To a solution consisting of 1-(2-phenylpyrimidin-5-yl)ethanone (Example 14, Step A, 46 mg, 0.23 mmol) and methyl nicotinate (35 mg, 0.25 mmol) in tetrahydrofuran (1 mL) was added a solution consisting of potassium tert-butoxide in tetrahydrofuran (0.28 mL, 0.28 mmol). The reaction mixture was stirred overnight. Analysis of the reaction mixture by TLC (1:3 ethyl acetate-hexanes) showed the 1-(2-phenylpyrimidin-5-yl)ethanone was not consumed. To the reaction mixture was added methyl nicotinate (118 mg, 0.86 mmol) and sodium hydride (10 mg, 0.23 mmol, 60% dispersion), and the reaction mixture was heated at 50° C. for one hour. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride and sodium chloride and the organic material was extracted three times with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered and concentrated to dryness to provide a crude material. To a solution consisting of this crude material in acetic acid was added excess hydrazine hydrate and the reaction mixture was heated at 50° C. for two hours followed by 80° C. overnight. The reaction mixture was diluted with saturated aqueous sodium bicarbonate and the organic material was extracted three times with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude material was chromatographed on silica (4 g) eluted with 1:4:5 v/v dichloromethane-ethyl acetate-hexane to 1:6:4 to afford the title compound (10 mg) as a tan solid; H-PGDS FPBA IC50: 1.3 μM.
