تفاعل #92106

معادلة التفاعل

5-bromoisoquinoline

tert-butyl 3-oxopiperazine-1-carboxylate

1,10-phenanthroline

K2CO3

→

Intermediate 21A

المردود 54.0%

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

المردود 54.0%

المذيبات

DMSO

ظروف التفاعل

المعالجة

1. 1
   أخرىThe mixture was degassed for 10 min
2. 2
   درجة الحرارةAfter cooling
3. 3
   أخرىdegassing with argon, more CuI
4. 4
   workup.ADDITIONwas added
5. 5
   درجة الحرارةheating
6. 6
   workup.WAITAfter 24 h
7. 7
   أخرىthe reaction was quenched with dilute NH4OH (15 mL)
8. 8
   استخلاصextracted with EtOAc (3×30 mL)
9. 9
   غسيلThe combined organic layers were washed with brine (15 mL)
10. 10
    تجفيفdried (MgSO4)
11. 11
    أخرىThe crude product was purified by normal phase chromatography
12. 12
    أخرىAfter partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer
13. 13
    غسيلwas washed with brine
14. 14
    تجفيفdried (MgSO4)

الإجراء التجريبي

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)+.

المصدر