反应详情

温度

-20 °C

To a cooled (−20° C.) solution of tert-butyl 4-[4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylate (1.20 g, 3.04 mmol) in tetrahydrofuran (15 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (435 mg, 1.21 mmol) in four portions over 15 min. The mixture was allowed to stir (−20° C.) for 3 h. The reaction was quenched with the addition saturated aqueous Na2SO3 (20 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (2×25 mL). The combined organics were dried (Na2SO4) and concentrated. The crude material was purified by ISCO® chromatography using a gradient of 25 to 75% ethyl acetate in hexanes. 1H-NMR indicated the presence of residual hydantoin side product, thus the material was partitioned between ethyl acetate (50 mL) and 5% aqueous K2CO3 (50 mL). The layers were separated and the organic layer was further washed with 5% aqueous K2CO3 (2×25 mL). The combined aqueous was back extracted with ethyl acetate (2×25 mL) and the combined organics were washed with brine, dried (Na2SO4) and concentrated to afford 340 mg (23%) of the desired product as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 7.91-7.83 (m, 3 H), 7.09 (s, 1 H), 7.00 (d, 2H), 3.50-3.42 (m, 4 H), 3.20-3.14 (m, 4 H), 1.42 (s, 9 H); ES-MS m/z 473.0 [M+H]+, HPLC RT (min) 3.25.

1. customThe reaction was quenched with the addition saturated aqueous Na2SO3 (20 mL)
2. temperatureto warm to rt
3. extractionThe mixture was extracted with ethyl acetate (2×25 mL)
4. dry with materialThe combined organics were dried (Na2SO4)
5. concentrationconcentrated
6. customThe crude material was purified by ISCO® chromatography
7. customthus the material was partitioned between ethyl acetate (50 mL) and 5% aqueous K2CO3 (50 mL)
8. customThe layers were separated
9. washthe organic layer was further washed with 5% aqueous K2CO3 (2×25 mL)
10. extractionThe combined aqueous was back extracted with ethyl acetate (2×25 mL)
11. washthe combined organics were washed with brine
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated