4-Methylmorpholine → HCID 57959388, compound

Participants

Reaction Steps

To a stirring mixture consisting of 2-phenylpyrimidine-5-carboxylic acid (Compound 17; synthesis described in Example 1, Steps 1-3 of WO 2007/041634 to Aldous et al., entitled “Pyrimidine Amide Compounds as PGDS Inhibitors”; 200 mg) in N,N-dimethylformamide (15 mL) was added successively N-methylmorpholine (Aldrich, 0.33 mL), N-phenethylenediamine (Acros, 173 mg), 1-hydroxybenzotriazole (209 mg), and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 227 mg). The reaction mixture was stirred overnight under an argon atmosphere and was subsequently concentrated slightly under reduced pressure. The concentrate was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL). The layers were separated and the organic phase was washed twice with water (2×200 mL) and once with brine solution (200 mL), was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give an off-white solid. Trituration with a small amount of absolute ethanol at room temperature, collection by vacuum filtration, and suction drying afforded the title compound as a white powder (0.230 g, 72.3% yield); 1H-NMR (300 MHz; CDCl3) δ 9.13 (s, 2H), 8.51 (dd, 2H), 7.61-7.51 (m, 3H), 7.21 (t, 2H), 6.79 (t, 1H), 6.70 (d, 2H), 6.57 (broad m, 1H), 3.99 (broad m, 1H), 3.75 (m, 2H), 3.48 (t, 2H); MS (APCl+) m/z 319.

Provenance & Evidence