反应详情

温度

100 °C

[5-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amine (P-1497, 1 equivalent) is dissolved in 25 mL of dioxane in a sealable vial. Cesium carbonate (2.1 equivalents), copper(I) iodide (1.5 equivalents), acetamide (174, 22 equivalents) and N,N′-dimethylethylenediamine (17 equivalents) are added. The vial is sealed and heated at 100° C. overnight. The reaction is added to ethyl acetate and brine and extracted. The organic layer is concentrated under vacuum and the resulting material dissolved in dichloromethane and purified by silica gel column chromatography, eluting with 0-10% methanol in dichloromethane. Appropriate fractions are concentrated, and the material dissolved in tetrahydrofuran for further purification on a C18 reverse phase column, eluting with 0-100% methanol (with 10% tetrahydrofuran)/water. Appropriated fractions are combined and concentrated under vacuum. The resulting material is triturated with methyl tert-butyl ether and filtered, washing with methyl tert-butyl ether, then heptane. The solid is dried under vacuum to provide the desired compound.

1. customThe vial is sealed
2. extractionextracted
3. concentrationThe organic layer is concentrated under vacuum
4. dissolutionthe resulting material dissolved in dichloromethane
5. custompurified by silica gel column chromatography
6. washeluting with 0-10% methanol in dichloromethane
7. concentrationAppropriate fractions are concentrated
8. dissolutionthe material dissolved in tetrahydrofuran for further purification on a C18 reverse phase column
9. washeluting with 0-100% methanol (with 10% tetrahydrofuran)/water
10. concentrationconcentrated under vacuum
11. customThe resulting material is triturated with methyl tert-butyl ether
12. filtrationfiltered
13. washwashing with methyl tert-butyl ether
14. customThe solid is dried under vacuum