反应详情

温度

100 °C

A mixture of ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (300 mg, 0.7 mmol), 2-piperidinone (90 mg, 0.91 mmol), Pd(OAc)2 (0.010 mg, 0.064 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.020 g, 0.049 mmol), and Cs2CO3 (0.28 g, 0.86 mmol) in dioxane (1 mL) was purged with nitrogen and then heated at 100° C. in a sealed vial for 1 h. The solution was allowed to cool and NH4Cl solution and EtOAc were added. The resulting layers were separated and the aqueous phase was extracted twice with EtOAc. The combined organic extracts were concentrated to dryness under reduced pressure. To the resulting residue, 1 mL of dioxane, 2 mL of THF, and 2 mL of 2 M NaOH were added. The reaction mixture was heated at 80° C. for 0.5 h. The mixture was neutralized with HCl and extracted with DCM. The combined organic extracts were evaporated under reduced pressure. The residue was dissolved in 20 mL of DMF and purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.) to afford the title compound (88 mg, 30%). LCMS calc. for C23H22N3O5 [M+H]+: m/z=420.2. found: 420.2.

1. customwas purged with nitrogen
2. temperatureto cool
3. additionNH4Cl solution and EtOAc were added
4. customThe resulting layers were separated
5. extractionthe aqueous phase was extracted twice with EtOAc
6. concentrationThe combined organic extracts were concentrated to dryness under reduced pressure
7. additionTo the resulting residue, 1 mL of dioxane, 2 mL of THF, and 2 mL of 2 M NaOH were added
8. temperatureThe reaction mixture was heated at 80° C. for 0.5 h
9. extractionextracted with DCM
10. customThe combined organic extracts were evaporated under reduced pressure
11. dissolutionThe residue was dissolved in 20 mL of DMF
12. custompurified by preparative HPLC (XBridge™ C18 column
13. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.)