反应详情

温度

100 °C

To a solution of 3-[(5-bromo-2-chloro-pyrimidin-4-yl)-butan-2-yl-amino]-N-methyl-propanamide (Intermediate 88; 559 mg, 1.60 mmol) in anhydrous 1,4-dioxane (15 mL) was added Caesium Carbonate (1.04 g, 3.19 mmol). Nitrogen was bubbled through the reaction mixture for 10 minutes, prior to addition of Tris(dibenzylideneacetone)dipalladium(0) (87 mg, 0.095 mmol) and XANTPHOS (88 mg, 0.152 mmol). The reaction was heated to 100° C. and stirred under nitrogen m for 18 hrs. The reaction mixture was cooled and diluted to ˜40 ml with DCM. The reaction mixture was filtered to remove insoluble material, washing filter cake through with DCM. The filtrate was evaporated to give a brown gum which was purified by flash chromatography on silica (40 g cartridge; ISCO companion) eluting with a 25-75% gradient of ethyl acetate in iso-hexane. Product containing fractions were combined and evaporated to give a waxy off white solid which was trituration with hot iso-hexane afforded, on cooling, and collection by suction filtration the title compound as a pale yellow solid (121 mg, 28%)

1. customNitrogen was bubbled through the reaction mixture for 10 minutes
2. temperatureThe reaction mixture was cooled
3. filtrationThe reaction mixture was filtered
4. customto remove insoluble material
5. washwashing
6. filtrationfilter cake through with DCM
7. customThe filtrate was evaporated
8. customto give a brown gum which
9. customwas purified by flash chromatography on silica (40 g cartridge; ISCO companion)
10. washeluting with a 25-75% gradient of ethyl acetate in iso-hexane
11. additionProduct containing fractions
12. customevaporated
13. customto give a waxy off white solid which
14. customafforded
15. temperatureon cooling
16. customcollection
17. filtrationby suction filtration the title compound as a pale yellow solid (121 mg, 28%)