反应详情

温度

80 °C

To a solution of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (5.50 g, 11.98 mmol), [4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amine (4.5 g, 18 mmol, 1.50 equiv.), and potassium iodide (<20 mg) in trifluoroethanol (200 mL) in a 300 mL sealed tube was added hydrochloric acid as a 4.0M solution in dioxane (12 mL, 48 mmol, 4 equiv.). The vessel was sealed and the resulting suspension was stirred rapidly at 80° C. for 12 hours. TLC/LCMS analysis indicates starting material still remains, so additional hydrochloric acid (5 mL as a 4.0M solution in dioxane) and potassium iodide (<20 mg) were added and heating was continued. Three such reactions were cooled and poured directly in saturated sodium bicarbonate/methylene chloride. The organic layer was collected, concentrated under reduced pressure, and then resuspended in diethylether. Sonication for 10 minutes was followed by filtration to give crude 8-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one as an orange solid with sufficient purity for use in the next transformation (23.5 g, ca 99% yield, purity 85-90%). ESIMS (M+H)+=655.

1. customThe vessel was sealed
2. temperatureheating
3. temperatureThree such reactions were cooled
4. customThe organic layer was collected
5. concentrationconcentrated under reduced pressure
6. customSonication for 10 minutes
7. filtrationwas followed by filtration