反应详情

温度

60 °C

A round-bottomed flask was charged with 6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxylic acid (0.1 g, 0.28 mmol, made by the method described in Example 1), n,n-diisopropylethylamine (0.07 mL, 0.42 mmol), o-(7-azabenzotriazol-1-yl)-n,n,n′,n-tetramethyluronium hexafluorophosphate (0.15 g, 0.39 mmol), and DMF (1 mL). This mixture was stirred for 15 min before N-(5-aminopyrimidin-2-yl)acetamide (0.045 g, 0.29 mmol, Step B) was introduced. The reaction mixture was stirred at 60° C. for 16 h, then partitioned between EtOAc (15 ml) and brine (10 mL). The aqueous layer was back exacted with EtOAc (3×10 mL) and the combined EtOAc layer was dried (Na2SO4) and concentrated. The crude product was dissolved in DCM and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 4% of MeOH in CH2Cl2, to provide N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide as an off-white solid. MS (ESI, pos. ion) m/z: 491 (M+1).

1. additionwas introduced
2. custompartitioned between EtOAc (15 ml) and brine (10 mL)
3. dry with materialthe combined EtOAc layer was dried (Na2SO4)
4. concentrationconcentrated
5. dissolutionThe crude product was dissolved in DCM
6. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
7. washeluting with a gradient of 0% to 4% of MeOH in CH2Cl2