3. washwashed with water
4. customdried on the suction
5. filtrationfilter

ORD record

ord-3b82c153793849d1b1767a4e618ea711

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536185B2