Citric Acid → HCID 22175437, compound

HRID 1797601Notes

Reaction equation

HRID 1797601 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:26]([OH:28])=O)=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:35][NH:36][O:37][CH3:38].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[N:11]([CH2:30][CH:31]([CH3:32])[CH3:33])[C:12](=[O:29])[C:13]2[C:18]([C:19]=1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[CH:17][C:16]([C:26]([N:36]([O:37][CH3:38])[CH3:35])=[O:28])=[CH:15][CH:14]=2)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 311Citric AcidHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22175400HCID 22175400, compound

Product 1

HCID 22175437HCID 22175437, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinecarboxylic acid (0.81 g, 1.8 mmol), N,O-dimethylhydroxylamine hydrochloride (0.211 g, 2.16 mmol), 1-hydroxy-1H-benzotriazole monohydrate (0.365 g, 2.7 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.517 g, 2.7 mmol) and N,N-dimethylformamide (10 mL) was added triethylamine (0.301 mL, 2.16 mmol), and the mixture was stirred at room temperature for 17 h. The reaction mixture was poured into 0.1 M aqueous citric acid solution (100 mL) and extracted 3 times with ethyl acetate (50 mL). The organic layers were combined, washed once with 0.1 M aqueous citric acid solution (50 mL), twice with saturated aqueous sodium hydrogencarbonate (50 mL) and once with saturated brine (50 mL), dried over anhydrous magnesium sulfate (15 g), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:4 (v/v)) to give tert-butyl(2-isobutyl-6-{[methoxy(methyl)amino]carbonyl}-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl)methylcarbamate (0.83 g, 94%) as a colorless, solid.

Workup

  1. extractionextracted 3 times with ethyl acetate (50 mL)
  2. washwashed once with 0.1 M aqueous citric acid solution (50 mL), twice with saturated aqueous sodium hydrogencarbonate (50 mL) and once with saturated brine (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate (15 g)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:4 (v/v))

Sources & evidence

ORD record
ord-320ac90b5d8e4904b39be4f7fcc9d829
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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