Diisopropylethylamine → N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence