反应详情

温度

72 °C

To a 10 mL reaction flask was added tert-butyl 4-methylenepiperidine-1-carboxylate (81 mg, 0.411 mmol) and was purged with N2(g) three times. 9-BBN (0.821 ml, 0.411 mmol) was added and the clear solution refluxed (72° C.) for 1 hour. The reaction was cooled to ambient temperature and then added directly to a mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (181 mg, 0.370 mmol; prepared as in Example 7, Step B), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (10.1 mg, 0.0123 mmol) and potassium carbonate (68.1 mg, 0.493 mmol) in DMF:H2O (1 mL:0.1 mL). The dark orange mixture was stirred at 60° C. for 6 hours, then cooled to ambient temperature and poured into water. The pH was adjusted to 11 with 1N NaOH, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (Biotage 25M) eluting with 3% MeOH/CH2Cl2 to afford the desired product. Yield: 25 mg, 11%. LRMS (APCI pos) m/e 562.1 (M+H).

1. customTo a 10 mL reaction flask
2. customwas purged with N2(g) three times
3. temperatureThe reaction was cooled to ambient temperature
4. temperaturecooled to ambient temperature
5. extractionthe aqueous layer was extracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. customevaporated
9. customThe residue was purified by silica gel column chromatography (Biotage 25M)
10. washeluting with 3% MeOH/CH2Cl2