反应详情

温度

100 °C

2′-chloro-9′-isopropyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 208; 88 mg, 0.32 mmol), 4-amino-5-chloro-2-fluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide (Intermediate 207; 101 mg, 0.36 mmol) and XANTPHOS (17 mg, 0.03 mmol) were dissolved in 1,4-dioxane (7.5 mL). Caesium carbonate (229 mg, 0.65 mmol) was added and the system purged with a stream of nitrogen for 15 minutes before tris(dibenzylideneacetone) palladium (II) (18 mg, 0.02 mmol) was 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 washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by column chromatography (2.5% 7N ammonia in MeOH/DCM) to yield the title compound as a pale yellow foam (148 mg, 90%).

1. additionwas added
2. customThe apparatus was evacuated
3. temperatureThe mixture was cooled
4. filtrationfiltered
5. customthe filtrate absorbed on to an SCX column, which
6. washwas washed with methanol
7. washeluted with ammonia in methanol
8. additionProduct containing fractions
9. concentrationwere concentrated
10. custompurified by column chromatography (2.5% 7N ammonia in MeOH/DCM)