Triethylaluminum → 4-[4-(5-Ethyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 717082Notes

Reaction equation

HRID 717082 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[NH:22][C:23](=[O:32])[C:24]4[C:29]([CH:30]=3)=[C:28](Br)[CH:27]=[CH:26][CH:25]=4)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Al](CC)(CC)[CH2:34][CH3:35]>C1COCC1.CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[NH:22][C:23](=[O:32])[C:24]4[C:29]([CH:30]=3)=[C:28]([CH2:34][CH3:35])[CH:27]=[CH:26][CH:25]=4)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 16682930TriethylaluminumHCID 717351534-[4-(5-Bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 717351544-[4-(5-Ethyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 2

HCID 178424406HCID 178424406, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-[4-(5-Bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.4 mmol) in anhydrous THF (4 mL) under N2 was added dichlorobis(tri-o-tolylphosphine)palladium(II) (14 mg, 0.02 mmol), CeCl3 (99 mg, 0.4 mmol) and AlEt3 (1M in hexanes, 1.5 mL, 1.2 mmol) and the reaction stirred at RT for 4 h. The reaction was quenched with ice, diluted with 0.5M aqueous Rochelle's salts (30 mL) and extracted with EtOAc (3×40 mL). The combined organics were washed with Rochelle's salts (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo and the crude residue purified by reverse phase preparative HPLC-MS to afford 4-[4-(5-ethyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester as an orange solid (83 mg, 61%).

Workup

  1. customThe reaction was quenched with ice
  2. additiondiluted with 0.5M aqueous Rochelle's salts (30 mL)
  3. extractionextracted with EtOAc (3×40 mL)
  4. washThe combined organics were washed with Rochelle's salts (2×50 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude residue purified by reverse phase preparative HPLC-MS

Sources & evidence

ORD record
ord-3922b63dc8294e0e9990f9cad0c34368
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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