反应详情

To a solution of 2-methoxypyrimidine-5-carboxylic acid (57 mg, 0.370 mmol), DIPEA (0.161 mL, 0.925 mmol), and toluene (3 mL) was added DPPA (0.104 mL, 0.481 mmol). The reaction was stirred at 80° C. for 2 h. (S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine hydrochloride (Intermediate 1) (134 mg, 0.376 mmol) was then added as a solid in one portion. After 16 h, the reaction was concentrated in vacuo and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0-100% EtOAc in hexane, to provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3): δ ppm 8.96 (s, 2H), 8.90 (d, J=3.8 Hz, 1H), 8.22 (d, J=7.5 Hz, 1H), 8.05 (d, J=6.9 Hz, 1H), 7.63-7.45 (m, 6H), 6.85 (d, J=7.7 Hz, 1H), 4.07 (s, 3H). MS (ESI pos. ion) m/z: 472.0 (M+H).

1. additionwas then added as a solid in one portion
2. concentrationthe reaction was concentrated in vacuo
3. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
4. washeluting with 0-100% EtOAc in hexane