反応 #92106

反応方程式

5-bromoisoquinoline

tert-butyl 3-oxopiperazine-1-carboxylate

1,10-phenanthroline

K2CO3

→

Intermediate 21A

収率 54.0%

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

収率 54.0%

溶媒

DMSO

反応条件

後処理

1. 1
   その他The mixture was degassed for 10 min
2. 2
   温度After cooling
3. 3
   その他degassing with argon, more CuI
4. 4
   workup.ADDITIONwas added
5. 5
   温度heating
6. 6
   workup.WAITAfter 24 h
7. 7
   その他the reaction was quenched with dilute NH4OH (15 mL)
8. 8
   抽出extracted with EtOAc (3×30 mL)
9. 9
   洗浄The combined organic layers were washed with brine (15 mL)
10. 10
    乾燥dried (MgSO4)
11. 11
    その他The crude product was purified by normal phase chromatography
12. 12
    その他After partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer
13. 13
    洗浄was washed with brine
14. 14
    乾燥dried (MgSO4)

実験手順

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)+.

出典