1,10-Phenanthroline → tert-Butyl 4-(isoquinolin-5-yl)-3-oxopiperazine-1-carboxylate

HRID 63828

반응식

HRID 63828 반응식
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[O:12]=[C:13]1[NH:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[CH:7]1[C:8]2[C:3](=[C:2]([N:18]3[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:14][C:13]3=[O:12])[CH:11]=[CH:10][CH:9]=2)[CH:4]=[CH:5][N:6]=1

참가 물질

7

반응물 4

HCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 7364875-BromoisoquinolineHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

생성물 1

HCID 131732696tert-Butyl 4-(isoquinolin-5-yl)-3-oxopiperazine-1-carboxylate수율 54%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
130 °C

실험 절차

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)+.

후처리

  1. customThe mixture was degassed for 10 min
  2. temperatureAfter cooling
  3. customdegassing with argon, more CuI
  4. additionwas added
  5. temperatureheating
  6. waitAfter 24 h
  7. customthe reaction was quenched with dilute NH4OH (15 mL)
  8. extractionextracted with EtOAc (3×30 mL)
  9. washThe combined organic layers were washed with brine (15 mL)
  10. dry with materialdried (MgSO4)
  11. customThe crude product was purified by normal phase chromatography
  12. customAfter partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer
  13. washwas washed with brine
  14. dry with materialdried (MgSO4)

출처 및 근거

ORD 기록
ord-f0027b1bae5f4804afe82ce71258eba7
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447110B2

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