反应详情

温度

100 °C

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 109 mg, 0.36 mmol), aniline (Intermediate 229; 83 mg, 0.324 mmol), and caesium carbonate (211 mg, 0.648 mmol) added to dioxane (3 mL) and the suspension bubbled with nitrogen for 10 minutes. Tris-dibenzylideneacetone dipalladium (II) (11 mg, 0.02 mmol) and XANTPHOS (17 mg, 0.03 mmol) were added and the mixture heated to 100° C. for 16 hours. The reaction mixture was cooled to room temperature filtered, and the filter cake 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. Product containing fractions were combined and evaporated and the residue purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (95 mg, 56%).

1. customthe suspension bubbled with nitrogen for 10 minutes
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfiltered
4. washthe filter cake 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. additionProduct containing fractions
10. customevaporated
11. customthe residue purified by base modified reverse phase preparative HPLC