反应详情

温度

90 °C

A resealable pressure tube, purged with argon, was charged with 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine (150 mg, 0.329 mmol), bis(triphenylphosphine)palladium(II) chloride (14 mg, 0.020 mmol), copper(I) iodide (3.8 mg, 0.020 mmol), and 3,3-dimethyl-1-butyne (0.101 mL, 0.823 mmol). This mixture was purged with argon for 10 minutes, followed by addition of acetonitrile (3.3 ml, 0.1 M). The pressure tube was sealed and the mixture inside heated to 90° C. for 16 hrs. The next day, the reaction was stopped, cooled to RT, diluted with dichloromethane and filtered over a plug of celite. Filtrate was concentrated to afford a 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 4-(3,3-dimethylbut-1-ynyl)-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine as a yellow solid. MS m/z=502 [M+H]+. Calc'd for C30H27N7O: 501.58.

1. customA resealable pressure tube, purged with argon
2. customThis mixture was purged with argon for 10 minutes
3. additionfollowed by addition of acetonitrile (3.3 ml, 0.1 M)
4. customThe pressure tube was sealed
5. temperaturecooled to RT
6. additiondiluted with dichloromethane
7. filtrationfiltered over a plug of celite
8. concentrationFiltrate was concentrated
9. customto afford a brown residue, which
10. customwas purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA)
11. additionbasified by addition of aq. NaHCO3
12. extractionextracted with ethyl acetate
13. dry with materialThe organic portion was dried with Na2SO4
14. filtrationfiltered
15. concentrationconcentrated