Triethylamine → HCID 22176276, compound

HRID 1797748Notes

Reaction equation

HRID 1797748 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:11]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:12](=[O:29])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:17][C:16](C(O)=O)=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:41])C=CC=CC=1.C([N:53]([CH2:56]C)CC)C.Cl.[CH3:59][O:60][NH2:61]>CN(C)C=O.O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[N:11]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:12](=[O:29])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:17][C:16]([NH:53][C:56]([NH:61][O:60][CH3:59])=[O:41])=[CH:15][CH:14]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 22175400HCID 22175400, compound

Product 1

HCID 22176276HCID 22176276, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

To solution of 3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-6-carboxylic acid (0.15 g, 0.33 mmol) in N,N-dimethylformamide (5 mL) was added diphenylphosphoryl azide (0.09 mL, 0.40 mmol) and triethylamine (0.056 mL, 0.40 mmol), and the mixture was stirred at room temperature for 2 h. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (30 mL×2). The organic layers were combined, washed with water (50 mL) and brine (20 mL), dried, over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in toluene (20 mL), and the solution was refluxed for 1 h. The reaction mixture was allowed to cool to room temperature, and a mixture of O-methylhydroxyamine hydrochloride (0.088 g, 0.40 mmol) and triethylamine (0.056 mL, 0.40 mmol) in N,N-dimethylformamide (2 mL) was added thereto. The resulting reaction mixture was stirred at room temperature for 1 h and then poured into water (100 mL). The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with 0.1M aqueous citric acid solution (20 mL) and brine (10 mL), dried over anhydrous, magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1 (v/v)) to give tert-butyl(2-isobutyl-6-{[(methoxyamino)carbonyl]amino}-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl)methylcarbamate (0.13 g, 81%) as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate (30 mL×2)
  2. washwashed with water (50 mL) and brine (20 mL)
  3. dry with materialdried, over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in toluene (20 mL)
  6. temperaturethe solution was refluxed for 1 h
  7. temperatureto cool to room temperature
  8. additionwas added
  9. customThe resulting reaction mixture
  10. stirringwas stirred at room temperature for 1 h
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted twice with ethyl acetate
  13. washwashed with 0.1M aqueous citric acid solution (20 mL) and brine (10 mL)
  14. dry with materialdried over anhydrous, magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1 (v/v))

Sources & evidence

ORD record
ord-3ab8b0b4c7e44a2fbdff835511a5fa69
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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