Cesium carbonate → Methyl 2-{3-[(tert-butoxycarbonyl)(4-methoxyphenyl)amino]propyl}-1-oxo-1,2-dihydroisoquinoline-7-carboxylate

HRID 1616159Notes

Reaction equation

HRID 1616159 reaction equation
Br[CH2:2][CH2:3][CH2:4][N:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][C:9]([C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:11]=2)[C:6]1=[O:19].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:31]([O:30][C:29]([N:28]([C:25]1[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=1)[CH2:2][CH2:3][CH2:4][N:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][C:9]([C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:11]=2)[C:6]1=[O:19])=[O:35])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2741326tert-Butyl-4-methoxycarbanilateHCID 67282659Methyl 2-(3-bromopropyl)-1-oxo-1,2-dihydroisoquinoline-7-carboxylate

Product 1

HCID 67281624Methyl 2-{3-[(tert-butoxycarbonyl)(4-methoxyphenyl)amino]propyl}-1-oxo-1,2-dihydroisoquinoline-7-carboxylateYield 39.3%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 2-(3-bromopropyl)-1-oxo-1,2-dihydroisoquinoline-7-carboxylate (0.19 g, 0.60 mmol) dissolved in DMF (10 mL) was added tert-butyl (4-methoxyphenyl)carbamate (0.20 g, 0.89 mmol), tetra-n-butylammonium iodide (0.44 g, 1.19 mmol) and cesium carbonate (0.39 g, 1.19 mmol). The reaction mixture was stirred at rt for 6 h. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (0% to 60% EtOAc/hexanes) to afford methyl 2-{3-[(tert-butoxycarbonyl)(4-methoxyphenyl)amino]propyl}-1-oxo-1,2-dihydroisoquinoline-7-carboxylate (0.11 g, 38%). LC-MS: (FA) ES+ 467.

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic phases were then washed with water, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash silica gel chromatography (0% to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a2c943e3d42949b981c06b3d9c86df78
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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