Cesium carbonate → 6-Aminoisoquinoline

Benzophenone imine (445 μL, 2.64 mmol) was added to a mixture of 6-bromoisoquinoline (500 mg, 2.4 mmol), BINAP (60 mg, 0.1 mmol), palladium acetate (12 mg, 0.05 mmol) and cesium carbonate (1.0 g, 3.07 mmol) in THF (10 ml) at room temperature. The mixture was degassed (N2×3) then heated at reflux under a nitrogen atmosphere for 16 hours. The reaction was then cooled to room temperature, partitioned between ethyl acetate (20 ml) and water (20 ml) and the aqueous phase extracted with ethyl acetate (20 ml). The combined organic phases were evaporated then re-dissolved in THF (15 ml). Hydrochloric acid (2N, aqueous, 4 ml) was added, then after stirring for 1 hour the THF was evaporated. The mixture was partitioned between ethyl acetate (20 ml) and 3M HCl (50 ml) and the aqueous phase washed with ethyl acetate (20 ml). The aqueous phase was basified (12N NaOH) then extracted with dichloromethane (3×50 ml). The combined organic phases were dried (Na2SO4) and evaporated to give the title compound (360 mg).

1. customThe mixture was degassed (N2×3)
2. temperaturethen heated
3. temperatureat reflux under a nitrogen atmosphere for 16 hours
4. custompartitioned between ethyl acetate (20 ml) and water (20 ml)
5. extractionthe aqueous phase extracted with ethyl acetate (20 ml)
6. customThe combined organic phases were evaporated
7. dissolutionthen re-dissolved in THF (15 ml)
8. additionHydrochloric acid (2N, aqueous, 4 ml) was added
9. customwas evaporated
10. customThe mixture was partitioned between ethyl acetate (20 ml) and 3M HCl (50 ml)
11. washthe aqueous phase washed with ethyl acetate (20 ml)
12. extractionthen extracted with dichloromethane (3×50 ml)
13. dry with materialThe combined organic phases were dried (Na2SO4)
14. customevaporated

ORD record

ord-40ed525822054e4fad6f0c829ed2b87a

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07285563B2