反应详情

温度

100 °C

10-chloro-2-cyclohexyl-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 266; 33 mg, 0.113 mmol), 4-amino-2,5-difluoro-N-(1-methyl-4-piperidyl)benzamide (Intermediate 59; 29 mg, 0.108 mmol) and caesium carbonate were added to dioxane (3 mL) and the suspension bubbled with nitrogen for 10 minutes. tris(dibenzylideneacetone) palladium (II) (4 mg, 0.006 mmol) and XANTPHOS (6 mg, 0.1 mmol) were added and the mixture heated at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and filtered. The filter-cake was washed with DCM and the filtrate evaporated. The residue was dissolved in DCM and purified on a silica column eluting with a gradient of 0-5% 2M ammonia in MeOH/DCM over 30 column volumes. Fractions containing product were combined and evaporated to a solid, which was triturated with isohexane then filtered and dried to yield the title compound as a pale yellow solid (46 mg, 81%).

1. customthe suspension bubbled with nitrogen for 10 minutes
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfiltered
4. washThe filter-cake was washed with DCM
5. customthe filtrate evaporated
6. dissolutionThe residue was dissolved in DCM
7. custompurified on a silica column
8. washeluting with a gradient of 0-5% 2M ammonia in MeOH/DCM over 30 column volumes
9. additionFractions containing product
10. customevaporated to a solid, which
11. customwas triturated with isohexane
12. filtrationthen filtered
13. customdried