反应详情

温度

110 °C

2′-chloro-9′-cyclohexyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 270; 100 mg, 0.31 mmol), 4-amino-N-(1-ethyl-4-piperidyl)-2,5-difluoro-benzamide (Intermediate 235; 98 mg, 0.34 mmol) and caesium carbonate (204 mg, 0.62 mmol) added to dioxane (5 mL) and the suspension bubbled with nitrogen for 10 minutes. Tris(dibenzylideneacetone) palladium (II) (18 mg, 0.02 mmol) and XANTPHOS (17 mg, 0.03 mmol) added and the mixture heated at 110° C. overnight. The mixture was filtered and the filtrate loaded onto an SCX-3 column was pre-wet with methanol and the column washed with methanol and eluted with 2% 7N ammonia/methanol. The ammoniacal fraction was evaporated and the residue purified by base modified reverse phase preparative HPLC to yield the title compound as a white crystalline solid (19 mg, 11%).

1. customthe suspension bubbled with nitrogen for 10 minutes
2. filtrationThe mixture was filtered
3. washthe column washed with methanol
4. washeluted with 2% 7N ammonia/methanol
5. customThe ammoniacal fraction was evaporated
6. customthe residue purified by base modified reverse phase preparative HPLC