Ethoxyacetyl chloride → 1-(2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol

HRID 1798864Notes

Reaction equation

HRID 1798864 reaction equation
[CH2:1]([O:3][CH2:4][C:5](Cl)=O)[CH3:2].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])=[N:16][CH:15]=[CH:14][CH:13]=2>N1C=CC=CC=1>[CH2:1]([O:3][CH2:4][C:5]1[N:19]([CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])[C:18]2[C:17]3[N:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[CH:10][C:9]=2[N:8]=1)[CH3:2]

Participants

4

Reactant 2

HCID 84189Ethoxyacetyl chlorideHCID 221726871,1-Dimethyl-2-[(3-amino[1,5]naphthyridin-4-yl)amino]ethanol

Product 1

HCID 672032571-(2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-olYield 85%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Under a nitrogen atmosphere, ethoxyacetyl chloride (19.1 g, 0.156 mol) was added over a period of 12 minutes to a mixture of 1-[(3-amino[1,5]naphthyridin-4-yl)amino]-2-methylpropan-2-ol (28.95 g, 0.125 mol) in pyridine (300 mL). The reaction mixture was stirred at ambient temperature for 4 hours and then at reflux for 4 hours. The reaction mixture was allowed to cool to ambient temperature overnight and then concentrated under high vacuum. The residue was dissolved in 5% potassium carbonate (200 mL) and then extracted with dichloromethane (200 mL). The extract was filtered to remove some insoluble material, dried over magnesium sulfate, filtered, and then concentrated under high vacuum. The residue was dissolved in dichloromethane (150 mL) and eluted through a short column of alumina. The eluent was concentrated under reduced pressure and air dried to provide 31.9 g of 1-(2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol.

Workup

  1. temperatureat reflux for 4 hours
  2. temperatureto cool to ambient temperature overnight
  3. concentrationconcentrated under high vacuum
  4. dissolutionThe residue was dissolved in 5% potassium carbonate (200 mL)
  5. extractionextracted with dichloromethane (200 mL)
  6. filtrationThe extract was filtered
  7. customto remove some insoluble material
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under high vacuum
  11. dissolutionThe residue was dissolved in dichloromethane (150 mL)
  12. washeluted through a short column of alumina
  13. concentrationThe eluent was concentrated under reduced pressure and air
  14. customdried

Sources & evidence

ORD record
ord-3e890fd966f24e659190d7d02b0373f4
Source dataset
uspto-grants-2013_01
Patent number
US08343993B2

Reaction notes

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