Sodium hydride → HCID 67282042, compound

HRID 1616164Notes

Reaction equation

HRID 1616164 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=2)[CH:7]=[CH:6][NH:5]1.Br[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C>[C:25]([O:24][C:23]([NH:22][CH2:21][CH2:20][CH2:19][N:5]1[CH:6]=[CH:7][C:8]2[C:13](=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=2)[C:4]1=[O:3])=[O:29])([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 60075037Methyl 1-oxo-1,2-dihydroisoquinoline-7-carboxylate

Product 1

HCID 67282042HCID 67282042, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a stirred suspension of sodium hydride (60% in mineral oil, 0.30 g, 7.4 mmol) in DMF (10 mL) under an atmosphere of nitrogen was added methyl 1-oxo-1,2-dihydroisoquinoline-7-carboxylate (1.0 g, 4.9 mmol) in DMF (10 mL) dropwise. The mixture was stirred for 30 mins, then tert-butyl (3-bromopropyl)carbamate (1.76 g, 7.4 mmol) dissolved in DMF (5 mL) was added dropwise via cannula and the resulting solution was stirred at rt overnight. The reaction was quenched 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 (20% to 90% EtOAc/hexanes) to afford methyl 2-{3-[(tert-butoxycarbonyl)amino]propyl}-1-oxo-1,2-dihydroisoquinoline-7-carboxylate (0.99 g, 56%). LC-MS: (FA) ES+ 361.

Workup

  1. additionwas added dropwise via cannula
  2. stirringthe resulting solution was stirred at rt overnight
  3. customThe reaction was quenched with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic phases were then washed with water, and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash silica gel chromatography (20% to 90% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7bbd9c20929445afac775f9e8e989331
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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