反应详情

温度

80 °C

A mixture of N-[3-(4-hydroxy-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6yloxy)-propyl]-methanesulfonamide (530 mg, 1.77 mmol) and POCl3 was heated at 80° C. for 1.5 h. The volatiles were removed and the residue was diluted with dichloromethane, washed successively with cold NaHCO3 solution and brine, dried, and concentrated in vacuo to afford the crude chloroimidate intermediate (610 mg), which was heated with 4-fluoro-2-methyl-1H-indol-5-ol (495 mg, 3.0 mmol) and K2CO3 (3.0 g, 22 mmol) in DMF (8 mL) at 80-85° C. for 2 h. The mixture was diluted with dichloromethane and the solid was filtered. The filtrate was concentrated and the residue was purified by silica gel flash column chromatography eluting with 30% ethyl acetate/dichloromethane. The desired product was further purified by preparative HPLC to afford the title compound (290 mg, 34% yield) as a tan solid.

1. customThe volatiles were removed
2. additionthe residue was diluted with dichloromethane
3. washwashed successively with cold NaHCO3 solution and brine
4. customdried
5. concentrationconcentrated in vacuo
6. customto afford the crude chloroimidate intermediate (610 mg), which
7. filtrationthe solid was filtered
8. concentrationThe filtrate was concentrated
9. customthe residue was purified by silica gel flash column chromatography
10. washeluting with 30% ethyl acetate/dichloromethane
11. customThe desired product was further purified by preparative HPLC