反应详情

温度

110 °C

[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product.

1. customthe solution is degassed under nitrogen
2. additionThe above solution is added over 10 hours to
3. customdegassed
4. temperatureHeating
5. additionafter the end of addition
6. temperatureThe reaction mixture is cooled
7. extractionextracted with EtOAc
8. dry with materialThe combined organic extracts are dried (Na2SO4)
9. concentrationconcentrated under reduced pressure
10. washFlash chromatography on silica with 10-50% EtOAc:hexanes gradient elution