反应详情

温度

95 °C

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylate (Intermediate 25, 0.598 g), N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.997 g), tris-(dibenzylideneacetone)dipalladium (0) (0.057 g) and tri-tert-butylphosphonium tetrafluoroborate (0.036 g) in dioxane (15 mL) and DMSO (1.5 mL) was de-gassed and purged with nitrogen then heated to 95° C. under an atmosphere of nitrogen for 2 hours. Further amounts of tris-(dibenzylideneacetone)dipalladium (0) (0.057 g) and tri-tert-butylphosphonium tetrafluoroborate (0.036 g) were added and the mixture stirred and heated at 95° C. for 2 hours. Further amounts of N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.997 g), tris-(dibenzylideneacetone)dipalladium (0) (0.057 g) and tri-tert-butylphosphonium tetrafluoroborate (0.036 g) were added and the mixture was stirred and heated at 95° C. for 30 minutes. After cooling, the mixture was diluted with ethyl acetate and washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-30% to give methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diaza-cyclopenta[a]naphthalene-6-carboxylate (0.158 g) as a light brown foam.

1. customwas de-gassed
2. custompurged with nitrogen
3. additionFurther amounts of tris-(dibenzylideneacetone)dipalladium (0) (0.057 g) and tri-tert-butylphosphonium tetrafluoroborate (0.036 g) were added
4. temperatureheated at 95° C. for 2 hours
5. additionFurther amounts of N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.997 g), tris-(dibenzylideneacetone)dipalladium (0) (0.057 g) and tri-tert-butylphosphonium tetrafluoroborate (0.036 g) were added
6. stirringthe mixture was stirred
7. temperatureheated at 95° C. for 30 minutes
8. temperatureAfter cooling
9. additionthe mixture was diluted with ethyl acetate
10. washwashed with water
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationThe filtrate was concentrated in vacuo
14. customthe residue was purified by chromatography on silica
15. washeluting with a mixture of methanol and DCM with a gradient of 0-30%