反应详情

温度

110 °C

A flask was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (391 mg, 0.55 mmol), 6-chloro-4-(5-(1-(dimethylamino)-2-methylpropan-2-yloxy)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (150 mg, 0.43 mmol), X-phos (31 mg, 0.06 mmol) and potassium phosphate tribasic (199 mg, 0.94 mmol). The mixture was taken up in n-butanol (2.8 ml) and water (0.67 ml) and vacuum de-gassed and placed under argon atmosphere. To this mixture was added bis(dibenzylideneacetone)palladium (17 mg, 0.03 mmol) and the vacuum de-gas cycle was repeated. The material was heated at 110° C. (oil bath) with vigorous stirring under argon atmosphere for 2.5 hours. The flask was cooled to ambient and the contents were taken up in water (35 ml) and ethyl acetate (35 ml). The contents were transferred to a separatory funnel and shaken. The organic phase was collected and washed with water (35 ml). The aqueous phases were back extracted with ethyl acetate (2×30 ml) and the organic phases combined, dried (magnesium sulfate), filtered and stripped. The remainder was purified by preparative thin layer chromatography (3 plates), eluting with 8% methanol/dichloromethane to provide desired product (together with some des-acetyl product) as a golden brown oil (312 mg). (M+H)+=684 (642) m/e.

1. customwater (0.67 ml) and vacuum de-gassed
2. customthe vacuum de-gas cycle
3. temperatureThe flask was cooled to ambient and the contents
4. customThe contents were transferred to a separatory funnel
5. stirringshaken
6. customThe organic phase was collected
7. washwashed with water (35 ml)
8. extractionThe aqueous phases were back extracted with ethyl acetate (2×30 ml)
9. dry with materialdried (magnesium sulfate)
10. filtrationfiltered
11. customThe remainder was purified by preparative thin layer chromatography (3 plates)
12. washeluting with 8% methanol/dichloromethane