反应详情

A solution of thiazol-2-amine (0.027 g, 0.273 mmol) in 3 mL of MeCN was treated with SEM-Cl (0.048 ml, 0.273 mmol), and the reaction mixture was allowed to stir for one hour. LC/MS showed mostly product, so 1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonyl chloride (Intermediate BBBB; 0.100 g, 0.248 mmol) was added as a solution in 3 mL of MeCN, followed by 1-methylimidazole (0.049 ml, 0.497 mmol). After stirring at room temperature for an additional hour, LC/MS showed mostly desired product. The reaction mixture was concentrated then dissolved in 4N HCl in dioxanes (1.862 ml, 7.45 mmol), and the reaction mixture was heated to 110° C. for 3 hours. The reaction mixture was concentrated and was purified by reverse phase column chromatography [C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-n-(thiazol-2-yl)phthalazine-6-sulfonamide. 1H NMR (acetonitrile-d3) δ ppm: 9.70 (s, 1H), 8.63 (s, 1H), 8.20 (d, J=8.7 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.62 (d, J=7.7 Hz, 1H), 7.45-7.53 (m, 2H), 7.02 (d, J=4.7 Hz, 1H), 6.65 (d, J=4.7 Hz, 1H), 3.75 (s, 3H). m/z (ESI) 467.0 (M+H)+

1. stirringAfter stirring at room temperature for an additional hour