反应详情

温度

70 °C

A resealable pressure vial was charged with 5,6-difluoro-N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine (0.14 g, 0.28 mmol), 3-(4-methylpiperazin-1-yl)propan-1-amine (0.18 g, 1.13 mmol), and 2-propanol (1.89 ml, 0.15 M). The reaction vessel was sealed and the mixture stirred at 70° C. for 16 h. The reaction mixture was cooled to RT, diluted with DCM, and washed with Aq. NaHCO3. The organic layer was collected, dried over Na2SO4, and concentrated to afford brown residue, which was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA). The product-containing fractions were combined, basified by addition of aq. NaHCO3 and extracted with ethyl acetate. The organic portion was dried with Na2SO4, filtered, and concentrated to afford pure 5,6-difluoro-N-(4-(3-(2-(3-(4-methylpiperazin-1-yl)propylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine as a yellow solid. MS m/z=572.2 [M+H]+. Calc'd for C30H31F2N9O: 571.62.

1. customThe reaction vessel was sealed
2. temperatureThe reaction mixture was cooled to RT
3. washwashed with Aq. NaHCO3
4. customThe organic layer was collected
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customto afford brown residue, which
8. customwas purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA)
9. additionbasified by addition of aq. NaHCO3
10. extractionextracted with ethyl acetate
11. dry with materialThe organic portion was dried with Na2SO4
12. filtrationfiltered
13. concentrationconcentrated