反应详情

温度

100 °C

4-Amino-5-chloro-2-fluorobenzoic acid tert-butyl ester (Intermediate 177; 123 mg, 0.5 mmol) was dissolved in dioxane (7.5 mL). 10-Chloro-2-cyclopentyl-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-8,10,12-trien-5-one (Intermediate 1; 155 mg, 0.55 mmol), XANTPHOS (27 mg, 0.05 mmol) and caesium carbonate (327 mg, 1.0 mmol) were added. The system was purged with a stream of nitrogen for 15 minutes and then tris(dibenzylideneacetone) palladium (II) (28 mg, 0.03 mmol) added. The apparatus was evacuated and backfilled with nitrogen (×3) and then heated at 100° C. for 3 hours. The mixture was cooled, filtered and the filtrate absorbed on to an SCX column, which was subsequently washed with methanol and eluted with ammonia in methanol. Product containing fractions were evaporated and the residue purified by column chromatography (2% MeOH/DCM) to yield the title compound as a pale yellow foam (225 mg, 92%).

1. customThe system was purged with a stream of nitrogen for 15 minutes
2. customThe apparatus was evacuated
3. temperatureThe mixture was cooled
4. filtrationfiltered
5. customthe filtrate absorbed on to an SCX column, which
6. washwas subsequently washed with methanol
7. washeluted with ammonia in methanol
8. additionProduct containing fractions
9. customwere evaporated
10. customthe residue purified by column chromatography (2% MeOH/DCM)