With triethylamine In N,N-dimethyl-formamide at 80℃;
23 Example 23 1-(4-chloroisoquinolin-1-yl)-3-(1',4-dimethyl-1-phenyl-1H,1'H-[3,4'-bipyrazol]-5-yl)urea
To a solution of phenyl l',4-dimethyl-l-phenyl-lH,l'H-3,4'-bipyrazol-5- ylcarbamate (Intermediate 3, 100 mg, 0.27 mmol) in DMA (3 mL) was added Et3N (0.13 mL, 0.94 mmol) and 4-chloroisoquinolin-l -amine (53 mg, 0.30 mmol). The reaction mixture was heated at 80 °C overnight. The reaction was partitioned between EtOAc and water, the aqueous layer was extracted with EtOAc, and the combined organic layers were washed with water and brine, dried and concentrated. The crude product was purified by reverse-phase column chromatography, eluting with 5-95% acetonitrile in water, to afford the title compound (12 mg, 10%). MS (apci) m/z = 458.1 (M+H).