反应详情

温度

100 °C

A mixture of (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amine (0.25 g, 1.0 eq, 0.8 mmol), 4-((1-(oxetan-3-yl)piperidin-4-yl)oxy)-3-(trifluoromethyl)aniline (0.3 g, 1.2 eq, 1.0 mmol), PTSA (0.14 g, 0.9 eq, 0.8 mmol) was taken in iPrOH (20 mL) and heated at 100° C. overnight. The volatiles were removed under vacuum to leave a crude solid. The crude mixture was dissolved in EtOAc (50 mL) and partitioned with 1N aqueous NaOH solution (25 mL). Organic layers were separated and the aqueous layer was washed with EtOAc (2×20 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum to leave a crude solid. The solid was purified by column chromatography on silica gel (ISCO System) using 2M NH3 in MeOH/CH2Cl2 (gradient system from 0:1 to 2:8) as eluent to give the product in 70% yield.

1. customThe volatiles were removed under vacuum
2. customto leave a crude solid
3. custompartitioned with 1N aqueous NaOH solution (25 mL)
4. customOrganic layers were separated
5. washthe aqueous layer was washed with EtOAc (2×20 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated under vacuum
8. customto leave a crude solid
9. customThe solid was purified by column chromatography on silica gel (ISCO System)
10. customto give the product in 70% yield