Reaktion #92106

Reaktionsgleichung

5-bromoisoquinoline

tert-butyl 3-oxopiperazine-1-carboxylate

1,10-phenanthroline

K2CO3

→

Intermediate 21A

Ausbeute 54.0%

tert-Butyl 4-(isoquinolin-5-yl)-3-oxopiperazine-1-carboxylate

Ausbeute 54.0%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed for 10 min
2. 2
   TemperaturAfter cooling
3. 3
   Sonstigedegassing with argon, more CuI
4. 4
   workup.ADDITIONwas added
5. 5
   Temperaturheating
6. 6
   workup.WAITAfter 24 h
7. 7
   Sonstigethe reaction was quenched with dilute NH4OH (15 mL)
8. 8
   Extraktionextracted with EtOAc (3×30 mL)
9. 9
   WaschenThe combined organic layers were washed with brine (15 mL)
10. 10
    Trocknendried (MgSO4)
11. 11
    SonstigeThe crude product was purified by normal phase chromatography
12. 12
    SonstigeAfter partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer
13. 13
    Waschenwas washed with brine
14. 14
    Trocknendried (MgSO4)

Vorschrift

To 5-bromoisoquinoline (0.3 g, 1.442 mmol) and tert-butyl 3-oxopiperazine-1-carboxylate (0.289 g, 1.442 mmol) was added DMSO (4 mL), 1,10-phenanthroline (0.026 g, 0.144 mmol) and K2CO3 (0.498 g, 3.60 mmol). The mixture was degassed for 10 min and then was added CuI (0.055 g, 0.288 mmol). The reaction was heated in a sealed tube in oil bath at 130° C. After 24 h, the reaction was incomplete. After cooling and degassing with argon, more CuI was added and heating was repeated. After 24 h, the reaction was quenched with dilute NH4OH (15 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (15 mL) and dried (MgSO4). The crude product was purified by normal phase chromatography followed by HPLC. After partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer was washed with brine and dried (MgSO4) to afford 0.157 g (54%) of Intermediate 21A as a white solid. MS (ESI) m/z: 328 (M+H)+.

Quelle