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

HRID 515769Notes

Reaction equation

HRID 515769 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

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), K2CO3 (0.498 g, 3.60 mmol). The mixture was degassed for 10 min. to the above mixture was then 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. Cooled and degassed with Ar, added more CuI 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 product was purified by normal phase chromatography followed by prep. HPLC. After partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), the organic layer was washed with brine and dried (MgSO4) to afford 0.157 g (54%) of Intermediate 18A as a white solid with recovered starting material. MS (ESI) m/z: 328 (M+H)+.

Workup

  1. customThe mixture was degassed for 10 min. to the above mixture
  2. temperatureCooled
  3. customdegassed with Ar
  4. additionadded more CuI
  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 product was purified by normal phase chromatography
  12. customAfter partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL)
  13. washthe organic layer was washed with brine
  14. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-94aa7e55597e4f008f2d80ffae141f3f
Source dataset
uspto-grants-2015_08
Patent number
US09108951B2

Reaction notes

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