1-Propanol → HCID 11632226, compound

HRID 598010Notes

Reaction equation

HRID 598010 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[CH:12]=[N:13][C:14]2[C:15]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[C:23]([CH2:29][O:30][CH2:31][CH3:32])=[N:22][C:16]=3[C:17]([NH2:21])=[N:18][C:19]=2[CH:20]=1.C(O)CC.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH2:31]([O:30][CH2:29][C:23]1[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[C:15]2[C:14]3[N:13]=[CH:12][C:11]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[CH:20][C:19]=3[N:18]=[C:17]([NH2:21])[C:16]=2[N:22]=1)[CH3:32]

Participants

8

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 67052511HCID 67052511, compound

Product 1

HCID 11632226HCID 11632226, compoundYield 67.4%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

Pyridine-3-boronic acid (0.39 g, 3.2 mmol) was added to 7-bromo-2-(ethoxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (1.0 g, 2.6 mmol) and 1-propanol (17 mL). The mixture was degassed and backfilled with nitrogen. Aqueous 2M sodium carbonate (1.6 mL), water (2 mL), triphenylphosphine (0.021 g, 0.079 mmol), and palladium (II) acetate (0.0058 g, 0.026 mmol) were added to the reaction mixture followed by subsequent degassing. The mixture became homogenous upon heating at reflux for 1 hour. After an additional 1 hour of heating, the reaction was cooled to ambient temperature and extracted into chloroform. The resulting solution was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by automated flash chromatography (using a silica gel cartridge, eluting with CMA:chloroform ranging in ratios from 0:100 to 30:70) and concentrated under reduced pressure. The product was recrystallized from acetonitrile, filtered, and dried at 60° C. under vacuum to provide 0.66 g of 2-(ethoxymethyl)-1-(2-methylpropyl)-7-(pyridin-3-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as a white solid, mp 177-179° C.

Workup

  1. customThe mixture was degassed
  2. temperatureupon heating
  3. temperatureat reflux for 1 hour
  4. temperatureAfter an additional 1 hour of heating
  5. extractionextracted into chloroform
  6. washThe resulting solution was washed with saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by automated flash chromatography (
  11. washeluting with CMA
  12. concentrationchloroform ranging in ratios from 0:100 to 30:70) and concentrated under reduced pressure
  13. customThe product was recrystallized from acetonitrile
  14. filtrationfiltered
  15. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-e61b9526305a4ba7a5ec82fbfc5aea95
Source dataset
uspto-grants-2011_03
Patent number
US07897609B2

Reaction notes

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