反应详情

To a 4.1° C. solution of 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol (71.55 g, 237 mmol) in DMA (350 mL) was added a DMA (350 mL) solution of phenyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (80.5 g, 230 mmol). The temperature rose to 18.4° C. and stabilized. The ice bath was removed and the reaction was stirred for 2 hours. An additional portion of 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol was added and the reaction was stirred for 2 hours. The reaction mixture was partitioned between isopropyl acetate (1.6 L) and water (2.4 L). The aqueous layer was removed and the organic layer was washed with 0.5 N NaOH (2×2.4 L) and then saturated brine (1×2.4 L). The organic layer was dried over Na2SO4 (300 g) and concentrated to yield 110.8 g (86.6%).

1. customrose to 18.4° C.
2. customThe ice bath was removed
3. additionAn additional portion of 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol was added
4. stirringthe reaction was stirred for 2 hours
5. customThe reaction mixture was partitioned between isopropyl acetate (1.6 L) and water (2.4 L)
6. customThe aqueous layer was removed
7. washthe organic layer was washed with 0.5 N NaOH (2×2.4 L)
8. dry with materialThe organic layer was dried over Na2SO4 (300 g)
9. concentrationconcentrated
10. customto yield 110.8 g (86.6%)